AU2016293619A1 - Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases - Google Patents

Abstract

The present invention provides novel peptide inhibitors of the interleukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel diseases.

Description

The present invention provides novel peptide inhibitors of the inter leukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel diseases.

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DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG).

Published:

— with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) — with sequence listing part of description (Rule 5.2(a)) (88) Date of publication of the international search report:

February 2017

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PCT/US2016/042680

PEPTIDE INHIBITORS OF INTERLEUKIN-23 RECEPTOR AND THEIR USE

TO TREAT INFLAMMATORY DISEASES

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to and is a continuation-in-part of U.S. Application No. 14/800,627 filed on July 15, 2015, and also claims priority to International Patent Application PCT/US2015/040658 filed on July 15, 2015, U.S. Provisional Application No. 62/264,820 filed on December 8, 2015, and U.S. Provisional Application No. 62/281,123 filed on January 20, 2016, all of which are incorporated by reference herein in theirentireties.

SEQUENCE LISTING [0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on July 15, 2016, is named PRTH-002-03WO_SL.txt and is 504 KB in size

FIELD OF THE INVENTION [0003] The present invention relates to novel peptide inhibitors of the interleukin-23 receptor, and their use to treat or prevent a variety of diseases and disorders, including inflammatory bowel disease, Crohn’s disease and psoriasis.

BACKGROUND [0004] The interleukin-23 (IL-23) cytokine has been implicated as playing a crucial role in the pathogenesis of autoimmune inflammation and related diseases and disorders, such as multiple sclerosis, asthma, rheumatoid arthritis, psoriasis, and inflammatory bowel diseases (IBDs), e.g., ulcerative colitis and Crohn’s disease. Studies in acute and chronic mouse models of IBD revealed a primary role of IL-23R and downstream effector cytokines in disease pathogenesis. IL-23R is expressed on various adaptive and innate immune cells including Thl7 cells, γδ T cells, natural killer (NK) cells, dendritic cells, macrophages, and innate lymphoid cells, which are found abundantly in the intestine. At the intestine mucosal surface, the gene expression and protein levels of IL-23R are found to be elevated in IBD patients. It is believed that IL-23

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PCT/US2016/042680 mediates this effect by promoting the development of a pathogenic CD4⁺ T cell population that produces IL-6, IL-17, and tumor necrosis factor (TNF).

[0005] Production of IL-23 is enriched in the intestine, where it is believed to play a key role in regulating the balance between tolerance and immunity through T-cell-dependent and T-cellindependent pathways of intestinal inflammation through effects on T-helper 1 (Thl) and Thl 7associated cytokines, as well as restraining regulatory T-cell responses in the gut, favoring inflammation. In addition, polymorphisms in the IL-23 receptor (IL-23R) have been associated with susceptibility to IBDs, further establishing the critical role of the IL-23 pathway in intestinal homeostasis.

[0006] Psoriasis, a chronic skin disease affecting about 2%-3% of the general population has been shown to be mediated by the body’s T cell inflammatory response mechanisms. 11-23 has one of several interleukins implicated as a key player in the pathogenesis of psoriasis, purportedly by maintaining chronic autoimmune inflammation via the induction of interleukin17, regulation of T memory cells, and activation of macrophages. Expression of IL-23 and IL23R has been shown to be increased in tissues of patients with psoriasis, and antibodies that neutralize IL-23 showed IL-23-dependent inhibition of psoriasis development in animal models of psoriasis.

[0007] IL-23 is a heterodimer composed of a unique pi9 subunit and the p40 subunit of IL-12, which is a cytokine involved in the development of interferon-γ (IFN-y)-producing T helper 1 (ThI) cells. Although IL-23 and IL-12 both contain the p40 subunit, they have different phenotypic properties. For example, animals deficient in IL-12 are susceptible to inflammatory autoimmune diseases, whereas IL-23 deficient animals are resistant, presumably due to a reduced number of CD4⁺ T cells producing IL-6, IL-17, and TNF in the CNS of IL-23-deficient animals. IL-23 binds to IL-23R, which is a heterodimeric receptor composed of IL-12RQ1 and IL-23R subunits. Binding of IL-23 to IL-23R activates the Jak-stat signaling molecules, Jak2, Tyk2, and Statl, Stat 3, Stat 4, and Stat 5, although Stat4 activation is substantially weaker and different DNA-binding Stat complexes form in response to IL-23 as compared with IL-12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with Stat3. In contrast to

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IL-12, which acts mainly on naive CD4(+) T cells, IL-23 preferentially acts on memory CD4(+) T cells.

[0008] Efforts have been made to identify therapeutic moieties that inhibit the IL-23 pathway, for use in treating IL-23-related diseases and disorders. A number of antibodies that bind to IL23 or IL-23R have been identified, including ustekinumab, a humanized antibody that binds IL23, which has been approved for the treatment of psoriasis. More recently, polypeptide inhibitors that bind to IL-23R and inhibit the binding of IL-23 to IL-23R have been identified (see, e.g., US Patent Application Publication No. US2013/0029907). Clinical trials in Crohn’s Disease or psoriasis with ustekinumab and briakinumab (which target the common p40 subunit) and tildrakizumab, guselkumab, MEDI2070, and BI-655066 (which target the unique pi9 subunit of IL-23) highlight the potential of IL-23 signaling blockade in treatment of human inflammatory diseases. While these findings are promising, challenges remain with respect to identifying stable and selective agents that preferentially target the IL-23 pathway in the intestine, which can be used for the treatment of intestinal inflammation, such as intestinal bowel diseases, including Crohn’s disease, ulcerative colitis and related disorders.

[0009] Clearly, there remains a need in the art for new therapeutics targeting the IL-23 pathway, which may be used to treat and prevent IL-23-asociated diseases, including those associated with autoimmune inflammation in the intestinal tract. In addition, compounds and methods for specific targeting of IL-23R from the luminal side of the gut may provide therapeutic benefit to IBD patients suffering from local inflammation of the intestinal tissue. The present invention addresses these needs by providing novel peptide inhibitors that bind IL-23R to inhibit IL-23 binding and signaling and which are suitable for oral administration.

BRIEF SUMMARY OF THE INVENTION [0010] The present invention provides inter alia novel peptide inhibitors of IL-23R and related methods of use.

In a first aspect, the present invention provides a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an ammo acid sequence of Formula (Xa): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12XI3-XI4-X15-X16-X17-X18-X19-X20 (Xa),

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PCT/US2016/042680 wherein:

XI, X2 and X3 are any amino acid or absent

X4 is any amino acid or chemical moiety capable of forming a bond with X9;

X5, X6, X7 and X8 are any amino acid;

X9 is any amino acid or chemical moiety capable of forming a bond with X4;

XI0, XI1, XI2, XI3, XI4 and XI5 are any amino acid; and

XI6, XI7, XI8, XI9 and X20 are any amino acid or absent;

wherein the peptide inhibitor is cyclized via a bond between X4 and X9, and wherein the peptide inhibitor inhibits the binding of an interleukin-23 (IL-23) to an IL-23 receptor.

[0011] In certain embodiments of Xa:

[0012] XI is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Ala, D-MeOrn, □MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Arg, Ser or Thr; X6 is Asp or Thr; X7 is Trp or 6-Chloro-Trp; X8 is Glu, Gln or Val; X9 is Cys, Abu or Pen; XI0 is 2-Nal, a Phe analog, Tyr, or a Tyr analog; XI1 is 1-Nal, 2-Nal, Phe(3,4-dimethoxy), 5HydroxyTrp, Phe(3,4-C12), Trp or Tyr(3-tBu); XI2 is 3-Pal, Acpc, Acbc, Acvc, Ache, Agp, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), a-MeLeu, α-MeOrn, a-MeSer, α-MeVal, Cav, Cha, Cit, Cpa, D-Asn, Glu, His, hLeu, hArg, Lys, Leu, Octgly, Orn, 4-amino-4-carboxy-piperidine, Arg, Ser, Thr or THP; XI3 is Cit, Asp, Dab, Dap, Phe, His, Dap(Peg2-Ac), Dap(pyroglutaric acid), Glu, HomoArg, Lys, Lys(Ac), Lys(Benzoic acid), Lys(glutaric acid), Lys(IVA), Lys(Peg4isoGlu-Palm), Lys(pyroglutaric acid), Lys(succinic acid), Asn, Orn, Gln, Arg, Thr or Val; XI4 is Asp, Dab(Ac), Dap(Ac), Phe, His, Lys(Ac), Met, Asn(isobutyl), Gln, Arg, Tyr or Asp(l,4diaminobutane); and XI5 is Ala, pAla, Glu, Gly, Asn, Gln, Arg or Ser.

[0013] In certain embodiments of Xa: XI is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Ala, α-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, Orn, Gln, Arg,

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Ser or Thr; X6 is Asp or Thr; X7 is Trp or 6-Chloro-Trp; X8 is Gln or Val; X9 is Cys, Abu or Pen; X10 is 2-Nal, a Phe analog, Tyr, or a Tyr analog; XI1 is 1-Nal, 2-Nal, Phe(3,4-dimethoxy),

5-HydroxyTrp, Phe(3,4-Cl2), Trp or Tyr(3-tBu); X12 is 3-Pal, Acpc, Acbc, Acvc, Ache, Agp, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), a-MeLeu, α-MeOrn, a-MeSer, α-MeVal, Cav, Cha, Cit, Cpa, D-Asn, His, hLeu, hArg, Lys, Leu, Octgly, Orn, 4-amino-4-carboxy-piperidine, or THP; XI3 is Cit, Asp, Dab, Dap, Phe, His, Dap(Peg2-Ac), Dap(pyroglutaric acid), Glu, hArg, Lys, Lys(Ac), Lys(Benzoic acid), Lys(glutaric acid), Lys(IVA), Lys(Peg4-isoGlu-Palm), Lys(pyroglutaric acid), Lys-(succinic acid), Asn, Orn,Gln, Arg, Thr or Val; XI4 is Dab(Ac), Dap(Ac), Phe, His, Lys(Ac), Met, Asn, Gln, Arg, or Tyr; and XI5 is Ala, betaAla, Gly, Asn, Gln, or Ser.

[0014] In certain embodiments of Xa: XI is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Dap, Dap(Ac), Gly, Lys, Gln, Arg, Ser,Thr or Asn; X6 is Thr; X7 is Trp or 6Chloro-Trp; X8 is Gln; X9 is Cys, Abu or Pen; XI0 is 2-Nal, a Phe analog, Tyr, or a Tyr analog; XI1 is 1-Nal, 2-Nal, Phe(3,4-dimethoxy), Phe(3,4-Cl2), or Trp; X12 is Acpc, Acbc, Acvc, Ache, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), α-MeLeu, a-MeOrn, a-MeSer, a-MeVal, Cha, Cit, hLeu, Lys, Leu, Arg or THP; XI3 is Cit, Asp, Dap, Dap(Peg2-Ac), Dap(pyroglutaric acid), Glu, hArg, Lys, Lys(Ac), Lys(Benzoic acid), Lys(glutaric acid), Lys(IVA), Lys(Peg4-isoGluPalm), Lys(pyroglutaric acid), Lys-(succinic acid), Asn, Orn,Gln, Arg, or Val; XI4 is Dab(Ac), Dap(Ac), His, Lys(Ac), Asn, Gln, or Tyr; and XI5 is Ala, betaAla, Gly, Asn, Gln, or Ser.

[0015] In certain embodiments of Xa: XI is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Dap, Dap(Ac), Gln, Ser, Thr or Asn; X6 is Thr; X7 is Trp; X8 is Gln; X9 is Cys, Abu or Pen; XI0 is a Phe analog, Tyr, or a Tyr analog; XI1 is 2-Nal or Trp; XI2 is Acpc, Acbc, Acvc, Ache, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), a-MeLeu, a-MeOrn, a-MeSer, aMeVal, hLeu, Leu, or THP; XI3 is Cit, Asp, Glu, Lys, Lys(Ac), Asn, or Gln; XI4 is Dab(Ac), Asn, or His; and XI5 is Ala, betaAla, Gly, Asn, or Gln.

[0016] In certain embodiments of Xa: X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Sec, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid, Abu, β-azido-Ala-OH, propargylglycine, 25

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PCT/US2016/042680 (3'-butenyl)glycine, 2-allylglycine, 2-(3 '-butenyl)gly cine, 2-(4'-pentenyl)glycine, 2-(5'hexenyl)glycine, or Abu; X7 is Trp, Glu, Gly, Ile, Asn, Pro, Arg, Thr or OctGly, or a corresponding α-methyl amino acid form of any of the foregoing; X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, or Ser, Sec, Abu, β-azido-Ala-OH, propargylglycine, 2-2-allylglycine, 2-(3'butenyl)glycine, 2-(4'-pentenyl)glycine, Ala, hCys, Abu, Met, MeCys, (D)Tyr or 2-(5'hexenyl)glycine; XI0 is Tyr, Phe(4-OMe), 1-Nal, 2-Nal, Aic, α-MePhe, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, His, hPhe(3,4-dimethoxy), hTyr, N-Me-Tyr, Trp, Phe(4-CONH2), Phe(4phenoxy), Thr, Tic, Tyr(3-tBu), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4-NH₂), Phe(4-F), Phe(3,5-F₂), Phe(4-CH₂CO₂H), Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF₃), Phe(4-OCH₃), Bip, Cha,

4-PyridylAlanine, βΙΥΓγτ, OctGly, Phe(4-N₃), Phe(4-Br), Phe[4-(2-aminoethoxy)] or Phe, a Phe analog, a Tyr analog, or a corresponding α-methyl amino acid form of any of the foregoing; XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl₂), Phe (3,4-F₂), Phe(4-CO₂H), βΙιΡΙΐ6(4-Ρ), αMe-Trp, 4-phenylcyclohexyl, Phe(4-CF₃), α-MePhe, βΙΤΝΑΙ, βΙιΡΙιε, βΙιΤγΓ, βΜΎρ, Nva(5phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe(4-OMe), Phe(4-Me), Trp(2,5,7-tri-tert-Butyl), Phe(4-Oallyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino, Phe(4-OBzl), Octgly, Glu(Bzl), 4Phenylbenzylalanine, Phe[4-(2-aminoethoxy)], 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp,

1,2,3,4-tetrahydro-norharman, Phe(4-CONH₂), Phe(3,4-Dimethoxy), Phe(2,3-Cl₂), Phe(2,3-F₂), Phe(4-F), 4-phenylcyclohexylalanine, Bip, or a corresponding α-methyl amino acid form of any of the foregoing; XI2 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butylAla, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acvc, Acbc, Agp, Aib, α-DiethylGly, aMeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Aib„ D-Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Tyr, Aib, a-MeLeu,α-MeOrn, βAib, β-Ala, βΙιΑΗ, βΙιΑ^, βΙΑευ, βΙΑ^Ι, β-spiro-pip, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gin, Ser, Thr, Tie, t-butyl-Gly, or a corresponding α-methyl amino acid form of any of the foregoing; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Arg, Orn, Val, βΙιΑΗ, Lys(Ac), (D)Asn, (D)Leu, (D)Phe, (D)Thr, Ala, α-MeLeu, Aib, β-Ala, β-Glu, βϋβη, βΙΑ^Ι, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, hLeu, Asn, Ogl, Pro, Gin, Ser, β-spiro-pip, Thr, Tba, Tie or Aib, Cit, hArg, Lys, Asn, Orn, Gin or a corresponding α-methyl amino acid form of any of the foregoing; XI4 is Phe, Tyr, Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr,

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TicPhPhe, Arg, Lys(Ac), His; Dap(Ac), Dab(Ac), Asp or a corresponding α-methyl amino acid form of any of the foregoing; XI5 is Gly, Ser, Thr, Gin, Ala, (D)Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Thr, Aea, Asp, Asn, Glu, Phe, Gly, Lys, Leu, Pro, Arg, β-Ala, Sarc, or a corresponding α-methyl amino acid form of any of the foregoing; XI6 is Asp, Glu, Ala, AEA, AEP, phAla, Gaba, Gly, Ser, Pro, Asn, Thr or absent, or a corresponding α-methyl amino acid form of any of the foregoing; and XI7 is Leu, Lys, Arg, Glu, Ser, Gly, Gin or absent, or a corresponding α-methyl amino acid form of any of the foregoing.

[0017] In certain embodiments of peptide inhibitors of Xa, the bond is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefin bond.

[0018] In particular embodiments of peptide inhibitors of Xa, X4 is Cys and X9 is Cys, and the bond is a disulfide bond. In particular embodiments, X4 is Pen and X9 is Pen, and the bond is a disulfide bond. In certain embodiments: X7 is Trp; XI0 is Phe, Tyr, a Phe analog, or a Tyr analog; XI1 is Trp, 1-Nal or 2-Nal; and XI2 is Aib, α-Me-Lys, a-Me-Leu, Ache, Acvc, Acpc, Acbc or THP. In certain embodiments: X7 is Trp; XI0 is Phe, Tyr, a Phe analog, or a Tyr analog; XI1 is Trp, 1-Nal or 2-Nal; and X12 is Aib, α-Me-Lys or a-Me-Leu. In particular embodiments, the peptide inhibitor comprises any of the following the amino acid sequences: Pen-Q-T-W-Q-Pen- [Phe(4-OMe)] - [2-Nal] - [ot-Me-Ly s] -E-N-G; Pen-N-T-W-Q- [Pen]- [Phe[4-(2aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-N; Pen-Q-T-W-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2Nal]-[a-MeLeu]-[Lys(Ac)]-N-N; or Pen-Q-T-W-Q-[Pen]-[Phe(4-CONH2)]-[2-Nal]-[oc-MeLys][Lys(Ac)]-N-N, wherein the peptide inhibitor comprises a disulfide bond between the two Pen amino acids.

[0019] In particular embodiments of peptide inhibitors of Xa, X4 is an amino acid, aliphatic acid, alicyclic acid or modified 2- methyl aromatic acid having a carbon side chain capable of forming a thioether bind with X9; X9 is a sulfur-containing amino acid capable of forming a thioether bond with X4, and the bond between X4 and X9 is a thioether bond. In certain embodiments, X4 is Abu, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercaptobutyric acid, 2-chloro-acetic acid, 3-chloro-propanoic acid, 4-chloro-butyric acid, 3-chloroisobutyric acid; and X9 is Abu, Cys, Pen, hCys, D-Pen, D-Cys, or D-hCys.In certain

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PCT/US2016/042680 embodiments, X4 is Abu; and X9 is Cys. In certain embodiments, X7 is Trp; XI0 is Phe, Tyr, a Phe analog, or a Tyr analog; XI1 is Trp, 1-Nal or 2-Nal; and XI2 is a-Me-Fys, α-Me-Feu, aMe-Ser, α-Me-Val, Ache, Acvc, Acpc, Acbc, or [4-amino-4-carboxy-tetrahydropyran]. In certain embodiments, X7 is Trp; XI0 is Phe, Tyr, a Phe analog, or a Tyr analog; XI1 is Trp, 1Nal or 2-Nal; and XI2 is α-Me-Lys or [4-amino-4-carboxy-tetrahydropyran]. In particular embodiments, the peptide inhibitor comprises any of the following amino acid sequences: [Abu]Q-T-W-Q-C-[Phe(4-OMe)]-[2-Nal]-[a-MeLys]-E-N-G; [Abu]-Q-T-W-Q-C-[Phe(4-(2aminoethoxy))]-W-[a-MeLys]-E-N-G; or [Abu]-Q-T-W-Q-C-[Phe[4-(2-aminoethoxy)]]-[2Nal]-[4-amino-4-carboxy-tetrahydropyran]-E-N-N, wherein the peptide inhibitor comprises a thioether bond between the Abu and the C.

[0020] In certain embodiments of peptide inhibitors of Xa: X4 is Pen, Cys or hCys; X5 is any amino acid; X6 is any amino acid; X7 is Trp, Bip, Gln, His, Glu(Bzl), 4-Phenylbenzylalanine, Tic, Phe[4-(2-aminoethoxy)], Phe(3,4-Cl2), Phe(4-OMe), 5-Hydroxy-Trp, 6-Chloro-Trp, NMeTrp, α-Me-Trp, 1,2,3,4 -tetrahydro-norharman, Phe(4-CO2H), Phe(4-CONH2), Phe(3,4Dimethoxy), Phe(4-CF₃), Phe(4-tBu), ββ-diPheAla, Glu, Gly, Ile, Asn, Pro, Arg, Thr or Octgly, or a corresponding α-methyl amino acid form of any of the foregoing; X8 is any amino acid; X9 is Pen, Cys or hCys; XI0 is 1-Nal, 2-Nal, Aic, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, 4-pyridylAla, Octgly, a Phe analog or a Tyr analog (optionally, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetyl-aminoethoxy)], Phe(4-Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guamdino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), or Phe(4-OBzl)), or a corresponding α-methyl amino acid form of any of the foregoing; XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl2), Phe (3,4-F2), Phe(4-CO2H), β1ιΡ1ΐ6(4-Ρ), α-Me-Trp, 4-phenylcyclohexyl, Phe(4-CF₃), α-MePhe, DhNal, QhPhe, βΙιΤγΓ, βΙιΤΓρ, Nva(5-phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe(4-OMe), Phe(4-Me), Trp(2,5,7tri-tert-Butyl), Phe(4-Oallyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino, Phe(4-OBzl), Octgly, Glu(Bzl), 4-Phenylbenzylalanine, Phe[4-(2-aminoethoxy)], 5-Hydroxy-Trp, 6-Chloro-Trp, NMeTrp, 1,2,3,4-tetrahydro-norharman, Phe(4-CONH2), Phe(3,4-OMe2) Phe(2,3-Cl2), Phe(2,3F2), Phe(4-F), 4-phenylcyclohexylalanine or Bip, or a corresponding α-methyl amino acid form of any of the foregoing; XI2 is α-MeFys, a-MeOrn, a-MePeu, a-MeVal, 4-amino-4-carboxytetrahydropyran, Ache, Acpc, Acbc, Acvc, MePeu, Aib, (D)Ala, (D)Asn, (D)Peu, (D)Asp,

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PCT/US2016/042680 (D)Phe, (D)Thr, 3-Pal, Aib, β-Ala, phGlu, phAla, phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gin, Arg, Ser, Thr or Tie, or a corresponding α-methyl amino acid form of any of the foregoing; XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, a-MeLeu, β-Ala, PhGlu, phAla, phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Lys, Arg, Orn, Dab, Dap, aDiethylGly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gin, Asp, Arg, Ser, spiro-pip, Thr, Tba, Tic, Val or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing; XI4 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Tic or Tyr, Lys(Ac), Orn or a corresponding α-methyl amino acid form of any of the foregoing; XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, Asn, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gin, Arg or Ser, β-Ala, Arg or a corresponding α-methyl amino acid form of any of the foregoing; XI6 is absent, Gly, Ala, Asp, Ser, Pro, Asn or Thr, or a corresponding a-methyl amino acid form of any of the foregoing; XI7 is absent, Glu, Ser, Gly or Gin, or a corresponding α-methyl amino acid form of any of the foregoing; XI8 is absent or any amino acid; XI9 is absent or any amino acid; and X20 is absent or any amino acid. In particular embodiments, the bond between X4 and X9 is a disulfide bond. In certain embodiments, XI, X2, and X3 are absent.In certain embodiments, XI7, XI9 and X20 are absent. In certain embodiments, one or both of X4 or X9 is Pen. In certain embodiments, both X4 and X9 are Pen. In particular embodiments, XI8 is (D)-Lys. In certain embodiments, the peptide inhibitors comprise one or more, two or more, three or more, or four of the following: X5 is Arg, Asn, Gin, Dap, Orn; X6 is Thr or Ser; X7 is Trp, 2-Nal, 1-Nal, Phe(4-OAllyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(Bzl) or Phe(4-Me), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, α-MeTrp or 1,2,3,4 tetrahydro-norharman; and X8 is Gin, Val, Phe, Glu, Lys. In certain embodiments, the peptide inhibitors comprise one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following: XI0 is Tyr, Phe(4-OBzl), Phe(4-OMe), Phe(4-CONH2), Phe(3,4-Cl₂), Phe(4-tBu), Phe(4-NH₂), Phe(4-Br), Phe(4-CN), Phe(4-CO₂H), Phe(4(2aminoethoxy)) or Phe(4-guanadino); XI1 is Trp, 2-Nal, 1-Nal, Phe(4-OAllyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(Bzl) or Phe(4-Me), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, α-MeTrp or 1,2,3,4 -tetrahydro-norharman; XI2 is Arg, α-MeLys a-MeLeu, Aib or a-MeOrn; X13 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; X15 is Gly, Sr or Ala; and X16 is absent or

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AEA. In certain embodiments, X4 and X9 are Pen; X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is Tyr, Phe(4-OMe) or 2-Nal; XI1 is Trp, 2-Nal or 1-Nal; X12 is Arg, aMeLys or aMeOrn; XI3 is Lys, Glu or Lys(Ac); XI4 is Phe or Asn; XI5 is Gly; and XI6 is absent. In certain embodiments, one or more of XI, X2 and X3 are absent; and one or more, two or more, three or more, or four of XI7, XI8, XI9 and X20 are absent.

[0021] In certain embodiments of peptide inhibitors of Xa: X4 is Abu, Pen, or Cys; X7 is Trp, Bip, Gln, His, Glu(Bzl), 4-Phenylbenzylalanine, Tic, Phe[4-(2-aminoethoxy)], Phe(3,4-Cl2), Phe(4-OMe), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, α-MeTrp, 1,2,3,4 -tetrahydronorharman, Phe(4-CO2H), Phe(4-CONH2), Phe(3,4-Dimethoxy), Phe(4-CF₃), ββ-diPheAla, Phe(4-tBu), Glu, Gly, Ile, Asn, Pro, Arg, Thr or Octgly, or a corresponding α-methyl amino acid form of any of the foregoing; X9 is Abu, Pen, or Cys; XI0 is 1-Nal, 2-Nal, Aic, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, 4-pyridylAla, Octgly a Phe analog or a Tyr analog, or a corresponding α-methyl amino acid form of any of the foregoing; XI1 is 2-Nal,

1-Nal, 2,4-dimethylPhe, Bip, 4-phenylcyclohexyl, Glu(Bzl), 4-Phenylbenzylalanine, Tic, Phe[4(2-aminoethoxy)], Phe(3,4-Cl2), Phe(3,4-F2), βΗΡΗβ(4-Ρ), Phe(4-OMe), 5-Hydroxy-Trp, 6Chloro-Trp, N-MeTrp, α-MeTrp, 1,2,3,4 -tetrahydro-norharman, Phe(4-CO2H), Phe(4CONH₂), Phe(3,4-Dimethoxy), Phe(4-CF₃), Phe(2,3-Cl₂), Phe(2,3-F₂),Phe(4-F), 4phenylcyclohexylalanine, α-MePhe, βΙιΝηΙ, βΤιΡΙοβ, βΙιΤγΓ, βΙιΤΓρ, Bip, Nva(5-phenyl), Phe, His, hPhe, Tqa, Trp, Tyr, Phe(4-Me), Trp(2,5,7-tri-tertButyl), Phe(4-OAllyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(4-OBzl), or Octgly, or a corresponding α-methyl amino acid form of any of the foregoing; XI2 is α-MeLys, a-MeOrn, a-MeLeu, MeLeu, Aib, (D)Ala, (D)Asn, (D)Leu, (D)Asp, (D)Phe, (D)Thr, 3-Pal, Aib, β-Ala, βΙιΟΙυ, βήΑΗ, βϋβη, βΙΛΑΙ, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, Ν-MeLeu, NMeArg, Ogl, Orn, Pro, Gln, Arg, Ser, Thr or Tie, or a corresponding α-methyl amino acid form of any of the foregoing; XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, α-MeLeu, βΑΗ, βΙιΟΙυ, βΙιΑΝ, βΡΑβυ, βΙΑ^Ι, β-spiro-pip, Cha, Chg, Asp, Arg, Orn, Dab, Dap, aDiethylGly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, spiro-pip, Thr, Tba, Tic, Val or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing; XI4 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr, or a

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PCT/US2016/042680 corresponding α-methyl amino acid form of any of the foregoing; XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, Asn, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser, or a corresponding α-methyl amino acid form of any of the foregoing, or XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, Asn, (D)Leu, (D)Phe, (D)Thr, Ala, Asn, Ser, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser, or a corresponding α-methyl amino acid form of any of the foregoing; XI6 is absent, Gly, Ala, Asp, Ser, Pro, Asn or Thr, or a corresponding a-methyl amino acid form of any of the foregoing; and XI7 is absent, Glu, Ser, Gly or Gln, or a corresponding α-methyl amino acid form of any of the foregoing. In particular embodiments, the peptide inhibitor is cyclized via an intramolecular bond between X4 and X9.In certain embodiments, one or more of XI, X2, and X3 are absent. In certain embodiments, one or more of XI7, XI9 and X20 are absent.In certain embodiments, one of X4 or X9 is Abu, and the other of X4 or X9 is not Abu.In certain embodiments, the peptide inhibitors comprise one or more, two or more, three or more, or four of the following: X5 is Arg, Gln, Dap or Orn; X6 is Thr or Ser; X7 is Trp, 2-Nal, 1-Nal, Phe(4-0Allyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(4-OBzl), Phe(4-Me), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, or α-MeTrp, 1,2,3,4 -tetrahydronorharman; and X8 is Gln, Val, Phe, Glu or Lys. In certain embodiments, the peptide inhibitors comprise one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following: XI0 is Tyr, Phe(4-OBzl), Phe(4-OMe), Phe(4-CONH2), Phe(3,4-Cl2), Phe(4-tBu), Phe(4-NH2), Phe(4-Br), Phe(4-CN), Phe(4-CO2H), Phe(4-(2aminoethoxy)) or Phe(4guanadino); XI1 is Trp, 2-Nal, 1-Nal, Phe(4-OAllyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(Bzl) or Phe(4-Me), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, α-MeTrp or 1,2,3,4 tetrahydro-norharman; XI2 is Arg, hLeu, (D)Asn, Aib, α-MeLys, a-MeLeu or a-MeOrn; XI3 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; XI5 is Gly, Ser or Ala, or XI5 is Asn, Gly, Ser, pAla or Ala; and XI6 is absent or AEA.

[0022] In particular embodiments of any of the peptide inhibitors, X4 and X9 are Pen. In particular embodiments, X4 and X9 form a disulfide bond.

[0023] In particular embodiments, X4 is Abu and X9 is Cys. In particular embodiments, X4 and X9 form a thioether bond.

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In particular embodiments, the peptide inhibitor comprises an amino acid sequence of any one of SEQ ID NOS: 365-370, 857-1029. In particular embodiments, the peptide inhibitor is cyclized via a bond between X4 and X9, and the peptide inhibitor inhibits the binding of an interleukin-23 (IL-23) to an IL-23 receptor.

[0024] In certain embodiments of peptide inhibitors of Xa, the peptide inhibitor comprises an amino acid sequence set forth in any of Formulas (V), (Va), (Vb), (Vc), (Vd), (Ve), (Vf), (Vg) and (Vh).

[0025] In certain embodiments of peptide inhibitors of Xa, the peptide inhibitor comprises any of the following amino acid sequences:

[Palm] - [isoGlu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib] - [Ly s(Ac)] NNNH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-isoGlu-Palm)]-NNNH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[ot-MeLys(Ac)]-[Lys(Ac)]-NN-NH₂;

[Octany 1] - [IsoGlu] - [PEG4] - [Pen]-NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]- [Aib] [Lys(Ac)]-NN-NH₂;

[Octanyl]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

[Palm] - [PEG4]- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -NN NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-Octanyl)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-Palm)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-Palm)]-[2-Nal]-[Aib]-[Lys(Ac)]NNNH₂;

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Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)-(PEG4-Lauryl)] - [2-Nal] - [ Aib]- [Lys(Ac)]-NNNH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(PEG4-Palm)-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[ot-MeLys(PEG4-Lauryl)]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-IsoGlu-Palm)]-[2-Nal]-[Aib][Lys(Ac)]-NN-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)-(PEG4-IsoGLu-Laury 1)] - [2-Nal] -[Aib][Lys(Ac)]-NN-NH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(PEG4-IsoGlu-Palm)]-[Lys(Ac)]NN-NH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(PEG4-IsoGlu-Lauryl)]-[Lys(Ac)]NN-NH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(IVA)]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(Biotin)]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[oc-MeLys(Octanyl)]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-[Lys(IVA)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(IVA)]-N-NH₂;

Ac-[Pen]-[Lys(Biotin)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Biotin)]-NNH₂;

Ac-[Pen]-[Lys(Octanyl)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(octanyl)]-NNH₂;

Ac-[Pen]-[Lys(Palm)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]~ [Aib]-[Lys(Ac)]-NN-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -Ly s(Palm)] -N-NH₂;

Ac-[Pen]-[Lys(PEG8)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(PEG8)]-N-NH₂;

Ac- [Pen] -K(Peg 11 -Palm)TWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] -NNNH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]—[Aib] - [Lys(Ac)] - [Ly s(Peg 11 -palm)]N-NH₂;

Ac-[Pen]-[Cit]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-[Lys(Ac)]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

Ac- [Pen] -NT- [Phe(3,4-OCH3 )2] -Q- [Pen] - [Phe[4-(2-aminoethoxy)]- [2-Nal]- [ Aib] - [Ly s(Ac)] NN-NH₂;

Ac- [Pen] -NT - [Phe(2,4-CH3 )2] -Q- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] -NNNH₂;

Ac- [Pen] -NT- [Phe(3 -CH3)] -Q- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib]- [Ly s(Ac)] -NNNH₂;

Ac- [Pen] -NT- [Phe(4-CH3)] -Q- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib]- [Ly s(Ac)] -NNNH₂;

Ac[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[PAla]NH₂;

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Ac-[(D)Tyr]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[PAla]NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-QN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-N-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[Lys(Ac)]-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-QQ-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-Q-[PAla]-NH2;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[Cit]-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-NNH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-Q-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-[Lys(Ac)]-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-[Cit]-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QN-[PAla]-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] -E- [Cit] -Q-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -N- [Cit] -NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -Q- [Cit] -NH₂;

Ac-[Pen]-[Cit]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib] -QNN-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib]-ENQ-NH₂;

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Ac-[Pen]-GPWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-PGWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-NTWN-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-NSWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-N-[Aib]-WQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-NTW-[Aib]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]N-[Aib]-NH2;

Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-[Lys(Ac)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]NNNH2;

Ac-[Pen]-QVWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-NT-[2-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac-[Pen]-NT-[l-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [a-MeLeu]- [Lys(Ac)] -NN-NH2;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [a-MeLys] - [Lys(Ac)] -NN-NH2;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]· [Lys(Ac)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]-[Lys(Ac)]-N-[PAla]-NH2;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]-N-[PAla]-NH2;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]· [Lys(Ac)]-N-[pAla]-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-LN-NH2;

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-GN-NH2;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-SN-NH2;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Aib]-N-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-FN-NH₂;

Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Tic]-[PAla]-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] - [nLeu] - [ β A la] -NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-G-[PAla]-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -R- [ β Ala] -NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-W-^Ala]-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]—[Aib] - [Lys(Ac)] -S - [ β A la] -NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]~ [Aib]-[Lys(Ac)]-L-^Ala]-NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-[AIB]-^Ala]-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]—[Aib] - [Ly s(Ac)] - [N-MeAla] - [β Ala] NH₂;

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[2-Nap]-^Ala]-NH₂;

Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -F - [β Ala] -NH₂;

Ac-[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[ 4-amino-4-carboxytetrahydropyran]-[Lys(Ac)]NNNH₂;

Biotin-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahy dropyran] -ENN-NH₂;

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Ac-cy clo [ [ Abu] -QTWQC]- [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4-carboxytetrahydropyran] - [Ly s(Ac)] -NN-NLB;

Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahydropyran] - [Ly s(Ac)] -NN-NLB;

Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahydropyran] - [Ly s(Ac)] -NN-NLB;

Ac-E-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahydropyran] -ENN-NLB;

Ac-[(D)Asp]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahydropyranJ-ENN-NEE;

Ac-R-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahydropyran] -ENN-NLB;

inoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2;

Ac-F-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy· tetrahydropyran] -ENN-NLB;

Ac- [(D)Phe] - [(D) Arg] -cyclo[ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4carboxy-tetrahydropyran]-ENN-NLB;

Ac- [2-Nal] - [(D) Arg] -cy clo[ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4carboxy-tetrahydropyran]-ENN-NLB;

Ac-T-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahydropyran] -ENN-NLB;

Ac-L-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahydropyran] -ENN-NLB;

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Ac-[(D)Gln]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahydropyran]-ENN-NH2;

Ac-[(D)Asn]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahydropyranfrENN-NEE;

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)-(PEG4-Alexa488)]-[2-Nal]-[4-amino-4carboxy-tetrahydropyran]-ENN-NH2;

[Alexa488]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]—[2-Nal]-[4-amino-4carboxy-tetrahydropyran]-ENN-NH2;

[Alexa647]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahydropyran]-ENN-NH2;

[Alexa-647]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2;

[Alexa647]-[PEG12]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2; and [Alexa488]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2, [0026] wherein the peptide inhibitor is cyclized via a disulfide bond between two Pen residues or by a thioether bond between Abu and a Cys residue, and wherein the peptide inhibitor inhibits the binding of an interleukin-23 (IL-23) to an IL-23 receptor.

[0027] In particular embodiments, any of the peptide inhibitors described herein comprise one or more half-life extension moiety and/or one or more linker moiety conjugated to the peptide inhibitor. In particular embodiments, the half-life extension moiety is conjugated to the peptide inhibitor via one or more linker moieties.

[0028] In certain embodiments, any of the peptide inhibitors described hereinfurther comprise a conjugated chemical substituent. In particular embodiments, the conjugated chemical substituent

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PCT/US2016/042680 is a lipophilic substituent or a polymeric moiety, e.g., Ac, Palm, gamaGlu-Palm, isoGlu-Palm, PEG2-Ac, PEG4-isoGlu-Palm, (PEG)s-Palm, succinic acid, glutaric acid, pyroglutaric acid, benzoic acid, IVA, octanoic acid, 1,4 diaminobutane, isobutyl, or biotin. In certain embodiments, the conjugated chemical substituent is a polyethylene glycol with a molecular mass of 400 Da to 40,000 Da.

[0029] In another aspect, the present invention includes peptide inhibitors comprising the structure of Formula I:

R'-X-R² (I) or a pharmaceutically acceptable salt or solvate thereof, wherein

R¹ is a bond, hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl, a C1-C6 alkyl, a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing;

R² is a bond, OH or NH2; and

X is any of the peptide sequences described herein, e.g., Xa, I, Ia-It, II, Ila-IId, III, Illa-IIIe, IV, IVa-IVb, V, or Va-Vh.

[0030] In a related aspect, the present invention includes a peptide dimer inhibitor of an interleukin-23 receptor, wherein the peptide dimer inhibitor comprises two peptide monomer subunits connected via one or more linker moieties, wherein each peptide monomer subunit has a sequence or structure set forth herein. In certain embodiments, one or both peptide monomer subunit is cyclized via an intramolecular bond between X4 and X9. In certain embodiments, one or both intramolecular bond is a disulfide bond, a thioether bond, a lactam bond, a selenoether, diselenide, or an olefin bond. In certain embodiments, the linker is any of those shown in Table 2 or described herein. In certain embodiments, the linker moiety is a diethylene glycol linker, an iminodiacetic acid (IDA) linker, a β-Ala-iminodiaceticacid (β-Ala-IDA) linker, or a PEG linker. In particular embodiments, the N-terminus of each peptide monomer subunit is connected by the linker moiety. In particular embodiments, the C-terminus of each peptide monomer subunit is connected by the linker moiety. In certain embodiments, the linker connects an internal amino

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PCT/US2016/042680 acid residue of at least one of the peptide monomer subunits to the N-terminus, C-terminus, or an internal amino acid residue of the other peptide monomer subunit.

[0031] In a further related aspect, the present invention includes a polynucleotide comprising a sequence encoding a peptide inhibitor of the present invention or one or both peptide monomer subunit of a peptide dimer inhibitor of the present invention. The present invention also includes a vector comprising the polynucleotide.

[0032] In another aspect, the present invention includes a pharmaceutical composition comprising a peptide inhibitor or a peptide dimer inhibitor of the present invention, and a pharmaceutically acceptable carrier, excipient, or diluent. In particular embodiments, the pharmaceutical composition comprises an enteric coating. In certain embodiments, the enteric coating protects and releases the pharmaceutical composition within a subject’s lower gastrointestinal system.

[0033] In another aspect, the present invention includes a method for treating or preventing a disease associated with IL-23 signalling, including but not limited to an Inflammatory Bowel Disease (IBD), ulcerative colitis, Crohn’s disease, Celiac disease (nontropical Sprue), enteropathy associated with seronegative arthropathies, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, chronic granulomatous disease, glycogen storage disease type lb, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Wiskott-Aldrich Syndrome, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, psoriasis, or graft versus host disease in a subject, comprising providing to the subject an effective amount of a peptide inhibitor or pharmaceutical composition of the present invention. In certain embodiments, the inflammatory bowel disease is ulcerative colitis or Crohn’s disease. In particular embodimnts, the peptide inhibitor or the peptide dimer inhibitor inhibits binding of an interleukin-23 (IL-23) to the interleukin-23 receptor (IL-23R). In certain embodiments, the pharmaceutical composition is provided to the subject by an oral, intravenous, peritoneal, intradermal, subcutaneous, intramuscular, intrathecal, inhalation, vaporization, nebulization,

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PCT/US2016/042680 sublingual, buccal, parenteral, rectal, intraocular, inhalation, vaginal, or topical route of administration. In particular embodiments, the pharmaceutical composition is provided orally for treating Inflammatory Bowel Disease (IBD), ulcerative colitis, Crohn’s disease. In certain embodiments, the pharmaceutical composition is provided to the subject topically, parenterally, intravenously, subcutaneously, peritonealy, or intravenously for treating psoriasis.

BRIEF DESCRIPTION OF THE DRAWINGS [0034] FIG. 1 Figure 1 provides an example of a rat IL-23 dose-response curve as measured by levels of IL-17A in the rat splenoctye assay.

[0035] Figure 2 is a graph showing IL-12-dependent production of IFNy from human PBMCs treated with the indicated amounts of Compound A or Compound B.

[0036] Figure 3 shows results for DAI values from Day 7. Statistical analysis for significance was determined using Student’s t-test (GraphPad Prism). Differences were noted as signficant *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

[0037] Figure 4 shows an alignment of the amino acid sequences of human IL23R, mouse IL23R, rat IL23R, chimp IL-23R, dog IL-23R and cow IL-23R, with highly conserved amino acid residues shaded. The region of mouse IL-23R lacking in the other IL-23R species shown is shown, and a region of IL23R that may be bound by certain peptide inhibitors of the present invention is indicated by a dashed line.

[0038] Figure 5 is a table outlining the study design for TNBS induced colitis in rats.

[0039] Figures 6A-6D are graphs showing colon weight to length (Figure 6A), colon wall thickness (Table 6B, colon macroscopic score (Table 6C) or myeloperoxidase (MPO) abundance in proximal colon extracts quantified by ELISA, following sham treatment, vehicle treatment, or treatment with the indicated amounts of anti-IL23pl9 antibody or Compound C. Values are shown as mean +SD. Statistical significance assessed by one-way ANOVA: *<0.05; **<0.01; ***p<0.001; ****p<0.0001; ns, not significant.

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PCT/US2016/042680 [0040] Figure 7 provides micrographs of colon lesions found in animals following sham treatment (upper left panel), vehicle treatment (upper right panel) showing transmural inflammation, presence of necrotic tissue, and mucosa devoid of crypts, anti-IL23pl9 antibody (lower left panel), or 160 mg/kg/d Compound C (lower right panel) showing restriction of lesions to the mucosa.

[0041] Figures 8A-8E are graphs showing inflammation (Figure 8A), mucosal necrosis (Figure 8B), grand loss (Figure 8C), colon wall thickness (Figure 8D) and histological score (Figure 8E) following vehicle treatment, treatment with anti-IL23pl9 antibody, or treatment with the indicated amount of Compound C [0042] Figure 9 shows the concentration of Compound C in the plasma and proximal colon determined one hour post last PO dose (left panel), and fold above IC75 of its activity as determined by the rat splenocyte assay (middle panel) and the rat IL23R ELISA assay (right panel).

[0043] Figure 10 provides a schematic diagram depicting the structure of certain peptide inhibitors and illustrating representative types of bonds between X4 and X9.

[0044] FIGS. 11A-11E show pharmacokinetic data for the IL-23R peptide inhibitor Peptide 993 (SEQ ID NO: 993). FIG. 11A shows the concentration of Peptide 993 in serum (nM) measured at different time points up to 24 hours after oral administration of Peptide 993. FIGS. 1 IB-1 ID show the concentration of Peptide 993 (in nM) in samples taken from the Peyer’s Patch (FIG. 11B), small intestine (FIG. 11C), and the colon (FIG. 11D). The dashed line indicates 350 mM. Fig 1 IE shows the amount of Peptide 993 detected in feces 24 hours after oral administration (% dose).

[0045] FIGS. 12A-12D summarize experiments comparing systemic treatments with prodnisolone or anti-IL-23pl9 neutralizing antibody with treatment with Peptide 993 by oral administration in the TNBS model of acute colitis. FIG. 12A shows the change in body weight (percentage) from day 0 to day 7 from sham, vehicle, and Peptide 993 treated rats. FIG. 12B shows the ratio of colon weight to colon length in mg/cm of colons harvested from rats at day 7. FIG. 12C shows the colon macroscopic score of colons harvested from rats at day 7. FIG. 12D.

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PCT/US2016/042680 shows the sum of histopathology scores for colons taken from sham, vehicle, and Peptide 993 treated rats. For all experiments, statistical comparisons between groups were performed with a

1-Way ANOVA followed by a post hoc test: * p< 0.05; ** p< 0.01; *** p< 0.001; **** p< 0.0001; ns, not significant.

[0046] FIGS. 13A-13C summarizes experiments comparing systemic treatments with prodnisolone or anti-IL-23pl9 neutralizing antibody with treatment with Peptide 1185 by oral administration in the TNBS model of acute colitis. FIG. 13A shows the change in body weight (percentage) from day 0 to day 7 from sham, vehicle, and Peptide 1185 treated rats. FIG. 13B shows the ratio of colon weight to colon length in mg/cm of colons harvested from rats at day 7. FIG. 13C shows the colon macroscopic score of colons harvested from rats at day 7. For all experiments, statistical comparisons between groups were performed with a 1-Way ANOVA followed by a post hoc test: * p< 0.05; ** p< 0.01; *** p< 0.001; **** p< 0.0001; ns, not significant.

[0047] FIGS. 14A-14D summarizes experiments comparing systemic treatments with prodnisolone or anti-IL-23pl9 neutralizing antibody with treatment with Peptide 980 by oral administration in the TNBS model of acute colitis. FIG. 14A shows the change in body weight (percentage) from day 0 to day 7 from sham, vehicle, and Peptide 980 treated rats. FIG. 14B shows the ratio of colon weight to colon length in mg/cm of colons harvested from rats at day 7. FIG. 13C shows the colon macroscopic score of colons harvested from rats at day 7. FIG. 14D. shows the sum of histopathology scores for colons taken from sham, vehicle, and Peptide 980 treated rats. For all experiments, statistical comparisons between groups were performed with a

1-Way ANOVA followed by a post hoc test: * p< 0.05; ** p< 0.01; *** p< 0.001; **** p< 0.0001; ns, not significant.

[0048] FIGS. 15A-15E show levels of disease and IL-23 directed biomarkers measured in colons from rats in the sham (not TNBS-exposed) experimental group, or TNBS-exposed experimental groups that received treatment with vehicle or Peptide 993. Data is shown for MPO (FIG. 15A), IL-6 (FIG. 15B), IL-1 beta (FIG. 15C), IL-22 (FIG. 15D), and IL-17A (FIG. 15E). For all experiments, statistical comparisons between groups were performed with a

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1-Way ANOVA followed by a post hoc test: * p< 0.05; ** p< 0.01; *** p< 0.001; **** p< 0.0001; ns, not significant.

[0049] FIGS. 16A-16B show levels of disease and IL-23 directed biomarkers measured in colons from rats in the sham (not TNBS-exposed) experimental group, or TNBS-exposed experimental groups that received treatment with vehicle or Peptide 980. Data is shown for MPO (FIG. 16A) and IL-22 (FIG. 16B). For all experiments, statistical comparisons between groups were performed with a 1-Way ANOVA followed by a post hoc test: * p< 0.05; ** p< 0.01; *** p< 0.001; **** p< 0.0001; ns, not significant [0050] FIGS. 17A-17D show Schild analysis of inhibitor peptides. FIG. 17A shows a graph depicting the % Emax response as a function of increasing concentrations of IL-23 in the presence of Peptide 993 in concentrations of 0 nM (closed circles), 0.3 nM (closed squares), 1 nM (triangles), 3 nM (inverted triangles), 10 nM (diamonds), 30 nM (open circles), or 100 nM (open squares). Properties of the curves are listed below the graph. FIG. 17B depicts results from the same set of experiments, and shows a graph displaying Log(dose ratio'¹) as a function of Peptide 993 concentration (M) on a logarithmic scale. Properties of the resulting linear function are displayed below the graph. FIG. 17C shows a graph depicting the % Emax response as a function of increasing concentrations of IL-23 in the presence of the peptide of SEQ ID NO: 1169 in concentrations of 0 nM (closed circles), 0.3 nM (closed squares), 1 nM (triangles), 3 nM (inverted triangles), 10 nM (diamonds), 30 nM (open circles), or 100 nM (open squares). Properties of the curves are listed below the graph. FIG. 17D shows a graph depicting the % Emax response as a function of increasing concentrations of IL-23 in the presence of the peptide of SEQ ID NO: 1211 in concentrations of 0 nM (closed circles), 0.3 nM (closed squares), 1 nM (triangles), 3 nM (inverted triangles), 10 nM (diamonds), 30 nM (open circles), or 100 nM (open squares). Properties of the curves are listed below the graph.

[0051] FIGS. 18A-18B show pharmacokinetic data for the IL-23R peptide inhibitor Peptide 1185. FIG. 18A shows the concentration of Peptide 1185 in serum and in samples taken from small intestine and the colon. Fig 18B shows the amount of Peptide 1185 detected in urine and feces 24 hours after oral administration (% dose).

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PCT/US2016/042680 [0052] FIGS. 19A and 19B show pharmacokinetic data for the IL-23R peptide inhibitor Peptide 980. FIG. 19A shows the concentration of Peptide 980 in serum and in samples taken from small intestine and the colon. Fig 19B shows the amount of Peptide 980 detected in urine and feces 24 hours after oral administration (% dose).

DETAILED DESCRIPTION OF THE INVENTION [0053] Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. Generally, nomenclature used in connection with, and techniques of, chemistry, molecular biology, cell and cancer biology, immunology, microbiology, pharmacology, and protein and nucleic acid chemistry, described herein, are those well-known and commonly used in the art.

[0054] As used herein, the following terms have the meanings ascribed to them unless specified otherwise.

[0055] Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising” will be understood to imply the inclusion of a stated integer (or components) or group of integers (or components), but not the exclusion of any other integer (or components) or group of integers (or components).

[0056] The singular forms “a,” “an,” and “the” include the plurals unless the context clearly dictates otherwise.

[0057] The term “including” is used to mean “including but not limited to.” “Including” and “including but not limited to” are used interchangeably.

[0058] The terms “patient,” “subject,” and “individual” may be used interchangeably and refer to either a human or a non-human animal. These terms include mammals such as humans, primates, livestock animals (e.g., bovines, porcines), companion animals (e.g., canines, felines) and rodents (e.g., mice and rats).

[0059] The term “peptide,” as used herein, refers broadly to a sequence of two or more amino acids joined together by peptide bonds. It should be understood that this term does not connote a

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PCT/US2016/042680 specific length of a polymer of amino acids, nor is it intended to imply or distinguish whether the polypeptide is produced using recombinant techniques, chemical or enzymatic synthesis, or is naturally occurring.

[0060] The recitations “sequence identity”, “percent identity”, “percent homology”, or, for example, comprising a “sequence 50% identical to,” as used herein, refer to the extent that sequences are identical on a nucleotide-by-nucleotide basis or an amino acid-by-amino acid basis over a window of comparison. Thus, a “percentage of sequence identity” may be calculated by comparing two optimally aligned sequences over the window of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, I) or the identical amino acid residue (e.g., Ala, Pro, Ser, Thr, Gly, Val, Leu, Ile, Phe, Tyr, Trp, Lys, Arg, His, Asp, Glu, Asn, Gin, Cys and Met) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity.

[0061] Calculations of sequence similarity or sequence identity between sequences (the terms are used interchangeably herein) can be performed as follows. To determine the percent identity of two amino acid sequences, or of two nucleic acid sequences, the sequences can be aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). In certain embodiments, the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, 60%, and even more preferably at least 70%, 80%, 90%, 100% of the length of the reference sequence. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position.

[0062] The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences.

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PCT/US2016/042680 [0063] The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In some embodiments, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch, (1970, J. Mol. Biol. 48: 444-453) algorithm which has been incorporated into the GAP program in the GCG software package, using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In yet another preferred embodiment, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package, using an NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. Another exemplary set of parameters includes a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5. The percent identity between two amino acid or nucleotide sequences can also be determined using the algorithm of E. Meyers and W. Miller (1989, Cabios, 4: 11-17) which has been incorporated into the ALIGN program (version 2.0), using a ΡΑΜΙ 20 weight residue table, a gap length penalty of 12 and a gap penalty of 4.

[0064] The peptide sequences described herein can be used as a “query sequence” to perform a search against public databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al., (1990, J. Mol. Biol, 215: 403-10). BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to nucleic acid molecules of the invention. BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to protein molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al. (Nucleic Acids Res. 25:3389-3402, 1997). When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used.

[0065] The term conservative substitution as used herein denotes that one or more amino acids are replaced by another, biologically similar residue. Examples include substitution of amino acid residues with similar characteristics, e.g., small amino acids, acidic amino acids, polar amino acids, basic amino acids, hydrophobic amino acids and aromatic amino acids. See, for

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PCT/US2016/042680 example, the table below. In some embodiments of the invention, one or more Met residues are substituted with norleucine (Nle) which is a bioisostere for Met, but which, as opposed to Met, is not readily oxidized. Another example of a conservative substitution with a residue normally not found in endogenous, mammalian peptides and proteins is the conservative substitution of Arg or Lys with, for example, ornithine, canavanine, aminoethylcysteine or another basic amino acid. In some embodiments, one or more cysteines of a peptide analogue of the invention may be substituted with another residue, such as a serine. For further information concerning phenotypically silent substitutions in peptides and proteins, see, for example, Bowie et.al. Science 247, 1306-1310, 1990. In the scheme below, conservative substitutions of amino acids are grouped by physicochemical properties. I: neutral, hydrophilic, II: acids and amides, III: basic, IV: hydrophobic, V: aromatic, bulky amino acids.

I	II	III	IV	V
A	N	H	M	F
S	D	R	F	Y
T	E	K	I	W
P	Q		V
G			C

[0066] In the scheme below, conservative substitutions of amino acids are grouped by physicochemical properties. VI: neutral or hydrophobic, VII: acidic, VIII: basic, IX: polar, X: aromatic.

VI	VII	VIII	IX	X
A	E	H	M	F
F	D	R	s	Y
I		K	T	W
P			c
G			N
V			Q

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PCT/US2016/042680 [0067] The term “amino acid” or “any amino acid” as used here refers to any and all amino acids, including naturally occurring amino acids (e.g., a-amino acids), unnatural amino acids, modified amino acids, and non-natural amino acids. It includes both D- and L-amino acids. Natural amino acids include those found in nature, such as, e.g., the 23 amino acids that combine into peptide chains to form the building-blocks of a vast array of proteins. These are primarily L stereoisomers, although a few D-amino acids occur in bacterial envelopes and some antibiotics. The 20 “standard,” natural amino acids are listed in the above tables. The “non-standard,” natural amino acids are pyrrolysine (found in methanogenic organisms and other eukaryotes), selenocysteine (present in many noneukaryotes as well as most eukaryotes), and Nformylmethionine (encoded by the start codon AUG in bacteria, mitochondria and chloroplasts). “Unnatural” or “non-natural” amino acids are non-proteinogenic amino acids (i.e., those not naturally encoded or found in the genetic code) that either occur naturally or are chemically synthesized. Over 140 unnatural amino acids are known and thousands of more combinations are possible. Examples of “unnatural” amino acids include β-amino acids (β³ and β²), homo-amino acids, proline and pyruvic acid derivatives, 3-substituted alanine derivatives, glycine derivatives, ring-substituted phenylalanine and tyrosine derivatives, linear core amino acids, diamino acids, D-amino acids, alpha-methyl amino acids and N-methyl amino acids. Unnatural or non-natural amino acids also include modified amino acids. “Modified” amino acids include amino acids (e.g., natural amino acids) that have been chemically modified to include a group, groups, or chemical moiety not naturally present on the amino acid. According to certain embodiments, a peptide inhibitor comprises an intramolecular bond between two amino acid residues present in the peptide inhibitor. It is understood that the amino acid residues that form the bond will be altered somewhat when bonded to each other as compared to when not bonded to each other. Reference to a particular amino acid is meant to encompass that amino acid in both its unbonded and bonded state. For example, the amino acid residue homoSerine (hSer) or homoSerine(Cl) in its unbonded form may take the form of 2-aminobutyric acid (Abu) when participating in an intramolecular bond according to the present invention. The present invention inclues both peptide inhibitors containing cross-links between X4 and X9, as well as the peptide inhibitors that do not contain cross-links between X4 and X9, e.g., before cross-link formation. As such, the names hSer and Abu are intended to indicate the same amino acids and are used interchangeably.

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PCT/US2016/042680 [0068] For the most part, the names of naturally occurring and non-naturally occurring aminoacyl residues used herein follow the naming conventions suggested by the IUPAC Commission on the Nomenclature of Organic Chemistry and the IUPAC-IUB Commission on Biochemical Nomenclature as set out in “Nomenclature of α-Amino Acids (Recommendations, 1974)” Biochemistry, 14(2), (1975). To the extent that the names and abbreviations of amino acids and aminoacyl residues employed in this specification and appended claims differ from those suggestions, they will be made clear to the reader. Some abbreviations useful in describing the invention are defined below in the following Table 1A.

[0069] Table 1A. Abbreviations of Non-Natural Amino Acids and Chemical Moieties (for amino acid derivatives, all L unless stated)

Abbreviation	Definition
Ac-	Acetyl
Hy	Hydrogen (Free N-terminal)
Dap	L-Diaminopropionic acid
Dab	L-Diaminobutyric acid
Orn	L-Ornathine
Pen	L-Penicillamine
Sarc	Sarcosine
Cit	L-Citrulline
Cav	L-Cavanine
Phe-(4-Guanidino)	4-Guanidine-L-Phenylalanine
N-MeArg	N-Methyl-L-Arginine
N-MeTrp	N-Methyl-L-Tryptophan
N-MeGln	N-Methyl-L-Glutamine

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N-MeAla	N-Methyl-L-Alanine
N-MeLys	N-Methyl-Lysine
N-MeAsn	N-Methyl-L-Asparagine
6-ChloroTrp	6-Chloro-L-Tryptophan
5-Hydroxy Trp	5-Hydroxy-L-Tryptophan
1,2,3,4-tetrahydro-norharman	L-1,2,3,4-tetrahydro-norharman
2-Nal (also referred to as 2-Nap)	L-2-Napthylalanine
1-Nal (also referred to as 1 -Nap)	L-1 -Napthylalanine
Phe(4-OMe)	4-Methoxy-L-phenylalanine
Abu	2-Aminobutyric acid
Bip	L-4,4’ -Biphenylalanine
pAla	beta-Alanine
phTyr	beta homo-L-Tyrosine
phTrp	beta homo-L-Trptophan
PhAla	beta homo-L-Alanine
PhLeu,	beta homo-L-Leucine
phVal	beta homo-L-Valine
Aib	2-aminoisobutyric acid
Azt	L-azetidine-2-carboxylic acid
Tic	(3S)-l,2,3,4-Tetrahydroisoquinoline-7-hydroxy-3-carboxylic Acid
Phe(4-OMe)	4-methoxy-L-phenylalanine

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N-Me-Lys	N-Methyl-L-Lysine
N-Me-Lys(Ac)	Ν-ε-Acetyl-D-lysine
CONH2	Carboxamide
COOH	Acid
3-Pal	L- 3 -Pyridy lalanine
Phe(4-F)	4-Fluoro-L-Phenylalanine
DMT	2,6-DimethylTyrosine
Phe(4-OMe)	4-Methoxyphenylalanine
hLeu	L-homoLeucine
hArg	L-homoArginine
a-MeLys	alpha-methyl-L-Lysine
a-MeOrn	alpha-methyl-L-Ornathine
a-MeLeu	alpha-methyl-L-Leucine
a-MeTrp	alpha-methyl-L-Tryptophan
a-MePhe	alpha-methyl-L-Phenylalanine
a-MeTyr	alpha-methyl-L-Tyrosine
a-DiethylGly	α-DiethylGly cine
Lys(Ac)	Ν-ε-acetyl-L-Lysine
DTT	Dithiothreotol
Nle	L-Norleucine
PhTrp	L- β-homoT ry pophan
PhPhe	L^-homophenylalanine
PhPro	L- β-homoproline

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Phe(4-CF3)	4-Trifluoromethyl-L-Phenylalanine
β-Glu	Ε-β-Glutamic acid
βΙΛ	Ε-β-homoglutamic acid
2-2-Indane	2-Aminoindane-2-carboxylic acid
1-1-Indane	1-Amino indane-1 -carboxylic acid
hCha	L-homocyclohexylalanine
Cyclobutyl	L-cyclobutylalanine
βΙιΡΙιβ	Ε-β-homo-phenylalanine
Gia	Gama-Carboxy-L-Glutamic acid
Cpa	Cyclopentyl-L-alanine
Cha	Cyclohexyl-L-alanine
Octgly	L-Octylglycine
Z-butyl-Ala	3-(/er/-butyl)-L-Ala-OH
/-butyl-Gly	/er/-butyl-glycine
AEP	3-(2-aminoethoxy)propanoic acid
AEA	(2-aminoethoxy)acetic acid
Phe(4-Phenoxy)]	4-Phenoxy-L-phenylalanine
Phe(4-OBzl)	O-Be/7zy’/-L-tyrosine
Phe(4-CONH2)	4-Carbamoyl-L-phenylalanine
Phe(4-CO2H)	4-Carboxy-L-phenylalanine
Phe(3,4-Cl2)	3,4 dichloro-L-phenylalanine
Tyr(3-t-Bu)	3-/-butyl-L-tyrosine

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Phe(t-Bu)	Z-butyl-L-phenylalanine
Phe[4-(2-aminoethoxy)]	c J 4-(2-aminoet	nh2 hoxy)-L-phenylalanine
Phe(4-CN)	4-cyano-L-phenylalanine
Phe(4-Br)	4-bromo-L-phenylalanine
Phe(4-NH2)	4-amino-L-phenylalanine
Phe(4-Me)	4-methyl-L-phenylalanine
4-Pyridylalanine	4-L-Pyridylalanine
4-amino-4-carboxy-piperidine	4-amino-z	H X h2n co2h -carboxy-piperidine
hPhe(3,4-dimethoxy)	3,4-dimethoxy-L-homophenylalanine
Phe(2,4-Me2)	2,4-dimethyl-L-phenylalanine
Phe(3,5-F2)	3,5 -difluoro-L-phenylalanine
Phe(penta-F)	pentafluoro-L-phenylalanine

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2,5,7-tert butyl Trp	2,5,7-Tris-tert-butyl-L-tryptophan
Tic
	L-l ,2,3,4,-tetrahydro-isoquinoline-3-carboxylic acid
Phe(4-0 Allyl)	O-ri//)7-L-Tyrosine
Phe(4-N3)	4-azidophenylalanine
Ache	9
	h2n co2h
	1 -aminocyclohexanecarboxylic acid
Acvc	9
	h2n co2h
	1 -aminocyclopentanecarboxylic acid
Aebe	9
	h2n co2h
	1-aminocyclobutanecarboxylic acid
Aepe	y
	h2n co2h

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	1 -aminocyclopropylcarboxylic acid
4-amino-4-carboxy- tetrahydropyran	X
(also referred as THP)	h2n co2h
	4-amino-4-carboxy-tetrahydropyran

[0070] Throughout the present specification, unless naturally occurring amino acids are referred to by their full name (e.g. alanine, arginine, etc.), they are designated by their conventional threeletter or single-letter abbreviations (e.g. Ala or A for alanine, Arg or R for arginine, etc.). Unless otherwise indicated, three-letter and single-letter abbreviations of amino acids refer to the L-isomeric form of the amino acid in question. The term “L-amino acid,” as used herein, refers to the “L” isomeric form of a peptide, and conversely the term “D-amino acid” refers to the “D” isomeric form of a peptide (e.g., Dasp, (D)Asp or D-Asp; Dphe, (D)Phe or D-Phe). Amino acid residues in the D isomeric form can be substituted for any L-amino acid residue, as long as the desired function is retained by the peptide. D-amino acids may be indicated as customary in lower case when referred to using single-letter abbreviations.

[0071] In the case of less common or non-naturally occurring amino acids, unless they are referred to by their full name (e.g. sarcosine, ornithine, etc.), frequently employed three- or fourcharacter codes are employed for residues thereof, including, Sar or Sarc (sarcosine, i.e. Nmethylglycine), Aib (α-aminoisobutyric acid), Dab (2,4-diaminobutanoic acid), Dapa (2,3diaminopropanoic acid), γ-Glu (γ-glutamic acid), Gaba (γ-aminobutanoic acid), β-Pro (pyrrolidine-3-carboxylic acid), and 8Ado (8-amino-3,6-dioxaoctanoic acid), Abu (2-amino butyric acid), βΙιΡτο (β-homoproline), BhPhe (β-homophenylalanine) and Bip (β,β diphenylalanine), and Ida (Iminodiacetic acid).

[0072] As is clear to the skilled artisan, the peptide sequences disclosed herein are shown proceeding from left to right, with the left end of the sequence being the N-terminus of the

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PCT/US2016/042680 peptide and the right end of the sequence being the C-terminus of the peptide. Among sequences disclosed herein are sequences incorporating a “Hy-” moiety at the amino terminus (N-terminus) of the sequence, and either an “-OH” moiety or an “-NH2” moiety at the carboxy terminus (Cterminus) of the sequence. In such cases, and unless otherwise indicated, a “Hy-” moiety at the N-terminus of the sequence in question indicates a hydrogen atom, corresponding to the presence of a free primary or secondary amino group at the N-terminus, while an “-OH” or an “-NH2” moiety at the C-terminus of the sequence indicates a hydroxy group or an amino group, corresponding to the presence of an amido (CONH2) group at the C-terminus, respectively. In each sequence of the invention, a C-terminal “-OH” moiety may be substituted for a C-terminal “-NH2” moiety, and vice-versa.

[0073] The term “DRP,” as used herein, refers to disulfide rich peptides.

[0074] The term “dimer,” as used herein, refers broadly to a peptide comprising two or more monomer subunits. Certain dimers comprise two DRPs. Dimers of the present invention include homodimers and heterodimers. A monomer subunit of a dimer may be linked at its C- or Nterminus, or it may be linked via internal amino acid residues. Each monomer subunit of a dimer may be linked through the same site, or each may be linked through a different site (e.g., Cterminus, N-terminus, or internal site).

[0075] The term “NH2,” as used herein, can refer to a free amino group present at the amino terminus of a polypeptide. The term “OH,” as used herein, can refer to a free carboxy group present at the carboxy terminus of a peptide. Further, the term “Ac,” as used herein, refers to Acetyl protection through acylation of the C- or N-terminus of a polypeptide. In certain peptides shown herein, the NH2 locates at the C-terminus of the peptide indicates an amino group.

[0076] The term “carboxy,” as used herein, refers to -CO2H.

[0077] The term “isostere replacement,” as used herein, refers to any amino acid or other analog moiety having chemical and/or structural properties similar to a specified amino acid.

[0078] The term “cyclized,” as used herein, refers to a reaction in which one part of a polypeptide molecule becomes linked to another part of the polypeptide molecule to form a closed ring, such as by forming a disulfide bridge or other similar bond.

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PCT/US2016/042680 [0079] The term “subunit,” as used herein, refers to one of a pair of polypeptide monomers that are joined to form a dimer peptide composition.

[0080] The term “linker moiety,” as used herein, refers broadly to a chemical structure that is capable of linking or joining together two peptide monomer subunits to form a dimer.

[0081] The term “pharmaceutically acceptable salt,” as used herein, represents salts or zwitterionic forms of the peptides or compounds of the present invention which are water or oilsoluble or dispersible, which are suitable for treatment of diseases without undue toxicity, irritation, and allergic response; which are commensurate with a reasonable benefit/risk ratio, and which are effective for their intended use. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting an amino group with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, formate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isethionate), lactate, maleate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, picrate, pivalate, propionate, succinate, tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, para-toluenesulfonate, and undecanoate. Also, amino groups in the compounds of the present invention can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. Examples of acids which can be employed to form therapeutically acceptable addition salts include inorganic acids such as hydrochloric, hydrobromic, sulfuric, and phosphoric, and organic acids such as oxalic, maleic, succinic, and citric. A pharmaceutically acceptable salt may suitably be a salt chosen, e.g., among acid addition salts and basic salts. Examples of acid addition salts include chloride salts, citrate salts and acetate salts. Examples of basic salts include salts where the cation is selected among alkali metal cations, such as sodium or potassium ions, alkaline earth metal cations, such as calcium or magnesium ions, as well as substituted ammonium ions, such as ions of the type N(R1)(R2)(R3)(R4)+, where Rl, R2, R3 and R4 independently will typically designate hydrogen, optionally substituted Cl-6-alkyl or optionally substituted C2-6-alkenyl.

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Examples of relevant Cl-6-alkyl groups include methyl, ethyl, 1-propyl and 2-propyl groups. Examples of C2-6-alkenyl groups of possible relevance include ethenyl, 1-propenyl and 2propenyl. Other examples of pharmaceutically acceptable salts are described in “Remington’s Pharmaceutical Sciences”, 17th edition, Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, PA, USA, 1985 (and more recent editions thereof), in the “Encyclopaedia of Pharmaceutical Technology”, 3rd edition, James Swarbrick (Ed.), Informa Healthcare USA (Inc.), NY, USA, 2007, and in J. Pharm. Sci. 66: 2 (1977). Also, for a review on suitable salts, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use by Stahl and Wermuth (Wiley-VCH, 2002). Other suitable base salts are formed from bases which form non-toxic salts. Representative examples include the aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine, and zinc salts. Hemisalts of acids and bases may also be formed, e.g., hemisulphate and hemicalcium salts.

[0082] The term “N(alpha)Methylation”, as used herein, describes the methylation of the alpha amine of an amino acid, also generally termed as an N-methylation.

[0083] The term “sym methylation” or “Arg-Me-sym”, as used herein, describes the symmetrical methylation of the two nitrogens of the guanidine group of arginine. Further, the term “asym methylation” or “Arg-Me-asym” describes the methylation of a single nitrogen of the guanidine group of arginine.

[0084] The term “acylating organic compounds”, as used herein refers to various compounds with carboxylic acid functionality that are used to acylate the N-terminus of an amino acid or a monomer or dimer, e.g., a monomer subunit prior to forming a C-terminal dimer. Non-limiting examples of acylating organic compounds include cyclopropylacetic acid, 4-Fluorobenzoic acid, 4-fluorophenylacetic acid, 3-Phenylpropionic acid, Succinic acid, Glutaric acid, Cyclopentane carboxylic acid, 3,3,3-trifluoropropeonic acid, 3-Fluoromethylbutyric acid, Tetrahedro-2HPyran-4-carboxylic acid.

[0085] The term “alkyl” includes a straight chain or branched, noncyclic or cyclic, saturated aliphatic hydrocarbon containing from 1 to 24 carbon atoms. Representative saturated straight chain alkyls include, but are not limited to, methyl, ethyl, «-propyl, «-butyl, «-pentyl, «-hexyl,

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PCT/US2016/042680 and the like, while saturated branched alkyls include, without limitation, isopropyl, sec-butyl, isobutyl, /er/-butyl, isopentyl, and the like. Representative saturated cyclic alkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like, while unsaturated cyclic alkyls include, without limitation, cyclopentenyl, cyclohexenyl, and the like.

[0086] The term “mammal” refers to any mammalian species such as a human, mouse, rat, dog, cat, hamster, guinea pig, rabbit, livestock, and the like.

[0087] As used herein, a “therapeutically effective amount” of the peptide inhibitor of the invention is meant to describe a sufficient amount of the peptide inhibitor to treat an IL-23/IL23R-related disease, including but not limited to any of the diseases and disorders described herein (for example, to reduce inflammation associated with IBD). In particular embodiments, the therapeutically effective amount will achieve a desired benefit/risk ratio applicable to any medical treatment.

[0088] An “analog” of an amino acid, e.g., a “Phe analog” or a “Tyr analog” means an analog of the referenced amino acid. A variety of amino acid analogs are known and available in the art, including Phe and Tyr analogs. In certain embodiments, an amino acid analog, e.g., a Phe analog or a Tyr analog comprises one, two, three, four or five substitutions as compared to Phe or Tyr, respectively. In certain embodiments, the substitutions are present in the side chains of the amino acids. In certain embodiments, a Phe analog has the structure Phe(R ), wherein R is a Hy, OH, CH₃, CO₂H, CONH₂, CONH₂OCH₂CH₂NH₂, /-Bu, OCH₂CH₂NH₂, phenoxy, OCH₃, OAllyl, Br, Cl, F, NH₂, N3, or guanadino. In certain embodiments, R² is CONH₂OCH₂CH₂NH₂, OCH₃, CONH₂, OCH₃ or CO₂H. Examples of Phe analogs include, but are not limited to: hPhe, Phe(4-OMe), α-Me-Phe, hPhe(3,4-dimethoxy), Phe(4-CONH₂), Phe(4-phenoxy), Phe(4guanadino), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4-OBzl), Phe(4-NH₂), BhPhe(4-F), Phe(4F), Phe(3,5 DiF), Phe(CH₂CO₂H), Phe(penta-F), Phe(3,4-Cl₂), Phe (3,4-F₂), Phe(4-CF₃), ββdiPheAla, Phe(4-N₃), Phe[4-(2-aminoethoxy)], 4-Phenylbenzylalanine, Phe(4-CONH₂), Phe(3,4Dimethoxy), Phe(4-CF₃), Phe(2,3-Cl₂), and Phe(2,3-F₂). Examples of Tyr analogs include, but are not limited to: hTyr, N-Me-Tyr, Tyr(3-/Bu), Tyr(4-N₃) and βΙιΤγΓ.

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Peptide Inhibitors of IL-23R [0089] Genome-wide association studies (GWAS) have demonstrated significant association of the IL-23 receptor (IL-23R) gene with inflammatory bowel disease (IBD), suggesting that perturbation of IL-23 signaling could be relevant to the pathogenesis of the disease. The present invention provides compositions and methods to modulate the IL-23 pathway through selective antagonism of IL-23R by oral treatment with peptides that are stable and restricted to the gastrointestinal (GI) tissue. Novel inhibitory peptides that are uniquely resistant to oxidative/reductive conditions and proteolytic degradation in a variety of assays that mimic the various compartments of the GI environment were identified. Functionally, these peptides potently neutralize IL-23-mediated signaling in a transformed human cell line and in human primary cells. The binding of IL-23R is selective, since the peptides do not block the interaction between IL-6 to IL-6R or antagonize the IL-12 signaling pathway. Furthermore, these orally delivered peptides are efficacious in attenuating colitis in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute rat model of IBD, as shown by a significant reduction in the ratio of colon weight to length, colon macroscopic score, neutrophil infiltration, and histopathology comparable to that of the control anti-IL-23pl9 mAh.

[0090] The present invention relates generally to peptides that have IL-23R antagonist activity, including both peptide monomers and peptide dimers. In certain embodiments, this invention demonstrates a new paradigm for treatment of IBD and other diseases and disorders by oral delivery of antagonists of IL-23. IBD represents a local inflammation of the intestinal tissue; therefore, advantageous therapeutic agents would act from the luminal side of the intestine, yielding high drug concentrations in diseased tissue, minimizing systemic availability and resulting in improved efficacy and safety when compared to systemic approaches. Oral administration of the compounds of the present invention is expected to maximize drug levels in diseased intestinal tissues while limiting drug concentrations in circulation, thereby providing efficacious, safe, and durable delivery for life-long treatment of IBD and other diseases and disorders.

[0091] In certain embodiments, the present invention relates to various peptides, or peptide dimers comprising hetero- or homo-monomer subunits, that form cyclized structures through disulfide or other bonds. In certain embodiments, the disulfide or other bonds are intramolecular

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PCT/US2016/042680 bonds. The cyclized structure of the peptide monomer inhibitors and the monomer subunits of the peptide dimer inhibitors has been shown to increase potency and selectivity of the peptide inhibitors. In certain embodiments, a peptide dimer inhibitor may include one or more intermolecular bonds linking the two monomer peptide subunits within the peptide dimer inhibitor, e.g., an intermolecular bridge between two cysteine residues, one in each peptide monomer subunit.

[0092] The present invention provides peptide inhibitors that bind to IL-23R, which may be monomers or dimers. In particular embodiments, the peptide inhibitors inhibit the binding of IL23 to IL-23R. In certain embodiments, the IL-23R is human IL-23R, and the IL-23 is human IL23. In certain embodiments, a peptide inhibitor of the present invention reduces IL-23 binding to IL-23R by at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% as compared to a negative control peptide. Methods of determining binding are known in the art and include ELISA assays, as described in the accompanying Examples.

[0093] In certain embodiments, a peptide inhibitor of the present invention has an IC50 of > 1 mM, < 1 mM, 500 nM to 1000 nM, < 500 nM, < 250 nM, < 100 nM, < 50 nM, < 25 nM, < 10 nM, < 5 nM, < 2 nM, < 1 nM, or < 5 mM, e.g., for inhibiting binding of IL-23 to IL-23R (e.g., human IL-23 and human IL-23R). Methods of determining activity are known in the art and include any of those described in the accompanying Examples.

[0094] In certain embodiments, a peptide inhibitor of the present invention has increased stability, increased gastrointestinal stability, or increased stability in stimulated intestinal fluid (SIF) or simulated gastric fluid (SGF), and/or under redox conditions (e.g., DTT) as compared to a control peptide. In certain embodiments, a control peptide is an unrelated peptide of the same or similar length. In particular embodiments, a control peptide is a peptide having the identical or a highly related amino acid sequence (e.g., > 90% sequence identity) as the peptide inhibitor. In particular embodiments, a control peptide is a peptide having the identical or a highly related amino acid sequence (e.g., > 90% sequence identity) as the peptide inhibitor, but which does not have a cyclized structure, e.g., through an intramolecular bond between two amino acid residues within the control peptide, or which is not dimerized, or which does not comprise a conjugate for

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PCT/US2016/042680 stabilization. In particular embodiments, the only difference between the peptide inhibitor and the control peptide is that the peptide inhibitor comprises one or more amino acid substitutions that introduce one or more amino acid residues into the peptide inhibitor, wherein the introduced amino residue(s) forms an intrasulfide disulfide or thioether bond with another amino acid residue in the peptide inhibitor. One example of a control for a peptide dimer inhibitor is a monomer having the same sequence as one of the monomer subunits present in the peptide dimer inhibitor. One example of a control for a peptide inhibitor comprising a conjugate is a peptide having the same sequence but not including the conjugated moiety. In certain embodiments, a control peptide is a peptide (e.g., a naturally-occurring peptide) corresponding to a region of IL23 that binds to IL-23R.

[0095] Methods of determining the stablity of a peptide are known in the art. In certain embodiments, the stability of a peptide inhibitor is determined using an SIF assay, e.g., as described in Example 3. In certain embodiments, the stability of a peptide inhibitor is determined using an SGF assay, e.g., as described in Example 3. In particular embodiments, a peptide inhibitor has a half-life (e.g., in SIF or SGF or DTT) under a given set of conditions (e.g., temperature) of greater than 1 minute, greater than 10 minutes, greater than 20 minutes, greater than 30 minutes, greater than 60 minutes, greater than 90 minutes, greater than 120 minutes, greater than 3 hours, or greater than four hours when exposed to SIF or SGF or DTT. In certain embodiments, the temperature is about 25 °C, about 4 °C, or about 37 °C, and the pH is a physiological pH, or a pH about 7.4.

[0096] In some embodiments, the half-life is measured in vitro using any suitable method known in the art, e.g., in some embodiments, the stability of a peptide of the present invention is determined by incubating the peptide with pre-warmed human serum (Sigma) at 37 ⁰ C. Samples are taken at various time points, typically up to 24 hours, and the stability of the sample is analyzed by separating the peptide or peptide dimer from the serum proteins and then analyzing for the presence of the peptide or peptide dimer of interest using LC-MS.

[0097] In some embodiments, a peptide inhibitor of the present invention exhibits improved solubility or improved aggregation characteristics as compared to a control peptide. Solubility may be determined via any suitable method known in the art. In some embodiments, suitable

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PCT/US2016/042680 methods known in the art for determining solubility include incubating peptides in various buffers (Acetate pH4.0, Acetate pH5.0, Phos/Citrate pH5.0, Phos Citrate pH6.0, Phos pH 6.0, Phos pH 7.0, Phos pH7.5, Strong PBS pH 7.5, Tris pH7.5, Tris pH 8.0, Glycine pH 9.0, Water, Acetic acid (pH 5.0 and other known in the art) and testing for aggregation or solubility using standard techniques. These include, but are not limited to, visual precipitation, dynamic light scattering, Circular Dichroism and fluorescent dyes to measure surface hydrophobicity, and detect aggregation or fibrillation, for example. In some embodiments, improved solubility means the peptide is more soluble in a given liquid than is a control peptide. In some embodiments, improved aggregation means the peptide has less aggregation in a given liquid under a given set of conditions than a control peptide.

[0098] In certain embodiments advantageous for achieving high compound concentrations in intestinal tissues when delivered orally, peptide inhibitors of the present invention are stable in the gastrointestinal (Gl) environment. Proteolytic metabolism in the Gl tract is driven by enzymes (including pepsins, trypsin, chymotrypsin, elastase, aminopeptidases, and carboxypeptidase A/B) that are secreted from the pancreas into the lumen or are produced as brush border enzymes. Proteases typically cleave peptides and proteins that are in an extended conformation. In the reducing environment of intestinal fluids, disulfide bonds may be broken, resulting in a linear peptide and rapid proteolysis. This luminal redox environment is largely determined by the Cys/CySS redox cycle. In enterocytes, relevant activities include numerous digestive enzymes such as CYP450 and UDP-glucuronsyl-transferase. Finally, bacteria, present in the large intestine at concentration ranging from IO¹⁰ to 10¹² CFU/ml, constitute another metabolic barrier. In certain embodiments, the peptide inhibitors are stable to various pHs that range from strongly acidic in the stomach (pH 1.5-1.9), trending towards basic in the small intestine (pH 6-7.5), and then weakly acidic in the colon (pH 5-7). Such peptide inhibitors are stable during their transit through the various Gl compartments, a process that has been estimated to take 3-4 h in the intestine and 6-48 h in the colon.

[0099] In some embodiments, the peptide inhibitors of the present invention have less degradation, e.g., over a period of time (i.e., more degradation stability), e.g., greater than or about 10% less, greater than or about 20% less, greater than or about 30% less, greater than or about 40 less, or greater than or about 50% less degradation than a control peptide. In some

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PCT/US2016/042680 embodiments, degradation stability is determined via any suitable method known in the art. In some embodiments, the degradation is enzymatic degradation. For example, in certain embodiments, the peptide inhibitors have reduced susceptibility to degradation by trypsin, chhrmotrypsin or elastase. In some embodiments, suitable methods known in the art for determining degradation stability include the method described in Hawe et al., J Pharm Sci, VOL. 101, No. 3, 2012, p 895-913, incorporated herein in its entirety. Such methods are in some embodiments used to select potent peptide sequences with enhanced shelf lifes. In particular embodiments, peptide stability is determined using a SIF assay or SGF assay as described herein.

[00100] In certain embodiments, peptide inhibitors of the present invention inhibit or reduce IL23-mediated inflammation. In related embodiments, peptide inhibibitors of the present invention inhibit or reduce IL-23-mediated secretion of one or more cytokines, e.g., by binding to IL-23R on the cell surface, thus inhibiting IL-23 binding to the cell. In particular embodiments, peptide inhibitors of the present invention inhibit or reduce IL-23-mediated activation of Jak2, Tyk2, Statl, Stat3, Stat4, or Stat5. Methods of determining inhibition of cytokine secretion and inhibition of signaling molecules are known in the art. For example, inhibiton of IL-23/IL-23R signaling may be determined by measuring inhibition of phospho-Stat3 levels in cell lysates, as decribed in the accompanying Examples, including Example 2.

[00101] In certain embodiments, peptide inhibitors of the present invention inhibit or reduce IL23-mediated inflammation. In related embodiments, peptide inhibibitors of the present invention inhibit or reduce IL-23-mediated secretion of one or more cytokines, e.g., by binding to IL-23R on the cell surface, thus inhibiting IL-23 binding to the cell. In particular embodiments, peptide inhibitors of the present invention inhibit or reduce IL-23-mediated activation of Jak2, Tyk2, Statl, Stat3, Stat4, or Stat5. Methods of determining inhibition of cytokine secretion and inhibition of signaling molecules are known in the art. For example, inhibiton of IL-23/IL-23R signaling may be determined by measuring inhibition of phospho-Stat3 levels in cell lysates, as decribed in the accompanying Examples, including Example 2.

[00102] In certain embodiments, peptide inhibitors have increased redox stability as compared to a control peptide. A variety of assays that may be used to determine redox stability are known

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PCT/US2016/042680 and available in the art. Any of these may be used to determine the redox stability of peptide inhibitors of the present invention.

[00103] In certain embodiments, the present invention provides various peptide inhibitors that bind or associate with the IL-23R, in vitro or in vivo, to disrupt or block binding between IL-23 and IL-23R. In certain embodiments, the peptide inhibitors bind and/or inhibit human IL-23R. In certain embodiments, the peptide inhibitors bind and/or inhibit both human and rodent IL23R. In certain embodiments, the peptide inhibitors bind and/or inhibit both human and rat IL23R. In particular embodiments, the peptide inhibitors inhibit rat IL-23R at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% as well as they bind or inhibit human IL-23R, e.g., as determined by an assay described herein. In certain embodiments, the peptide inhibitors preferentially bind and/or inhibit human and/or rat IL-23R as compared to mouse IL-23R. In particular embodiments, the peptide inhibitors preferentially bind to rat IL23R as compared to mouse IL-23R. In particular embodiments, the peptide inhibitors preferentially bind to human IL-23R as compared to mouse IL-23R. In certain embodiments, binding of a peptide inhibitor to mouse IL-23R is less than 75%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of binding of the same peptide inhibitor to human IL-23R and/or rat IL-23R. In certain embodiments of peptide inhibitors that preferentially bind and/or inhibit human IL-23R and/or rat IL-23R as compared to mouse IL-23R, the peptide inhibitor binds to a region of IL-23R that is disrupted by the presence of additional amino acids present in mouse IL-23R but not human IL-23R or rat IL-23. In one embodiment, the additional amino acids present in the mouse IL-23R are in the region corresponding to about amino acid residue 315 to about amino acid residue 340 of the mouse IL23R protein, e.g., amino acid region NWQPWSSPFVHQTSQETGKR (see, e.g., Figure 4). In particular embodiments, the peptide inhibitors bind to a region of human IL-23R from about amino acid 230 to about amino acid residue 370.

[00104] In certain embodiments, peptide inhibitors show Gl-restricted localization following oral administration. In particular embodiments, greater than 50%, greater than 60%, greater than 70%, greater than 80%, or greater than 90% of orally administered peptide inhibitor is localized to gastrointestinal organs and tissues. In particular embodiments, blood plasma levels of orally administered peptide inhibitor are less than 20%, less than 10%, less than 5%, less than 2%, less

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PCT/US2016/042680 than 1% or less than 0.5% the levels of peptide inhibitor found in the small intestine mucosa, colon mucosa, or proximal colon.

[00105] The various peptide inhibitors of the invention may be constructed solely of natural amino acids. Alternatively, the peptide inhibitors may include non-natural amino acids including, but not limited to, modified amino acids. In certain embodiments, modified amino acids include natural amino acids that have been chemically modified to include a group, groups, or chemical moiety not naturally present on the amino acid. The peptide inhibitors of the invention may additionally include one or more D-amino acids. Still further, the peptide inhibitors of the invention may include amino acid analogs.

[00106] In certain embodiments, peptide inhibitors of the present invention include one or more modified or unnatural amino acids. For example, in certain embodiments, a peptide inhibitor includes one or more of Dab, Dap, Pen, Sarc, Cit, Cav, hLeu, 2-Nal, D-l-Nal, D-2-Nal, Phe(4OMe), PhTrp, α-MePhe, a-MeTyr, a-MeTrp, β-HPhe, Phe(4-CF₃), 2-2-Indane, 1-1-Indane, Cyclobutyl, β-hPhe, Gia, Phe(4-NH2), hPhe, 1-Nal, Nle, homoamino acids, D-amino acids, 4,4’Biphenylalanine (Bip), cyclobutyl-Ala, hCha, hhPhe, PGIu, Phe(4-Guanidino), Phe[4-(2aminoethoxy)], Phe[4-(2-acetylaminoethoxy)], Phe(4-CONH₂), Phe(4-Me), Tyr(Bzl), or Tyr(Me), Phe(3,4-diF₂), Phe(3,4-Cl₂), Phe(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2acetylaminoethoxy)], Phe(Br), Phe(4-CONH₂), Phe(Cl), Phe(4-CN), Phe(4-guadino), Phe(4-Me), Phe(4-NH₂), Phe(4-N3), Tyr, Tyr(Bzl), or Tyr(Me), Phe(3,4-dimethoxy), 5-HydroxyTrp, Phe(3,4-Cl₂), Tyr(3-tBu), and various N-methylated amino acids and alpha-methyl amino acids. In some embodiments of the present invention, a peptide inhibitor includes one or more nonnatural amino acids shown in Table 1A. One having skill in the art will appreciate that other modified or unnatural amino acids, and various other substitutions of natural amino acids with modified or unnatural amino acids, may be made to achieve similar desired results, and such substitutions are within the teaching and spirit of the present invention. In certain embodiments, peptide inhibitors of the present invention include any of those described herein, including but not limited to any of those comprising an amino acid sequence or peptide inhibitor structure shown in any one of the tables herein, the accompanying sequence listing or the accompanying figures, wherein one or more residues is substituted with a modified or unnatural amino acid.

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PCT/US2016/042680 [00107] The present invention also includes any of the peptide inhibitors described herein in either a free or a salt form. Thus, embodiments of any of the peptide inhibitors described herein (and related methods of use thereof) include a pharmaceutically acceptable salt of the peptide inhibitor.

[00108] The present invention also includes variants of any of the peptide inhibitors described herein, including but not limited to any of those comprising a sequence shown in any one of the tables herein, the accompanying sequence listing or the accompanying figures, wherein one or more L-amino acid residue is substituted with the D isomeric form of the amino acid residue, e.g., an L-Ala is substituted with a D-Ala.

[00109] In particular embodiments of the peptide inhibitors described herein, they comprise one or more unnatural or non-natural amino acid residue.

[00110] The present invention also includes any of the peptide monomer inhibitors described herein linked to a linker moiety, including any of the specific linker moieties described herein. In particular embodiments, a linker is attached to an N-terminal or C-terminal amino acid, while in other embodiments, a linker is attached to an internal amino acid. In particular embodiments, a linker is attached to two internal amino acids, e.g., an internal amino acid in each of two monomer subunits that form a dimer. In some embodiments of the present invention, a peptide inhibitor is attached to one or more linker moieties shown.

[00111] The present invention also includes peptides and peptide dimers comprising a peptide having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the peptide sequence of a peptide inhibitor described herein. In particular embodiments, peptide inhibitors of the present invention comprise a core peptide sequence and one or more N-terminal and/or Cterminal modification (e.g., Ac and NH₂) and/or one or more conjugated linker moiety and/or half-life extension moiety. As used herein, the core peptide sequence is the amino acid sequence of the peptide absent such modifications and conjugates. For example, for the peptide inhibitor: [Palm] - [isoGlu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] NN-NH2, the core peptide sequence is: [Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal][Aib]-[Lys(Ac)]-NN.

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PCT/US2016/042680 [00112] In certain embodiments, a peptide inhibitor or a monomer subunit of a peptide inhibitor of the present invention comprises, consists essentially of, or consists of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, 7 to 20 amino acid residues, 8 to 20 amino acid residues, 9 to 20 amino acid residues, 10 to 20 amino acid residues, 7 to 18 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues, and, optionally, one or more additional non-amino acid moieties, such as a conjugated chemical moiety, e.g., a PEG or linker moiety. In particular embodiments, a peptide inhibitor of the present invention (or a monomer subunit thereof), including but not limited to those of any embodiments of Formula X, Formula I, Formula II, Formula III, Formula IV, or Formula V is greater than 10, greater than 12, greater than 15, greater than 20, greater than 25, greater than 30 or greater than 35 amino acids, e.g., 35 to 50 amino acids. In certain embodiments, a peptide inhibitor (or a monomer subunit thereof) is less than 50, less than 35, less than 30, less than 25, less than 20, less than 15, less than 12, or less than 10 amino acids. In particular embodiments, a monomer subunit of a peptide inhibitor (or a peptide monomer inhibitor) comprises or consists of 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 ammo acid residues. In particular embodiments, a monomer subunit of a peptide inhibitor of the present invention comprises or consists of 10 to 18 amino acid residues and, optionally, one or more additional non-amino acid moieties, such as a conjugated chemical moiety, e.g., a PEG or linker moiety. In various embodiments, the monomer subunit comprises or consists of 7 to 35 amino acid residues, 7 to 20 amino acid residues, 8 to 20 amino acid residues, 9 to 20 amino acid residues, 10 to 20 amino acid residues, 8 to 18 amino acid residues, 8 to 19 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues. In particular embodiments of any of the various Formulas described herein, X comprises or consists of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, 7 to 18 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues.

[00113] Certain illustrative peptide inhibitors described herein comprise 12 or more amino acid residues. However, the present invention also includes peptide inhibitors comprising a fragment

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PCT/US2016/042680 of any of the peptide sequences described herein, including peptide inhibitors having 7, 8, 9, 10, or 11 amino acid residues. For example, peptide inhibitors of the present invention include peptides comprising or consisting of X4-X9, X4-X10, X4-X11, X4-X12, X4-X13, X4-X14, X4XI5, or X4-X16. In particular embodiments, the present invention includes peptide inhibitors having any of the sequences described herein, including but not limited to, those shown in any of the formulas described herein, the sequence listing, or any of the tables provided herein, wherein one or more of ΧΙΟ, XI1, X12, X13, X14, X15, or X16 is absent. In particular embodiments, one or more of XI3, XI4, XI5 or XI6 is absent.

[00114] In particular embodiments of the present invention, the peptide inhibitors, or X regions thereof, are not present within an antibody. In particular embodiments, the peptide inhibitors, or X regions thereof, are not present within a Vh or Vl region of an antibody.

[00115] In particular embodiments of the peptide inhibitors described herein, they comprise one or more unnatural or non-natural amino acid residue.

[00116] In particular embodiments, peptide inhibitors of the present invention are cyclized via a cyclic amide bond, a disulfide bond, or a thioether bond. In particular embodiments, the bond is an intramolecular bond between two amino acid residues within the peptide inhibitor or a monomer subunit thereof.

Peptide Inhibitors [00117] Peptide inhibitors of the present invention include peptides having any of the amino acid sequences described herein, compounds having any of the structures described herein, including compounds comprising any of the peptide sequences described herein, and dimers of any of such peptides and compounds. Peptide inihibitors on the present invention include both peptides not having and those having a bond between X4 and X9, e.g., before and after a cross-link is introduced between X4 and X9. Illustrative peptides of the invention comprise an amino acid sequence or structure described in any of the accompanying tables, Examples, figures and sequence listing.

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PCT/US2016/042680 [00118] In certain embodiments, the present invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Xa):

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Xa) wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is any amino acid or chemical moiety capable of forming a bond with X9;

X5 is any amino acid;

X6 is any amino acid;

X7 is any amino acid;

X8 is any amino acid;

X9 is any amino acid or chemical moiety capable of forming a bond with X4;

XI0 is any amino acid;

XII is any amino acid;

XI2 is any amino acid;

XI3 is any amino acid;

XI4 is any amino acid;

XI5 is any amino acid,

XI6 is any amino acid or absent;

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PCT/US2016/042680

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00119] wherein X4 and X9 are capable of forming a bond with each other. In particular embodiments, the bond is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefin bond. In particular embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via the bond between X4 and X9. In certain embodiments, the peptide inhibitor inhibits the binding of an interleukin-23 (IL-23) to an IL-23 receptor. In particular embodiments, when X4 is not an amino acid, then XI, X2, and X3 are absent. In certain embodiments, XI is a D-amino acid or absent. In certain embodiments, X2 is a D-amino acid or absent. In certain embodiments, X3 is a D-amino acid or absent. In certain embodiments, XI6 is a D-amino acid or absent. In certain embodiments, XI7 is a D-amino acid or absent. In certain embodiments, XI8 is a D-amino acid or absent. In certain embodiments, XI9 is a D-amino acid or absent. In certain embodiments, X20 is a D-amino acid or absent.

[00120] In one embodiment of the peptide inhibitor of Formula Xa,

XI is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln or absent;

X4 is Cys, Abu or Pen;

X5 is Ala, α-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gin, Arg, Ser or Thr;

X6 is Asp or Thr;

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X7 is Trp or 6-Chloro-Trp;

X8 is Glu, Gin or Val;

X9 is Cys, Abu or Pen;

XI0 is 2-Nal, a Phe analog, Tyr, or a Tyr analog, wherein in particular embodiments, XI0 is 2Nal, Phe(3,4-diF2), Phe(3,4-Cl2), Phe(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2acetylaminoethoxy)], Phe(Br), Phe(4-CONH2), Phe(Cl), Phe(4-CN), Phe(4-guadino), Phe(4-Me), Phe(4-NH₂), Phe(4-N3), Tyr, Tyr(Bzl), or Tyr(Me);

XI1 is 1-Nal, 2-Nal, Phe(3,4-dimethoxy), 5-HydroxyTrp, Phe(3,4-Cl2), Trp or Tyr(3-tBu);

XI2 is 3-Pal, Acpc, Acbc, Acvc, Ache, Agp, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), aMeLeu, a- α-MeOrn, a-MeSer, α-MeVal, Cav, Cha, Cit, Cpa, D-Asn, Glu, His, hLeu, hArg, Lys, Leu, Octgly, Orn, piperidine, Arg, Ser, Thr or THP;

XI3 is Cit, Asp, Dab, Dap, Phe, His, Dap(Peg2-Ac), Dap(pyroglutaric acid), Glu, hArg, Lys, Lys(Ac), Lys(Benzoic acid), Lys(glutaric acid), Lys(IVA), Lys(Peg4-isoGlu-Palm), Lys(pyroglutaric acid), Lys-succinic acid, Asn, Orn,Gin, Arg, Thr or Val;

XI4 is Asp, Dab(Ac), Dap(Ac), Phe, His, Lys(Ac), Met, Asn(isobutyl), Gin, Arg, Tyr or Asp(l ,4-diaminobutane);

XI5 is Ala, beta Ala, Glu, Gly, Asn, Gin, Arg or Ser,

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

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PCT/US2016/042680 [00121] IN certain embodiments, X3 is absent. In particular embodiments, XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments, X4 and X9 are Cys, and X4 and X9 are linked via a disulfide bond. In particular embodiments, X4 is Abu and X9 is Pen, and X4 and X9 are linked via a thioether bond. In particular embodiments, X4 is Abu and X9 is Cys, and X4 and X9 are linked via a thioether bond.

[00122] In another embodiment of the peptide inhibitor of Formula Xa,

XI is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln or absent;

X4 is Cys, Abu or Pen;

X5 is Ala, a-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, Orn, Gln, Arg, Ser or Thr;

X6 is Asp or Thr;

X7 is Trp or 6-Chloro-Trp;

X8 is Gln or Val;

X9 is Cys, Abu or Pen;

XI0 is 2-Nal, a Phe analog, Tyr, or a Tyr analog, wherein in particular embodiments, XI0 is 2Nal, Phe(3,4-diF2), Phe(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-acetylaminoethoxy)], Phe(Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guadino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Tyr, Tyr(Bzl), or Tyr(Me);

XII is 1-Nal, 2-Nal, Phe(3,4-dimethoxy), 5-HydroxyTrp, Phe(3,4-Cl₂), Trp or Tyr(3-tBu);

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PCT/US2016/042680

XI2 is 3-Pal, Acpc, Acbc, Acvc, Ache, Agp, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), aMeLeu, α-MeOrn, a-MeSer, α-MeVal, Cav, Cha, Cit, Cpa, D-Asn, His, hLeu, hArg, Lys, Leu, Octgly, Orn, 4-amino-4-carboxy-piperidine, or THP;

XI3 is Cit, Asp, Dab, Dap, Phe, His, Dap(Peg2-Ac), Dap(pyroglutaric acid), Glu, hArg, Lys, Lys(Ac), Lys(Benzoic acid), Lys(glutaric acid), Lys(IVA), Lys(Peg4-isoGlu-Palm), Lys(pyroglutaric acid), Lys-succinic acid, Asn, Orn,Gln, Arg, Thr or Val;

XI4 is Dab(Ac), Dap(Ac), Phe, His, Lys(Ac), Met, Asn, Gln, Arg, or Tyr;

XI5 is Ala, βΑΗ, Gly, Asn, Gln, or Ser,

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00123] In some embodiments, X3 is absent. In particular embodiments, XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments, X4 and X9 are Cys, and X4 and X9 are linked via a disulfide bond. In particular embodiments, X4 is Abu and X9 is Pen, and X4 and X9 are linked via a thioether bond. In particular embodiments, X4 is Abu and X9 is Cys, and X4 and X9 are linked via a thioether bond.

[00124] In another embodiment of the peptide inhibitor of Formula Xa,

XI is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln or absent;

X4 is Cys, Abu or Pen;

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X5 is Dap, Dap(Ac), Gly, Lys, Gln, Arg, Ser,Thr or Asn;

X6 is Thr;

X7 is Trp or 6-Chloro-Trp;

X8 is Gln;

X9 is Cys, Abu or Pen;

XI0 is 2-Nal, a Phe analog, Tyr, or a Tyr analog, wherein in particular embodiments, XI0 is 2Nal, Phe(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-acetylaminoethoxy)], Phe(4-CONH2), Phe(4Me), Phe(4-NH2), Tyr, Tyr(Bzl), or Tyr(Me);

XI1 is 1-Nal, 2-Nal, Phe(3,4-dimethoxy), Phe(3,4-Cl2), or Trp;

XI2 is Acpc, Acbc, Acvc, Ache, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), α-MeLeu, aMeOrn, a-MeSer, a-MeVal, Cha, Cit, hLeu, Lys, Leu, Arg or THP;

XI3 is Cit, Asp, Dap, Dap(Peg2-Ac), Dap(pyroglutaric acid), Glu, hArg, Lys, Lys(Ac), Lys(Benzoic acid), Lys(glutaric acid), Lys(IVA), Lys(Peg4-isoGlu-Palm), Lys(pyroglutaric acid), Lys(succinic acid), Asn, Orn,Gln, Arg, or Val;

XI4 is Dab(Ac), Dap(Ac), His, Lys(Ac), Asn, Gln, or Tyr;

XI5 is Ala, betaAla, Gly, Asn, Gln, or Ser,

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

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PCT/US2016/042680 [00125] In some embodiments, X3 is absent. In particular embodiments, XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments, X4 and X9 are Cys, and X4 and X9 are linked via a disulfide bond. In particular embodiments, X4 is Abu and X9 is Pen, and X4 and X9 are linked via a thioether bond. In particular embodiments, X4 is Abu and X9 is Cys, and X4 and X9 are linked via a thioether bond.

[00126] In another embodiment of the peptide inhibitor of Formula Xa,

XI is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln or absent;

X4 is Cys, Abu or Pen;

X5 is Dap, Dap(Ac), Gln, Ser, Thr or Asn;

X6 is Thr;

X7 is Trp;

X8 is Gln;

X9 is Cys, Abu or Pen;

XI0 is a Phe analog, Tyr, or a Tyr analog, wherein in particular embodiments, XI0 is Phe[4-(2aminoethoxy)], Phe[4-(2-acetylaminoethoxy)], Phe(4-CONH2), Phe(4-Me), Tyr, Tyr(Bzl), or Tyr(Me);

XII is 2-Nal or Trp;

XI2 is Acpc, Acbc, Acvc, Ache, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), α-MeLeu, aMeOrn, a-MeSer, a-MeVal, hLeu, Leu, or THP;

XI3 is Cit, Asp, Glu, Lys, Lys(Ac), Asn, or Gln;

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XI4 is Dab(Ac), Asn, or His;

XI5 is Ala, betaAla, Gly, Asn, or Gin;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00127] In some embodiments, X3 is absent. In particular embodiments, XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments, X4 and X9 are Cys, and X4 and X9 are linked via a disulfide bond. In particular embodiments, X4 is Abu and X9 is Pen, and X4 and X9 are linked via a thioether bond. In particular embodiments, X4 is Abu and X9 is Cys, and X4 and X9 are linked via a thioether bond.

[00128] In particular embodiments, the peptide inhibitor comprises the amino acid sequence set forth in any of the various formula described herein, e.g., Ia-It, Ila-IId, Illa-IIIe, or IV.

[00129] In certain embodiments, the present invention includes a peptide inhibitor of an interleukin-23 receptor, wherein the peptide inhibitor has the structure of Formula I:

R'-X-R² (I) [00130] or a pharmaceutically acceptable salt or solvate thereof, [00131] wherein R¹ is a bond, hydrogen, an C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl C1-C6 alkyl, a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing;

[00132] R² is a bond, OH or NH₂; and

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PCT/US2016/042680 [00133]X is an amino acid sequence, e.g., an amino acid comprising 7 to 35 amino acid residues. In certain embodiments, R is OH or NH2.

[00134] In certain embodiments, X comprises a sequence of Formula Xa.

[00135] In particular embodiments of formula (I), X comprises the sequence of Formula la:

XI-X2-X3-X4-X5-X6-W-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (la) wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Fys, Orn, Dap, Dab, D-Dap, DDab, D-Asp, D-Glu, D-Fys, Sec, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3chloro-isobutyric acid, Abu, β-azido-Ala-OH, propargylglycine, 2-(3'-butenyl)glycine, 2allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, 2-(5'-hexenyl)glycine or absent;

X5 is Ala, Arg, Glu, Phe, Feu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Feu, D-Thr, D-Ser, , a-MeOrn, α-MeSer, CitDap, Dab, Dap (Ac), Gly, Fys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln,

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Fys;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Fys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Fys, Asp, Feu, Val, Phe, Ser, Sec, Abu, β-azido-Ala-OH, propargylglycine, 2-2allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, or 2-(5'-hexenyl)glycine;

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X10 is Tyr, Phe, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu)

X12 is His, Phe, Arg, N-Me-His, or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butylGly 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, aMeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin;

XI4 is Phe, Tyr phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac), or Asp;

XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

In particular embodiments of la: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, DArg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib or D-Sarc; X10 is Tyr or Phe; XI1 is Trp, 1Nal or 2-Nal; X12 is His, Phe, Arg, N-Me-His, or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butylAla or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, βήΑΗ, or Aib; X14 is Phe, Tyr or βΗΡήε; XI5 is Gly, Ser, Thr, Gin, Ala or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, βήΑΗ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00136] In particular embodiments, X4 is present.

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PCT/US2016/042680 [00137] In certain embodiments, the peptide inhibitor is cyclized.

[00138] In certain embodiments, the peptide inhibitor is linear or not cyclized.

[00139] In certain embodiments, the peptide inhibitor is cyclized, or contains an intramolecular bond, between X4 and X9.

[00140] In certain embodiments of Formula I, X comprises the sequence of Formula lb:

XI-X2-X3-X4-X5-X6-W-X8-X9-X10-X11 -XI2-X13-XI4-X15-X16-X17-X18-X19-X20 (lb), [00141] wherein:

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, DAsp, D-Glu, D-Lys, Sec, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercaptobutyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3-chloroisobutyric acid, Abu, β-azido-Ala-OH, propargylglycine, 2-(3'-butenyl)glycine, 2-2-allylglycine,

2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, 2-(5'-hexenyl)glycine, or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, oc-MeOrn, α-MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Sec, Abu, β-azido-Ala-OH, propargylglycine, 2-allylglycine, 2-(3'butenyl)glycine, 2-(4'-pentenyl)glycine, or 2-(5'-hexenyl)glycine;

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X10 is Tyr, Phe, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂), Tyr(3-t-Bu)

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butyl-Gly4amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, a-MeLys, a-MeLys(Ac), a-Me-Leu, a-MeOrn, a-MeSer, a-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAlaAib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln

XI4 is Phe, Tyr, or phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gln, Ala, or Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid, or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00142] In particular embodiments of lb: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, DAla, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib or D-Sarc; X10 is Tyr or Phe; XI1 is Trp, 1-Nal or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, tbutyl-Ala or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, βhAla or Aib; XI4 is Phe, Tyr or βhPhe; XI5 is Gly, Ser, Thr, Gln, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, βhAla, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00143] In particular embodiments, X4 is present.

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PCT/US2016/042680 [00144] In certain embodiments, the peptide inhibitor is cyclized.

[00145] In certain embodiments, the peptide inhibitor is linear or not cyclized.

[00146] In certain embodiments, the peptide inhibitor is cyclized, or contains an intramolecular bond, between X4 and X9.

[00147] In certain embodiments of Formula I, X comprises the sequence of Formula Ic:

XI-X2-X3-X4-X5-X6-W-X8-X9-Y-Xl 1 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Ic) [00148] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, DDab, D-Asp, D-Glu, D-Lys, Sec, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3chloro-isobutyric acid, Abu, β-azido-Ala-OH, propargylglycine, 2-allylglycine, 2-(3'butenyl)glycine, 2-(4'-pentenyl)glycine, 2-(5'-hexenyl)glycine, or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, oc-MeOrn, α-MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gin

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gin, Glu, or Lys;

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X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Sec, Abu, β-azido-Ala-OH, propargylglycine, 2-allylglycine, 2-(3'butenyl)glycine, 2-(4'-pentenyl)glycine, or 2-(5'-hexenyl)glycine;

XI1 is Trp, 1-Nal, 2-Nal Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu)

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala t-butyl-Gly; 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, aMeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, or Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00149] In particular embodiments of lc, X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, DAla, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; XI1 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butylGly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, or Aib; XI4 is Phe, Tyr, or phPhe; XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, βΙιΑΝ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00150] In particular embodiments, X4 is present.

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PCT/US2016/042680 [00151] In certain embodiments, the peptide inhibitor is cyclized.

[00152] In certain embodiments, the peptide inhibitor is linear or not cyclized.

[00153] In certain embodiments, the peptide inhibitor is cyclized, or contains an intramolecular bond, between X4 and X9.

[00154] In certain embodiments of Formlua I, X comprises the sequence of Formula Id:

X1-X2-X3-C-X5-X6-W-X8-C-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Id) [00155] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, a-MeOrn, α-MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X10 is Tyr Phe, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr

XII is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂), Tyr(3-t-Bu)

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, a66

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MeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His, Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00156] wherein X4 and X9 are optionally linked by a intramolecular disulphide bridge.

[00157] In certain embodiments of Id: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; XI0 is Tyr or Phe; XI1 is Trp,

1-Nal, or 2-Nal; XI2 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butylAla, or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, βΙιΑΗ, or Aib; X14 is Phe, Tyr, or βΤιΡΙοβ; XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, βΙιΑΗ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00158] In certain embodiments of Formula I, X comprises the sequence of Formula Ie:

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Ie) [00159] wherein

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XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Pen, hCys, D-Pen, D-Cys, or D-hCys;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, oc-MeOrn, α-MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Pen, hCys, D-Pen, D-Cys, D-hCys;

X10 is Tyr, Phe Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XII is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu);

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, aMeLys, a-MeLys(Ac), α-Me-Leu, oc-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

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XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00160] wherein X4 and X9 are optionally linked by a intramolecular disulphide bridge.

[00161] In certain embodiments of Ie: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; XI0 is Tyr or Phe; XI1 is Trp, 1-Nal, or 2-Nal; XI2 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butylAla, or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, or Aib; X14 is Phe, Tyr, or phPhe; XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, phAla, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00162] In particular embodiments, X4 is present.

[00163] In certain embodiments, the peptide inhibitor is cyclized.

[00164] In certain embodiments, the peptide inhibitor is linear or not cyclized.

[00165] In certain embodiments, the peptide inhibitor is cyclized, or contains an intramolecular bond, between X4 and X9.

[00166] In particular embodiments, X4 and X9 and both Pen.

[00167] In certain embodiments of Formula I, X comprises the sequence of Formula If:

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (If) [00168] wherein

XI is any amino acid or absent;

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X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, or Asp;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, oc-MeOrn, α-MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, or Asp;

X10 is Tyr, Phe, Phe(3,4-F2), Phe(3,4-C12), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4Me), Phe(4-NH2), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu);

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butylGly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, aMeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

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XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00169] wherein X4 and X9 are optionally cyclized through an intramolecular bond.

[00170] In certain embodiments of If: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; X6 is Asp, Thr, Asn, Phe, DAsp, D-Thr, D-Asn, or D-Phe; X8 is Val, Gln, Glu, or Lys; X9 is Glu, Lys, Orn, Dap, Dab, DDap, D-Dab, D-Asp, D-Glu, D-Lys, or Asp; X10 is Tyr or Phe;; XI1 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butylGly; ;X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, or Aib; XI4 is Phe, Tyr, or phPhe; XI5 is Gly, Ser, Thr, Gln, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, phAla, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00171] In certain embodiments, the intramolecular bond is a lactam bond.

[00172]In certain embodiments of Formula I, X comprises the sequence of Formula Ig:

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Ig) [00173] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is β-azido-Ala-OH, or propargylglycine;

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X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, a-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gin;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gin, Glu, or Lys;

X9 is β-azido-Ala-OH or propargylglycine, ;

X10 is Tyr, Phe, Phe(3,4-F₂), Phe(3,4-Cl₂), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂) or Tyr(3-t-Bu)

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Feu, Cit, hFeu, 3-Pal, t-butyl-Ala, or t-butylGly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, aMeFys, a-MeFys(Ac), α-Me-Feu, oc-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Fys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Feu, Fys, Val, βήΑΗ, Aib, Fys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Fys, Asn, Orn, or Gin;

XI4 is Phe, Tyr, βΗΡήε, Asn, Arg, Qin, Fys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent,

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PCT/US2016/042680 [00174] wherein X4 and X9 are optionally cyclized through an intramolecular triazole ring.

[00175] In particular embodiments of Ig: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, DAla, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe; X8 is Val, Gln, Glu, or Lys; X9 is β-azido-Ala-OH or propargylglycine; X10 is Tyr or Phe; XI1 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-MeHis, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, βΙιΑΝ, or Aib; X14 is Phe, Tyr, or βΡιΡΡιε; XI5 is Gly, Ser, Thr, Gln, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, βήΛΗ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00176] In certain embodiments of Formula I, X comprises the sequence of Formula lh:

X1-X2-X3-C-X5-X6-W-X8-C-Y-X11-H-X13-F-X15-X16-X17-X18-X19-X20 (lh) [00177] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, or 2-(5'-hexenyl)glycine;

X5 is Ala, Arg, Sarc, α-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, NMeArg, Orn or Gln;

X6 is Asp, Thr, or Asn;

X8 is Val, Gln, or Glu;

X9 is 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, or 2-(5'-hexenyl)glycine;

XII is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu)

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XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00178] wherein X4 and X9 are optionally cyclized via an intramolecular ring closing methasis to give the corresponding olefins.

[00179] In particular embodiments of Ih: X5 is Ala, Arg, or Sarc; X6 is Asp, Thr, or Asn; XI1 is Trp, 1-Nal, or 2-Nal; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΡιΑΝ, Val, or Aib; XI5 is Gly, Ser, Thr, Gln, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, βΡιΑΝ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00180] In certain embodiments of Formula I, X comprises the sequence of Formula Ii:

XI-X2-X3-X4-X5-X6-W-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Ii), [00181] wherein:

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

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X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, or 3-chloro-isobutyric acid;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc, α-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, NMeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, or Abu;

X10 is Tyr, Phe, Phe(3,4-F₂), Phe(3,4-Cl₂), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂) or Tyr(3-t-Bu)

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, aMeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

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XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00182] wherein X4 and X9 are optionally cyclized via an intramolecular thioether bond.

[00183] In particular embodiments of Ii: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, DAla, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe; X10 is Tyr or Phe; XI1 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, or Aib; X14 is Phe, Tyr, or phPhe; XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, phAla, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00184] In certain embodiments of Formula I, X comprises the sequence of Formula Ij:

XI-X2-X3-X4-X5-X6-W-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Ij), [00185] wherein:

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Sec, 2-chloromethylbenzoic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3-chloroisobutyric acid, or Abu;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, oc-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gin;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

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X8 is Val, Gin, Glu, or Lys;

X9 is Sec or Abu;

X10 is Tyr, Phe, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2aminoethoxy), Phe[4-(2-(acetyl-aminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH2), Phe(4-N3), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu);

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache, Acpc, Acbc, Agp, Aib, a-DiethylGly, α-MeLys, aMeLys(Ac), α-Me-Leu, a-MeOrn, a-MeSer, a-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00186] wherein X4 and X9 are optionally cyclized via an intramolecular thioseleno or diselenide bond.

[00187] In particular embodiments of Ij: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, DAla, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; XI1 is

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Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, tbutyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, or Aib; XI4 is Phe, Tyr, or phPhe; XI5 is Gly, Ser, Thr, Gln, Ala, or Sarc; XI6 is Asp, Glu, Ala, AEA, AEP, PhAla, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00188]In certain embodiments of Formula I, X comprises the sequence of Formula Ik:

XI-X2-X3-X4-X5-X6-W-X8-X9-X10-X11 -XI2-X13-XI4-X15-X16-X17-X18-X19-X20 (Ik), [00189] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Fys, Orn, Dap, Dab, D-Dap, DDab, D-Asp, D-Glu, D-Fys or absent;

X5 is Ala, Arg, Glu, Phe, Feu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Feu, D-Thr, D-Ser, a-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Fys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Fys;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Fys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Fys, Asp, Feu, Val, Phe, or Ser;

X10 is Tyr, Phe, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XII is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu);

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XI2 is His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, tbutyl-Gly,4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Aebe, Aeve, Agp, Aib, aDiethylGly, α-MeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp or absent;

XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn or absent;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00190] In particular embodiments of Ik: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, DAla, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; XI1 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3Pal, t-butyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, βhAla, Aib or absent; XI4 is Phe, Tyr, βhPhe or absent; XI5 is Gly, Ser, Thr, Gin, Ala, Sarc or absent; XI6 is Asp, Glu, Ala, AEA, AEP, βhAla, Gaba, Leu, or absent; and XI7 is Leu, Lys, Arg, or absent.

In certain embodiments of Formula I, X comprises or consists of the sequence of Formula II:

XI-X2-X3-X4-X5-X6-W-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (II), [00191] wherein

XI is any amino acid or absent;

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X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, DDab, D-Asp, D-Glu, D-Lys or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, a-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, or Ser;

X10 is Tyr, Phe, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XI1 is Trp, 1-Nal, 2-Nal,, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu);

X12 is His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, tbutyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, aDiethylGly, α-MeLys, a-MeLys(Ac), α-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln or absent;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp or absent;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg or Asn or absent;

XI6 is any amino acid or absent;

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XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00192] In particular embodiments of II: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, or Sarc; X10 is Tyr or Phe; XI1 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, phAla, Aib or absent; X14 is Phe, Tyr, phPhe or absent; XI5 is Gly, Ser, Thr, Gin, Ala, Sarc or absent; XI6 is Asp, Glu, Ala, AEA, AEP, phAla, Gaba, Leu, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00193] In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin. In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, or Aib.

[00194] In certain embodiments, X14 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp. In certain embodiments, XI4 is Phe, Tyr, or phPhe.

[00195] In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn. In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc.

[00196] In certain embodiments, X12 is alpha amino acid, e.g., 4-amino-4-carboxytetrahydropyran, Ache Acpc, Acbc, Aib, a-MeGly(diethyl), α-MeLys, a-MeLys(Ac), a-MeLeu, α-MeOrn, a-MeSer, a-MeVal.

[00197] In certain embodiments, XI3 is present.

[00198] In certain embodiments, XI3 and X14 are present.

[00199] In certain embodiments, XI3, X14 and XI5 are present.

[00200] In particular embodiments, X4 is present.

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PCT/US2016/042680 [00201] In certain embodiments, the peptide inhibitor is cyclized.

[00202] In certain embodiments, the peptide inhibitor is linear or not cyclized.

[00203] In certain embodiments, the peptide inhibitor is cyclized, or contains an intramolecular bond, between X4 and X9.

[00204] In certain embodiments of the peptide inhibitor of Formula I, X comprises or consists of the sequence of Formula Im:

XI-X2-X3-X4-X5-X6-W-X8-X9-Y-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Im), [00205] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, DDab, D-Asp, D-Glu, D-Lys or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, α-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, or Ser;

XII is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2); 5-Hydroxy-Trp, Phe(3,4-0^), or Tyr(3-t-Bu);

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butylGly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, a82

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MeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin or absent;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac), or Asp or absent;

XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn or absent;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00206] In certain embodiments of Im: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, or Sarc; XI1 is Trp, 1-Nal, or 2-Nal; XI2 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, tbutyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ, Val, Aib or absent; XI4 is Phe, Tyr, βΙιΡΙιε or absent; XI5 is Gly, Ser, Thr, Gin, Ala, Sarc or absent; XI6 is Asp, Glu, Ala, AEA, AEP, βΙιΑΝ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00207] In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ, or Aib. In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin.

[00208] In certain embodiments, X14 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp. In certain embodiments, XI4 is Phe, Tyr, or phPhe.

[00209] In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc, β-Ala, Glu, Arg or Asn. In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc.

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PCT/US2016/042680 [00210] In certain embodiments, X12 is alpha amino acid, e.g., 4-amino-4-carboxytetrahydropyran, Ache Acpc, Acbc, Aib, a-MeGly(diethyl), α-MeLys, a-MeLys(Ac), a-MeLeu, a-MeOrn, a-MeSer, a-MeVal.

[00211]In certain embodiments, X13 is present.

[00212] In certain embodiments, XI3 and X14 are present.

[00213]In certain embodiments, X13, X14, and X15 are present.

[00214] In particular embodiments, X4 is present.

[00215] In certain embodiments, the peptide inhibitor is cyclized.

[00216] In certain embodiments, the peptide inhibitor is linear or not cyclized.

[00217] In certain embodiments, the peptide inhibitor is cyclized, or contains an intramolecular bond, between X4 and X9.

[00218] In certain embodiments of the peptide inhibitor of Formula I, X comprises or consists of the sequence of Formula In:

XI-X2-X3-C-X5-X6-W-X8-C-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (In) [00219] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, α-MeOrn, a-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

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X10 is Tyr Phe, Phe(3,4-F₂), Phe(3,4-Cl₂), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂) or Tyr(3-t-Bu);

X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butylGly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, aMeLys, a-MeLys(Ac), α-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln or absent;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp or absent;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg or Asn or absent;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00220] wherein the Cys at position X4 and and the Cys at position X9 are optionally linked by a disulphide bridge.

[00221] In certain embodiments of In: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, aMeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln; X10 is Tyr, Phe, Phe(3,4-F₂), Phe(3,4-Cl₂), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr; XI1 is Trp, 1-Nal, 2-Nal, Phe(3,485

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OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂) or Tyr(3-t-Bu); X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), α-Me-Leu, aMeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin or absent; XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp or absent; XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn or absent; XI6 is Asp, Glu, Ala, AEA, AEP, βΡιΑΗ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00222] In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙτΑΗ, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin. In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΡιΑΗ, or Aib.

[00223] In certain embodiments, X14 is Phe, Tyr, βΡιΡΡιβ, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp. In certain embodiments, XI4 is Phe, Tyr, or phPhe.

[00224] In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn. In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc.

[00225]In certain embodiments, X12 is an alpha amino acid, e.g., 4-amino-4-carboxytetrahydropyran, Ache Acpc, Acbc, Acvc, Aib, α-DiethylGly, a-MeLys, a-MeLys(Ac), a-MeLeu, α-MeOrn, a-MeSer, a-MeVal.

[00226] In certain embodiments, XI3 is present.

[00227] In certain embodiments, XI3 and X14 are present.

[00228] In certain embodiments, XI3, X14 and XI5 are present.

[00229] In certain embodiments of the peptide inhibitor of Formula I, X comprises or consists of the sequence of Formula Io:

XI-X2-X3-C-X5-X6-W-X8-C-Y-Xl 1 -H-Xl 3-X14-X15-X16-X17-X18-X19-X20 (Io) [00230] wherein

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XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, oc-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

XII is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu);

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln or absent;

XI4 is Phe, Tyr, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp or absent;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg or Asn or absent;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00231] wherein the Cys at position X4 and and the Cys at position X9 are optionally linked by a disulphide bridge.

[00232] In certain embodiments of Io: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, aMeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln; XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe₂), 5-Hydroxy-Trp, Phe(3,4-Cl₂) or Tyr(3-t-Bu); X13 is

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Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Gin or absent; XI4 is Phe, Tyr, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) Asp or absent; XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn or absent; XI6 is Asp, Glu, Glu, Ala, AEA, AEP, βΙιΑΗ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00233]In certain embodiments, X12 is an alpha amino acid, e.g., 4-amino-4-carboxytetrahydropyran, Ache Acpc, Acbc, Acvc, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), a-MeLeu, α-MeOrn, a-MeSer, a-MeVal.

[00234] In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΗ, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin. In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΤι A la or Aib.

[00235] In certain embodiments, X14 is Phe, Tyr, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp. In certain embodiments, XI4 is Phe or Tyr.

[00236] In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn. In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala or Sarc.

[00237] In certain embodiments, XI3 is present.

[00238] In certain embodiments, XI3 and X14 are present.

[00239] In certain embodiments, XI3, X14 and XI5 are present.

[00240] In certain embodiments of the peptide inhibitor of Formula I, X comprises or consists of the sequence of Formula Ip:

X1-X2-X3-C-X5-X6-W-X8-C-Y-X11-H-X13-F-X15-X16-X17-X18-X19-X20 (Ip) [00241] wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

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X3 is any amino acid or absent;

X5 is Ala, Arg, Sarc, oc-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, NMeArg, Orn or Gln;

X6 is Asp, Thr, or Asn;

X8 is Val, Gln, or Glu;

XI1 is Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu);

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Gln or absent;

XI5 is Gly, Ser, Thr, Gln, Ala, Sarc, β-Ala, Glu, Arg Asn or absent;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00242] wherein the Cys at position X4 and and the Cys at position X9 are optionally linked by a disulphide bridge.

[00243] In certain embodimetns of Ip: X5 is Ala, Arg, or Sarc; XI1 is Trp, 1-Nal, or 2-Nal; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ, Val, Aib or absent; XI5 is Gly, Ser, Thr, Gln, Ala, Sarc or absent; XI6 is Asp, Glu, Ala, AEA, AEP, βΙιΑΝ, Gaba, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00244] In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln. In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ or Aib.

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PCT/US2016/042680 [00245] In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala or Sarc, β-Ala, Glu, Arg or Asn. In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala or Sarc.

[00246] In certain embodiments, XI3 is present.

[00247] In certain embodiments, XI3 and X14 are present.

[00248] In certain embodiments, XI3, X14 and XI5 are present.

[00249] In certain embodiments of the peptide inhibitor of Formula I, X comprises or consists of the sequence of Formula Iq:

XI-X2-X3-C-X5-X6-W-X8-C-X10-X11 -XI2-X13-XI4-X15-X16-X17-X18-X19-X20 (Iq), wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X5 is Ala, Arg, Glu, Phe, Feu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Feu, D-Thr, D-Ser, D-Aib, D-Sarc, oc-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Fys, Asn, N-MeGln, N-MeArg, Orn or Gin;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gin, Glu, or Fys;

X10 is Tyr, Phe, Phe(3,4-F₂), Phe(3,4-Cl₂), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetylaminoethoxy)], Phe(4-Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XII is Trp, 1-Nal, 2-Nal,, Phe(3,4-OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂) or Tyr(3-t-Bu);

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XI2 is His, Phe, Arg, N-Me-His, Val, or D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, tbutyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Aebe, Acvc, Agp, Aib, aDiethylGly, α-MeLys, a-MeLys(Ac), α-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Gin or absent;

XI4 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac), Asp or absent;

XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg, Asn or absent;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, [00250] wherein the Cys at position X4 and and the Cys at position X9 are optionally linked.

[00251] In certain embodiments of Iq: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; XI0 is Tyr or Phe; XI1 is Trp, 1-Nal, or 2-Nal; XI2 is His, Phe, Arg, N-Me-His, Val, or D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Val, Aib or absent; XI4 is Phe, Tyr, phPhe or absent; XI5 is Gly, Ser, Thr, Gin, Ala, Sarc or absent; XI6 is Asp, Glu, Ala, AEA, AEP, phAla, Gaba, Leu, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00252] In certain embodiments, X12 is alpha amino acid, e.g., 4-amino-4-carboxytetrahydropyran, Ache Acpc, Acbc, Acvc, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), a-MeLeu, a-MeOrn, a-MeSer, a-MeVal.

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PCT/US2016/042680 [00253] In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin. In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, phAla or Aib.

[00254] In certain embodiments, X14 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac), or Asp. In certain embodiments, XI4 is Phe, Tyr or phPhe.

[00255] In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, Sarc, β-Ala, Glu, Arg or Asn. In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala or Sarc.

[00256] In certain embodiments, XI3 is present.

[00257] In certain embodiments, XI3 and X14 are present.

[00258] In certain embodiments, XI3, X14 and XI5 are present.

[00259] In certain embodiments, Iq comprises or consists of the sequence of Formula Iq’:

XI-X2-X3-C-X5-X6-W-X8-C-X10-X11 -XI2-X13-X14-X15 (Iq’), wherein XI-XI4 have the definition provided for Iq, and wherein the Cys at position X4 and and the Cys at position X9 are optionally linked.

[00260] In certain embodiments of Iq’: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, or D-Sarc; XI0 is Tyr or Phe; XI1 is Trp, 1-Nal, or 2-Nal; XI2 is His, Phe, Arg, N-Me-His, Val, or D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, or t-butyl-Gly; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ, Val, Aib or absent; X14 is Phe, Tyr, βΡιΡΤιβ or absent; XI5 is Gly, Ser, Thr, Gin, Ala, Sarc or absent; XI6 is Asp, Glu, Ala, AEA, AEP, βΙιΑΝ, Gaba, Leu, or absent; and XI7 is Leu, Lys, Arg, or absent.

[00261] In certain embodiments, XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, βΙιΑΝ, Aib, Lys(Ac),

Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gin. In certain embodiments, XI3 is Thr, Sarc,

Glu, Phe, Arg, Leu, Lys, βΡι A la or Aib.

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PCT/US2016/042680 [00262] In certain embodiments, X14 is Phe, Tyr, phPhe, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp. In certain embodiments, XI4 is Phe, Tyr or phPhe.

[00263] In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala or Sarc, β-Ala, Glu, Arg or Asn. In certain embodiments, XI4 is Phe, Tyr or phPhe.

[00264] In certain embodiments, XI3 is present.

[00265] In certain embodiments, XI3 and X14 are present.

[00266] In certain embodiments, XI3, X14 and XI5 are present.

[00267] In certain embodiments of the peptide inhibitor of Formula I, X comprises or consists of the sequence of Formula Ir:

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Ir) wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, DDab, D-Asp, D-Glu, D-Lys, Sec, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3chloro-isobutyric acid, Abu, β-azido-Ala-OH, propargylglycine, 2-(3'-butenyl)glycine, 2allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, 2-(5 '-hexenyl)glycine, Abu or absent;

X5 is any amino acid;

X6 is any amino acid;

X7 is Trp, Glu, Gly, Ile, Asn, Pro, Arg, Thr or OctGly, or a corresponding a-methyl amino acid form of any of the foregoing;

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X8 is any amino acid;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, or Ser, Sec, Abu, β-azido-Ala-OH, propargylglycine, 2-2allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, Ala, hCys, Abu, Met, MeCys, (D)Tyr or 2-(5'-hexenyl)gly cine;

XI0 is Tyr, Phe(4-OMe), 1-Nal, 2-Nal, Aic, α-MePhe, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, His, hPhe(3,4-dimethoxy), hTyr, N-Me-Tyr, Trp, Phe(4-CONH2), Phe(4-phenoxy), Thr, Tic, Tyr(3-tBu), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4-NH₂), Phe(4-F), Phe(3,5-F₂), Phe(4CH₂CO₂H), Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF₃), Bip, Cha, 4-PyridylAlanine, βΙιΤγτ, OctGly, Phe(4-N₃), Phe(4-Br), Phe[4-(2-aminoethoxy)] or Phe, a Phe analog, a Tyr analog, or a corresponding α-methyl amino acid form of any of the foregoing;

XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl₂), Phe (3,4-F₂), Phe(4-CO₂H), β1ιΡ1ΐ6(4F), α-Me-Trp, 4-phenylcyclohexyl, Phe(4-CF₃), , Phe(3,4-OMe₂), α-MePhe, βΙΑΝαΙ, βΙιΡΙιε, βΙιΤνΓ, βΙιΤτρ, Nva(5-phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe(4-OMe), Phe(4-Me), Trp(2,5,7-tri-tert-Butyl), Phe(4-Oallyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino, Phe(4-OBzl), Octgly, Glu(Bzl), 4-Phenylbenzylalanine, Phe[4-(2-aminoethoxy)], 5-Hydroxy-Trp, 6-ChloroTrp, N-MeTrp, 1,2,3,4-tetrahydro-norharman, Phe(4-CONH₂), Phe(3,4-Dimethoxy), Phe(2,3Cl₂), Phe(2,3-F₂), Phe(4-F), 4-phenylcyclohexylalanine or Bip, or a corresponding a-methyl amino acid form of any of the foregoing;

XI2 is His, Phe, Arg, N-Me-His, or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, a-MeLys, D-Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Tyr, Aib, a-MeLeu, α-MeOrn, βAib, β-Ala, βΙιΑΗ, βΙιΑ^, βϋεη, βΙΑ^Ι, β-spiro-pip, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr, Tie or t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, a-MeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, aMeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys or a corresponding α-methyl amino acid form of any of the foregoing;

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XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Asn, Cit, Lys, Arg, Orn, Val, phAla, Lys(Ac), (D)Asn, (D)Leu, (D)Phe, (D)Thr, Ala, α-MeLeu, Aib, β-Ala, β-Glu, βΜ^εη, βhVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, hLeu, Asn, Ogl, Pro, Gln, Ser, β-spiro-pip, Thr, Tba, Tie or Aib, or a corresponding α-methyl amino acid form of any of the foregoing;

XI4 is Phe, Tyr, Glu, Gly, His, Lys, Leu, Met, Asn, Lys(Ac), Dap(Ac), Asp, Pro, Gln, Arg, Ser, Thr, Tic or βΜ^ιε, or a corresponding α-methyl amino acid form of any of the foregoing;

XI5 is Gly, Ser, Thr, Gln, Ala, (D)Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Thr, Aea, Asp, Asn, Glu, Phe, Gly, Lys, Leu, Pro, Arg, β-Ala, or Sarc, or a corresponding α-methyl amino acid form of any of the foregoing;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00268] In particular embodiments, the peptide is cyclized via X4 and X9.

[00269] In particular embodiments, X3 is Glu, D-Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln.

[00270]In certain embodiments of Ir: XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl2), Phe (3,4-F2), Phe(4-CO2H), βυ4ιε(4-Ρ), α-Me-Trp, 4-phenylcyclohexyl, Phe(4-CF₃), a-MePhe, βhNal, βhPhe, βhTyr, βhTrp, Nva(5-phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe(4-OMe), Phe(4-Me), Trp(2,5,7-tri-tert-Butyl), Phe(4-Oallyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino, Phe(4-OBzl), Octgly, Glu(Bzl), 4-Phenylbenzylalanine, Phe[4-(2-aminoethoxy)], 5-HydroxyTrp, 6-Chloro-Trp, N-MeTrp, 1,2,3,4-tetrahydro-norharman, Phe(4-CONH₂), Phe(3,4Dimethoxy), Phe(2,3-Cl2), Phe(2,3-F2), Phe(4-F), 4-phenylcyclohexylalanine or Bip, or a corresponding α-methyl amino acid form of any of the foregoing; XI2 is His, Phe, Arg, N-Me95

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His, or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, α-MeLys, D-Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Tyr, Aib, α-MeLeu, a-MeOrn, β-Aib, β-Ala, βhAla, βhArg, βΜ^ι, βhVal, β-spiro-pip, Glu, hArg, lie, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gin, Ser, Thr, Tie or tbutyl-Gly, or a corresponding α-methyl amino acid form of any of the foregoing; XI3 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Arg, Orn, Val, βhAla, Lys(Ac), (D)Asn, (D)Leu, (D)Phe, (D)Thr, Ala, α-MeLeu, Aib, β-Ala, β-Glu, βΜ^ι, βhVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, aDiethylGly, hLeu, Asn, Ogl, Pro, Gin, Ser, β-spiro-pip, Thr, Tba, Tie or Aib, or a corresponding α-methyl amino acid form of any of the foregoing; XI4 is Phe, Tyr, Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Tic or βhPhe, or a corresponding α-methyl amino acid form of any of the foregoing; XI5 is Gly, Ser, Thr, Gin, Ala, (D)Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Thr, Aea, Asp, Asn, Glu, Phe, Gly, Lys, Leu, Pro, Arg or Sarc, or a corresponding amethyl amino acid form of any of the foregoing; XI6 is Asp, Glu, Ala, AEA, AEP, βhAla, Gaba, Gly, Ser, Pro, Asn, Thr or absent, or a corresponding α-methyl amino acid form of any of the foregoing; and XI7 is Leu, Lys, Arg, Glu, Ser, Gly, Gin or absent, or a corresponding a-methyl amino acid form of any of the foregoing.

[00271] In certain embodiments, both X4 and X9 are Pen. In particular embodiments, X4 and X9 are cyclized via a disulfide bond.

[00272] In certain embodiments, X4 is Abu and X9 is Cys. In certain embodiments, X4 and X9 are cyclized via a thioether bond.

[00273] In particular embodiments, X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, DArg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, D-Aib, Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me-Ala, N-Me-Asn, N-Me-Lys, N-Me-Gln, Orn, Pro, Pen, Gin, Val, aMe-Lys, aMe-Orn, or D-Sarc, α-MeOrn, a-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, NMeArg, or Gin. In certain embodiments, X5 is Gin or Asn. In particular embodiments, X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, DAib, Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me-Ala, N-Me-Asn, N-Me-Lys, N-Me-Gln, N-Me-Arg, Orn, Pro, Pen, Gin, Val, aMe-Lys, aMe-Orn, or D-Sarc.In certain embodiments, X5 is Gin.

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PCT/US2016/042680 [00274] In particular embodiments, X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, Glu, Arg, Ser or D-Phe. In particular embodiments, X6 is Thr.

[00275] In particular embodiments, X7 is Trp.

[00276] In particular embodiments, X8 is Val, Gln, Glu, Phe, Asn, Pro, Arg, Thr, Trp or Lys. In particular embodiments, X8 is Gln.

[00277] In particular embodiments, XI, X2 and X3 are absent.

[00278] In certain embodiments, XI1 is a Trp analog.

[00279] In particular embodiments, XI0 is a Phe analog. In particular embodiments, XI0 is Phe(4-OMe), Phe(4-CONH2), or Phe[4-(2-aminoethoxy)] (also referred to herein as Phe[42ae)]). In particular embodiments, XI0 is Phe(4-OMe) or Phe[4-(2-aminoethoxy)] (also referred to herein as Phe[4-2ae)]).

[00280] In particular embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI1 is 2-Nal.

[00281] In certain embodiments, XI2 is α-MeLys, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), α-Me-Leu, α-MeOrn, aMeSer, or α-MeVal. In certain embodiments, XI2 is a-MeLys.

[00282] In certain embodiments, XI3 is Glu or Lys(Ac). In certain embodiments, XI3 is Glu.

[00283] In certain embodiments, X14 is Asn.

[00284] In certain embodiments, XI5 is Gly or Asn. In certain embodiments, XI5 is Gly.

[00285] In certain embodiments, one or more, two or more, three or more, or four or more of XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments, XI6, XI7, XI8, XI9 and X20 are absent.

[00286]In particular embodiments of Ir, X4 and X9 are Cys, X7 is Trp, and XI8 is [(D)Lys], In particular embodiments of Ir, X4 and X9 are Cys, X7 is Trp, X10 is Tyr, and X18 is [(D)Lys], In particular embodiments of Ir, X4 and X9 are Cys, X7 is Trp, XI, X2 and X3 are absent, XI7 is

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PCT/US2016/042680 absent, XI8 is [(D)Lys], and XI9 and X20 are absent. In particular embodiments of Ir, X4 and X9 are Cys, X7 and XI1 are Trp, XI0 is Tyr, and XI8 is [(D)Lys. In certain embodiments, XI, X2, and X3 are absent; and in certain embodiments, XI7 is absent.

[00287] In particular embodiments of Ir, X4 and X9 are Pen, and XI2 is α-MeLys. In particular embodiments of Ir, X4 and X9 are Pen, X12 is α-MeLys, and X16, X17, XI8, X19 and X20 are absent. In particular embodiments of Ir, X4 and X9 are Pen, XI2 is α-MeLys, 4-amino-4carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, a-MeLys(Ac), aMe-Leu, α-MeOrn, a-MeSer, α-MeVal, XI6, XI7, XI8, XI9 and X20 are absent, and X7 is Trp. In particular embodiments of Ir, X4 and X9 are Pen, XI2 is α-MeLys, XI6, XI7, XI8, XI9 and X20 are absent, and X7 is Trp. In particular embodiments of Ir, X4 and X9 are Pen, X7 is Trp, and X12 is a-MeLys. In certain embodiments, XI, X2, and X3 are absent. In particular embodiments, there is a disulfide bond between X4 and X9.

[00288] In particular embodiments of Ir, X4 is Abu, X9 is Cys, and X12 is 4-amino-4-carboxytetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, a-DiethylGly, a-MeLys, or a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, or α-MeVal. In particular embodiments of Ir, X4 is Abu, X9 is Cys, and XI2 is α-MeLys. In particular embodiments of Ir, X4 is Abu, X9 is Cys, XI2 is aMeLys, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, a-DiethylGly, α-MeLys, or a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, or α-MeVal and XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments of Ir, X4 is Abu, X9 is Cys, XI2 is aMeLys, and XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments of Ir, X4 is Abu, X9 is Cys, XI2 is α-MeLys, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, a-DiethylGly, α-MeLys, or a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, or aMeVal, XI6, XI7, XI8, XI9 and X20 are absent, and X7 is Trp. In particular embodiments of Ir, X4 is Abu, X9 is Cys, XI2 is α-MeLys, XI6, XI7, XI8, XI9 and X20 are absent, and X7 is Trp. In particular embodiments of Ir, X4 is Abu, X9 is Cys, X7 is Trp, and XI2 is α-MeLys. In certain embodiments, XI, X2, and X3 are absent. In particular embodiments, there is a thioether bond between X4 and X9.

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PCT/US2016/042680 [00289] In certain embodiments of the peptide inhibitor of Formula I, X comprises or consists of the sequence of Formula Is:

Xl-X2-X3-C-X5-X6-W-X8-C-X10-Xll-X12-X13-X14-G-X16-X17-X18-X19-X20(Is) wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X5 is any amino acid;

X6 is any amino acid;

X8 is any amino acid;

X10 is Tyr, 1-Nal 2-Nal, Phe(3,4-F₂), Phe(3,4-Cl₂), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2(acetyl-aminoethoxy)], Phe(4-Br), Phe(4-CONH₂), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-OBzl) or Tyr;

XII is Trp 1-Nal, Phe(3,4-OMe₂) 5-Hydroxy-Trp, Phe(3,4-Cl₂) or Tyr(3-t-Bu);

XI2 is Arg, Lys, His, hArg, Cit, Orn, 1-Nal, D-Ala, D-Leu, D-Phe, D-Asn, D-Asp, Agp, Leu, PhLeu, Aib, phAla, phVal, phArg, hLeu, Dap, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, a-DiethylGly, α-MeLys, a-MeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, α-MeVal, Cha, Cit, Cpa, (D)Asn, Glu, hArg, or Lys;

XI3 is Cha, Ogl, Aib, Leu, Val, Dab, Glu, Lys, phLeu, phAla, phVal PGlu, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Lys(Ac), or Gln;

X14 is Phe, Tic, Asn Tyr, Asn, Arg, Qin, Lys(Ac), His; Dap(Ac), Dab(Ac) or Asp;

XI6 is any amino acid;

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XI7 is absent;

XI8 is D-Lys;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00290] In particular embodiments of Is: XI0 is Tyr, 1-Nal or 2-Nal; XI1 is Trp or 1-Nal; XI2 is Arg, Lys, His, hArg, Cit, Orn, 1-Nal, D-Ala, D-Leu, D-Phe, D-Asn, D-Asp, Agp, Leu, phLeu, Aib, phAla, phVal, phArg, hLeu or Dap; XI3 is Cha, Ogl, Aib, Leu, Val, Dab, Glu, Lys, phLeu, PhAla, phVal or PGLu; X14 is Phe, Tic, Asn or Tyr; and X16 is AEA, Ala or βΑΗ.

[00291] In particular embodiments, X5 is Glu, Arg, Ala, N-Me-Arg, N-Me-Ala, N-Me-Gln, Orn, N-Me-Asn, N-Me-Lys, Ser, Gln, Orn, Asn or Dap. In particular embodiments, X5 is Glu, Arg, Ala, N-Me-Arg, N-Me-Ala, N-Me-Gln, Orn, N-Me-Asn, N-Me-Lys, Ser, Asn or Dap.

[00292] In particular embodiments, X6 is Asp or Thr.

[00293] In particular embodiments, X8 is Gln or Val.

[00294] In particular embodiments, the peptide of Is is cyclized via a disulfide bond between X4 and X9.

[00295] In certain embodiments of the peptide inhibitor of Lormula I, X comprises or consists of the sequence of Lormula It:

XI-X2-X3-C-X5-X6-W-X8-C-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (It) wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

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X5 is any amino acid;

X6 is any amino acid;

X8 is any amino acid;

XI0 is Tyr, 1-Nal, 2-Nal, Phe[4-(2-aminoethoxy)], Phe(4-CONH2), Phe(4-OMe);

XI1 is Trp, 1-Nal, 2-Nal, Bip, , Phe(3,4-OMe2) 5-Hydroxy-Trp,;

XI2 is Arg, His, 3-Pal, Leu, Thr, Gln, Asn, Glu, Ile, Phe, Ser, Lys, hLeu, α-MeLeu, D-Leu, DAsn, h-Leu, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, aDiethylGly, α-MeLys, a-MeLys(Ac), a-Me-Leu, a-MeOrn, a-MeSer or a-MeVal;

XI3 is Thr, Glu, Tyr, Lys, Gln, Asn, Lys, Lys (Ac), Asp, Arg, Ala, Ser, Leu;

XI4 is Phe, Tyr, Asn, Gly, Ser, Met, Arg, His, Lys, Leu or Gln;

XI5 is Gly, Ser, Arg, Leu, Asp, Ala, β-Ala, Glu, Arg or Asn;

XI6 is absent or any amino acid;

XI7 is absent or any amino acid;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent.

[00296] In certain embodiments of It: XI0 is Tyr, 1-Nal or 2-Nal; XI1 is Trp, 1-Nal, 2-Nal or Bip; XI2 is Arg, His, 3-Pal, Leu, Thr, Gln, Asn, Glu, Ile, Phe, Ser, Lys, hLeu, α-MeLeu, D-Leu, D-Asn, or h-Leu; XI3 is Thr, Glu, Tyr, Lys, Gln, Asn, Lys, Asp, Arg, Ala, Ser, Leu; XI5 is Gly, Ser, Arg, Leu, Asp or Ala; XI6 is absent or Asn, Glu, Phe, Ala, Gly, Pro, Asp, Gln, Ser, Thr, DGlu or Lys; and XI7 is absent or Pro, Arg, Glu, Asp, Ser, Gly or Gln.

[00297] In particular embodiments, X5 is Ser, Asp, Asn, Gln, Ala, Met, Arg, His or Gly. In particular embodiments, X5 is Ser, Asp, Gln, Ala, Met, Arg, His or Gly.

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PCT/US2016/042680 [00298] In particular embodiments, X6 is any Asp, Ser or Thr.

[00299] In particular embodiments, X8 is Gln, Glu or Thr.

[00300] In particular embodiments, the peptide of It is cyclized via a disulfide bond between X4 and X9.

[00301] In a further embodiment, the present invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Va):

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Va) wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any D-amino acid or absent;

X4 is Cys, hCys, Pen, hPen, Abu, Ser, hSer or chemical moiety capable of forming a bond with X9;

X5 is Ala, oc-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Arg, Ser or Thr;

X6 is Thr, Ser, Asp, Ile or any amino acid;

X7 is Trp, 6-Chloro-Trp, 1-Nap or 2-Nap;

X8 is Glu, Gln, Asn, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-L-y-glutamyl)), or Lys(N-sPalmitoyl;

X9 is Cys, hCys, Pen, hPen Abu, or any amino acid or chemical moiety capable of forming a bond with X4;

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X10 is 2-Nal, a Phe analog, Tyr, or a Tyr analog;

XI1 is 1-Nal, 2-Nal, Phe(3,4-dimethoxy), 5-HydroxyTrp, Phe(3,4-Cl2), Trp or Tyr(3-tBu);

XI2 is Aib, 4-amino-4-carboxy-tetrahydropyran, any alpha-methylamino acid, alpha-ethylamino acid, Ache, Acvc, Acbc Acpc, 4-amino-4-carboxy-piperidine, 3-Pal, Agp, a-DiethylGly, α-MeLys, a-MeLys(Ac), α-MeLeu, a- α-MeOrn, a-MeSer, α-MeVal, Cav, Cha, Cit, Cpa, DAsn, Glu, His, hLeu, hArg, Lys, Leu, Octgly, Orn, piperidine, Arg, Ser, Thr or THP;

XI3 is Lys(Ac), Gln, Cit, Glu, or any amino acid;

XI4 is Asn, Gln, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-L-Y-glutamyl)), Lys(N-sPalmitoyl), or any amino acid;

XI5 is β-Ala, Asn, Gly, Gln, Ala, Ser, Aib or Cit;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, wherein X4 and X9 are capable of forming a bond with each other. In particular embodiments, the bond is a ether, disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via the bond between X4 and X9.

[00302] In certain embodiments, XI is a D-amino acid or absent. In certain embodiments, X2 is a D-amino acid or absent.

[00303] In certain embodiments, XI6 is a D-amino acid or absent. In certain embodiments, XI7 is a D-amino acid or absent. In certain embodiments, XI8 is a D-amino acid or absent. In

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PCT/US2016/042680 certain embodiments, XI9 is a D-amino acid or absent. In certain embodiments, X20 is a Damino acid or absent.

[00304]In particular embodiments of Formula (la), X10 is 2-Nal, Phe(3,4-diF2), Phe(3,4-Cl2), Phe(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-acetylaminoethoxy)], Phe(Br), Phe(4-CONH2), Phe(Cl), Phe(4-CN), Phe(4-guadino), Phe(4-Me), Phe(4-NH2), Phe(4-N₃), Tyr, Tyr(Bzl), or Tyr(Me). In certain embodiments of Formula (la), XI0 is Phe(4-ZR), Phe(3-ZR), oe Phe(2-ZR), where R= CH₂(CH₂)„Y and n=l-25, Z=NH, O, CO, CONH, or CH₂, and Y=NH₂, CO₂H, OH, or CH₃ [00305] In a further related embodiments, the present invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Vb):

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Vb) wherein

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is D-Arg, D-Phe, any D amino acid or absent;

X4 is Cys, hCys, Pen, hPen, Abu, or a chemical moiety capable of forming a bond with X9;

X5 is Gln, Asn, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-L-y-glutamyl)), or Lys(N-sPalmitoyl);

X6 is Thr, Ser, Asp, Ile or any amino acid;

X7 is Trp, 1-Nap or 2-Nap;

X8 is Gln, Asn, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-L-y-glutamyl)), or Lys(N-sPalmitoyl;

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X9 is Cys, hCys, Pen, hPen, Abu, any amino acid or a chemical moiety capable of forming a bond with X4;

X10 is Phe[4-(2-aminoethoxy)], Phe[4-(2-acetylaminoethoxy)], Phe(4-CONH2), Phe(4-guadino), Phe(4-NH₂), Tyr(Me) or Phe(4-ZR), where R= CH₂(CH₂)„Y; n=l-25; Z= O, CO, NH, CONH, or CH₂; and Y=NH₂, CO₂H, OH, or CH_3;

XI1 is 2-Nal or Trp;

XI2 is Aib, 4-amino-4-carboxy-tetrahydropyran, a-DiethylGly, α-MeLys, a-MeLys(Ac), aMeLeu, α-MeOrn, a-MeSer, α-MeVal, acid, Ache, Acvc, Acbc Acpc, or 4-amino-4-carboxypiperidine;

XI3 is Lys(Ac), Gin, Cit, Glu, or any amino acid;

XI4 is Asn, Gin, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-L-Y-glutamyl)), Lys(N-sPalmitoyl), or any amino acid;

XI5 is β-Ala, Asn, Gin, Ala, Ser, or Aib;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

X20 is any amino acid or absent, wherein X4 and X9 are capable of forming a bond with each other. In particular embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via the bond between X4 and X9.

[00306] In certain embodiments, XI is a D-amino acid or absent. In certain embodiments, X2 is a D-amino acid or absent.

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PCT/US2016/042680 [00307] In certain embodiments, XI6 is a D-amino acid or absent. In certain embodiments, XI7 is a D-amino acid or absent. In certain embodiments, XI8 is a D-amino acid or absent. In certain embodiments, XI9 is a D-amino acid or absent. In certain embodiments, X20 is a Damino acid or absent.

[00308] In another related embodiment, the present invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Vc):

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Vc) wherein

XI is absent;

X2 is absent;

X3 is D-Arg or absent;

X4 is Cys, Pen, Abu, or a chemical moiety capable of forming a bond with X9;

X5 is Gin, Asn, Lys(Ac), Cit, or Cav;

X6 is Thr or Ser;

X7 is Trp, 1-Nap or 2-Nap;

X8 is Gin, Asn, Lys(Ac), Cit, or Cav;

X9 is Cys, hCys, Pen, hPen, Abu, or any amino acid or chemical moiety capable of forming a bond with X4;

X10 is Phe[4-(2-aminoethoxy)], Phe(4-CONH2) or Phe(4-OR) where R= CH₂(CH₂)_nY; n=l-25; and Y=NH₂, CO₂H, OH, or CH₃;

XII is Trp or 2-Nal;

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XI2 is Aib, 4-amino-4-carboxy-tetrahydropyran, α-MeLys, a-MeLys(Ac), α-MeLeu, Ache, Acvc, Acbc or Acpc;

XI3 is Lys(Ac) or Glu;

X14 is Asn, Gin, Lys(Ac), Lys(N-8-(N-a-Palmitoyl-L-y-glutamyl)), or Lys(N-s-Palmitoyl);

XI5 is Gly, β-Ala, Asn, Gin, Ala, Ser, or Aib;

XI6 is absent;

XI7 is absent;

XI8 is absent;

XI9 is absent; and

X20 is absent, wherein X4 and X9 are capable of forming a bond with each other. In particular embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via the bond between X4 and X9.

[00309] In certain embodiments, XI is a D-amino acid or absent. In certain embodiments, X2 is a D-amino acid or absent.

[00310] In certain embodiments, XI6 is a D-amino acid or absent. In certain embodiments, XI7 is a D-amino acid or absent. In certain embodiments, XI8 is a D-amino acid or absent. In certain embodiments, XI9 is a D-amino acid or absent. In certain embodiments, X20 is a Damino acid or absent.

[00311] In another related embodiment, the present invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Vd):

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Vd)

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PCT/US2016/042680 wherein

XI is absent;

X2 is absent;

X3 is absent;

X4 is Pen or Abu;

X5 is Gin or Asn;

X6 is Thr or Ser;

X7 is Trp;

X8 is Gin or Asn;

X9 is Pen or Cys;

XI0 is Phe[4-(2-aminoethoxy)] or Phe(4-CONH2);

XII is Trp or 2-Nal;

XI2 is Aib, 4-amino-4-carboxy-tetrahydropyran, a-MeLys, α-MeLeu, or Ache;

XI3 is Lys(Ac) or Glu;

X14 is Asn, Gin or Lys(Ac);

XI5 is Gly, Ala, Ser, β-Ala, Asn, or Gin;

XI6 is absent;

XI7 is absent;

XI8 is absent;

XI9 is absent; and

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X20 is absent, wherein X4 and X9 are capable of forming a bond with each other. In particular embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via the bond between X4 and X9.

[00312] Any of the peptide inhibitors of the present invention (e.g., any of those of Formula I (e.g., Ix, Ia-It) may be further defined, e.g., as described below. It is understood that each of the further defining features described herein may be applied to any peptide inhibitors where the amino acids designated at particular positions allow the presence of the further defining feature.

[00313] In certain embodiments, any of the Phe[4-(2-aminoethoxy)] residues present in a peptide inhibitor may be substituted by Phe[4-(2-acetylaminoethoxy)].

[00314] In certain embodiments, X1-X20 are any of the amino acids shown in the corresponding position relative to the cyclized Pen-Pen or cyclized Abu-Cys residues of the illustrative peptide inhibitors set forth in Tables 2-5.

[00315] In certain embodiments, any of the peptides inhibitors described herein, including but not limited to those of Formulas (X), (Va), (Vb), Vc), (Vd), (Ve), (Vf), (Vg) or (Vh), further comprises a linker or spacer moiety between any two amino acid residues of the peptide. In particular embodiments, the linker or spacer moiety is a PEG moiety.

[00316] In certain embodiments, the peptide inhibitor is cyclized by a disulphide bridge.

[00317] In certain embodiments, XI0 is Tyr, Phe[4-(2-aminoethoxy)], Phe(4-CONH2) or Phe(4OMe). In certain embodiments, XI0 is Tyr.

[00318] In certain embodiments, XI1 is 2-Nal, Trp, or 5-Hydroxy-Trp. In certain embodiments, XI1 is Trp.

[00319] In certain embodiments, XI0 is Tyr or Phe[4-(2-aminoethoxy)], and XI1 is Trp or 2-Nal. In certain embodiments, XI0 is Tyr and XI1 is Trp.

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PCT/US2016/042680 [00320] In particular embodiments, X4 and X9 are both Cys.

[00321] In particular embodiments, X4 is Cys, Pen, hCys, or absent.

[00322] In particular embodiments, X7 and XI1 are not both W.

[00323] In particular embodiments, X7 and XI1 are both W.

[00324] In particular embodiments, X7 and XI1 are both W, XI0 is Y, and X4 and X9 are both Cys.

[00325] In particular embodiments, XI5 is Gly, Asn, β-ala or Ser. In particular embodiments, XI5 is Gly or Ser.

[00326] In particular embodiments, XI6 is AEA or AEP.

[00327] In particular embodiments, XI0 is Tyr, Phe or Phe[4-(2-aminoethoxy). In particular embodiments, XI0 is Tyr or Phe.

[00328] In particular embodiments, XI1 is Trp or 2-Nal. In particular embodiments, XI1 is Trp.

[00329] In particular embodiments, XI, X2 and X3 are absent.

[00330] In particular embodiments, XI8, XI9 and X20 are absent.

[00331] In particular embodiments, XI, X2, X3, XI8, XI9 and X20 are absent.

[00332] In particular embodiments, one or more of XI, X2 or X3 are present.

[00333] In particular embodiments of any of Ix, Ia-Ir, one of XI, X2 and X3 is present and the other two are absent. In one embodiment, the XI, X2 or X3 present is Ala.

[00334] In certain embodiments, X3 is present. In particular embodiments, X3 is Glu, (D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln. In certain embodiments, X3 is (D)Arg or (D)Phe. In particular embodiments, XI and X2 are absent and X3 is present.

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PCT/US2016/042680 [00335] In particular embodiments, two of XI, X2 and X3 are present and the other one is absent. In certain embodiments, the two present consist of SG, NK, DA, PE, QV or DR.

[00336] In particular embodiments, XI, X2 and X3 are present. In certain embodiments, XI, X2 and X3 consist of ADQ, KEN, VQE, GEE, DGF, NAD, ERN, RVG, KAN, or YED.

[00337] In certain embodiments, the peptide comprises an AEP residue. In particular embodiments, any of XI5, XI6, XI7, XI8, XI9 or X20 is AEP.

[00338] In certain embodiments of any of the peptide inhibitors or peptide monomer subunits, XI3 is Thr, Sarc, Glu, Phe, Arg, Feu, Fys, Fys(Ac), phAla, or Aib. In certain embodiments of any of the peptide inhibitors or peptide monomer subunits, XI3 is Thr, Sarc, Glu, Phe, Arg, Feu, Fys, phAla, or Aib. In certain embodiments, XI4 is Phe, Asn, Tyr, or phPhe. In certain embodiments, XI4 is Phe, Tyr, or phPhe. In certain embodiments, XI5 is Gly, Asn Ser, Thr, Gin, Ala, or Sarc. In certain embodiments, XI5 is Gly, Ser, Thr, Gin, Ala, or Sarc. In certain embodiments, X12 is alpha amino acid, e.g., 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Aib, α-DiethylGly, oc-MeFys, a-MePys(Ac), α-Me-Feu, oc-MeOrn, α-MeSer, or aMeVal.

[00339] In certain embodiments, XI3 is present.

[00340] In certain embodiments, XI3 and 14 are present.

[00341] In certain embodiments, XI3, X14 and XI5 are present.

[00342] In particular embodiments of any one of Ia-It, one or more of X16-X20 are present. In particular embodiments, two or more or three or more of X16-X20 are present. In particular embodiments, XI8 is [(D)Pys], In particular embodiments, XI7 is absent, and XI8 is [(D)Pys], In certain embodiments wherein X4 and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, and XI8 is [(D)Pys], In particular embodiments wherein X4 and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, X10 is Tyr or Phe[4-(2-aminoethoxy)], and X18 is [(D)Pys], In particular embodiments wherein X4 and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, XI0 is Tyr, and XI8 is [(D)Pys], In particular embodiments wherein X4 and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, XI, X2 and X3 are absent, XI7 is absent, XI8 is [(D)Pys], and XI9 and

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X20 are absent. In particular embodiments of Ir, X4 and X9 are Cys, X7 and XI1 are Trp, XI0 is Tyr, and XI8 is [(D)Lys. In certain embodiments, XI, X2, and X3 are absent; and in certain embodiments, XI7 is absent.

[00343] In certain embodiments, any of the peptide inhibitors (or monomer subunits) described herein is cyclized. In particular embodiments, the peptide inhibitor is cyclized via a bond between two or more internal amino acids of the peptide inhibitor. In particular embodiments, cyclized peptide inhibitors are not cyclized via a bond between the N-terminal and C-terminal amino acids of the peptide inhibitor. In certain embodiments, one of the amino acid residues participating in the intramolecular bond cyclizing the peptide in the amino terminal amino acid residue. In certain embodiments, any of the peptide inhibitors in cyclized via a peptide bond between its N-terminal amino acid and its C-terminal amino acid.

[00344] In certain embodiments of any of the peptide inhibitors, or one or both monomer subunits thereof, the peptide inhibitor (or one or both monomer subunit thereof) is cyclized via an intramolecular bond between X4 and X9 or by a triazole ring. In particular embodiments, the intramolecular bond is any disulfide bond, a thioether bond, a lactam bond, a triazole, a selenoether bond, a diselendide bond, or an olefin bond.

[00345] In one embodiment, X4 and X9 of the peptide inhibitor (or one or both monomer subunits thereof) are Cys, Pen, hCys, D-Pen, D-Cys or D-hCys, and the intramolecular bond is a disulfide bond. In certain embodiments, both X4 and X9 are Cys, or both X4 and X9 are Pen, and the intramolecular bond is a disulfide bond.

[00346] In one embodiment, X4 and X9 of the peptide inhibitor (or one or both monomer subunits thereof) are Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu or D-Lys, and the intramolecular bond is a lactam bond.

[00347] In one embodiment, X4 is Abu, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, or 3chloro-isobutyric acid; X9 is Abu, Cys, Pen, hCys, D-Pen, D-Cys or D-hCys; and the intramolecular bond is a thioether bond. In certain embodiments, X4 is Abu and X9 is Pen, and the intramolecular bond is a thioether bond. In particular embodiments, X4 is a 2-methylbenzoyl

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PCT/US2016/042680 moiety capable of forming a thioether bond with X9, and X9 is selected from Cys, N-Me-Cys, D-Cys, hCys, Pen, and D-Pen. In particular embodiments, X4 is Abu and X9 is Cys, and the intramolecular bond is a thioether bond. In particular instances, a peptide monomer, dimer, or subunit thereof of any of the Formulas and peptides described herein, X4 is selected from the group consisting of modified Ser, modified hSer (e.g., Homo-Ser-Cl), a suitable isostere, and corresponding D-amino acids. In other instances, X4 is an aliphatic acid having from one to four carbons and forming a thioether bond with X9. In some instances, X4 is a five- or six-membered alicyclic acid having a modified 2-methyl group that forms a thioether bond with X9. In some embodiments, X4 is a 2-methylbenzoyl moiety. In certain embodiments, X4 is selected from Cys, hCys, Pen, and a 2-methylbenzoyl moiety. In certain embodiments, X4 is selected from the group consisting of a modified Ser, a modified hSer, a suitable isostere, and corresponding Damino acids. In one embodiment, X4 is a hSerCl (before the thioether bond is formed with X9 whereby the Cl is removed) or a hSer precursor (e.g., homoSer(O-TBDMS). In other instances, X4 is an aliphatic acid having from one to four carbons and forming a thioether bond with X9. In some instances, X4 is a five- or six-membered alicyclic acid having a modified 2-methyl group that forms a thioether bond with X9. In some instances, X4 is a 2-methylbenzoyl moiety. In certain embodiments wherein X4 is not an amino acid but is a chemical moiety that binds to X9, XI, X2, and X3 are absent, and X4 is conjugated to or bound to X5. In some embodiments, the amino acid directly carboxyl to X9 is an aromatic amino acid. In certain embodiments, X4 is an amino acid, while in other embodiments, X4 is another chemical moiety capable of binding to X9, e.g., to form a thioether bond. In particular embodiments, X4 is another chemical moiety selected from any of the non-amino acid moieties described herein for X4. In particular embodiments wherein X4 is another chemical moiety, XI, X2 and X3 are absent, and the another chemical moiety is bound to or conjugated to X5. In certain embodiments, X4 is defined as a chemical moiety including a group such as a chloride, e.g., in 2-chloromethylbenzoic acid, 2chloro-acetic acid, 3-choropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid. However, the skilled artisan will appreciate that once the peptide has undergone ring closing cyclization to form a thioether bond between X4 and X9, the chloride group is no longer present. The description of chemical moieties at X4 that include a reactant group such as chloride thus means both the group with the chloride and also the group without the chloride, i.e., after formation of the bond with X9.The present invention also includes peptides comprising the same

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PCT/US2016/042680 structure as shown in any of the other formulas or tables described herein, but where the thioether bond is in the reverse orientation. In such embodiments of the invention, it may generally be considered that the amino acid residues or other chemical moieties shown at X4 are instead present at X9, and the amino acid residues shown at X9 are instead present at X4, i.e., the amino acid residue comprising the sulfur of the resulting thioether bond is located at X4 instead of X9, and the amino acid residue or other moiety having a carbon side chain capable of forming a thioether bond with X4 is located at X9. In this reverse orientation, however, the amino acid or chemical moiety at position X9 is one that comprises a free amine. For example, in particular embodiments, the amino acid at X9 is a protected homoserine, such as, e.g., homoserine (OTBDMS). Thus, in particular reverse orientation embodiments of peptide inhibitors of any of the formulas described herein, X9 is an amino acid residue having a side chain with one or two carbons, and forming a thioether bond with X4, and X4 is selected from the group consisting of Cys, N-Me-Cys, D-Cys, HCys, Pen, and D-Pen. Specific examples of amino acid residues and other chemical moieties present at corresponding positions of other formulas and tables are described herein.

[00348] One of skill in the art will appreciate that certain amino acids and other chemical moieties are modified when bound to another molecule. For example, an amino acid side chain may be modified when it forms an intramolecular bridge with another amino acid side chain, e.g., one or more hydrogen may be removed or replaced by the bond. In addition, when hSer-Cl binds to an amino acid such as Cys or Pen via a thioether bond, the Cl moiety is released. Accordingly, as used herein, reference to an amino acid or modified amino acid, such as hSer-Cl, present in a peptide dimer of the present invention (e.g., at position X4 or position X9) is meant to include the form of such amino acid or modified amino acid present in the peptide both before and after forming the intramolecular bond.

[00349] In certain embodiments, the peptide inhibitor of the peptide inhibitor (or one or both monomer subunits thereof) is cyclized through a triazole ring. In certain embodiments, the peptide inhibitor of the peptide inhibitor (or one or both monomer subunits thereof) is linear or not cyclized. In certain embodiments of any of the peptide inhibitors described herein, including both monomer peptide inhibitors and dimer peptide inhibitors, one (or both) peptide monomer subunits comprise or consist of a cyclized peptide having a structure or sequence set forth in any

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PCT/US2016/042680 of lx, la, lb, Ic, Id, Ie, If, Ig, lh, Ii, Ij, Ik, II, Im, In, Io, Ip, Iq, Iq’, Ir, Is or It, Ila-IId, Illa-IIIe, Iva, or IVb.

[00350] In certain embodiments of any of the peptide inhibitors or monomer subunits, X7 and XI1 are both W.

[00351] In certain embodiments of any of the peptide inhibitors or monomer subunits, X7 and XI1 are not both W. In particular embodiments, X7 is W and XI1 is not W.

[00352] In certain embodiments of any of the peptide inhibitors or monomer subunits, X4 and X9 are amino acid residues capable of forming an intramolecular bond between each other that is a thioether bond, a lactam bond, a triazole, a selenoether, a diselenide bond, or an olefin bond.

[00353] In certain embodiments, X7 and XI1 are both W, XI0 is Y, Phe[4-(2-aminoethoxy) or Phe(CONH2), and X4 and X9 are amino acid residues capable of forming an intramolecular bond between each other that is a thioether bond, a lactam bond, a triazole, a selenoether, a diselenide bond, or an olefin bond. In certain embodiments, X7 and XI1 are both W, XI0 is Y, and X4 and X9 are amino acid residues capable of forming an intramolecular bond between each other that is a thioether bond, a lactam bond, a triazole, a selenoether, a diselenide bond, or an olefin bond.

[00354] In certain embodiments, X7 and XI1 are both W, XI0 is Y, and X4 and X9 are both C.

[00355] In certain embodiments, X4 and X9 are each Cys, Pen, hCys, D-Pen, D-Cys or D-hCys, and the intramolecular bond is a disulfide bond.

[00356] In certain embodiments, X4 and X9 are each Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, DDab, D-Asp, D-Glu or D-Lys, and the intramolecular bond is a lactam bond.

[00357] In certain embodiments, X4 and X9 are each β-azido-Ala-OH or propargylglycine, and the peptide inhibitor (or monomer subunit) is cyclized through a triazole ring.

[00358] In certain embodiments, X4 and X9 are each 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4'pentenyl)glycine, or 2-(5'-hexenyl)glycinem and the peptide inhibitor (or monomer subunit) is cyclized via ring closing methasis to give the corresponding olefin / “stapled peptide.”

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PCT/US2016/042680 [00359] In certain embodiments, X4 is 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3chloro-isobutyric acid, or hSer(Cl); X9 is hSer(Cl), Cys, Pen, hCys, D-Pen, D-Cys or D-hCys; and the intramolecular bond is a thioether bond. In certain embodiments, X4 is 2chloromethylbenzoic acid or hSer(Cl); X9 is Cys or Pen, and the intramolecular bond is a thioether bond. In certain embodiments, X4 is Abu, and X9 is Cys or Pen.

[00360] In certain embodiments, X4 is 2-chloromethylbenzoic acid, 2-chloro-acetic acid, 3-choropropanoic acid, 4-chloro-butyric acid, 3-chloro-isobutyric acid, Abu or Sec; X9 is Abu or Sec; and the intramolecular bond is a selenoether bond.

[00361] In certain embodiments, the intramolecular bond between X4 and X9 is a diselenide bond.

[00362] In certain embodiments of any of the peptide inhibitors described herein that contain two amino acid residues, e.g., cysteine residues, joined by an intramolecular bond, e.g., disulphide bond, the two amino acid residues participating in the intramolecular bond are not both located at either the N-terminal or C-terminal position of the peptide inhibitor. In certain embodiments, neither of the two amino acid residues, e.g., cysteines, particpating in the intramolecular bond is located at the N-terminal or C-terminal position of the peptide inhibitor. In other words, in certain embodiments, at least one, or both, of the two amino acid residues, e.g., cysteines, participating in the intramolecular bond are internal amino acid residues of the peptide inhibitor. In certain embodiments, neither of the two amino acid resiudes, e.g., cysteines, participating in the intramolecular bond is located at the C-terminal position of the peptide inhibitor. At certain embodiment, the two amino acid residues participating in the intramolecular bond are Cys, Pen, hCys, D-Pen, D-Cys or D-hCys residues. In certain embodiments, the two amino acid residues participating in the intramolecular bond are located at X4 and X9. In one embodiment, there is a disulfide bond between the amino acid resiudes, e.g., cysteines or Pen residues, at X4 and X9. In particular embodiments, both X4 and X9 are Pen. In certain embodiments, one or both peptide monomer subunits in the peptide inhibitor is cyclized via a disulfide bond between two Pen residues, e.g., at positions X4 and X9.

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PCT/US2016/042680 [00363] In particular embodiments of any of the peptide inhibitors described herein, one or both peptide monomer subunits present in the peptide inhibitor, whether it is a monomer or a dimer, is cyclic or cyclized, e.g., by an intramolecular bond, such as a disulfide bond, between two cysteine residues present in the peptide monomer or peptide monomer subunit. In certain embodiments, a peptide inhibitor comprises two or more cysteine residues. In some embodiments, the peptide inhibitor is cyclized via an intramolecular disulfide bond between the two cysteine residues. In particular embodiments of peptide inhibitors having any of the Formulas described herein, the two cysteines occur at positions X4 and X9. In other embodiments, one or both peptide monomer subunits in the peptide inhibitor is cyclized via a disulfide bond between two Pen residues, e.g., at positions X4 and X9.

[00364] In some embodiments, a peptide inhibitor has a structure of any of the Formulas described herein (e.g., Formula I) and comprises a disulfide bond, e.g., an intramolecular disulfide bond, or a thioether bond. Illustrative examples of such peptide inhibitors are shown in Tables 3A-3H and 4A, 4B, 9, 11 or 15. Such disulfide bonded peptides may have a particular advantage in that the disulfide bonds enhance structural stability and can improve biological activity of many bioactive peptides. However, in certain situations, these bonds are labile to reducing agents. One of skill in the art will appreciate that disulfide is amenable to simple isosteric replacement. Illustrative examples of such replacements include, but are not limited to, thioethers, dithioethers, selenoethers, diselenides, triazoles, lacatams, alkane and alkene groups. Accordingly, in certain embodiments of any of the peptide inhibitors described herein, one, two or more cysteine residues are substitued, e.g., with a thioether, dithioether, selenoether, diselenide, triazoles, lacatam, alkane or alkene group, including but not limited to any of those shown below or described herein. In particular embodiments, two of these substituted groups form a bond (e.g., an intramolecular bond), thus cyclizing the peptide inhibitor or one or both monomer subunits thereof.

[00365] In certain embodiments, a peptide inhibitor of the present invention comprises or consists of an amino acid sequence shown herein, e.g., in any one of Tables 3A-3H, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15. In certain embodiments, a peptide inhibitor of the present invention has a structure shown herein, e.g., in any one of Tables 3A-3H, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

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PCT/US2016/042680 [00366] In certain embodiments, the present invention includes a peptide inhibitor that comprises a core consensus sequence selected from one of the following (shown in N-terminal to Cterminal direction):

X1X2X2WX2X1X2W;

X1X2X2WX2X1X2 (1-Nal);

X1X2X2WX2X1X2 (2-Nal);

X1X2X2WX2X1YW;

XiX₂X₂WX₂XiY( 1-Nal);

XiX₂X₂WX₂XiY(2-Nal);

X1X2X2WX2X1X2X2;

X₁X₂X₂WX₂XiX₂X₂X₂X₂X₂-[(D)Lys];

X1X2X2WX2X1X3X2;

XiX₂X₂WX₂XiX₃( 1-Nal); and X1X2X2WX2X1X3 (2-Nal).

[00367] wherein W is tryptophan, Y is tyrosine, each the two XI residues are amino acids or other chemical moieties capable of forming an intramolecular bond with each other; each X2 is independently selected from all amino acids, which include, e.g., natural amino acids, L-amino acids, D-amino acids, non-natural amino acids, and unnatural amino acids; and X3 is any amino acid. In particular embodiments, X3 is Phe, a Phe analog (e.g., Phe[4-(2-aminoethoxy)] or Phe(4-CONH2)), Tyr, or a Tyr analog (e.g., Tyr(Me)). In particular embodiments, each XI is selected from Cys, Pen and Abu. In particular embodiments, each XI is Cys. In certain embodiments, each XI is Pen. In certain embodiments, one XI is Cys and the other XI is Abu. In particular embodiments, the N-terminal XI is Abu and the C-terminal XI is Cys. In particular embodiments, the N-terminal XI is Cys and the C-terminal XI is Abu. In particular embodiments, the residues between the two XI residues are Gin, Thr, Trp and Gin. In particular embodiments, each XI is selected from Cys, Pen and Abu; and X3 is Phe, a Phe analog (e.g., Phe[4-(2-aminoethoxy)] or Phe(4-carbomide)), Tyr, or a Tyr analog (e.g., Tyr(Me)). In particular embodiments, X3 is a Phe analog.

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PCT/US2016/042680 [00368] In certain embodiments, peptide inhibitors of the present invention comprises any of the following consensus sequences, wherein XI, X2, X3, X4, X5, X6, X7, X8, X9, X10, XI1, X12, X13, X14 and X15 are defined as shown in any of the various Formula or peptide inhibitors described herein:

XI-X2-X3 -Pen-X5-X6-W-X8-Pen-Xl 0-X11 -XI2-X13-X14-X15;

Pen-X5-X6-W-Q-Pen;

Pen-X5-X6-W-X8-Pen;

Pen-X5 -X6-W-X8-Pen- [Phe(4-CONH2)];

Pen-X5-X6-W-X8-Pen-[Phe[4-(2-aminoethoxy)]];

XI-X2-X3 -Abu-X5-X6-W-X8-C-X9-Xl 0-X11 -XI2-X13-X14-X15;

Abu-X5-X6-W-Q-C;

Abu-X5-X6-W-X8-C;

Abu-X5-X6-W-X8-C-[Phe(4-CONH2)]; or

Abu-X5-X6-W-X8-C-[Phe[4-(2-aminoethoxy)]].

[00369] In certain embodiments of any of the peptide inhibitors or monomer subunits, X7 and XI1 are both W. In certain embodiments of any of the peptide inhibitors, X7 and XI1 are both W, and XI0 is Y. In certain embodiments, X7 and XI1 are both W and XI0 is Phe[4-(2aminoethoxy)] or Phe(4-OMe) .

[00370] In certain embodiments of any of the peptide inhibitors or monomer subunits, X7 and XI1 are not both W.

[00371] In certain embodiments of peptide inhibitors of Formula I, X4 and X9 are each Pen, and the intramolecular bond is a disulfide bond.

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PCT/US2016/042680 [00372] In certain embodiments, a peptide inhibitor of the present invention comprises or consists of an amino acid sequence shown in any one of the tables, sequence listing or the accompanying figures herein.

[00373] In certain embodiments of any of the peptide inhibitors described herein that contain two amino acid residues, e.g., Pen residues, joined by an intramolecular bond, e.g., disulphide bond, one or both of the two amino acid residues participating in the intramolecular bond are not located at either the N-terminal or C-terminal position of the peptide inhibitor. In certain embodiments, neither of the two amino acid residues, e.g., Pen, particpating in the intramolecular bond is located at the N-terminal or C-terminal position of the peptide inhibitor. In other words, in certain embodiments, at least one, or both, of the two amino acid residues, e.g., Pens, participating in the intramolecular bond are internal amino acid residues of the peptide inhibitor. In certain embodiments, neither of the two amino acid residues, e.g., Pens, participating in the intramolecular bond is located at the C-terminal position of the peptide inhibitor.

[00374] In some embodiments, wherein a peptide of the invention is conjugated to an acidic compound such as, e.g., isovaleric acid, isobutyric acid, valeric acid, and the like, the presence of such a conjugation is referenced in the acid form. So, for example, but not to be limited in any way, instead of indicating a conjugation of isovaleric acid to a peptide by referencing isovaleroyl (e.g., isovaleroyl-[Pen]-QTWQ[Pen]-[Phe(4-OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2 in some embodiments, the present application references such a conjugation as isovaleric acid[Pen]-QTWQ[Pen]-[Phe(4-OMe)]-[2-Nal]-[a-MeFys]-[Fys(Ac)]-NG-NH₂.

[00375] The present invention further includes peptide inhibitors that selectively bind to an epitope or binding domain present within amino acid residues 230 - 349 of the human IL23R protein. In particular embodiments, the peptide inhibitor binds human IL23R and not mouse IL23R. In certain embodiments, the peptide inhibitor also binds to rat IL-23R.

[00376] In certain embodiments of peptide inhibitors of Formula I, X4 is Abu; X9 is Cys, Pen, homocys, and the intramolecular bond is a thioether bond.

[00377] In certain embodiments, peptide inhibitors do not include compounds, disclosed in PCT Application No. PCT/US2014/030352 or PCT Application No. PCT/US2015/038370.

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Illustrative Peptide Inhibitors Comprising Pen-Pen Disulfide Bonds [00378] In certain embodiments, the present invention includes a peptide inhibitor of an interleukin-23 receptor, wherein the peptide inhibitor has the structure of Formula II:

R'-X-R² (II) [00379] or a pharmaceutically acceptable salt or solvate thereof, wherein R¹ is a bond, hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl, a C1-C6 alkyl, a C1-C20 alkanoyl, an alkylsulphonate, an acid, γ-Glu or pGlu, appended to the N-terminus, and including PEGylated versions (e.g., 200 Da to 60,000 Da), alone or as a spacer of any of the foregoing;

[00380] R² is a bond, OH or NH2; and [00381]X is an amino acid sequence of 8 to 20 amino acids or 8 to 35 amino acids.

[00382] In particular embodiments of peptide inhibitor of Formula II, X comprises or consists of the sequence of Formula Ila:

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Ila) wherein

XI is absent or any amino acid;

X2 is absent or any amino acid;

X3 is absent or any amino acid;

X4 is Pen, Cys or homo-Cys;

X5 is any amino acid;

X6 is any amino acid;

X7 is Trp, Bip, Gln, His, Glu(Bzl), 4-Phenylbenzylalanine, Tic, Phe[4-(2-aminoethoxy)], Phe(3,4-Cl2), Phe(4-OMe), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, α-Me-Trp, 1,2,3,4 tetrahydro-norharman, Phe(4-CO2H), Phe(4-CONH₂), Phe(3,4-Dimethoxy), Phe(4-CF₃), Phe(4-tBu), ββ-diPheAla, Glu, Gly, Ile, Asn, Pro, Arg, Thr or Octgly, or a corresponding amethyl amino acid form of any of the foregoing;

X8 is any amino acid;

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X9 is Pen, Cys or hCys;

XI0 is 1-Nal, 2-Nal, Aic, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, 4pyridylAla, Octgly, a Phe analog or a Tyr analog (optionally, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetyl-aminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), or Phe(4OBzl)), or a corresponding α-methyl amino acid form of any of the foregoing;

XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl₂), Phe (3,4-F₂), Phe(4-CO₂H), phPhe(4F), α-Me-Trp, 4-phenylcyclohexyl, Phe(4-CF₃), α-MePhe, phNal, phPhe, PhTyr, phTrp, Nva(5phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe(4-OMe), Phe(4-Me), Trp(2,5,7-tri-tert-Butyl), Phe(4-Oallyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino, Phe(4-OBzl), Octgly, Glu(Bzl), 4Phenylbenzylalanine, Phe[4-(2-aminoethoxy)], 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp,

1,2,3,4-tetrahydro-norharman, Phe(4-CONH2), Phe(3,4-OMe2) Phe(2,3-Cl2), Phe(2,3-F2), Phe(4F), 4-phenylcyclohexylalanine or Bip, or a corresponding α-methyl amino acid form of any of the foregoing;

XI2 is a-MeLys, α-MeOrn, a-MeLeu, α-MeVal, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, MeLeu, Aib, (D)Ala, (D)Asn, (D)Leu, (D)Asp, (D)Phe, (D)Thr, 3-Pal, Aib, β-Ala, phGlu, phAla, phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, Ν-MeLeu, N-MeArg, Ogl, Orn, Pro, Gin, Arg, Ser, Thr or Tie, or a corresponding α-methyl amino acid form of any of the foregoing;

XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, α-MeLeu, β-Ala, phGlu, phAla, PhLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Lys, Arg, Orn, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gin, Asp, Arg, Ser, spiro-pip, Thr, Tba, Tic, Val or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing;

X14 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Tic or Tyr,

Lys(Ac), Orn or a corresponding α-methyl amino acid form of any of the foregoing;

XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, Asn, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gin, Arg or Ser, β-Ala, Arg or a corresponding α-methyl amino acid form of any of the foregoing;

XI6 is absent, Gly, Ala, Asp, Ser, Pro, Asn or Thr, or a corresponding α-methyl amino acid form of any of the foregoing;

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XI7 is absent, Glu, Ser, Gly or Gin, or a corresponding α-methyl amino acid form of any of the foregoing;

XI8 is absent or any amino acid;

XI9 is absent or any amino acid; and

X20 is absent or any amino acid.

[00383] In certain embodiments of Ila: XI0 is 1-Nal, 2-Nal, Aic, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, 4-pyridylAla, Octgly, a Phe analog or a Tyr analog, or a corresponding α-methyl amino acid form of any of the foregoing; XI1 is 2-Nal, 1-Nal, 2,4dimethylPhe, Bip, Phe(3,4-Cl₂), Phe (3,4-F₂), Phe(4-CO₂H), phPhe(4-F), a-Me-Trp, 4phenylcyclohexyl, Phe(4-CF₃), α-MePhe, phNal, phPhe, PhTyr, phTrp, Nva(5-phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe(4-OMe), Phe(4-Me), Trp(2,5,7-tri-tert-Butyl), Phe(4-Oallyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino, Phe(4-OBzl), Octgly, Glu(Bzl), 4Phenylbenzylalanine, Phe[4-(2-aminoethoxy)], 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp,

1,2,3,4-tetrahydro-norharman, Phe(4-CONH₂), Phe(3,4-Dimethoxy), Phe(2,3-Cl₂), Phe(2,3-F₂), Phe(4-F), 4-phenylcyclohexylalanine or Bip, or a corresponding α-methyl amino acid form of any of the foregoing; XI2 is a-MeLys, α-MeOrn, a-MeLeu, MeLeu, Aib, (D)Ala, (D)Asn, (D)Leu, (D)Asp, (D)Phe, (D)Thr, 3-Pal, Aib, β-Ala, phGlu, phAla, phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, NMeLeu, N-MeArg, Ogl, Orn, Pro, Gin, Arg, Ser, Thr or Tie, or a corresponding α-methyl amino acid form of any of the foregoing; XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, a-MeLeu, β-Ala, phGlu, phAla, phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Lys, Arg, Orn, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gin, Asp, Arg, Ser, spiro-pip, Thr, Tba, Tic, Val or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing; X14 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Tic or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing; and XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, Asn, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gin, Arg or Ser, or a corresponding α-methyl amino acid form of any of the foregoing.

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PCT/US2016/042680 [00384] In certain embodiments, X3 is present. In particular embodiments, X3 is Glu,(D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln. In certain embodiments, X3 is (D)Arg or (D)Phe. In particular embodiments, XI and X2 are absent and X3 is present.

[00385] In certain embodiments, X5 is Gln, Ala, Cit, Asp, Dab, Dap, Cit Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-Me-Ala, N-Me-Asn, N-Me-Lys, α-Me-Lys, oc-Me-Orn, N-MeGln, N-Me-Arg, oc-MeSer, Orn, Pro, Arg, Ser, Thr, or Val. In certain embodiments, X5 is Gln, Ala, Cit, Asp, Dab, Dap, Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-Me-Ala, N-Me-Asn, N-Me-Lys, aMe-Lys, aMe-Orn, N-Me-Gln, N-Me-Arg, Orn, Pro, Arg, Ser, Thr, or Val. In certain embodiments, X5 is Gln or Asn.

[00386] In certain embodiments, X6 is Thr, Asp, Glu, Phe, Asn, Pro, Arg, or Ser.

[00387] In certain embodiments, X7 is Trp.

[00388] In certain embodiments, X8 is Gln, Glu, Phe, Lys, Asn, Pro, Arg, Val, Thr, or Trp.

[00389] In certain embodiments, XI0 is a Tyr analog or a Phe analog. In particular embodiments, XI0 is a Phe analog.

[00390] In certain embodiments wherein XI0 is a Phe analog, XI0 is selected from hPhe, Phe(4OMe), oc-Me-Phe, hPhe(3,4-dimethoxy), Phe(4-CONH2), Phe(4-phenoxy), Phe(4-guanadino), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4-OBzl), Phe(4-NH₂), Phe(4-F), Phe(3,5 DiF), Phe(CH₂CO₂H), Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF₃), ββ-diPheAla, Phe(4-N₃) and Phe[4-(2aminoethoxy)]. In particular embodiments, XI0 is Phe(4-OMe) or Phe[4-(2-aminoethoxy)]. In particular embodiments, XI0 is Phe(4-OMe), Phe(4-CONH₂) or Phe[4-(2-aminoethoxy)]. In certain embodiments where XI0 wherein XI0 is a Phe analog, XI0 is selected from hPhe, Phe(4OMe), oc-Me-Phe, hPhe(3,4-dimethoxy), Phe(4-CONH₂), Phe(4-phenoxy), Phe(4-guanadino), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4-OBzl), Phe(4-NH₂), Phe(4-F), Phe(3,5 DiF), Phe(CH₂CO₂H), Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF₃), ββ-diPheAla, Phe(4-N₃) and Phe[4-(2aminoethoxy)]. In particular embodiments, XI0 is Phe(4-OMe).

[00391] In certain embodiments where XI0 is a Tyr analog, XI0 is selected from hTyr, oc-MeTyr, N-Me-Tyr, Tyr(3-tBu), Phe(4-CONH₂), Phe[4-(2-aminoethoxy)], and bhTyr. In certain

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PCT/US2016/042680 embodiments where XI0 is a Tyr analog, XI0 is selected from hTyr, α-MeTyr, N-Me-Tyr, Tyr(3-tBu), and bhTyr.

[00392] In certain embodiments, XI0 is Tyr, Phe(4-OMe), Phe[4-(2-aminoethoxy)], Phe(4CONH2), or 2-Nal. In certain embodiments, XI0 is Phe(4-OMe) or Phe[4-(2-aminoethoxy)]. In certain embodiments, XI0 is not Tyr.

In certain embodiments, XI1 is a Trp analog. In particular embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI1 is 2-Nal.

[00393] In certain embodiments, X12 is Aib, α-MeLys or a-MeLeu.

[00394] In particular embodiments of a peptide inhibitor of Formula II, one or both of X4 or X9 is Pen. In particular embodiments, both X4 and X9 are Pen.

[00395] In certain embodiments, the peptide inhibitor of Formula II is cyclized. In particular embodiments, the peptide inhibitor of Formula II is cyclized via an intramolecular bond between X4 and X9. In particular embodiments, the intramolecular bond is a disulfide bond. In particular embodiments, X4 and X9 are both Pen.

[00396] In certain embodiments, the peptide inhibitor of Formula II is linear or not cyclized. In particular embodiments of the linear peptide inhibitor of Formula I, X4 and/or X9 are any amino acid.

[00397] In particular embodiments of a peptide inhibitor of Formula II, one or more, two or more, or all three of XI, X2, and X3 are absent. In certain embodiments, XI is absent. In certain embodiments, XI and X2 are absent. In certain embodiments, XI, X2 and X3 are absent.

[00398] In particular embodiments of a peptide inhibitor of Formula II, one or more, two or more, three or more, four or more, or all of XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments of a peptide inhibitor of Formula I, one or more, two or more, three or more, or all of XI7, XI8, XI9 and X20 are absent. In certain embodiments, one or more, two or more, or all three of XI7, XI9 and X20 are absent. In certain embodiments, one or more of XI, X2 and X3

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PCT/US2016/042680 are absent; and one or more, two or more, three or more, or four of XI7, XI8, XI9 and X20 are absent.

[00399] In particular embodiments of a peptide inhibitor of Formula II, XI8 is (D)-Lys. In certain embodiments, XI8 is (D)-Lys and XI7 is absent.

[00400] In particular embodiments of a peptide inhibitor of Formula II, the peptide inhibitor comprises one or more, two or more, three or more, or four of the following features: X5 is Asn, Arg or Gln; X6 is Thr; X7 is Trp; and X8 is Gln. In particular embodiments of a peptide inhibitor of Formula I, X4 is Pen; X5 is Gln, Asn or Arg; X6 is Thr; X7 is Trp, 5-hydroxy-Trp, 6-chloroTrp, N-MeTrp, alpha-Me-Trp, or 1,2,3,4-tetrahydro-norharman; X8 is Gln; and X9 is Pen. In particular embodiments, X5 is Gln. In certain embodiments, XI, X2 and X3 are absent. In particular embodiments, both X4 and X9 are Pen.

[00401] In particular embodiments of a peptide inhibitor of Formula II, the peptide inhibitor comprises one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following features: XI0 is Tyr, a Phe analog, a Tyr analog or 2-Nal; XI1 is Trp, 5hydroxy-Trp, 6-chloro-Trp, N-MeTrp, alpha-Me-Trp, 1,2,3,4-tetrahydro-norharman, 2-Nal or 1Nal; XI2 is Aib, α-MeLys, α-MeOrn and α-MeLeu; XI3 is Lys, Glu or Lys(Ac); XI4 is Phe or Asn; XI5 is Gly, Ser or Ala; and XI6 is absent or AEA. In certain embodiments, XI0 is Tyr, Phe(4-OMe), Phe[4-(2-aminoethoxy)], Phe/CONtL), or 2-Nal. In certain embodiments, XI1 is

2-Nal or 1-Nal. In certain embodiments, XI0 is not Tyr. In certain embodiments, XI, X2 and X3 are absent. In particular embodiments, both X4 and X9 are Pen.

[00402] In particular embodiments of a peptide inhibitor of Formula II, the peptide inhibitor comprises one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven of the following features: X5 is Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln; XI0 is a Phe analog; XI1 is Trp, 2-Nal or 1-Nal; X12 is Aib, α-MeLys or a-MeOrn; XI3 is Lys, Glu or Lys(Ac); X14 is Asn; XI5 is Gly, Ser or Ala; and XI6 is absent or AEA. In certain embodiments, XI0 is Phe(4-OMe) or Phe[4-(2aminoethoxy)]. In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent. In particular embodiments, both X4 and X9 are Pen.

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PCT/US2016/042680 [00403] In particular embodiments of a peptide inhibitor of Formula II, the peptide is cyclized via X4 and X9; X4 and X9 are Pen; X5 is Gin; X6 is Thr; X7 is Trp; X8 is Gin; XI0 is Tyr, a Phe analog or 2-Nal; XI1 is Trp, 2-Nal or 1-Nal; XI2 is Arg, a-MeLys, α-MeOm, or a-MeLeu; X13 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; X15 is Gly, Ser or Ala; and X16 is absent. In certain embodiments, XI0 is Tyr, Phe(4-OMe), Phe[4-(2-aminoethoxy)], Phe(4-OMe) or 2-Nal. In certain embodiments, XI0 is Phe(4-OMe). In certain embodiments, XI0 is not Tyr. In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent.

[00404] In particular embodiments of a peptide inhibitor of Formula II, the peptide is cyclized via X4 and X9; X4 and X9 are Pen; X5 is Gin; X6 is Thr; X7 is Trp; X8 is Gin; XI0 is Tyr, Phe(4OMe) or 2-Nal; XI1 is Trp, 2-Nal or 1-Nal; XI2 is Arg, α-MeLys or α-MeOrn; XI3 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; XI5 is Gly; and X16 is absent. In certain embodiments, X10 is Phe(4-OMe). In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent.

[00405] In particular embodiments of a peptide inhibitor of Formula II, the peptide is cyclized via X4 and X9; X4 and X9 are Pen; X5 is Gin; X6 is Thr; X7 is Trp; X8 is Gin; XI0 is Phe(4-OMe) or Phe[4-(2-aminoethoxy)]; XI1 is Trp, 2-Nal or 1-Nal; X12 is a-MeLys, α-MeOrn, or aMeLeu; XI3 is Lys, Glu or Lys(Ac); X14 is Asn; XI5 is Gly, Ser or Ala; and XI6 is absent. In certain embodiments, XI0 is Phe(4-OMe). In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent.

[00406] In particular embodiments of a peptide inhibitor of Formula II, XI0 is not Tyr.

[00407] In certain embodiments, the present invention includes a peptide, optionally 8 to 35, 8 to 20, 8 to 16 or 8 to 12 amino acids in length, optionally cyclized, comprising or consisting of having a core sequence of Formula lib:

Pen-Xaa5-Xaa6-Trp-Xaa8-Pen-Xaal 0-[(2-Nal)] (lib) [00408] wherein Xaa5, Xaa6 and Xaa8 are any amino acid residue; and XaalO is a Phe analogue, wherein the peptide inhibits binding of IL-23 to IL-23R. In particular embodiments, XI0 is a Phe analog selected from α-Me-Phe, Phe(4-OMe), Phe(4-OBzl), Phe(4-OMe), Phe(4-CONH2),

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Phe(3,4-Cl₂), Phe(4-tBu), Phe(4-NH₂), Phe(4-Br), Phe(4-CN), Phe(4-CO₂H), Phe[4-(2aminoethoxy)] or Phe(4-guanadino). In particular embodiments, XaalO is Phe(4-OMe) or Phe[4-(2-aminoethoxy)]. In one embodiment, XaalO is Phe(4-OMe). In certain embodiments, the peptide is cyclized via an intramolecular bond between Pen at Xaa4 and Pen at Xaa9. In particular embodiments, the peptide is a peptide inhibitor of Formula II, and wherein in certain embodiments, XI, X2 and X3 are absent. In particular embodiments, the peptide inhibits the binding of IL-23 to IL-23R. In certain embodiments, a peptide of Formula lib further comprises an amino acid bound to the N-terminal Pen residue. In particular embodiments, the bound amino acid is Glu,(D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln. In certain embodiments, it is is (D)Arg or (D)Phe.

[00409] In certain embodiments, the present invention includes a peptide, optionally 8 to 35, 8 to 20, 8 to 16, or 8 to 12 amino acids in length, optionally cyclized, comprising or consisting of a core sequence of Formula lie:

Pen-Xaa5-Xaa6-Trp-Xaa8-Pen-Xaal0-[(2-Nal)] (lie) [00410] wherein Xaa5, Xaa6 and Xaa8 are any amino acid residue; and XaalO is Tyr, a Phe analog, a-Me-Tyr, α-Me-Trp or 2-Nal, wherein the peptide inhibits binding of IL-23 to IL-23R. In certain embodiments, XI0 is Tyr, Phe(4-OMe), Phe[4-(2-aminoethoxy)], α-Me-Tyr, a-MePhe, α-Me-Trp or 2-Nal. In certain embodiments, XaalO is Tyr, Phe(4-OMe), Phe(CONH₂), Phe[4-(2-aminoethoxy)] or 2-Nal. In certain embodiments, XaalO is Tyr, Phe(4-OMe), Phe[4-(2aminoethoxy)] or 2-Nal. In particular embodiments, XaalO is Phe(4-OMe) or Phe[4-(2aminoethoxy)]. In one embodiment, XaalO is Phe[4-(2-aminoethoxy)] or Phe(CONH₂). In particular embodiments, XaalO is Phe(4-OMe) or Phe[4-(2-aminoethoxy)]. In one embodiment, XaalO is Phe[4-(2-aminoethoxy)]. In certain embodiments, XaalO is not Tyr. In certain embodiments, the peptide is cyclized via an intramolecular bond between Pen at Xaa4 and Pen at Xaa9. In particular embodiments, the peptide is a peptide inhibitor of Formula II, and wherein in certain embodiments, XI, X2 and X3 are absent. In particular embodiments, the peptide inhibits the binding of IL-23 to IL-23R. In certain embodiments, a peptide of Formula lie further comprises an amino acid bound to the N-terminal Pen residue. In particular embodiments, the

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PCT/US2016/042680 bound amino acid is Glu,(D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln. In certain embodiments, it is is (D)Arg or (D)Phe.

[00411]In certain embodiments, the present invention includes a peptide, optionally 8 to 35, 8 to 20, 8 to 16 or 8 to 12 amino acids in length, optionally cyclized, comprising or consisting of a core sequence of Formula lid:

Pen-Xaa5-Xaa6-Trp-Xaa8-Pen- Phe[4-(2-aminoethoxy)]-[2-Nal] (lid) [00412] wherein Xaa5, Xaa6 and Xaa8 are any amino acid residue. In certain embodiments, the peptide comprises a disulfide bond between Xaa4 and Xaa9. In certain embodiments, the peptide is a peptide inhibitor of Formula I, and wherein in certain embodiments, XI, X2 and X3 are absent. In particular embodiments, the peptide inhibits the binding of IL-23 to IL-23R. In certain embodiments, a peptide of Formula lid further comprises an amino acid bound to the N-terminal Pen residue. In particular embodiments, the bound amino acid is Glu,(D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln. In certain embodiments, it is is (D)Arg or (D)Phe.

[00413] In particular embodiments of a peptide inhibitor of Formula II, the peptide inhibitor has a structure shown in any of Tables 2, 3, 4A, 4B, 8, 11 or 15 or comprises an amino acid sequence set forth in Tables 2, 3, 4A, 4B, 8, 11 or 15.

Table 2. Illustrative Di-Pen Inhibitors [Palm]-[isoGlu]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-isoGlu-Palm)]-NN-NH₂

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(Ac)]-[Lys(Ac)]-NN-NH₂ [Octanyl]-[lsoGlu]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂ [Octanyl]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂ [Palm]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-Octanyl)]-NN-NH₂

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-Palm)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-Palm)]-[2-Nal]-[Aib]-[Lys(Ac)]NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-Lauryl)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(PEG4-Palm)-[Lys(Ac)]-NN-NH2

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(PEG4-Lauryl)]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-lsoGlu-Palm)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]- [Phe[4-(2-aminoethoxy)-(PEG4-lsoGLu-Lauryl)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(PEG4-lsoGlu-Palm)]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-a-Me-K(PEG4-lsoGlu-Lauryl)]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(IVA)]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(Biotin)]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(Octanyl)]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-[Lys(IVA)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(IVA)]-N-NH2

Ac-[Pen]-[Lys(Biotin)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Biotin)]-N-NH2

Ac-[Pen]-[Lys(Octanyl)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(octanyl)]-N-NH2

Ac-[Pen]-[Lys(Palm)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-Lys(Palm)]-N-NH2

Ac-[Pen]-[Lys(PEG8)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-NN-NH2

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-[Lys(PEG8)]-N-NH2

Ac-[Pen]-K(Pegll-Palm)TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-[Lys(Pegll-palm)]-N-NH2

Ac-[Pen]-[Cit]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-[Lys(Ac)]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NT-[Phe(3,4-OCH3)2]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NT-[Phe(2,4-CH3)2]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NT-[Phe(3-CH3)]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NT-[Phe(4-CH3)]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-N-[pAla]-NH2

Ac-[(D)Tyr]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-QN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-N-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[Lys(Ac)]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-QQ-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-Q-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[Cit]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-NNH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-Q-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-[Lys(Ac)]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-[Cit]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QN-[pAla]-NH2

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-E-[Cit]-Q-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-CitNCitNH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Cit]-Q-[Cit]-NH2

Ac-[Pen]-[Cit]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QNN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-ENQ-NH2

Ac-[Pen]-GPWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-PGWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWN-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NSWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-N-[Aib]-WQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTW-[Aib]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]N-[Aib]-NH2

Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-[Lys(Ac)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]NNNH2

Ac-[Pen]-QVWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NT-[2-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NT-[l-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN- nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]-[Lys(Ac)]-N-[pAla]-NH2

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]-N-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-N- [βΑΐ3]-ΝΗ2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-LN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-GN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-SN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Aib]-N-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-FN-NH2

Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Tic]-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[nLeu]-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-G-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-R-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-W-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-S-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-L-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-[AIB]-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-[N-MeAla]-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[2-Nap]-[pAla]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-F-[pAla]-NH2

Ac-[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[ 4-amino-4-carboxy-tetrahydropyran][Lys(Ac)]-NN-NH2

Table 3. Illustrative Peptides Containing the Ac-[Pen]-XXWX-[Pen]-XXXX Motif and Analogues Thereof

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nn-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nne-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnf-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnk-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnn-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- NNW-NH

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nng-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnt-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnpk-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnpg-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnep-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngk-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnpt-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnkgf-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngw-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngq-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnggg-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnkkk-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nneee-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnfff-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnttt-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngggr-nh2

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Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngggf-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnggge-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngggq-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngggt-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]nnggggr-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnggggf-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nngggge-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnggggq-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnggggt-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnrrrrr-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnfffff-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nneeeee-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnqqqqq-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nnttttt-nh2

Ac-GGG-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahyd ropyran][Lys(Ac)]-NN-NH2

Ac-RRR-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahyd ropyran][Lys(Ac)]-NN-NH2

Ac-FFF-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

Ac-EEE-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

Ac-QQQ-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

Ac-TTT-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

Ac-RG-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahyd ropyran]-[Lys(Ac)]nn-nh2

Ac-FG-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nn-nh2

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Ac-EG-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nn-nh2

Ac-QG-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

Ac-TG-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nn-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Palm)]- nn-nh2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(isoGlu- Palm)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(PEGll- Palm)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ahx- Palm)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(isoGlu- Ahx-Palm)]-NN-NH2

[Palm]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

[Palm-isoGlu]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

[Palm-PEGll]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

[Palm-Ahx]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

[Palm-Ahx-isoGlu]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-[Lys(Ac)]-NN-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- NN-Lys[Palm]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- NN-Lys[isoGlu-Palm]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- NN-Lys[PEGll-Palm]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- NN-Lys[Ahx-Palm]-NH2

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- NN-Lys[isoGlu-Ahx-Palm]-NH2

Illustrative Peptide Inhibitors Comprising Thioether Bonds [00414] In certain embodiments, the present invention includes a peptide inhibitor of an interleukin-23 receptor, wherein the peptide inhibitor has the structure of Formula III:

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R'-X-R² (III) [00415] or a pharmaceutically acceptable salt or solvate thereof, [00416] wherein R¹ is a bond, hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl, a C1-C6 alkyl, a C1-C20 alkanoyl, an alkylsulphonate, an acid, γ-Glu or pGlu, appended to the Nterminus, and including PEGylated versions (e.g., 200 Da to 60,000 Da), alone or as a spacer of any of the foregoing;

[00417] R² is a bond, OH or NH2; and [00418]X is an amino acid sequence of 8 to 20 amino acids or 8 to 35 amino acids, [00419] In particular embodiments of peptide inhibitors of Formula III, X comprises or consists of the sequence of Formula Ilia:

XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11 -XI2-X13-XI4-X15-X16-X17-X18-X19-X20 (Ilia) wherein

XI is absent or any amino acid;

X2 is absent or any amino acid;

X3 is absent or any amino acid;

X4 is Abu, Pen, or Cys;

X5 is any amino acid;

X6 is any amino acid;

X7 is Trp, Bip, Gln, His, Glu(Bzl), 4-Phenylbenzylalanine, Tic, Phe[4-(2-aminoethoxy)], Phe(3,4-Cl2), Phe(4-OMe), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, a-MeTrp, 1,2,3,4 tetrahydro-norharman, Phe(4-CO2H), Phe(4-CONH2), Phe(3,4-(OCH₃)2), Phe(4-CF₃), ββdiPheAla, Phe(4-tBu), Glu, Gly, Ile, Asn, Pro, Arg, Thr or Octgly, or a corresponding a-methyl amino acid form of any of the foregoing;

X8 is any amino acid;

X9 is Abu, Pen, or Cys;

XI0 is 1-Nal, 2-Nal, Aic, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, 4pyridylAla, Octgly a Phe analog or a Tyr analog (optionally, Phe(3,4-F2), Phe(3,4-Cl2), F(3-Me),

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Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetyl-aminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN), Phe(4-guanidino), Phe(4-Me), Phe(4-NH₂), Phe(4-N₃), Phe(4-OMe), Phe(4-0Bzl)), or a corresponding α-methyl amino acid form of any of the foregoing;

XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, 4-phenylcyclohexyl, Glu(Bzl), 4Phenylbenzylalanine, Tic, Phe[4-(2-aminoethoxy)], Phe(3,4-Cl2), Phe(3,4-F2), phPhe(4-F), Phe(4-OMe), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, α-MeTrp, 1,2,3,4 -tetrahydronorharman, Phe(4-CO2H), Phe(4-CONH2), Phe(3,4-Dimethoxy), Phe(4-CF₃), Phe(2,3-Cl2), Phe(3,4-Cl2), Phe(2,3-F2),Phe(4-F), 4-phenylcyclohexylalanine, α-MePhe, phNal, phPhe, PhTyr, PhTrp, Bip, Nva(5-phenyl), Phe, His, hPhe, Tqa, Trp, Tyr, Phe(4-Me), Trp(2,5,7-tri-tertButyl), Phe(4-OAllyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(4-OBzl), or Octgly, or a corresponding α-methyl amino acid form of any of the foregoing;

XI2 is α-MeLys, α-MeOrn, α-MeLeu, MeLeu, Aib, (D)Ala, (D)Asn, (D)Leu, (D)Asp, (D)Phe, (D)Thr, 3-Pal, Aib, β-Ala, phGlu, phAla, phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Arg, Ser, Thr or Tie, amino-4-carboxy-tetrahydropyran (THP), Ache Acpc, Acbc,

Acvc, Aib, or a corresponding α-methyl amino acid form of any of the foregoing;

XI3 is Lys Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, α-MeLeu, PAla, phGlu, phAla, PhLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Arg, Orn, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, spiro-pip, Thr, Tba, Tic, Val or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing;

X14 is Asn, Glu, Phe, Gly, His, Lys, Lys (Ac), Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic, Asp or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing;

XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, Asn, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg, β-Ala, or Ser, or a corresponding α-methyl amino acid form of any of the foregoing;

XI6 is absent, Gly, Ala, Asp, Ser, Pro, Asn or Thr, or a corresponding α-methyl amino acid form of any of the foregoing;

XI7 is absent, Glu, Ser, Gly or Gln, or a corresponding α-methyl amino acid form of any of the foregoing;

XI8 is absent or any amino acid;

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XI9 is absent or any amino acid; and

X20 is absent or any amino acid.

[00420] In certain embdoiments, X14 is Asn, Glu, Phe, Gly, His, Lys, Lys (Ac), Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Tic, or Tyr, or a corresponding α-methyl amino acid form of any of the foregoing [00421] In certain embodiments of Ilia: X7 is Trp, Bip, Gin, His, Glu(Bzl), 4Phenylbenzylalanine, Tic, Phe[4-(2-aminoethoxy)], Phe(3,4-Cl2), Phe(4-OMe), 5-Hydroxy-Trp,

6-Chloro-Trp, N-MeTrp, α-MeTrp, 1,2,3,4 -tetrahydro-norharman, Phe(4-CO2H), Phe(4CONH2), Phe(3,4-Dimethoxy), Phe(4-CF₃), ββ-diPheAla, Phe(4-tBu), Glu, Gly, Ile, Asn, Pro, Arg, Thr or Octgly, or a corresponding α-methyl amino acid form of any of the foregoing; XI0 is 1-Nal, 2-Nal, Aic, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, 4pyridylAla, Octgly a Phe analog or a Tyr analog, or a corresponding α-methyl amino acid form of any of the foregoing; XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, 4-phenylcyclohexyl, Glu(Bzl), 4-Phenylbenzylalanine, Tic, Phe[4-(2-aminoethoxy)], Phe(3,4-Cl2), Phe(3,4-F2), β1ιΡ1ΐ6(4-Ρ), Phe(4-OMe), 5-Hydroxy-Trp, 6-Chloro-Trp, N-MeTrp, α-MeTrp, 1,2,3,4 tetrahydro-norharman, Phe(4-CO2H), Phe(4-CONH2), Phe(3,4-Dimethoxy), Phe(4-CF₃), Phe(2,3-Cl2), Phe(2,3-F2),Phe(4-F), 4-phenylcyclohexylalanine, α-MePhe, βΙιΝηΙ, βΙιΡΙιε, βΙΠγΓ, βήΤΓρ, Bip, Nva(5-phenyl), Phe, His, hPhe, Tqa, Trp, Tyr, Phe(4-Me), Trp(2,5,7-tri-tertButyl), Phe(4-OAllyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(4-OBzl), or Octgly, or a corresponding α-methyl amino acid form of any of the foregoing; XI2 is α-MeLys, a-MeOrn, a-MeLeu, MeLeu, Aib, (D)Ala, (D)Asn, (D)Leu, (D)Asp, (D)Phe, (D)Thr, 3-Pal, Aib, β-Ala, βΙιΟΙυ, βΙιΑΝ, βΙΤευ, βΙΑΧΙ, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gin, Arg, Ser, Thr or Tie, or a corresponding α-methyl amino acid form of any of the foregoing; XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, ά-MeLeu, βΑΝ, βΙιΟΙυ, βΙιΑΝ, βΙΑβυ, βΙΑΧΙ, βspiro-pip, Cha, Chg, Asp, Arg, Orn, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gin, Asp, Arg, Ser, spiro-pip, Thr, Tba, Tic, Val or Tyr, or a corresponding a-methyl amino acid form of any of the foregoing; XI4 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Tic or Tyr, or a corresponding α-methyl amino acid form of any of the

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PCT/US2016/042680 foregoing; and XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, Asn, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gin, Arg or Ser, or a corresponding α-methyl amino acid form of any of the foregoing.

[00422] In certain embodiments, X3 is present. In particular embodiments, X3 is Glu,(D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln. In certain embodiments, it is (D)Arg or (D)Phe.

[00423] In particular embodiments, X5 is Gin, Ala, Cys, Cit, Asp, Dab, Dap, Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-Me-Ala, N-M-Asn, N-Me-Lys, N-Me-Gln, N-Me-Arg, Orn, Pro, Pen, Gin, Arg, Ser, Thr, or Val.

[00424] In particular emodiments, X6 is Thr, Asp, Glu, Phe, Asn, Pro, Arg, Ser, or Thr.

[00425] In particular embodiments, X8 is Gin, Glu, Phe, Lys, Asn, Pro, Arg, Val, Thr, or Trp.

[00426] In certain embodiments, XI0 is a Tyr analog or a Phe analog. In particular embodiments, XI0 is Phe(4-OMe), Phe(CONH2) or Phe[4-(2-aminoethoxy)]. In certain embodiments, XI0 is a Tyr analog or a Phe analog. In particular embodiments, XI0 is Phe(4-OMe) or Phe[4-(2aminoethoxy)].

[00427] In certain embodiments where XI0 is a the Phe analog, XI0 is selected from hPhe, Phe(4-OMe), α-MePhe, hPhe(3,4-dimethoxy), Phe(4-CONH2), Phe(4-O-Bzl)), Phe(4guanadino), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4-NH₂), Phe(4-F), Phe(3,5 DiF), Phe(CH₂CO₂H), Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF3), ββ-diPheAla, Phe(4-N₃) and Phe[4-(2aminoethoxy)]. In particular embodiments, XI0 is Phe[4-(2-aminoethoxy)] or Phe(CONH₂). In particular embodiments, XI0 is Phe[4-(2-aminoethoxy)].

[00428] In certain embodiments where XI0 is a Tyr analog, XI0 is selected from hTyr, N-MeTyr, Tyr(3-tBu), Phe(4-OMe) and bhTyr. In particular embodiments, XI0 is Phe(4-OMe).

[00429] In particular embodiments, XI0 is Tyr, Phe(4-OMe), Phe(4-OBzl), Phe(4-OMe), Phe(4CONH₂), Phe(3,4-Cl₂), Phe(4-tBu), Phe(4-NH2), Phe(4-Br), Phe(4-CN), Phe(4-carboxy), Phe[4(2aminoethoxy)] or Phe(4-guanadino). In particular embodiments, XI0 is not Tyr.

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PCT/US2016/042680 [00430] In certain embodiments, XI1 is Trp or a Trp analog. In particular embodiments, XI1 is

2-Nal or 1-Nal.

[00431] In particular embodiments, the peptide inhibitor of Formula III is cyclized. In certain embodiments, the peptide inhibitor is cyclized via an intramolecular bond between X4 and X9. In certain embodiments, the intramolecular bond is a thioether bond.

[00432] In certain embodiments, the peptide inhibitor of Formula III is linear or not cyclized. In particular embodoiments of the linear peptide inhibitor of Formula III, X4 and/or X9 are any amino acid.

[00433] In particular embodiments of a peptide inhibitor of Formula III, one or more, two or more, or all three of XI, X2, and X3 are absent. In certain embodiments, XI is absent. In certain embodiments, XI and X2 are absent. In certain embodiments, XI, X2 and X3 are absent.

[00434] In particular embodiments of a peptide inhibitor of Formula III, one or more, two or more, three or more, four or more, or all of XI6, XI7, XI8, XI9 and X20 are absent. In particular embodiments of a peptide inhibitor of Formula III, one or more, two or more, three or more, or all of XI7, XI8, XI9 and X20 are absent. In certain embodiments, one or more, two or more, or all three of XI7, XI9 and X20 are absent. In certain embodiments, one or more of XI, X2 and X3 are absent; and one or more, two or more, three or more, or four of XI7, XI8, XI9 and X20 are absent.

[00435] In particular embodiments of a peptide inhibitor of Formula III, one of X4 or X9 is Abu, and the other of X4 or X9 is not Abu. In certain embodiments, X4 is Abu and X9 is Cys.

[00436] In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, or four of the following features: X5 is Arg or Gln; X6 is Thr; X7 is Trp; and X8 is Gln. In particular embodiments, X5 is Gln, X6 is Thr, X7 is Trp, and X8 is Gln. In certain embodiments, X5 is Gln. In certain embodiments, XI, X2 and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

[00437] In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following

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PCT/US2016/042680 features: X10 is Tyr or a Phe analog; XI1 is Trp, 2-Nal, 1-Nal, Phe(4-O-Allyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(4-OBzl) or Phe(4-Me); X12 is Arg, hLeu, (D)Asn, or any alpha methyl amino acids including, Aib, α-MeLys, a-MeLeu or α-MeOrn; XI3 is Lys, Glu or Lys(Ac); XI4 is Phe or Asn; XI5 is β-Ala, Gin, Gly, Ser, Ala; and XI6 is absent or AEA. In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following features: XI0 is Tyr or a Phe analog; XI1 is Trp, 2-Nal, 1-Nal, Phe(4-O-Allyl), Tyr(3-tBu), Phe(4-tBu), Phe(4guanidino), Phe(4-OBzl) or Phe(4-Me); XI2 is Arg, hLeu, (D)Asn, or any alpha methyl amino acids including, Aib, α-MeLys, a-MeLeu or a-MeOm; X13 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; XI5 is Gly, Ser, Ala; and XI6 is absent or AEA. In certain embodiments, the Phe analog is Phe(4-OBzl), Phe(4-OMe), Phe(4-CONH₂), Phe(3,4-Cl₂), Phe(4-tBu), Phe(4-NH2), Phe(4-Br), Phe(4-CN), Phe(4-carboxy), Phe[4-(2aminoethoxy)] or Phe(4-guanadino). In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

[00438] In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following features: X10 is Tyr or a Phe analog; XI1 is Trp, 2-Nal, 1-Nal, Phe(4-O-Allyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(4-OBzl) or Phe(4-Me); XI2 is Arg, hLeu, (D)Asn, 4-amino4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, a-MeLys, aMeLys(Ac), a-Me-Leu, α-MeOrn, a-MeSer, a-MeVal„ XI3 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; XI5 is Gly; and XI6 is absent or AEA. In certain embodiments, the Phe analog is Phe(4-OBzl), Phe(4-OMe), Phe(4-CONH₂), Phe(3,4-C12), Phe(4-tBu), Phe(4-NH₂), Phe(4-Br), Phe(4-CN), Phe(4-carboxy), Phe(4-(2aminoethoxy)) or Phe(4-guanadino). In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

[00439] In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven of the following features: X5 is Arg or Gin; X6 is Thr; X7 is Trp; X8 is Gin; X10 is a Phe analog; XI1 is Trp, 2-Nal, 1-Nal, Phe(4-O-Allyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(Bzl) or Phe(4-Me); X12 is Aib, α-MeLys, a-MeLeu, 4142

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PCT/US2016/042680 amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, a-MeLys, a-MeLys(Ac), a-Me-Leu, a-MeSer, a-MeVal,a-MeOrn; XI3 is Lys, Glu or Lys(Ac); XI4 is Phe or Asn; XI5 is β-ala, Gly, Ser, Ala; and XI6 is absent or AEA. In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven of the following features: X5 is Arg or Gin; X6 is Thr; X7 is Trp; X8 is Gin; XI0 is a Phe analog; XI1 is Trp, 2-Nal, 1-Nal, Phe(4-O-Allyl), Tyr(3-tBu), Phe(4-tBu), Phe(4guanidino), Phe(Bzl) or Phe(4-Me); X12 is Aib, α-MeLys, a-MeLeu or α-MeOrn; X13 is Lys, Glu or Lys(Ac); XI4 is Phe or Asn; XI5 is Gly, Ser, Ala; and XI6 is absent or AEA. In certain embodiments, the Phe analog is Phe(4-OBzl), Phe(4-OMe), Phe[4-(2aminoethoxy)], Phe(4CONH₂), Phe(3,4-Cl₂), Phe(4-tBu), Phe(4-NH₂), Phe(4-Br), Phe(4-CN), Phe(4-CO₂H), or Phe(4guanadino). In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

[00440] In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven of the following features: X5 is Arg or Gin; X6 isThr; X7 is Trp; X8 is Gin; X10 is Tyr or a Phe analog; XI1 is Trp, 2-Nal, 1-Nal, Phe(4-O-Allyl), Tyr(3tBu), Phe(4-tBu), Phe(4-guanidino), Phe(Bzl) or Phe(4-Me); XI2 is Arg, hLeu, (D)Asn, 4amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Aib, α-DiethylGly, a-MeLys, aMeLys(Ac), a-Me-Leu, a-MeSer, a-MeVal„ XI3 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; XI5 is β-Ala, Asn or Gly; and XI6 is absent or AEA. In particular embodiments, a peptide inhibitor of Formula III comprises one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven of the following features: X5 is Arg or Gin; X6 isThr; X7 is Trp; X8 is Gin; XI0 is Tyr or a Phe analog; XI1 is Trp, 2-Nal, 1-Nal, Phe(4-O-Allyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Phe(Bzl) or Phe(4-Me); X12 is Arg, hLeu, (D)Asn, α-MeLys, a-MeLeu or α-MeOrn, Aib; X13 is Lys, Glu or Lys(Ac); X14 is Phe or Asn; XI5 is Gly; and XI6 is absent or AEA. In certain embodiments, the Phe analog is Phe(4-OBzl), Phe(4OMe), Phe(4-CONH₂), Phe(3,4-Cl₂), Phe(4tBu), Phe(4-NH₂), Phe(4-Br), Phe(4-CN), Phe(4-CO₂H), Phe(4-(2-aminoethoxy)) or Phe(4143

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PCT/US2016/042680 guanidino). In certain embodiments, XI1 is 2-Nal or 1-Nal. In certain embodiments, XI, X2 and X3 are absent, n certain embodiments, X4 is Abu and X9 is Cys.

[00441] In certain embodiments, the present invention includes a peptide of 8 to 20, 8 to 16 or 8 to 12 amino acids, optionally cyclized, comprising or consisting of a core sequence of Formula Illb:

Xaa4-Xaa5-Xaa6-Trp-Xaa8-Xaa9-Xaal0-Xaal 1 (Illb) [00442] wherein Xaa4 and Xaa9 are each independently selected from Abu and Cys, wherein Xaa4 and Xaa9 are not both the same; Xaa5, Xaa6 and Xaa8 are any amino acid residue; Xaa 10 is Tyr, a Phe analog or 2-Nal, and Xaal 1 is 2-Nal or Trp, wherein the peptide inhibits binding of IL-23 to IL-23R. In particular embodiments, XaalO is Phe(4-OMe), 2-Nal, or Phe[4-(2aminoethoxy)]. In one embodiment, XaalO is Phe(4-OMe). In one embodiment, Xaa7 is Phe[4(2-aminoethoxy)]. In one embodiment, Xaall is 2-Nal. In certain embodiments, the peptide is cyclized via Xaa4 and Xaa9. In particular embodiments, the Phe analog is Phe[4(2aminoethoxy)] or Phe(4-OMe). In certain embodiments, Xaa4 is Abu and Xaa9 is Cys, and the peptide is cyclized via Xaa4 and Xaa9. In particular embodiments, the peptide is a peptide inhibitor of Formula III, and wherein in certain embodiments, XI, X2 and X3 are absent. In particular embodiments, the peptide inhibits the binding of IL-23 to IL-23R. In certain embodiments, a peptide of Formula Illb comprises a Glu,(D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2Nal, Thr, Leu, or (D)Gln bound to Xaa4. In certain embodiments, it is (D)Arg or (D)Phe.

[00443] In certain embodiments, the present invention includes a peptide of 8 to 20, 8 to 16 or 8 to 12 amino acids, optionally cyclized, comprising or consisting of a core sequence of Formula IIIc:

Abu-Xaa5-Xaa6-Trp-Xaa8-Cys-[Phe(4-OMe)]-(2-Nal) (IIIc) [00444] wherein Xaa5, Xaa6 and Xaa8 are any amino acid residue; and wherein the peptide inhibits binding of IL-23 to IL-23R. In certain embodiments, the peptide is cyclized via Abu at Xaa4 and Cys at Xaa9. In certain embodiments, the peptide is a peptide inhibitor of Formula III, and wherein in certain embodiments, XI, X2 and X3 are absent. In particular embodiments, the peptide inhibits the binding of IL-23 to IL-23R. In certain embodiments, a peptide of Formula

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IIIc comprises a Glu, (D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln bound to Abu. In certain embodiments, it is (D)Arg or (D)Phe.

[00445] In certain embodiments, the present invention includes a peptide of 8 to 20, 8 to 16 or 8 to 12 amino acids, optionally cyclized, comprising or consisting of a core sequence of Formula Hid:

Abu-Xaa5-Xaa6-Trp-Xaa8-Cys-Xaal0-Trp (Hid) [00446] wherein Xaa5, Xaa6 and Xaa8 are any amino acid residue; XaalO is a modified Phe; and wherein the peptide inhibits binding of IL-23 to IL-23R. In particular embodiments, the modified Phe is Phe(4-tBu), Phe(4-guanidino), Phe[4-(2-aminoethoxy)], Phe(4-CO2H), Phe(4CN), Phe(4-Br), Phe(4-NH₂), PHe(CONH₂) or Phe(4-Me). In particular embodiments, the modified Phe is Phe(4-tBu), Phe(4-guanidino), Phe[4-(2-aminoethoxy)], Phe(4-CO₂H), Phe(4CN), Phe(4-Br), Phe(4-NH₂), or Phe(4-Me). In one embodiment, XaalO is Phe[4-(2aminoethoxy)] or Phe(4-OMe). In one embodiment, XaalO is Phe[4-(2-aminoethoxy)]. In certain embodiments, the peptide is cyclized via Abu at Xaa4 and Cys at Xaa9. In certain embodiments, the peptide is a peptide inhibitor of Formula III, and wherein in certain embodiments, XI, X2 and X3 are absent. In particular embodiments, the peptide inhibits the binding of IL-23 to IL23R. In certain embodiments, a peptide of Formula Hid comprises a Glu, (D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln bound to Abu. In certain embodiments, it is (D)Arg or (D)Phe.

[00447] In certain embodiments, the present invention includes a peptide, optionally 8 to 20, 8 to 16 or 8 to 12 amino acids, optionally cyclized, comprising or consisting of a core sequence of Formula Hie:

Abu-Xaa5-Xaa6-Trp-Xaa8-Cys- Phe[4-(2-aminoethoxy)]-[2-Nal] (Hie) [00448] wherein Xaa5, Xaa6 and Xaa8 are any amino acid residue. In certain embodiments, the peptide is cyclized via Abu at Xaa4 and Cys at Xaa9. In certain embodiments, the peptide is a peptide inhibitor of Formula III, and wherein in certain embodiments, XI, X2 and X3 are absent. In particular embodiments, the peptide inhibits the binding of IL-23 to IL-23R. In certain

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PCT/US2016/042680 embodiments, a peptide of Formula Illb comprises a Glu, (D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2Nal, Thr, Leu, or (D)Gln bound to Abu. In certain embodiments, it is (D)Arg or (D)Phe.

[00449] In one embodiment, Xaa5 and Xaa8 is Gin. In one embodiment, Xaa6 is Thr. In certain embodiments, the peptide is cyclized via Abu at Xaa4 and Cys at Xaa9.

[00450] In particular embodiments of a peptide inhibitor of Formula III, the peptide inhibitor has a structure shown in any of Tables 5A-5C or comprises an amino acid sequence set forth in Tables 5A-5C.

[00451] In certain aspects, the present invention provides a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Vf):

XI -X2-X3-Abu-X5-X6-X7-X8-Cys-Xl 0-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Vf), wherein:

XI is absent;

X2 is absent or X2 is D-Asp, E, R, D-Arg, F, D-Phe, 2-Nal, T, L, D-Gln, or D-Asn;

X3 is D-Arg;

X5 is N, Q, Cit, Lys, or a Lys conjugate (e.g., Lys(IVA), Lys(biotin), Lys(octanyl), Lys(Palm), Lys(PEG), Lys(PEG8), Lys(PEGl 1-Palm), Lys(Ac));

X6 is T, S or V;

X7 is W, 1-Nal, or 2-Nal;

X8 is Q, Cit, N, Aib or Lys(Ac);

XI0 is Phe[4-(2-aminoethoxy)], Phe[4-(2-acetylaminoethoxy)] or Phe(4-CONH2);

XII is 2-Nal;

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XI2 is 4-amino-4-carboxy-tetrahydropyran, Aib, aMeLeu, aMeLys, or an aMeLys conjugate (e.g., aMeLys(Ac), ocMeLys(PEG4-Palm), aMeLys(PEG4Lauryl), a.MeLys(PEG4IsoGluPalm), a.MeLys(PEG4IsoGluLauryl), aMeLys(IVA), aMeLys(bi otin), or aMeLys(octanyl));

X13 is Q, E, Cit or a Lys conjugate (e.g., Lys(Ac), Lys(PEG4-isoGlu-Palm), Lys(PEG4-octanyl), Lys(PEG4-Palm), Lys(biotin), Lys(octanyl), Lys(Palm), Pys(PEG8), or Lys(PEGll-Palm));

X14 is N, Cit, Q, L, G, S, Aib, F, 2-Nap, N-Me-Ala, R, W, nLeu, Tic or a Lys conjugate (e.g., Lys(Ac));

XI5 is N, Cit, Q, PAla, Lys(Ac) or Aib; and

XI6, XI7, XI8, XI9 andX20 are absent.

In particular embodiments, X2 is D-Asp, E, R, D-Arg, F, D-Phe, 2-Nal, T, L, D-Gln, or

D-Asn [00452] In certain aspects, the present invention provides a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Vh):

XI -X2-X3-Abu-X5-X6-X7-X8-Cys-Xl 0-X11 -XI2-X13-X14-X15-X16-X17-X18-X19-X20 (Vh), wherein:

XI is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any D-amino acid or absent;

X4 is Cys, hCys, Pen, hPen, Abu, Ser, hSer or chemical moiety capable of forming a bond with X9;

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X5 is Ala, α-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Arg, Ser, Glu or Thr;

X6 is Thr, Ser, Asp, Ile or any amino acid;

X7 is Trp, 6-Chloro-Trp, 1-Nap or 2-Nap;

X8 is Glu, Gln, Asn, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-L-Y-glutamyl)), or Lys(N-sPalmitoyl;

X9 is Cys, hCys, Pen, hPen Abu, or any amino acid or chemical moiety capable of forming a bond with X4;

XI0 is 2-Nal, a Phe analog, Tyr, or a Tyr analog;

XI1 is 1-Nal, 2-Nal, Phe(3,4-dimethoxy), 5-HydroxyTrp, Phe(3,4-C12), Trp or Tyr(3-tBu);

XI2 is Aib, 4-amino-4-carboxy-tetrahydropyran, any alpha-methylamino acid, alpha-ethylamino acid, Ache, Acvc, Acbc Acpc, 4-amino-4-carboxy-piperidine, 3-Pal, Agp, □-DiethylGly, α-MeLys, a-MeLys(Ac), α-MeLeu, a-MeOrn, a-MeSer, a-MeVal, Cav, Cha, Cit, Cpa, D-Asn, Glu, His, hLeu, hArg, Lys, Leu, Octgly, Orn, piperidine, Arg, Ser, Thr or THP;

XI3 is Lys(Ac), Gln, Cit, Glu, or any amino acid;

XI4 is Asn, Gln, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-L-Y-glutamyl)), Lys(N-sPalmitoyl), Asp, or any amino acid;

XI5 is β-Ala, Asn, Gly, Gln, Ala, Ser, Aib, Asp or Cit;

XI6 is any amino acid or absent;

XI7 is any amino acid or absent;

XI8 is any amino acid or absent;

XI9 is any amino acid or absent; and

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X20 is any amino acid or absent.

[00453] In certain embodiments of any of the peptide inhibitors described herein, including but not limited to those of Formula (If) and (Ih), the peptide inhibitor is cyclized via a bond, e.g., a thioether bond, between X4 and X9. In certain embodiments, the peptide inhibitor inhibits the binding of an interleukin-23 (IF-23) to an IF-23 receptor.

[00454] In certain embodiments, XI, X2 and X3 are absent. In certain embodiments, XI and X2 are absent. In certain embodiments, XI is a D-amino acid or absent. In certain embodiments, X2 is a D-amino acid or absent.

[00455] In certain embdoiments, X5 is Ala, α-MeOrn, α-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gin, Arg, Ser, or Thr;

[00456] In certain embodiments, X5 is N, X6 is Τ, X7 is W, or X8 is Q. In certain embodiments, X5 is N, X6 is Τ, X7 is W, and X8 is Q.

[00457] In certain embodiments, X5 is Q, X6 is Τ, X7 is W, or X8 is Q. In certain embodiments, X5 is Q, X6 is Τ, X7 is W, and X8 is Q.

[00458] In certain embodiments, X5 is N, X6 is Τ, X7 is W, and X8 is Cit.

[00459] In certain embodiments, XI0 is Phe[4-(2-aminoethoxy)].

[00460] In certain embodiments, XI2 is 4-amino-4-carboxy-tetrahydropyran, Aib, aMeLeu, or aMeLys. In certain embodiments, XI2 is 4-amino-4-carboxy-tetrahydropyran.

[00461] In certain embodiments, XI3 is E or Lys(Ac). In certain embodiments, XI3 is Lys(Ac).

[00462] In certain embodiments, X14 is Asn, Gin, Lys(Ac), Cit, Cav, Lys(N-8-(N-a-Palmitoyl-Lγ-glutamyl)), Lys(N-8-Palmitoyl), or any amino acid;

[00463] In certain embdoiments, XI5 is β-Ala, Asn, Gly, Gin, Ala, Ser, Aib, or Cit.

[00464] In certain embodiments, X14 is N.

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PCT/US2016/042680 [00465] In certain embodiments, XI5 is N.

[00466] In certain embodiments, XI6 is a D-amino acid or absent. In certain embodiments, XI7 is a D-amino acid or absent. In certain embodiments, XI8 is a D-amino acid or absent. In certain embodiments, XI9 is a D-amino acid or absent. In certain embodiments, X20 is a Damino acid or absent.

[00467] In certain embodiments, X2 is absent; X3 is absent; X5 is Q, X6 is T, X7 is W, and X8 is Q; XI0 is Phe[4-(2-aminoethoxy)]; XI2 is 4-amino-4-carboxy-tetrahydropyran, Aib, aMeLeu, or aMeLys; X13 is E or Lys(Ac); X14 is N; and XI5 is N. In certain embodiments, X12 is 4amino-4-carboxy-tetrahydropyran and XI3 is Lys(Ac).

[00468] In certain embodiments, any of the amino acids of the peptide inhibitor are connected by a linker moiety, e.g., a PEG.

[00469] In certain embodiments, the N-terminus of the peptide inhibitor comprises an Ac group.

[00470] In certain embodiments, the C-terminus of the peptide inhibitor comprises an NH₂ group.

[00471] In certain embodiments, the present invention includes a peptide comprising or consisting of an amino acid sequence shown in any of the Table 4s or Table 5s, or a peptide inhibitor comprising or consisting of a structure shown in any of the Table 4s or Table 5s (or a pharmaceutically acceptable salt thereof). In particular embodiments, the peptide does not include the conjugated moieties but does include the Abu residue. In particular embodiments, the peptide or inhibitor comprises a thioether bond between the two Abu and Cys residues, or between the two outermost amino acids within the brackets folloing the term “cyclo”, which indicated the presence of a cyclic structure. In particular embodiments, the inhibitor is an acetate salt. The peptide sequence of illustrative inhibitors is shown in Tables 4 and 5 from N-term to C-term, with conjugated moieties, and N-terminal Ac and/or C-terminal NH₂ groups indicated. The cyclic structure is indicated by “Cyclo” as illustrated in Table 5, indicating the presence of a thioether bond between the bracketed Abu at X4 and Cys at X9.

Table 4, Illustrative Thioether Peptide Inhibitors

Biotin-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]ENN-NH₂

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Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN- nh2

Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2

Ac-E-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-[(D)Asp]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

Ac-R-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-[(D)Arg]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

Ac-F-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahyd ropyran]enn-nh2

Ac-[(D)Phe]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

Ac-[2-Nal]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

Ac-T-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-L-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-[(D)Gln]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

Ac-[(D)Asn]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)-(PEG4-Alexa488)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

[Alexa488]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]--[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

[Alexa647]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

[Alexa-647]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-[Lys(Ac)]-NN-NH2

[Alexa647]-[PEG12]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-[Lys(Ac)]-NN-NH2

[Alexa488]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-[Lys(Ac)]-NN-NH2

Table 5A, Illustrative Thioether Peptide Inhibitors

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_N' >_r-[Phe(4-OMe)]-[2-Nal]-XXXX-NH₂ '' Ο

Ac-Cyclo-[[Abu]-XXWXC]-[Phe(4-OMe)]-[2-Nal]-XXXX-NH₂

Sequence

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN- nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENNE- nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENNF- nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENNK- nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENNN- nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennw-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENNT- nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENNG- nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennpk-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennpg-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennep-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngk-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennpt-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngf-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngw-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngq-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennggg-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennkkk-nh2

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Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enneee-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennfff-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennttt-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngggr-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngggf-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennggge-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngggq-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngggt-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennggggr-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennggggf-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngggge-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennggggq-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennggggt-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennrrrrr-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enngfffff-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enneeeee-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennqqqqq-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ennttttt-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN- nh2

Ac-GGG-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-RRR-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-FFF-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

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Ac-EEE-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-QQQ-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-TTT-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-RG-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-FG-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-EG-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahyd ropyran]enn-nh2

Ac-QG-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahyd ropyran]enn-nh2

Ac-TG-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- enn-nh2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Palm)]-NN-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(PEGll-Palm)]-NN-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(isoGlu-Palm)]-NN-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ahx-Palm)]-NN-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(isoGlu-Ahx-Palm)]-NN-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(isoGlu-Ahx-Palm)]-NN-NH2

[Palm]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahyd ropyran]enn-nh2

[Palm-isoGlu]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

[Palm-PEGll]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

[Palm-Ahx]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

[Palm-Ahx-isoGlu]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy- tetrahydropyran]-ENN-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN- Lys[Palm]-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN- Lys[Pegll-Palm]-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN- Lys[isoGlu-Palm]-NH2

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Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN- Lys[Ahx-Palm]-NH2

Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN- Lys[isoGlu-Ahx-Palm]-NH2

Table 5B. Illustrative Thioether Peptides

Ac-[D-Arg]- Cyclo-[Abu-QTWQC]-[Phe(4-2ae)]-[2-Nal]-[THP]-ENN-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWQC]-[Phe(4-2ae)]-[2-Nal]-[THP]]-END-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWQC]-[Phe(4-2ae)]-[2-Nal]-[THP]-EDN-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWEC]-[Phe(4-2ae)]-[2-Nal]-[THP]-ENN-NH2

Ac-[D-Arg]- Cyclo-[Abu-ETWQC]-[Phe(4-2ae)]-[2-Nal]-[THP]-ENN-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWQC]-[Phe(4-2ae)]-[2-Nal]-[THP]-EDD-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWEC]-[Phe(4-2ae)]-[2-Nal]-[THP]-END-NH2

Ac-[D-Arg]- Cyclo-[Abu-ETWQC]-[Phe(4-2ae)]-[2-Nal]-[Tetrahydropyran-A]-END-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWEC]-[Phe(4-2ae)]-[2-Nal]-[THP]-EDN-NH2

Ac-[D-Arg]- Cyclo-[Abu-ETWQC]-[Phe(4-2ae)]-[2-Nal]-[Tetrahydropyran-A]-EDN-NH2

Ac-[D-Arg]- Cyclo-[Abu-ETWEC]-[Phe(4-2ae)]-[2-Nal]-[THP]-ENN-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWQC]-[Phe(4-2ae)]-[2-Nal]-[THP]-ENN-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWQC]-[Phe(4-2ae)]-[2-Nal]-[THP]-END-NH2

Ac-[D-Arg]- Cyclo-[Abu-QTWQC]-[Phe(4-2ae)]-[2-Nal]-[Tetrahydropyran-A]-EDN-NH2

Ac-[D-Arg]- Cyclo-[Abu-ETWEC]-[Phe(4-2ae)]-[2-Nal]-[THP]-ENN-NH2

Ac-[D-Arg]- Cyclo-[Abu-ETWQC]-[Phe(4-2ae)]-[2-Nal]-[Tetrahydropan-A]-ENN-OH

Ilustrative Peptide Inhibitors Containing Cyclic Amides

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PCT/US2016/042680 [00472] In certain embodiments, the present invention includes a peptide inhibitor of an interleukin-23 receptor, wherein the peptide inhibitor has the structure of Formula IV:

R'-X-R² (IV) [00473] or a pharmaceutically acceptable salt or solvate thereof, [00474] wherein R¹ is a bond, hydrogen, an C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl C1-C6 alkyl, a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing;

[00475] R² is a bond, OH or NH₂; and [00476] X is an amino acid sequence of 8 to 20 amino acids, comprising or consisting of the sequence of Formula IVa:

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (IVa) [00477] wherein

XI is absent or any amino acid;

X2 is absent or any amino acid;

X3 is absent or any amino acid;

X4 is Dap, Dab, Glu, Asp, (D)-Asp or (D)-Dab;

X5 is Gin, Ala, Cys, Cit, Asp, Dab, Dap, Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-MeAla, N-M-Asn, N-Me-Lys, N-Me-Gln, N-Me-Arg, Orn, Pro, Pen, Gin, Arg, Ser, Thr, or Val;

X6 is Thr, Asp, Glu, Phe, Asn, Pro, Arg, Ser, or Thr;

X7 is Trp, Glu, Gly, Ile, Asn, Pro, Arg, Thr or OctGly;

X8 is Gin, Glu, Phe, Lys, Asn,, Pro, Arg, Thr, or Trp;

X9 is Dap, Dab, Glu, Asp, (D)-Asp or (D)-Dab;

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X10 is Tyr(0Me)Phe(4-0Me), 1-Nal, 2-Nal, Aic, a-MePhe, Bip, (D)Cys, Cha, DMT, (D)Tyr), Glu, Phe, His, hPhe(3,4-dimethoxy), hTyr, N-Me-Tyr, Trp, Phe(4-CONH2), Phe(4-phenoxy), Thr, Tic, Tyr, Tyr(3-tBu), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4-NH₂), Phe(4-F), Phe(3,5F₂),Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF₃), Bip, Cha, 4-pyridylalanine, PhTyr, OctGly, Phe(4N₃), Phe(4-Br) or Phe[4-(2-aminoethoxy)];

XI1 is 2-Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl₂), Phe(3,5-F₂), Phe(4-CONH₂), Phe(4-F), 4-phenylcyclohexylalanine, Phe(4-CF₃), α-MePhe, phPhe, PhTyr, PhTrp, BIP, Nva(5-phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe(4-OMe), Phe(4-Me), Trp(2,5,7-tri-tertButyl), Phe(4OAllyl), Tyr(3-tBu), Phe(4-tBu), Phe(4-guanidino), Tyr(Bzl), or OctGly;

XI2 is a-MeLys, α-MeOrn, a-MeLeu, Aib, (D)Ala, (D)Asn, (D)Leu, (D)Asp, (D)Phe, (D)Thr,

3-Pal, Aib, β-Ala, β-Glu, phAla, phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, aDiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gin, Arg, Ser, Thr Tie, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, aDiethylGly, a-MeLys, a-MeLys(Ac), a-Me-Leu, a-MeSer, a-MeVal„

XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, ά-MeLeu, Aib, β-Ala, β-Glu, PhAla,phLeu, phVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, Lys, Lys(Ac), Leu, Asn, Ogl, Pro, Gin, Arg, Ser, β-spiro-pip, Thr, Tba, Tic, Val or Tyr;

X14 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Tic or Tyr;

XI5 is β-ala, Asn, Gly, (D)Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gin, Arg or Ser;

XI6 is absent, Gly, Ala, Asp, Ser, Pro, Asn or Thr;

XI7 is absent, Glu, Ser, Gly or Gin;

XI8 is absent or any amino acid;

XI9 is absent or any amino acid; and

X20 is absent or any amino acid.

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PCT/US2016/042680 [00478] In certain embodiments of IVa: X12 is α-MeLys, a-MeOrn, α-MeLeu, Aib, (D)Ala, (D)Asn, (D)Leu, (D)Asp, (D)Phe, (D)Thr, 3-Pal, Aib, β-Ala, β-Glu, βήΑΗ, βϋεη, βΕν^Ι, βspiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Arg, Ser, Thr or Tie; XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Thr, (D)Phe, Ala, Aib, α-MeLeu, Aib, β-Ala, β-Glu, βΙιΑΗ,βϋεη, βΚν^Ι, β-spiropip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, Glu, Phe, hLeuLys, Leu, Asn, Ogl, Pro, Gln, Arg, Ser, β-spiro-pip, Thr, Tba, Tic, Val or Tyr; XI4 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr; and XI5 is Gly, (D)Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser.

[00479] In particular embodiments of a peptide inhibitor of Formula (IV): X5 is Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me-Ala, N-Me-Asn, N-Me-Lys, N-Me-Gln, N-MeArg, Orn, Pro, Pen, Gln, Val; X6 is Glu, Arg, Ser; X7 is Trp, Glu, Gly, Ile, Asn, Pro, Arg, Thr or OctGly; X8 is Phe, Asn, Pro, Arg, Thr, Trp; XI0 is Phe(4-OMe), 1-Nal, 2-Nal, Aic, a-MePhe, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, His, hPhe(3,4-dimethoxy), hTyr, N-Me-Tyr, Trp, Phe(4CONH₂), Phe-(4-phenoxy), Thr, Tic, Tyr(3-tBu), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4NH₂), Phe(4-F), Phe(3,5-F₂), PheCH₂CO₂H, Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF₃), Bip, Cha,

4-PyridylAlanine, βΙιΤγΓ, OctgGly, Tyr(4-N₃), Phe(4-Br), Phe[4-(2-aminoethoxy)]; XI1 is 2Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl₂), Phe(3,5-F₂), Phe(4-CONH₂), Phe(4-F),4phenylcyclohexyl, Phe(4-CF₃), α-MePhe, Nal, βΙιΡΙιε, βΙιΤγΓ, βΙΥΗρ, BIP, Nva(5-phenyl), Phe, His, hPhe, Tic, Tqa, Tyr, Phe(4-OMe), Phe(4-Me), Tyr(2,5,7-tri-tert-Butyl), Phe(4-OAllyl), Phe(3-tBu), Phe(4-tBu), Phe(4-guanidino), Tyr(Bzl), OctGly; XI2 is α-Me-Lys, D-Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Tyr, Aib, α-MeLeu, a-MeOrn, Aib, β-Ala, βΙιΑΗ, βΙιΑ^, βϋεη, βΙΑ^Ι, β-spiro-pip, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr, Tie, 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, α-DiethylGly, a-MeLys(Ac), , aMeSer, a-MeVal; XI3 is Lys, Lys(Ac), (D)Asn, (D)Leu, (D)Phe, (D)Thr, Ala, α-MeLeu, Aib, βAla, β-Glu, βϋβη, βΙΛ^Ι, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, hLeu, Asn, Ogl, Pro, Gln, Ser, Thr, Tba, Tie; XI4 is Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic; XI5 is (D)Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Thr, Aea, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Asn, Arg or β-Ala; XI6 is Gly, Ser, Pro, Asn, Thr; or XI7 is Glu, Ser, Gly, Gln.

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PCT/US2016/042680 [00480] In particular embodiments of a peptide inhibitor of Formula (IV): X5 is Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me-Ala, N-Me-Asn, N-Me-Lys, N-Me-Gln, N-MeArg, Orn, Pro, Pen, Gln, Val; X6 is Glu, Arg, Ser; X7 is Trp, Glu, Gly, Ile, Asn, Pro, Arg, Thr or OctGly; X8 is Phe, Asn, Pro, Arg, Thr, Trp; XI0 is Phe(4-OMe), 1-Nal, 2-Nal, Aic, a-MePhe, Bip, (D)Cys, Cha, DMT, (D)Tyr, Glu, His, hPhe(3,4-dimethoxy), hTyr, N-Me-Tyr, Trp, Phe(4CONH2), Phe-(4-phenoxy), Thr, Tic, Tyr(3-tBu), Phe(4-tBu), Phe(4-CN), Phe(4-Br), Phe(4NH₂), Phe(4-F), Phe(3,5-F₂), PheCH₂CO₂H, Phe(penta-F), Phe(3,4-Cl₂), Phe(4-CF₃), Bip, Cha, 4-PyridylAlanine, PhTyr, OctgGly, Tyr(4-N₃), Phe(4-Br), Phe[4-(2-aminoethoxy)]; XI1 is 2Nal, 1-Nal, 2,4-dimethylPhe, Bip, Phe(3,4-Cl₂), Phe(3,5-F₂), Phe(4-CONH₂), Phe(4-F),4phenylcyclohexyl, Phe(4-CF₃), α-MePhe, Nal, phPhe, PhTyr, phTrp, BIP, Nva(5-phenyl), Phe, His, hPhe, Tic, Tqa, Tyr, Phe(4-OMe), Phe(4-Me), Tyr(2,5,7-tri-tert-Butyl), Phe(4-OAllyl), Phe(3-tBu), Phe(4-tBu), Phe(4-guanidino), Tyr(Bzl), OctGly; XI2 is α-Me-Lys, D-Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Tyr, Aib, a-MeLeu, α-MeOrn, Aib, β-Ala, phAla, PhArg, phLeu, PhVal, β-spiro-pip, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr, Tie; XI3 is Lys(Ac), (D)Asn, (D)Leu, (D)Phe, (D)Thr, Ala, α-MeLeu, Aib, β-Ala, β-Glu, phLeu, PhVal, β-spiro-pip, Cha, Chg, Asp, Dab, Dap, α-DiethylGly, hLeu, Asn, Ogl, Pro, Gln, Ser, Thr, Tba, Tie; X14 is Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic; XI5 is (D)Ala, (D)Asn, (D)Asp, (D)Leu, (D)Phe, (D)Thr, Aea, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Arg; XI6 is Gly, Ser, Pro, Asn, Thr; or XI7 is Glu, Ser, Gly, Gln.

[00481] In certain embodiments, the peptide inhibitor is cyclized. In particular embodiments, the peptide is cyclized through an intramolecular bond between X4 and X9. In particular embodiments, the intramolecular bond is an amide bond.

[00482] In certain embodiments, the peptide inhibitor is linear or not cyclized.

[00483] In particular embodiments of a peptide inhibitor of Formula IV, one or more, two or more, or all three of XI, X2, and X3 are absent.

[00484] In certain embodiments, X3 is Glu, (D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln. In certain embodiments, X3 is (D)Arg or (D)Phe.

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PCT/US2016/042680 [00485] In particular embodiments of a peptide inhibitor of Formula IV, one or more, two or more, or all three of XI7, XI9 and X20 are absent.

[00486] In particular embodiments of a peptide inhibitor of Formula IV, X4 is Dap, Dab, or (D)Dab, and X9 is Glu, (D)Asp, or Asp. In particular embodiments of a peptide inhibitor of Formula I, X4 is Glu, (D)Asp or Asp, and X9 is Dab, Dap or (D)Dab.

[00487] In particular embodiments of a peptide inhibitor of Formula IV, XI8 is (D)-Fys. In certain embodiments, XI7 is absent and XI8 is (D)-Fys.

[00488] In particular embodiments of a peptide inhibitor of Formula IV, the peptide inhibitor includes one or more, two or more, three or more, or all four of the following features: X5 is Gin; X6 isThr; X7 is Trp; and X8 is Gin.

[00489] In particular embodiments of a peptide inhibitor of Formula IV, the peptide inhibitor includes one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following features: XI0 is Tyr, Phe[4-(2-aminoethoxy)], Phe(4-CONH2) or Phe(4OMe); XI1 is 2-Nal or Trp; X12 is 4-amino-4-carboxy-tetrahydropyran, Ache Acpc, Acbc, Acvc, Aib, a-DiethylGly, α-MeFys, a-MeFys(Ac), α-Me-Leu, a-MeOrn, α-MeSer, a-MeVal, or Arg; XI3 is Glu or Fys(Ac); XI4 is Asn; XI5 is Gly, Asn, or β-Ala; and XI6 is AEA. In particular embodiments of a peptide inhibitor of Formula IV, the peptide inhibitor includes one or more, two or more, three or more, four or more, five or more, six or more, or seven of the following features: XI0 is Tyr; XI1 is Trp; XI2 is Arg; XI3 is Glu; XI4 is Asn; XI5 is Gly; and XI6 is AEA.

[00490] In particular embodiments of a peptide inhibitor of Formula IV, the peptide inhibitor includes one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more ten or more or all of the following features: X5 is Gin; X6 isThr; X7 is Trp; X8 is Gin; XI0 is Tyr; XI1 is Trp; XI2 is Arg; XI3 is Glu or Lys(Ac); XI4 is Asn; XI5 is Gly; and XI6 is AEA. In particular embodiments of a peptide inhibitor of Formula IV, the peptide inhibitor includes one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more ten or more or all of the following

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PCT/US2016/042680 features: X5 is Gin; X6 isThr; X7 is Trp; X8 is Gin; XI0 is Tyr; XI1 is Trp; X12 is Arg; XI3 is Glu; XI4 is Asn; XI5 is Gly; and XI6 is AEA.

[00491] In certain embodiments of a peptide inhibitor of Formula IV, the peptide is cyclized via X4 and X9; X5, X6, X7 and X8 are Gin, Thr, Trp, and Gin, respectively; and XI0, XI1, XI2, X13, X14, X15, and X16 are Tyr, Trp, Arg, Glu, Asn, Gly, and AEA, respectively.

[00492] In certain embodiments, the present invention includes a peptide of 8 to 20 amino acids, optionally cyclized, comprising or consisting of having a core sequence comprising:

Xaa4-Xaa5-Xaa6-Trp-Xaa8-Xaa9-[Phe(4-OMe)]-[ 2-Nal] (Formula IVb) [00493] wherein Xaa4 and Xaa9 are each independently selected from Dap, Dab, Glu, Asp, (D)Asp and(D)-Dab, wherein Xaa4 and Xaa9 are capable of forming an intramolecular bond, e.g., a cyclic amide; and Xaa5, Xaa6 and Xaa8 are any amino acid residue, wherein the peptide inhibits binding of IL-23 to IL-23R. In particular embodiments, the peptide inhibitor is a peptide inhibitor of Formula IV. In particular embodiments, the peptide inhibits the binding of IL-23 to IL-23R.

[00494] In certain embodiments, of a peptide inhibitor of Formula IV, the peptide inhibitor has a structure shown in Table 7 or comprises an amino acid sequence set forth in Table 7.

[00495] Certain illustrative peptide inhibitors of the present invention are also shown in any of Formulas (Va), (Vb), (Vc), (Vd), (Ve), (Vf), (Vg) and (Vh), and in Tables 2-5, which provide the amino acid sequence of selected peptide inhibitors. These peptide inhibitors are acetate salts.

Optional Characteristics of Peptide Inhibitors [00496] Any of the peptide inhibitors of the present invention may be further defined, e.g., as described below. It is understood that each of the further defining features described herein may be applied to any peptide inhibitors where the amino acids designated at particular positions allow the presence of the further defining feature.

[00497] In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor is cyclized.

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PCT/US2016/042680 [00498] In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor or monomer subunit thereof is linear or not cyclized. In certain embodiments where the peptide is linear or not cyclized, X4 and X9 can be any amino acid.

[00499] In certain embodiments, the peptide inhibitor is cyclized, e.g., through X4 and X9.

[00500] In various embodiments, R¹ is a bond, hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl C1-C6 alkyl, or a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing, e.g., acetyl. It is understood that the R¹ may replace or be present in addition to the typical amine group located at the amino terminus of a peptide. It is further understood that R¹ may be absent. In certain embodiments, the peptide inhibitor comprises an Nterminus selected from hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl C1-C6 alkyl, or a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing, e.g., acetyl. In particular embodiments of any of the peptide inhibitors described herein, R¹ or the N-terminal moiety is hydrogen. In certain embodiments, R¹ is a bond, e.g., a covalent bond.

[00501] In certain embodiments of any of the peptide inhibitors having any of the various Formulas set forth herein, R¹ or the N-terminal moiety is selected from methyl, acetyl, formyl, benzoyl, trifluoroacetyl, isovaleryl, isobutyryl, octanyl, and the conjugated amides of lauric acid, hexadecanoic acid, and γ-Glu-hexadecanoic acid. In one embodiment, R¹ or the N-terminal moiety is pGlu. In certain embodiments, R¹ is hydrogen. In particular embodiments, R¹ is acetyl, whereby the peptide inhibitor is acylated at its N-terminus, e.g., to cap or protect an N-terminal amino acid residue, e.g., an N-terminal Pen or Abu residue.

[00502] In certain embodiments of any of the peptide inhibitors described herein, R¹ or the Nterminal moiety is an acid. In certain embodiments, R¹ or the N-terminal moiety is an acid selected from acetic acid, formic acid, benzoic acid, trifluoroacetic acid, isovaleric acid, isobutyric acid, octanoic acid, lauric acid, hexadecanoic acid, 4-Biphenylacetic acid, 4fluorophenylacetic acid, gallic acid, pyroglutamic acid, cyclopentanepropionic acid, glycolic acid, oxalic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, palmitic acid, benzoic acid, 3-(4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, 4-methylbicyclo(2.2.2)-oct-2-ene-l -carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl

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PCT/US2016/042680 sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, an alkylsulfonic acid and an arylsulfonic acid.

[00503] In particular embodiments, R¹ or the N-terminal moiety is an alkylsulfonic acid selected from methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, and 2hydroxyethanesulfonic acid.

[00504] In particular embodiments, R¹ or the N-terminal moiety is an arylsulfonic acid selected from benzenesulfonic acid, 4- chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4toluenesulfonic acid, and camphorsulfonic acid.

[00505] In some embodiments, wherein a peptide of the present invention comprises a conjugation to an acidic compound such as, e.g., isovaleric acid, isobutyric acid, valeric acid, and the like, the presence of such a conjugation is referenced in the acid form. So, for example, but not to be limited in any way, instead of indicating a conjugation of isovaleric acid to a peptide by referencing isovaleroyl (e.g., isovaleroyl-[Pen]-QTWQ[Pen]-[Phe(4-OMe)]-[2-Nal]-[a-MeLys][Lys(Ac)]-NG-NH2, in some embodiments, the present application references such a conjugation as isovaleric acid-[Pen]-QTWQ[Pen]-[Phe(4-OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH₂. Reference to the conjugation in its acid form is intended to encompass the form present in the peptide inhibitor.

[00506]In certain embodiments, the peptide inhibitor comprises a C-terminus (e.g., R² or the Ctermial moiety) selected from a bond, OH or NH2. In certain embodiments, R² is a bond. In various embodiments of any of the peptide inhibitors having any of the various Formulas set forth herein, R or the C-terminal moiety is OH or NH2 It is understood that the R or the Cterminal moiety may replace or be present in addition to the carboxyl group typically located at the carboxy terminus of a peptide. It is further understood that R² may be absent.

[00507] In particular embodiments of any of the peptide inhibitors having any of the various Formulae set forth herein, X comprises or consists of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, 7 to 20 amino acid residues, 8 to 20 amino acid residues, 9 to 20 amino acid residues, 7 to 18

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PCT/US2016/042680 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues.

[00508] In certain embodiments of any of the Formulae set forth herein, X either or both does not comprise or does not consist of an amino acid sequence set forth in US Patent Application Publication No. US2013/0029907. In certain embodiments of any of the Formulae set forth herein, X either or both does not comprise or does not consist of an amino acid sequence set forth in US Patent Application Publication No. US2013/0172272.

[00509] In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or each monomer subunit thereof, comprises or consists of at least 3, at least 4 at least 5, at least 6, or at least 7 amino acid residues carboxy terminal of the X9 amino acid residue. In particular embodiments of any of the peptide inhibitors described herein, the peptide inhibitor comprises 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 3 to 5, 3 to 4, 3, 4, 5, 6, 7, 8, 9, 10, or 11 amino acid residues carboxy terminal of the X9 amino acid residue.

[00510] In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or each monomer subunit thereof, comprises or consists of 4 amino acid residues between X4 and X9. In one embodiment, both X4 and X9 are cysteines.

[00511] In certain embodiments, a peptide inhibitor of any of the Formulae described herein comprises the amino acid residues or moieties indicated as X4-X15. In particular embodiments, the peptide inhibitor does not include XI-X3 or X16-X20. In certain embodiments, the peptide inhibitors include an N-terminal extension of one to three amino acid residues corresponding to any of X1-X3. In particular embodiments, any one or more of XI, X2 and X3, when present, are a D-amino acid. In certain embodiments, the peptide inhibitors include an C-terminal extension of one to five amino acid residues corresponding to any of X16-X20. In particular embodiments, any one or more of XI6, XI7, XI8, XI9 and X20, when present, are a D-amino acid. Illustrative amino acid residues that may be present in the N-terminal and/or C-terminal extensions are shown in Tables 3 and 5. These tables each show a first peptide inhibitor, with derivates thereof comprising N-terminal extensions, C-terminal extensions, and/or conjugated moieties. The present invention includes derivatives of any fo the peptide inhibitors described herein comprising one or more such N-terminal extension, C-terminal extension, and/or

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PCT/US2016/042680 conjugated moiety. In certain embodiments, any of the amino acid residues shown in the extended positions in Tables 3 and 5 may be present in any combination in a peptide inhibitor of the present invention. In particular embodiments, the N-terminal and/or C-terminal extensions are associated with an increased half-life, e.g., upon administration to a subject.

[00512] In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or each monomer subunit thereof, comprises the amino acid sequence motif, W-X-XY-W, e.g., at positions X7-X11. In certain embodiments, the peptide inhibitor, or each monomer subunit thereof, comprises the amino acid sequence motif, C-X-X-W-X-C-Y-W, e.g., at positions X4-X11. In certain embodiments, the peptide inhibitor, or each monomer subunit thereof, comprises the amino acid sequence motif, Pen-X-X-W-X-Pen-Y-W, e.g., at positions X4-X11. In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or both monomer subunit thereof, does not comprise the amino acid sequence motif, W-X-X-Y-W, e.g., at positions X7-X11, where X is any amino acid.

[00513] In certain embodiments of any of the Formula or peptide inhibitors described herein, the peptide inhibitor comprises one or more amino acid residues N-terminal to X4. In particular embodiments, X3 is present. In certain embodiments, X3 is Glu, (D)Glu, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, or (D)Gln. In certain embodiments, X3 is (D)Arg or (D)Phe.

[00514] In particular embodiments of any of the Formula or peptide inhibitors described herein, the peptide inhibitor comprises an amino acid at X2. In particular embodiments, X2 is Glu, (D)Asp, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln, or (D)Asn. In certain embodiments, X2 and X3 are present. In particular embodiments, X2 is Glu, (D)Asp, Arg, (D)Arg, Phe, (D)Phe, 2-Nal, Thr, Leu, (D)Gln, or (D)As, and X3 is (D)Arg.

[00515] In certain embodiments, a peptide inhibitor of the present invention, or one or both monomer subunits thereof, comprises, optionally at its C-terminus, one of the following amino acid sequences:

ENG;

ENN;

[4-amino-4-carboxy-tetrahy dropyran] -ENN;

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PCT/US2016/042680 [Lys(Ac)]-NN;

[a-MeLys]-ENG;

[α-MeLys]- [Lys(Ac)]-NN;

[α-MeLeu]- [Lys(Ac)]-NN [a-MeLeu]-ENG;

[a-MeOrn]-[Lys(Ac)]-NG;

[a-MeLeu]-ENG;

Aib- [Ly s(Ac)] -N G;

Aib- [Ly s(Ac)] -NN;

NG-[AEA]-[(D)-Lys];

[Dapa]-NG-[AEA]-[(D)-Lys];

[Orn] -NG- [ AEA]- [(D)-Ly s];

[a-MeLys]-ENN;

[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN;

[Achc]-[Lys(Ac)]-NN; or [Acpc] - [Lys(Ac)] -NN.

[00516] In particular embodiments, one of these amino acid sequences constitutes the terminal Cterminal amino acids of the peptide. In particular embodiment, these amino acid sequences correspond to XI3-X15 orX12-X15 or X14-X16 or X13-X17.

[00517] In certain embodiments, a peptide inhibitor of the present invention, or one or both monomer subunits thereof, comprises, optionally at its C-terminus, one of the following amino acid sequences:

WQCY-[2-Nal]-[a-MeLys];

WQC- [Phe(4-OMe)] - [2-Nal]- [a-MeLys];

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WQC- [Phe(4-OMe)]-[2-Nal]- [Ai b];

WQ- [Pen] - [Phe(4-OMe)] - [2-Nal]- [a-MeLys];

W-Xaa8-C-Phe[4-(2-aminoethoxy)] -[2-Nal];

W-Xaa8-C-Phe[4-(2-aminoethoxy)] -[1-Nal] ;

W-Xaa8-C-Phe[4-(2-aminoethoxy)]; or [00518]W-Xaa8-C-[Phe(4-OCH₃)]. In particular embodiments, one of these amino acid sequences constitutes the terminal C-terminal amino acids of the peptide. In particular embodiment, these amino acid sequences correspond to X7 to X12 or X7 to XI1 or X7 to XI0.

[00519] In certain embodiments of any of the peptide inhibitors described herein, including both peptide monomer inhibitors and monomer subunits of peptide dimer inhibitors, the peptide monomer inhibitor or monomer subunit is cyclized via a peptide bond between its N-terminal amino acid residue and its C-terminal amino acid residue. In particular embodiments, the peptide inhibitor (or monomer subunit thereof) comprises both an intramolecular bond between X4 and X9 and a peptide bond between its N-terminal amino acid residue and its C-terminal amino acid residue. In certain embodiments, the intramolecular bond is any of those described herein, e.g., a disulfide bond or a thioether bond.

[00520] In certain embodiments, the present invention includes a peptide inhibitor that comprises a core consensus sequence selected from one of the following (shown in N-terminal to Cterminal direction):

Xl-X2-X3-Pen-X5-X6-W-X8-Pen-X10-Xll-X12-X13-X14-X15;

Pen-X5-X6-W-Q-Pen;

Pen-X5-X6-W-X8-Pen;

Pen-X5 -X6-W-X8-Pen- [Phe(4-CONH2)]; and

Pen-X5 -X6-W-X8-Pen- [Phe [4- (2-aminoethoxy)] ],

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PCT/US2016/042680 wherein the Pen residues arejoined by an intramolecular bond, e.g., disulphide bond. XI, X2, X3, X5, X6, X8, ΧΙΟ, XI1, X12, X13, X14, and XI5 may be any amino acid. In some embodiment X5 is Arg, Asn, Gln, Dap, Orn; X6 is Thr or Ser; and X8 is Gln, Val, Phe, Glu, Lys. In particular embodiments, XI, X2, X3, X5, X6, X8, X10, XU, X12, X13, X14, and X15 are defined as described in any of the various Formulas and peptide inhibitors described herein.

[00521] In certain embodiments, the present invention includes a peptide inhibitor that comprises a core consensus sequence selected from one of the following (shown in N-terminal to Cterminal direction):

XI -X2-X3-Abu-X5-X6-W-X8-C-X9-Xl 0-X11 -XI2-X13 -XI4-X15;

Abu-X5-X6-W-Q-C;

Abu-X5-X6-W-X8-C;

Abu-X5-X6-W-X8-C-[Phe(4-CONH2)]; and

Abu-X5-X6-W-X8-C-[Phe[4-(2-aminoethoxy)]], where Abu and C are linked through a intra moleculer thiother bond. XI, X2, X3, X5, X6, X8, X10, XI1, X12, X13, X14, and X15 may be any amino acid. In some embodiment X5 is Arg, Asn, Gln, Dap, Orn; X6 is Thr or Ser; and X8 is Gln, Val, Phe, Glu, Lys. In particular embodiments, XI, X2, X3, X5, X6, X8, X10, XU, X12, X13, X14, and X15 are defined as described in any of the various Formulas and peptide inhibitors described herein.

[00522] In certain embodiments, any of the peptide inhibitors described herein may be further cyclized via a peptide bond between its N-terminal amino acid residue and its C-terminal amino acid residue. In particular embodiments, the peptide inhibitor comprises a peptide bond between X3 or X4 and any one of X9, X10, XU, X12, X13, X14, X15, X16, X17, XI8, X19 or X20. In particular embodiments, peptide inhibitors of the present invention comprise a peptide bond between their N-terminal and C-terminal amino acid residues, and they also comprise an intramolecular bond between X4 and X9. In certain embodiments, the intramolecular bond is a disulfide bond, a thioether bond, a lactam bond or any of the other bonds described herein.

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Peptide Dimers [00523] In certain embodiments, the present invention includes dimers of the monomer peptide inhibitors described herein, including dimers of any of the monomer peptide inhibitors described herein or in the accompanyingtables, figures or sequences listing. These dimers fall within the scope of the general term “peptide inhibitors” as used herein. Illustrative dimers of the present invention are also shown in the accompanying tables, which indicate the dimerized monomer subnits in brackets followed by the linker. Unless otherwise indicated, the subunits are linked via their C-termini. The term “dimer,” as in a peptide dimer, refers to compounds in which two peptide monomer subinits are linked. A peptide dimer inhibitor of the present invention may comprise two identical monomer subunits, resulting in a homodimer, or two non-identical monomer subunits, resulting in a heterodimer. A cysteine dimer comprises two peptide monomer subunits linked through a disulfide bond between a cysteine residue in one monomer subunit and a cysteine residue in the other monomer subunit.

[00524] In some embodiments, the peptide inhibitors of the present invention may be active in a dimer conformation, in particular when free cysteine residues are present in the peptide. In certain embodiments, this occurs either as a synthesized dimer or, in particular, when a free cysteine monomer peptide is present and under oxidizing conditions, dimerizes. In some embodiments, the dimer is a homodimer. In other embodiments, the dimer is a heterodimer.

[00525] In certain embodiments, a peptide dimer inhibitor of the present invention is a peptide dimer comprising two peptide inhibitors of the invention, including but not limited to a homodimer or heterdimer comprising any of the peptide sequences shown herein, e.g., in Tables 3A-3H, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

[00526] Certain amino acid sequences listed in Tables 3A-3H, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 are shown using one letter codes for amino acids. Where only the monomer peptide inhibitor sequences are shown; however it is understood that, in certain embodiments, these monomer peptide inhibitors, i.e., monomer subunits, are dimerized to form peptide dimer inhibitors, in accordance with the present teaching and as shown generally, e.g., in Tables SASH, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

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PCT/US2016/042680 [00527] In certain embodiments, monomer subunits of the present invention may be dimerized by a suitable linking moiety, e.g., a disulphide bridge between two cysteine residues, one in each peptide monomer subunit, or by another suitable linker moiety, including but not limited to those defined herein. Some of the monomer subunits are shown having C- and N-termini that both comprise free amine. Thus, to produce a peptide dimer inhibitor, the monomer subunit may be modified to eliminate either the C- or N-terminal free amine, thereby permitting dimerization at the remaining free amine. Further, in some instances, a terminal end of one or more monomer subunits is acylated with an acylating organic compound selected from the group consisting of: Trifluoropentyl, Acetyl, Octonyl, Butyl, Pentyl, Hexyl, Palmityl, Trifluoromethyl butyric, cyclopentane carboxylic, cyclopropylacetic, 4-fluorobenzoic, 4-fluorophenyl acetic, 3Phenylpropionic, tetrahedro-2H-pyran-4carboxylic, succinic acid, and glutaric acid. In some instances, monomer subunits comprise both a free carboxy terminal and a free amino terminal, whereby a user may selectively modify the subunit to achieve dimerization at a desired terminus. One having skill in the art therefore, will appreciate that the monomer subunits of the instant invention may be selectively modified to achieve a single, specific amine for a desired dimerization.

[00528] It is further understood that the C-terminal residues of the monomer subunits disclosed herein are optionally amides. Further, it is understood that, in certain embodiments, dimerization at the C-terminus is facilitated by using a suitable amino acid with a side chain having amine functionality, as is generally understood in the art. Regarding the N-terminal residues, it is generally understood that dimerization may be achieved through the free amine of the terminal residue, or may be achieved by using a suitable amino acid side chain having a free amine, as is generally understood in the art.

[00529] The linker moieties connecting monomer subunits may include any structure, length, and/or size that is compatible with the teachings herein. In at least one embodiment, a linker moiety is selected from the non-limiting group consisting of cysteine, lysine, DIG, PEG4, PEG4biotin, PEG13, PEG25, PEG1K, PEG2K, PEG3.4K, PEG4K, PEG5K, IDA, ADA, Boc-IDA, Glutaric acid, Isophthalic acid, 1,3-phenylenediacetic acid, 1,4-phenylenediacetic acid, 1,2phenylenediacetic acid, Triazine, Boc-Triazine, IDA-biotin, PEG4-Biotin, AADA, suitable aliphatics, aromatics, heteroaromatics, and polyethylene glycol based linkers having a molecular

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PCT/US2016/042680 weight from approximately 400Da to approximately 40,000Da. Non-limiting examples of suitable linker moieties are provided in Table 2A.

Table 2A. Illustrative Linker Moieties

Abbrivation	Discription	Structure
DIG	DIGlycolic acid,	c o
PEG4	Bifunctional PEG linker with 4 PolyEthylene Glycol units	0 0
PEG13	Bifunctional PEG linker with 13 PolyEthylene Glycol units	C 0
PEG25	Bifunctional PEG linker with 25 PolyEthylene Glycol units	0 0
PEG1K	Bifunctional PEG linker with PolyEthylene Glycol Mol wt of 1 OOODa
PEG2K	Bifunctional PEG linker with PolyEthylene Glycol Mol wt of 2000Da
PEG3.4K	Bifunctional PEG linker with PolyEthylene Glycol Mol wt of 3400Da
PEG5K	Bifunctional PEG linker with PolyEthylene Glycol Mol wt of 5 OOODa
DIG	DIGly colic acid	AA

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β-Ala-IDA	β-Ala-Iminodiacetic acid	O AM Ο=ζ V
Boc-β Ala-IDA	Boc- β -Ala-Iminodiacetic acid	y- > s Λ Q Q
Ac-β -Ala IDA	Ac- β -Ala-Iminodiacetic acid	0 0=^ 0
ΙϋΑ-β-Ala- Palm	Palmityl- β -Ala-Iminodiacetic acid	< O )=0
GTA	Glutaric acid	O O
PMA	Pemilic acid	Π· H r-y

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AZA	Azelaic acid
DDA	Dodecanedioic acid	0 0
IPA	Isopthalic aicd
1,3-PDA	1,3- Phenylenediacetic acid	χθχ
1,4-PDA	1,4- Phenylenediacetic acid	=<ζ~
1,2-PDA	1,2- Phenylenediacetic acid	0 Q 0 0 o
Triazine	Amino propyl Triazine di-acid	Q H—< '— s>°

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Boc- Triazine	Boc-Triazine di-acid	ί X Jh ''To'Sl^ f-' A A o
ADA	Amino diacetic acid (which may also referred to as Iminodiacetic acid)	0 o
AADA	n-Acetyl amino acetic acid (which may also referred to as N-acetyl Iminodiacetic acid)	0 Ύ 0
PEG4B iotin	PEG4-Biotin (Product number 10199, QuantaBioDesign)
IDA-Biotin	N-Biotin- β -Ala-Iminodiacetic acid	O ) OH

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Lys

Lysine

h2n /oh h2n 0

[00530] In some embodiments, a peptide dimer inhibitor is dimerized via a linker moiety. In some embodiments, a peptide dimer inhibitor is dimerized via an intermolecular disulfide bond formed between two cysteine residues, one in each monomer subunit. In some embodiments, a peptide dimer inhibitor is dimerized via both a linker moiety and an intermolecular disulfide bond formed between two cysteine residues. In some embodiments, the intramolecular bond is a thioether, lactam, triazole, selenoether, diselenide or olefin, instead of the disulfide bond.

[00531] An illustrative diageam of one embodiments of a dimer is shown below:

o

Compound D

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PCT/US2016/042680 [00532] One having skill in the art will appreciate that the linker (e.g., C- and N-terminal linker) moieties disclosed herein are non-limiting examples of suitable, and that the present invention may include any suitable linker moiety. Thus, some embodiments of the present invention comprises a homo- or heterodimer peptide inhibitor comprised of two monomer subunits selected from the peptides shown in any of tables herein or comprising or consisting of a sequence presented in any of tables herein, wherein the C- or N-termini of the respective monomer subunits (or internal amino acid residues) are linked by any suitable linker moiety to provide a dimer peptide inhibitor having IL-23R inhibitory activity. In certain embodiments, a linker binds to the N- or C-terminus of one monomer subunit and an internal amino acid residue of the other monomer subunit making up the dimer. In certain embodiments, a linker binds to an internal amino acid residue of one monomer subunit and an internal amino acid residue of the other monomer subunit making up the dimer. In further embodiments, a linker binds to the N-or C-terminus of both subunits.

[00533] In particular embodiments, a peptide inhibitor of the present invention comprise two or more polypeptide sequences of monomer peptide inhibitors described herein.

[00534] In one embodiment, a peptide dimer inhibitor of the present invention comprises two peptide monomer subunits connected via one or more linker moieties, wherein each peptide monomer subunit comprises or consists of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, 7 to 20 amino acid residues, 8 to 20 amino acid residues, 9 to 20 amino acid residues, 7 to 18 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues and comprises the sequence of Formula la, as described herein.

[00535] In particular embodiments, one or both of the monomer subunits comprise the sequence of any one of Formula Formula X, Formula I, II, III, IV or V as described herein.

[00536] In certain embodiments, a peptide dimer inhibitor comprises two peptide monomer subunits connected via one or more linker moieties, wherein each peptide monomer subunit is 820 amino acids in length and comprises a sequence of any one of the formulas describd herein, e.g., Formula X, Formula I, II, III, IV or V. In certain embodiments, a peptide dimer inhibitor

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PCT/US2016/042680 comprises two peptide monomer subunits connected via one or more linker moieties, wherein each peptide monomer subunit is 8-20 amino acids in length and comprises a sequence of any one of Formula X, Formula I, II, III, IV or V.

[00537] In certain embodiments, a peptide dimer inhibitor has the structure of Formula VI:

(Rj-X-R^-L (VI) [00538] or a pharmaceutically acceptable salt or solvate thereof, [00539] wherein each R¹ is independently absent, a bond (e.g., a covalent bond), or RI is selected from hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl C1-C6 alkyl, a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing;

[00540] each R² is independently absent, a bond (e.g., a covalent bond), or selected from OH or NH₂;

[00541] L is a linker moiety; and [00542] each X is an independently selected peptide monomer subunit comprising or consisting of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, 7 to 20 amino acid residues, 8 to 20 amino acid residues, 9 to 20 amino acid residues, 7 to 18 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues amino acids in length, each comprising or consisting of the sequence of Formula la, as described herein. In particular embodiments, each peptide monomer subunit comprises or consists of a sequence of Formula lx, la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, II, Im, In, Io, Ip, Iq, Iq’, Is, It, Ila, lib, lie, lid, Ilia, Illb, IIIc, Hid, Hie, IVa, IVb, or Va-Vh as described herein.

[00543] In certain embodiments, one or both peptide monomer subunit of a peptide dimer inhibitor is cyclized, e.g., via an intramolecular bond between X4 and X9. In certain embodiments wherein both peptide monomer subunits are cyclized, the intramolecular bond may be the same or different between the two peptide monomer subinits. In certain embodiments, one

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PCT/US2016/042680 or both intramolecular bond is a disulfide bond, a thioether bond, a lactam bond, a selenoether, diselenide, or an olefin bond.

[00544] In one embodiment, X4 and X9 of the one or both cyclized peptide monomer subunit is independently selected from Cys, Pen, hCys, D-Pen, D-Cys and D-hCys, and the intramolecular bond is a disulfide bond.

[00545] In one embodiment, X4 and X9 of the one or both cyclized peptide monomer subunit is independently selected from Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu and D-Lys, and the intramolecular bond is a lactam bond.

[00546] In one embodiment, X4 and X9 of the one or both cyclized peptide monomer subunit are each independently selected from β-azido-Ala-OH, propargylglycine, and the peptide dimer inhibitor is cyclized through a triazole ring. In one embodiment, X4 and X9 of the one or both cyclized peptide monomer subunit are each independently selected from 2-allylglycine, 2-(3'butenyl)glycine, 2-(4'-pentenyl)glycine, 2-(5'-hexenyl)glycine, and the peptide dimer inhibitor is cyclized vi a ring closing methasis to give the corresponding olefins / ‘stapled peptides’.

[00547] In one embodiment, X4 of one or both cyclized peptide monomer subunit is 2chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid,

3-choro-propanoic acid, 4-chloro-butyric acid, 3-chloro-isobutyric acid, or hSer(Cl), X9 of one or both cyclized peptide monomer subunit is hSer(Cl), Cys, Pen, hCys, D-Pen, D-Cys or D-hCys, and the intramolecular bond is a thioether bond.

[00548] In one embodiment, X4 of one or both cyclized peptide monomer subunit is 2chloromethylbenzoic acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3chloro-isobutyric acid, hSer(Cl), or Sec, X9 of one or both cyclized peptide monomer subunit is hSer(Cl) or Sec, and the intramolecular bond is a selenoether bond.

[00549] In certain embodiments, one or both intramolecular bond is a diselenide bond.

[00550] In certain embodiments, one or both peptide monomer subunits is linear or not cyclized.

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PCT/US2016/042680 [00551] In particular embodiments, of the peptide dimer inhibitors, each X7 and each XI1 are both W. In certain embodiments, each X7 and each XI1 are both W, each XI0 is Y, and each X4 and X9 are both C. In certain embodiments, each X7 and each XI1 are both W, each XI0 is Y, and each X4 and X9 are amino acids capable of forming an intramolecular bond that is a thioether bond, a lactam bond, a triazole, a selenoether, a diselenide bond, or an olefin bond.

[00552] In certain embodiments of the peptide dimer inhibitors, one or both peptide monomer subunit has a structure shown herein, e.g., in Tables 3A-3I, or comprises an amino acid sequence shown herein, e.g., as set forth in Tables 3A-3I, or wherein the peptide dimer inhibitor has a structure shown herein, e.g., in Table 3F, or comprises an amino acid sequence shown herein, e.g., as set forth in Table 3F.

[00553]In particular embodiments, each R¹ is independently a bond (e.g., a covalent bond), or selected from hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl C1-C6 alkyl, a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing. In particular embodimetns, the N-terminus of each subunit includes a moiety selected from hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl C1-C6 alkyl, a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing.

[00554] In certain embodiments of any of the peptide inhibitors having any of the various Formulae set forth herein, each R¹ (or N-terminal moiety) is selected from methyl, acetyl, formyl, benzoyl, trifluoroacetyl, isovaleryl, isobutyryl, octanyl, and the conjugated amides of lauric acid, hexadecanoic acid, and γ-Glu-hexadecanoic acid.

[00555]In particular embodiments, each R² (or C-terminal moiety) is independently a bond (e.g., a covalent bond), or selected from OH or NH2.

[00556] In particular embodiments of any of the peptide inhibitors having any of the various Formulae set forth herein, each X comprises or consists of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, 7 to 18 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues.

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PCT/US2016/042680 [00557] In particular embodiments, one or both X comprises or consists of the sequence of any one of the formulas described herein. In certain embodiments of any of the peptide inhibitors, including dimers, or Formulae set forth herein, an X does not comprise or consist of an amino acid sequence set forth in US Patent Application Publication No. US2013/0029907. In certain embodiments of any of the peptide inhibitors, including dimers, or formulas set forth herein, an X does not comprise or consist of an amino acid sequence set forth in US Patent Application Publication No. US2013/0172272.

[00558] In particular embodiments of peptide inhibitors of the present invention (both monomers and dimers) comprising Cys at position X4 and Cys at position X9, the Cys at position X4 and and the Cys at position X9 are linked by a disulphide bridge.

[00559] In particular embodiments of peptide inhibitors of the present invention, each X7 and each XI1 are not both W.

[00560] In particular embodiments of peptide inhibitors of the present invention, each X7 and each XI1 are both W.

[00561] In particular embodiments of peptide inhibitors of the present invention, each X7 and each XI1 are both W, XI0 is Y, and X4 and X9 are both C.

[00562] In certain embodiments, at least two cysteine residues of the peptide dimer inhibitor are linked by a disulphide bridge, either intramolecular or intermolecular.

[00563]In particular embodiments of either or both monomer subunit (e.g., Ix, Ia-It where permissible) present in a peptide dimer inhibitor, X4 and X9 are both Cys.

[00564]In particular embodiments of either or both monomer subunit (e.g., Ix, Ia-It where permissible) present in a peptide dimer inhibitor, X7 and XI1 are both W.

[00565]In particular embodiments of either or both monomer subunit (e.g., Ia-It where permissible) present in a peptide dimer inhibitor, X7 and XI1 are both W, XI0 is Y, and X4 and X9 are both Cys.

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PCT/US2016/042680 [00566]In particular embodiments of either or both monomer subunit (e.g., Ia-It where permissible) present in a peptide dimer inhibitor, XI5 is Gly or Ser.

[00567]In particular embodiments of either or both monomer subunit (e.g., Ia-It where permissible) present in a peptide dimer inhibitor, XI6 is AEA or AEP.

[00568]In particular embodiments of either or both monomer subunit (e.g., Ia-It where permissible) present in a peptide dimer inhibitor, XI0 is Tyr or Phe, or an analog of Tyr or Phe.

[00569]In particular embodiments of either or both monomer subunit (e.g., Ia-It where permissible) present in a peptide dimer inhibitor, XI1 is Trp.

[00570] In particular embodiments of any of the peptide dimer inhibitors described herein, either or both R¹ is hydrogen.

[00571] In particular embodiments of peptide dimer inhibitors of the present invention, the linker moiety (L) is any of the linkers described herein or shown in Table 2A or 2B. In certain embodiments, L is a lysine linker, a diethylene glycol linker, an iminodiacetic acid (IDA) linker, a β-Ala-iminodiaceticacid (β-Ala-IDA) linker, or a PEG linker.

[00572] In various embodiments of any of the peptide dimer inhibitors, each of the peptide monomer subunits is attached to a linker moiety via its N-terminus, C-terminus, or an internal amino acid residue.

[00573] In certain embodiments of any of the peptide dimer inhibitors, the N-terminus of each peptide monomer subunit is connected by a linker moiety.

[00574] In certain embodiments of any of the peptide dimer inhibitors, the C-terminus of each peptide monomer subunit is connected by a linker moiety.

[00575] In certain embodiments of any of the peptide dimer inhibitors, each peptide monomer subunit is connected by a linker moiety attached to an internal amino acid.

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PCT/US2016/042680 [00576] In certain embodiements of peptide dimer inhibitors, the linker moiety is a diethylene glycol linker, an iminodiacetic acid (IDA) linker, a β-Ala-iminodiaceticacid (β-Ala-IDA) linker, or a PEG linker.

[00577] In certain embodiments of the peptide dimer inhibitors, one or both peptide monomer subunit has a structure shown in any of the tables in the Examples or comprises an amino acid sequence set forth in any of the tables in the Examples.

[00578] In certain embodiments of any of the peptide inhibitors, including dimers, or Formulae set forth herein, an X does not comprise or consist of an amino acid sequence set forth in US Patent Application Publication No. US2013/0029907. In certain embodiments of any of the peptide inhibitors, including dimers, or Formulas set forth herein, an X does not comprise or consist of an amino acid sequence set forth in US Patent Application Publication No. US2013/0172272.

[00579] In particular embodiments of peptide inhibitors of the present invention, each X7 and each XI1 are both W, XI0 is Y, and X4 and X9 are both Pen.

In certain embodiments, at least two cysteine residues of the peptide dimer inhibitor are linked by a disulphide bridge, either intramolecular or intermolecular.

Peptide Inhibitor Conjugates and Biopolymers [00580] In certain embodiments, peptide inhibitors of the present invention, including both monomers and dimers, comprise one or more conjugated chemical substituents, such as lipophilic substituents and polymeric moieties, which may be referred to herein as half-life extension moieties. Without wishing to be bound by any particular theory, it is believed that the lipophilic substituent binds to albumin in the bloodstream, thereby shielding the peptide inhibitor from enzymatic degradation, and thus enhancing its half-life. In addition, it is believed that polymeric moieties enhance half-life and reduce clearance in the bloodstream.

[00581] In additional embodiments, any of the peptide inhibitors, e.g. petides of Formulas (Va)(Vh), further comprise a linker moiety attached to an amino acid residue present in the inhibitor, e.g., a linker moiety may be bound to a side chain of any amino acid of the peptide inhibitor, to

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PCT/US2016/042680 the N-terminal amino acid of the peptide inhibitor, or to the C-terminal amino acid of the peptide inhibitor.

[00582] In additional embodiments, any of the peptide inhibitors e.g. petides of Formulas (Va)(Vh), further comprise half-life extension moiety attached to an amino acid residue present in the inhibitor, e.g., a half-life extension moiety may be bound to a side chain of any amino acid of the peptide inhibitor, to the N-terminal amino acid of the peptide inhibitor, or to the C-terminal amino acid of the peptide inhibitor.

[00583] In additional embodiments, any of the peptide inhibitors e.g. petides of Formulas (Va)(Vh), further comprise half-life extension moiety attached to a linker moiety that is attached to an amino acid residue present in the inhibitor, e.g., a half-life extension moiety may be bound to a linker moiety that is bound to a side chain of any amino acid of the peptide inhibitor, to the Nterminal amino acid of the peptide inhibitor, or to the C-terminal amino acid of the peptide inhibitor.

[00584] In particular embodiments, an IL23R analogue comprises a half-life extension moiety having the structure shown below, wherein n=0 to 24 or n=14 to 24:

n=0 to 24 x=ch₃, co₂h, nh₂, oh [00585] In certain embodiments, a IL23R analogue of the present invention comprises a half-life extension moiety shown in Table 7.

Table 7. Illustrative Half-Life Extension Moieties

#	Half-Life Extension Moietys
	O
Cl
	Cl2 (Laurie acid)

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PCT/US2016/042680 [00586] In certain embodiments, a half-life extension moiety is bound directly to a peptide inhibitor, while in other embodiments, a half-life extension moiety is bound to the peptide inhibitor via a linker moiety, e.g., any of those depicted in Tables 6 or 8.

[00587] Table 8. Illustrative Linker Moieties_

#	Linker Moiety
LI	O co2h IsoGlu
L2	nh2 JV 1 Dapa
L3	(	H , Ahx
L4	Lipidic based linkers: n=l to 24 O
L5	C	H 5 PEG1
L6	o PEG2

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[00588] In particular embodiments, a peptide inhibitor of the present invention comprises any of the linker moieties shown in Table 8 and any of the half-life extension moieties shown in Table 7, including any of the following combinations shown in Table 9a.

Table 9a. Illustrative Combinations of Linkers and Half-Life Extension Moieties in Peptide Inhibitors

Linker	Half-Life Extension Moiety		Linker	Half-Life Extension Moiety		Linker	Half-Life Extension Moiety
Ll	Cl	Ll	C2	Ll	C3
L2	Cl	L2	C2	L2	C3
L3	Cl	L3	C2	L3	C3
L4	Cl	L4	C2	L4	C3
L5	Cl	L5	C2	L5	C3
L6	Cl	L6	C2	L6	C3
L7	Cl	L7	C2	L7	C3
L8	Cl	L8	C2	L8	C3
L9	Cl	L9	C2	L9	C3
L10	Cl	L10	C2	L10	C3
Lll	Cl	Lll	C2	Lll	C3
L12	Cl	L12	C2	L12	C3
L13	Cl	L13	C2	L13	C3
L14	Cl	L14	C2	L14	C3
L15	Cl	L15	C2	L15	C3
Linker	Half-Life Extension		Linker	Half-Life Extension		Linker	Half-Life Extension

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	Moiety			Moiety			Moiety
LI	C4	LI	C5	LI	C6
L2	C4	L2	C5	L2	C6
L3	C4	L3	C5	L3	C6
L4	C4	L4	C5	L4	C6
L5	C4	L5	C5	L5	C6
L6	C4	L6	C5	L6	C6
L7	C4	L7	C5	L7	C6
L8	C4	L8	C5	L8	C6
L9	C4	L9	C5	L9	C6
L10	C4	L10	C5	L10	C6
Lll	C4	Lll	C5	Lll	C6
L12	C4	L12	C5	L12	C6
L13	C4	L13	C5	L13	C6
L14	C4	L14	C5	L14	C6
LI 5	C4	L15	C5	LI 5	C6

Linker	Half-Life Extension Moiety
LI	C7
L2	C7
L3	C7
L4	C7
L5	C7
L6	C7
L7	C7
L8	C7
L9	C7
L10	C7
Lll	C7
L12	C7
L13	C7
L14	C7
LI 5	C7

Linker	Half-Life Extension Moiety
LI	C8
L2	C8
L3	C8
L4	C8
L5	C8
L6	C8
L7	C8
L8	C8
L9	C8
L10	C8
Lll	C8
L12	C8
L13	C8
L14	C8
L15	C8

Linker	Half-Life Extension Moiety
LI	C9
L2	C9
L3	C9
L4	C9
L5	C9
L6	C9
L7	C9
L8	C9
L9	C9
L10	C9
Lll	C9
L12	C9
L13	C9
L14	C9
LI 5	C9

Linker	Half-Life Extension Moiety
LI	CIO
L2	CIO
L3	CIO
L4	CIO
L5	CIO

Linker	Half-Life Extension Moiety
L6	CIO
L7	CIO
L8	CIO
L9	CIO
L10	CIO

Linker	Half-Life Extension Moiety
Lll	CIO
L12	CIO
L13	CIO
L14	CIO
LI 5	CIO

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PCT/US2016/042680 [00589] In some embodiments there may be multiple linkers present between the peptide the conjugated moiety, e.g., half-life extension moiety, e.g., as depicted in Table 9b.

Table 9b. Illustrative Combinations of Linkers and Half-Life Extension Moieties in Peptide Inhibitors

Linker	Half-Life Extension Moiety
L1-L2	CIO
L2-L5-L3	CIO
L3-L8	CIO
L1-L2-L3	CIO
L5-L3-L3-L3	CIO

Linker	Half-Life Extension Moiety
L1-L2	C8
L2-L5-L3	C8
L3-L8	C8
L1-L2-L3	C8
L5-L3-L3-L3	C8

[00590] Illustrative examples of peptide inhibitors of the present invention, including those having a conjugates linker and/or half-life extension moiety are shown below. All amino acids are L amino acids unless otherwise stated. The present invention also includes salt forms of any of these peptide inhibitors, including, but not limited to, acetate salts thereof.

Example 1: cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahy dropyran] -ENN-NH₂

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HN

Example la: Ac-[(D)-Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino4-carboxy-tetrahydropyran]-ENN-NH2

Example 2: Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahy dropyran] - [Ly s(Ac)] -NN-NH₂

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Half-Life Extension Moiety

Example 3: cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)-(Linker-Half-Life

Moiety)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2

Extension

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Example 3a: Ac-[(D)-Arg]cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)-(Linker-Half-Life Extension Moiety)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2

Example 4: cyclo [ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4-carboxytetrahydropyran]-[Lys(Linker-Half-Life Extension Moiety)]-NN-NH₂

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Ο nh₂

Example 4a: Ac-[(D)-Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino4-carboxy-tetrahydropyran]-[Lys(Linker-Half-Life Extension Moiety)]-NN-NH₂

Example 5: cyclo [ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4-carboxytetrahydropyran]-ENN-[Lys(Linker-Half-Life Extension Moiety)]-NH₂

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I lall'-l.ife Extension Moicly

HN

Example 5a: Ac[(D)-Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino4-carboxy-tetrahydropyran]-ENN-[Lys(Linker-Half-Life Extension Moiety)]-NH2

Example 6: [Half-Life Extension Moiety-Linker]-[cyclo[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2

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NH

Example 6a: [Half-Life Extension Moiety-Linker]-[(D)-Arg]-[cyclo[[Abu]-QTWQC]-[Phe[4 (2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2

o

Example 7: [Half-Life Extension Moiety-Linker]-[Pen]-NTWQ-[Pen]-[Phe[4-(aminoethoxy)] [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2

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Example 8: Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahydropyran]-[Lys(Ac)]-NN-[Lys(Linker-Half-Life Extension Moiety)]-NH₂ f Half-Life Extension Moiety

.....I

-¹Linker

NH

O

Example 9: Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(aminoethoxy)-(Linker-Half-Life Extension

Moiety)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH₂

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H₂N^J

J HN—f Linker —f^Half-1

I / ^Exten r^aX ⁰ I

O

O 'Half-Life ' _L Extension Moiety^

Example 10: Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahydropyran]-[Lys(Linker-Half-Life Extension Moiety )]-NN-NH2.

[00591] In certain embodiments, the half-life of a peptide inhibitor of the invention that includes a conjugated chemical substituent, i.e., a half-life extension moiety, is at least 100%, at least 120%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500% of the half-life of the same peptide inhibitor but without the conjugated chemical substituent. In certain embodiments, the lipophilic substituents and/or polypermic moieties enhance the permeability of the peptide inhibitor through the epithelium and/or its retention in the lamina propria. In certain embodiments, the permeability through the epithelium and/or the retention in the lamina propria of a peptide inhibitor of the invention that includes a conjugated chemical substituent is at 100%, at least 120%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500% of the half-life of the same peptide inhibitor but without the conjugated chemical substituent.

[00592]In one embodiment, a side chain of one or more amino acid residues (e.g., Lys residues) in a peptide inhibitor of the invention is conjugated (e.g., covalently attached) to a lipophilic substituent. The lipophilic substituent may be covalently bonded to an atom in the amino acid side chain, or alternatively may be conjugated to the amino acid side chain via one or more spacers. The spacer, when present, may provide spacing between the peptide analogue and the lipophilic substituent. In particular embodiments, the peptide inhibitor comprises any of the conjugated moieties shown in Tables 2-5.

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PCT/US2016/042680 [00593] In certain embodiments, the lipophilic substituent may comprise a hydrocarbon chain having from 4 to 30 C atoms, for example at least 8 or 12 C atoms, and preferably 24 C atoms or fewer, or 20 C atoms or fewer. The hydrocarbon chain may be linear or branched and may be saturated or unsaturated. In certain embodiments, the hydrocarbon chain is substituted with a moiety which forms part of the attachment to the amino acid side chain or the spacer, for example an acyl group, a sulfonyl group, an N atom, an O atom or an S atom. In some embodiments, the hydrocarbon chain is substituted with an acyl group, and accordingly the hydrocarbon chain may form part of an alkanoyl group, for example palmitoyl, caproyl, lauroyl, myristoyl or stearoyl.

[00594] A lipophilic substituent may be conjugated to any amino acid side chain in a peptide inhibitor of the invention. In certain embodiment, the amino acid side chain includes a carboxy, hydroxyl, thiol, amide or amine group, for forming an ester, a sulphonyl ester, a thioester, an amide or a sulphonamide with the spacer or lipophilic substituent. For example, the lipophilic substituent may be conjugated to Asn, Asp, Glu, Gln, His, Lys, Arg, Ser, Thr, Tyr, Trp, Cys or Dbu, Dpr or Orn. In certain embodiments, the lipophilic substituent is conjugated to Lys. An amino acid shown as Lys in any of the formula provided herein may be replaced by, e.g., Dbu, Dpr or Orn where a lipophilic substituent is added.

[00595] In certain embodiments, the peptide inhibitors of the present invention may be modified, e.g., to enhance stability, increase permeability, or enhance drug like characteristics, through conjugation of a chemical moiety to one or more amino acid side chain within the peptide. For example, the N(epsilon) of lysine N(epsilon), the β-carboxyl of aspartic, or the γ-carboxyl of glutamic acid may be appropriately functionalized. Thus, to produce the modified peptide, an amino acid within the peptide may be appropriately modified. Further, in some instances, the side chain is acylated with an acylating organic compound selected from the group consisting of: Trifluoropentyl, Acetyl, Octonyl, Butyl, Pentyl, Hexyl, Palmityl, Trifluoromethyl butyric, cyclopentane carboxylic, cyclopropylacetic, 4-fluorobenzoic, 4-fluorophenyl acetic, 3Phenylpropionic, tetrahedro-2H-pyran-4carboxylic, succinic acid glutaric acid or bile acids. One having skill is the art will appreciate that a series of conjugates can be linked, e.g., for example PEG4, isoglu and combinations thereof. One having skill is the art will appreciate that an amino

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Table IB. Examples of modified Lysine, Asp and Asn within the peptide

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[00596] In further embodiments of the present invention, alternatively or additionally, a sidechain of one or more amino acid residues in a peptide inhibitor of the invention is conjugated to a polymeric moiety, for example, in order to increase solubility and/or half-life in vivo (e.g. in

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[00597] As used herein, “Polyethylene glycol” or “PEG” is a poly ether compound of general formula H-(O-CH2-CH2)n-OH. PEGs are also known as polyethylene oxides (PEOs) or polyoxyethylenes (POEs), depending on their molecular weight PEO, PEE, or POG, as used herein, refers to an oligomer or polymer of ethylene oxide. The three names are chemically synonymous, but PEG has tended to refer to oligomers and polymers with a molecular mass below 20,000 Da, PEO to polymers with a molecular mass above 20,000 Da, and POE to a polymer of any molecular mass. PEG and PEO are liquids or low-melting solids, depending on their molecular weights. Throughout this disclosure, the 3 names are used indistinguishably. PEGs are prepared by polymerization of ethylene oxide and are commercially available over a wide range of molecular weights from 300 Da to 10,000,000 Da. While PEG and PEO with different molecular weights find use in different applications, and have different physical properties (e.g. viscosity) due to chain length effects, their chemical properties are nearly identical. The polymeric moiety is preferably water-soluble (amphiphilic or hydrophilic), nontoxic, and pharmaceutically inert. Suitable polymeric moieties include polyethylene glycols (PEG), homo- or co-polymers of PEG, a monomethyl-substituted polymer of PEG (mPEG), or polyoxyethylene glycerol (POG). See, for example, Int. J. Hematology 68:1 (1998); Bioconjugate Chem. 6:150 (1995); and Crit. Rev. Therap. Drug Carrier Sys. 9:249 (1992). Also encompassed are PEGs that are prepared for purpose of half life extension, for example, monoactivated, alkoxy-terminated polyalkylene oxides (POA’s) such as mono-methoxy-terminated polyethyelene glycols (mPEG’s); bis activated polyethylene oxides (glycols) or other PEG derivatives are also contemplated. Suitable polymers will vary substantially by weights ranging from about 200 Da to about 40,000 Da or from about 200 Da to about 60,000 Da are usually selected for the purposes of the present invention. In certain embodiments, PEGs having molecular weights from 200 to 2,000 or from 200 to 500 are used. Different forms of PEG may also be used, depending on the initiator used for the polymerization process - a common common initiator is a monofunctional methyl ether PEG, or methoxypoly(ethylene glycol), abbreviated mPEG.

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PCT/US2016/042680 [00598] Lower-molecular-weight PEGs are also available as pure oligomers, referred to as monodisperse, uniform, or discrete. These are used in certain embodiments of the present invention.

[00599] PEGs are also available with different geometries: branched PEGs have three to ten PEG chains emanating from a central core group; star PEGs have 10 to 100 PEG chains emanating from a central core group; and comb PEGs have multiple PEG chains normally grafted onto a polymer backbone. PEGs can also be linear. The numbers that are often included in the names of PEGs indicate their average molecular weights (e.g. a PEG with n = 9 would have an average molecular weight of approximately 400 daltons, and would be labeled PEG 400.

[00600] As used herein, “PEGylation” is the act of covalently coupling a PEG structure to the peptide inhibitor of the invention, which is then referred to as a “PEGylated peptide inhibitor”. In certain embodiments, the PEG of the PEGylated side chain is a PEG with a molecular weight from about 200 to about 40,000. In some embodiments, a spacer of a peptide of formula I, formula I’, or formula I” is PEGylated. In certain embodiments, the PEG of a PEGylated spacer is PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, or PEG11. In certain embodiments, the PEG of a PEGylated spacer is PEG3 or PEG8.

[00601] Other suitable polymeric moieties include poly-amino acids such as poly-lysine, polyaspartic acid and poly-glutamic acid (see for example Gombotz, et al. (1995), Bioconjugate Chem., vol. 6: 332-351; Hudecz, et al. (1992), Bioconjugate Chem., vol. 3, 49-57 and Tsukada, et al. (1984), J. Natl. Cancer Inst., vol. 73, : 721-729. The polymeric moiety may be straightchain or branched. In some embodiments, it has a molecular weight of 500-40,000 Da, for example 500-10,000 Da, 1000-5000 Da, 10,000-20,000 Da, or 20,000-40,000 Da.

[00602] In some embodiments, a peptide inhibitor of the invention may comprise two or more such polymeric moieties, in which case the total molecular weight of all such moieties will generally fall within the ranges provided above.

[00603] In some embodiments, the polymeric moiety is coupled (by covalent linkage) to an amino, carboxyl or thiol group of an amino acid side chain. Certain examples are the thiol group

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[00604] The skilled worker will be well aware of suitable techniques which can be used to perform the coupling reaction. For example, a PEG moiety bearing a methoxy group can be coupled to a Cys thiol group by a maleimido linkage using reagents commercially available from Nektar Therapeutics AL. See also WO 2008/101017, and the references cited above, for details of suitable chemistry. A maleimide-functionalised PEG may also be conjugated to the side-chain sulfhydryl group of a Cys residue.

[00605] As used herein, disulfide bond oxidation can occur within a single step or is a two step process. As used herein, for a single oxidation step, the trityl protecting group is often employed during assembly, allowing deprotection during cleavage, followed by solution oxidation. When a second disulfide bond is required, one has the option of native or selective oxidation. For selective oxidation requiring orthogonal protecting groups, Acm and Trityl is used as the protecting groups for cysteine. Cleavage results in the removal of one protecting pair of cysteine allowing oxidation of this pair. The second oxidative deprotection step of the cysteine protected Acm group is then performed. For native oxidation, the trityl protecting group is used for all cysteines, allowing for natural folding of the peptide. A skilled worker will be well aware of suitable techniques which can be used to perform the oxidation step.

[00606] Several chemical moieties, including poly(ethylene)glycol, react with functional groups present in the twenty naturally occurring amino acids, such as, for example, the epsilon amino group in lysine amino acid residues, the thiol present in cysteine amino acid residues, or other nucleophilic amino acid side chains. When multiple naturally occurring amino acids react in a peptide inhibitor, these non-specific chemical reactions result in a final peptide inhibitor that contains many isomers of peptides conjugated to one or more poly(ethylene)glycol strands at different locations within the peptide inhibitor.

[00607] One advantage of certain embodiments of the present invention includes the ability to add one or more chemical moiety (such as PEG) by incorporating one or more non-natural amino acid(s) that possess unique functional groups that react with an activated PEG by way of chemistry that is unreactive with the naturally occurring amino acids present in the peptide

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PCT/US2016/042680 inhibitor. For example, azide and alkyne groups are unreactive with all naturally occurring functional groups in a protein. Thus, a non-natural amino acid may be incorporated in one or more specific sites in a peptide inhibitor where PEG or another modification is desired without the undesirable non-specific reactions. In certain embodiments, the particular chemistry involved in the reaction results in a stable, covalent link between the PEG strand and the peptide inhibitor. In addition, such reactions may be performed in mild aqueous conditions that are not damaging to most peptides. In certain embodiments, the non-natural amino acid residue is AHA.

[00608] Chemical moieties attached to natural amino acids are limited in number and scope. By contrast, chemical moieties attached to non-natural amino acids can utilize a significantly greater spectrum of useful chemistries by which to attach the chemical moiety to the target molecule. Essentially any target molecule, including any protein (or portion thereof) that includes a nonnatural amino acid, e.g., a non-natural amino acid containing a reactive site or side chain where a chemical moiety may attach, such as an aldehyde- or keto-derivatized amino acid, can serve as a substrate for attaching a chemical moiety.

[00609]Numerous chemical moieties may be joined or linked to a particular molecule through various known methods in the art. A variety of such methods are described in U.S. Patent No. 8,568,706. As an illustrative example, azide moieties may be useful in conjugating chemical moieties such as PEG or others described herein. The azide moiety serves as a reactive functional group, and is absent in most naturally occurring compounds (thus it is unreactive with the native amino acids of naturally occurring compounds). Azides also undergo a selective ligation with a limited number of reaction partners, and azides are small and can be introduced to biological samples without altering the molecular size of significantly. One reaction that allows incorporation or introduction of azides to molecules is the copper-mediated Huisgen [3+2] cycloaddition of an azide. This reaction can be used for the selective PEGylation of peptide inhibitors. (Tornoe et al., J. Org. Chem. 67: 3057, 2002; Rostovtsev et al., Angew. Chem., Int. Ed. 41: 596, 2002; and Wang et al., J. Am. Chem. Soc. 125: 3192, 2003, Speers et al., J. Am. Chem. Soc., 2003, 125, 4686).

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Illustrative Peptide Inhibitors and Peptide Dimer Inhibitors, and Methods of Making the Same [00610] The present invention thus provides various peptide inhibitors which bind or associate with IL-23, to disrupt or block binding between IL-23 and IL-23R.

[00611] Illustrative peptide inhibitors and peptide dimer inhibitors of the present invention are shown in Tables 3A-3H, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 provides the amino acid sequence of selected monomer peptide inhibitors and peptide dimer inhibitors, and indicates the linker moiety present in the peptide dimer inhibitors. According to the protocols discussed herein, a number of the peptide inhibitors and peptide dimer inhibitors shown in the accompanying tables were synthesized and cyclyzed. Tables E3A-E3H, E4A, E4B, E5A-E5C, E6, E7, E8, E9, E10, Ell, E12, E13, E14 or E15 provide the IC50 values for selected monomer peptide inhibitors and peptide dimer inhibitors in inhibiting IL-23 binding to the IL-23R, or in inhibiting IL-23 signaling as determined by measuring changes in phospho-STAT3 levels, as described in the accompanying Examples. Illustrative peptide inhibitors of the present invention are shown in Formulas (V), and in Tables 2-5, which provide the amino acid sequence of selected peptide inhibitors. These peptide inhibitors are acetate salts.

[00612] The peptide inhibitors of the present invention may be synthesized by many techniques that are known to those skilled in the art. In certain embodiments, monomer subunits are synthesized, purified, and dimerized using the techniques described in the accompanying Examples. In certain embodiments, the present invention provides a method of producing a peptide inhibitor (or monomer subunit thereof) of the present invention, comprising chemically synthesizing a peptide comprising, consisting of, or consisting essentially of a peptide having an amino acid sequence described herein, including but not limited to any of the amino acid sequences set forth in any of Formulas I, II, III, IV, V or VI or tables herein. In other embodiments, the peptide is recombinantly synthesized, instead of being chemically synthesized. In certain embodiments, the peptide inhibitor is a dimer, and the method comprises synthezing both monomer subunits of the peptide dimer inhibitor and then dimerizing the two monomer subunits to produce the peptide dimer inhibitor. In various embodiments, dimerization is accomplished via any of the various methods described herein. In particular embodiments, methods of producing a peptide inhibitor (or monomer subunit thereof) further comprise cyclizing the peptide inhibitor (or monomer subunit thereof) after its synthesis. In particular

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PCT/US2016/042680 embodiments, cyclization is accomplished via any of the various methods described herein. In certain embodiments, the present invention provides a method of producing a peptide inhibitor (or monomer subunit thereof) of the present invention, comprising introducing an intramolecular bond, e.g., a disulfide, an amide, or a thioether bond between two amino acids residues within a peptide comprising, consisting of, or consisting essentially of a peptide having an amino acid sequence described herein, including but not limited to any of the amino acid sequences set forth in any of Formulas I, II, III, IV, V or VI, or the accompanying Examples, Tables, or Sequence Listing.

[00613] In related embodiments, the present invention includes polynucleotides that encode a polypeptide having a sequence set forth in any one of Formulas I, II, III, IV, V or VI, or the accompanying Examples, Tables, or Sequence Listing.

[00614]In addition, the present invention includes vectors, e.g., expression vectors, comprising a polynucleotide of the present invention.

Methods of Treatment [00615] In certain embodiments, the present invention includes methods of inhibiting IL-23 binding to an IL-23R on a cell, comprising contacting the IL-23 with a peptide inhibitor of the present invention. In certain embodiments, the cell is a mammalian cell. In particular embodiments, the method is performed in vitro or in vivo. Inhibition of binding may be determined by a variety of routine experimental methods and assays known in the art.

[00616] In certain embodiments, the present invention includes methods of inhibiting IL-23 signaling by a cell, comprising contacting the IL-23 with a peptide inhibitor of the present invention. In certain embodiments, the cell is a mammalian cell. In particular embodiments, the method is performed in vitro or in vivo. In particular embodiments, the inhibition of IL-23 signalling may be determined by measuring changes in phospho-STAT3 levels in the cell.

[00617] In some embodiments, the present invention provides methods for treating a subject afflicted with a condition or indication associated with IL-21 or IL-23R (e.g., activation of the IL-23/IL-23R signaling pathway), wherein the method comprises administering to the subject a peptide inhibitor of the present invention. In one embodiment, a method is provided for treating

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PCT/US2016/042680 a subject afflicted with a condition or indication characterized by inappropriate, deregulated, or increased IL-23 or IL-23R activity or signaling, comprising administering to the individual a peptide inhibitor of the present invention in an amount sufficient to inhibit (partially or fully) binding of IL-23 to IL-23R in the subject. In particular embodiments, the inhibition of IL-23 binding to IL-23R occurs in particular organs or tissues of the subject, e.g., the stomach, small intestine, large intestine/colon, intestinal mucosa, lamina propria, Peyer’s Patches, mesenteric lymph nodes, or lymphatic ducts.

[00618] In some embodiments, methods of the present invention comprise providing a peptide inhibitor of the present invention to a subject in need thereof. In particular embodiments, the subject in need thereof has been diagnosed with or has been determined to be at risk of developing a disease or disorder associated with IL-23/IL-23R. In particular embodiments, the subject is a mammal.

[00619] In certain embodiments, the disease or disorder is autoimmune inflammation and related diseases and disorders, such as multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel diseases (IBDs), juvenile IBD, adolescent IBD, Crohn’s disease, sarcoidosis, Systemic Lupus Erythematosus, ankylosing spondylitis (axial spondyloarthritis), psoriatic arthritis, or psoriasis. In particular embodiments, the disease or disorder is psoriasis (e.g., plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, Palmo-Plantar Pustulosis, psoriasis vulgaris, or erythrodermic psoriasis), atopic dermatitis, acne ectopica, ulcerative colitis, Crohn’s disease, Celiac disease (nontropical Sprue), enteropathy associated with seronegative arthropathies, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis/esophagitis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, chronic granulomatous disease, glycogen storage disease type lb, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, WiskottAldrich Syndrome, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral-associated enteropathy, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, uveitis, or graft versus host disease.

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PCT/US2016/042680 [00620] In certain related embodiments, the present invention provides a method of selectively inhibiting IL-23 or IL-23R signaling (or the binding of IL-23 to IL-23R) in a subject in need thereof, comprising providing to the subject a peptide inhibitor of the present invention. In particular embodiments, the present invention includes a method of selectively inhibiting IL-23 or IL-23R signaling (or the binding of IL-23 to IL-23R) in the GI tract of a subject in need thereof, comprising providing to the subject a peptide inhibitor of the present invention by oral administration. In particular embodiments, exposure of the administered peptide inhibitor in GI tissues (e.g., small intestine or colon) is at least 10-fold, at least 20-fold, at least 50-fold, or at least 100-fold greater than the exposure in the blood. In particular embodiments, the present invention includes a method of selectively inhibiting IL23 or IL23R signaling (or the binding of IL23 to IL23R) in the GI tract of a subject in need thereof, comprising providing to the subject a peptide inhibitor, wherein the peptide inhibitor does not block the interaction between IL-6 and IL-6R or antagonize the IL-12 signaling pathway. In a further related embodiment, the present invention includes a method of inhibiting GI inflammation and/or neutrophil infiltration to the GI, comprising providing to a subject in need thereof a peptide inhibitor of the present invention.In some embodiments, methods of the present invention comprise providing a peptide inhibitor of the present invention (i.e., a first therapeutic agent) to a subject in need thereof in combination with a second therapeutic agent. In certain embodiments, the second therapeutic agent is provided to the subject before and/or simultaneously with and/or after the peptide inhibitor is administered to the subject. In particular embodiments, the second therapeutic agent is an anti-inflammatory agent. In certain embodiments, the second therapeutic agent is a nonsteroidal anti-inflammatory drug, steroid, or immune modulating agent. In another embodiment, the method comprises administering to the subject a third therapeutic agent. In certain embodiments, the second therapeutic agent is an antibody that binds IL-23 or IL-23R.

[00621] In particular embodiments, the peptide inhibitor, or the pharmaceutical composition comprising a peptide inhibitor, is suspended in a sustained-release matrix. A sustained-release matrix, as used herein, is a matrix made of materials, usually polymers, which are degradable by enzymatic or acid-base hydrolysis or by dissolution. Once inserted into the body, the matrix is acted upon by enzymes and body fluids. A sustained-release matrix desirably is chosen from biocompatible materials such as liposomes, polylactides (polylactic acid), polyglycolide (polymer of glycolic acid), polylactide co-glycolide (copolymers of lactic acid and glycolic acid)

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PCT/US2016/042680 polyanhydrides, poly(ortho)esters, polypeptides, hyaluronic acid, collagen, chondroitin sulfate, carboxylic acids, fatty acids, phospholipids, polysaccharides, nucleic acids, polyamino acids, amino acids such as phenylalanine, tyrosine, isoleucine, polynucleotides, polyvinyl propylene, polyvinylpyrrolidone and silicone. One embodiment of a biodegradable matrix is a matrix of one of either polylactide, polyglycolide, or polylactide co-glycolide (co-polymers of lactic acid and glycolic acid).

[00622] In certain embodiments, the present invention includes pharmacetical compositions comprising one or more peptide inhibitors of the present invention and a pharmaceutically acceptable carrier, diluent or excipient. A pharmaceutically acceptable carrier, diluent or excipient refers to a non-toxic solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like.

[00623] In certain embodiments, the compositions are administered orally, parenterally, intracisternally, intravaginally, intraperitoneally, intrarectally, topically (as by powders, ointments, drops, suppository, or transdermal patch), by inhalation (such as intranasal spray), ocularly (such as intraocularly) or buccally. The term “parenteral” as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous, intradermal and intraarticular injection and infusion. Accordingly, in certain embodiments, the compositions are formulated for delivery by any of these routes of administration.

[00624]In certain embodiments, pharmaceutical compositions for parenteral injection comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders, for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), carboxymethylcellulose and suitable mixtures thereof, β-cyclodextrin, vegetable oils (such as olive oil), and injectable organic esters such as ethyl oleate. Proper fluidity may be

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PCT/US2016/042680 maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. Thes compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents, and dispersing agents. Prolonged absorption of an injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption, such as aluminum monostearate and gelatin.

[00625] Injectable depot forms include those made by forming microencapsule matrices of the peptide inhibitor in one or more biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters), poly(anhydrides), and (poly)glycols, such as PEG. Depending upon the ratio of peptide to polymer and the nature of the particular polymer employed, the rate of release of the peptide inhibitor can be controlled. Depot injectable formulations are also prepared by entrapping the peptide inhibitor in liposomes or microemulsions compatible with body tissues.

[00626] The injectable formulations may be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use.

[00627] Topical administration includes administration to the skin or mucosa, including surfaces of the lung and eye. Compositions for topical lung administration, including those for inhalation and intranasal, may involve solutions and suspensions in aqueous and non-aqueous formulations and can be prepared as a dry powder which may be pressurized or non-pressurized. In nonpressurized powder compositions, the active ingredientmay be finely divided form may be used in admixture with a larger-sized pharmaceutically acceptable inert carrier comprising particles having a size, for example, of up to 100 micrometers in diameter. Suitable inert carriers include sugars such as lactose.

[00628] Alternatively, the composition may be pressurized and contain a compressed gas, such as nitrogen or a liquefied gas propellant. The liquefied propellant medium and indeed the total composition may bey such that the active ingredient does not dissolve therein to any substantial extent. The pressurized composition may also contain a surface active agent, such as a liquid or

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PCT/US2016/042680 solid non-ionic surface active agent or may be a solid anionic surface active agent. It is preferred to use the solid anionic surface active agent in the form of a sodium salt.

[00629] A further form of topical administration is to the eye. A peptide inhibitor of the invention may be delivered in a pharmaceutically acceptable ophthalmic vehicle, such that the peptide inhibitor is maintained in contact with the ocular surface for a sufficient time period to allow the peptide inhibitor to penetrate the corneal and internal regions of the eye, as for example the anterior chamber, posterior chamber, vitreous body, aqueous humor, vitreous humor, cornea, iris/ciliary, lens, choroid/retina and sclera. The pharmaceutically acceptable ophthalmic vehicle may, for example, be an ointment, vegetable oil or an encapsulating material. Alternatively, the peptide inhibitors of the invention may be injected directly into the vitreous and aqueous humour.

[00630] Compositions for rectal or vaginal administration include suppositories which may be prepared by mixing the peptide inhibitorss of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax, which are solid at room temperature but liquid at body temperature and, therefore, melt in the rectum or vaginal cavity and release the active compound.

[00631] Peptide inhibitors of the present invention may also be administered in liposomes or other lipid-based carriers. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a peptide inhibitor of the present invention, stabilizers, preservatives, excipients, and the like. In certain embodiments, the lipids comprise phospholipids, including the phosphatidyl cholines (lecithins) and serines, both natural and synthetic. Methods to form liposomes are known in the art.

[00632] Pharmaceutical compositions to be used in the invention suitable for parenteral administration may comprise sterile aqueous solutions and/or suspensions of the peptide inhibitos made isotonic with the blood of the recipient, generally using sodium chloride, glycerin, glucose, mannitol, sorbitol, and the like.

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PCT/US2016/042680 [00633] In some aspects, the invention provides a pharmaceutical composition for oral delivery. Compositions and peptide inhibitors of the instant invention may be prepared for oral administration according to any of the methods, techniques, and/or delivery vehicles described herein. Further, one having skill in the art will appreciate that the peptide inhibitors of the instant invention may be modified or integrated into a system or delivery vehicle that is not disclosed herein, yet is well known in the art and compatible for use in oral delivery of peptides.

[00634] In certain embodiments, formulations for oral administration may comprise adjuvants (e.g. resorcinols and/or nonionic surfactants such as polyoxyethylene oleyl ether and nhexadecylpolyethylene ether) to artificially increase the permeability of the intestinal walls, and/or enzymatic inhibitors (e.g. pancreatic trypsin inhibitors, diisopropylfluorophosphate (DFF) or trasylol) to inhibit enzymatic degradation. In certain embodiments, the peptide inhibitor of a solid-type dosage form for oral administration can be mixed with at least one additive, such as sucrose, lactose, cellulose, mannitol, trehalose, raffinose, maltitol, dextran, starches, agar, alginates, chitins, chitosans, pectins, gum tragacanth, gum arabic, gelatin, collagen, casein, albumin, synthetic or semisynthetic polymer, or glyceride. These dosage forms can also contain other type(s) of additives, e.g., inactive diluting agent, lubricant such as magnesium stearate, paraben, preserving agent such as sorbic acid, ascorbic acid, alpha-tocopherol, antioxidants such as cysteine, disintegrators, binders, thickeners, buffering agents, pH adjusting agents, sweetening agents, flavoring agents or perfuming agents.

[00635] In particular embodiments, oral dosage forms or unit doses compatible for use with the peptide inhibitors of the present invention may include a mixture of peptide inhibitor and nondrug components or excipients, as well as other non-reusable materials that may be considered either as an ingredient or packaging. Oral compositions may include at least one of a liquid, a solid, and a semi-solid dosage forms. In some embodiments, an oral dosage form is provided comprising an effective amount of peptide inhibitor, wherein the dosage form comprises at least one of a pill, a tablet, a capsule, a gel, a paste, a drink, a syrup, ointment, and suppository. In some instances, an oral dosage form is provided that is designed and configured to achieve delayed release of the peptide inhibitor in the subject’s small intestine and/or colon.

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PCT/US2016/042680 [00636] In one embodiment, an oral pharmaceutical composition comprising a peptide inhibitor of the present invention comprises an enteric coating that is designed to delay release of the peptide inhibitor in the small intestine. In at least some embodiments, a pharmaceutical composition is provided which comprises a peptide inhibitor of the present invention and a protease inhibitor, such as aprotinin, in a delayed release pharmaceutical formulation. In some instances, pharmaceutical compositions of the instant invention comprise an enteric coat that is soluble in gastric juice at a pH of about 5.0 or higher. In at least one embodiment, a pharmaceutical composition is provided comprising an enteric coating comprising a polymer having dissociable carboxylic groups, such as derivatives of cellulose, including hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate and cellulose acetate trimellitate and similar derivatives of cellulose and other carbohydrate polymers.

[00637] In one embodiment, a pharmaceutical composition comprising a peptide inhibitor of the present invention is provided in an enteric coating, the enteric coating being designed to protect and release the pharmaceutical composition in a controlled manner within the subject’s lower gastrointestinal system, and to avoid systemic side effects. In addition to enteric coatings, the peptide inhibitors of the instant invention may be encapsulated, coated, engaged or otherwise associated within any compatible oral drug delivery system or component. For example, in some embodiments a peptide inhibitor of the present invention is provided in a lipid carrier system comprising at least one of polymeric hydrogels, nanoparticles, microspheres, micelles, and other lipid systems.

[00638] To overcome peptide degradation in the small intestine, some embodiments of the present invention comprise a hydrogel polymer carrier system in which a peptide inhibitor of the present invention is contained, whereby the hydrogel polymer protects the peptide inhibitor from proteolysis in the small intestine and/or colon. The peptide inhibitors of the present invention may further be formulated for compatible use with a carrier system that is designed to increase the dissolution kinetics and enhance intestinal absorption of the peptide. These methods include the use of liposomes, micelles and nanoparticles to increase GI tract permeation of peptides.

[00639] Various bioresponsive systems may also be combined with one or more peptide inhibitor of the present invention to provide a pharmaceutical agent for oral delivery. In some

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PCT/US2016/042680 embodiments, a peptide inhibitor of the instant invention is used in combination with a bioresponsive system, such as hydrogels and mucoadhesive polymers with hydrogen bonding groups (e.g., PEG, poly(methacrylic) acid [PMAA], cellulose, Eudragit®, chitosan and alginate) to provide a therapeutic agent for oral administration. Other embodiments include a method for optimizing or prolonging drug residence time for a peptide inhibitor disclosed herein, wherein the surface of the peptide inhibitor surface is modified to comprise mucoadhesive properties through hydrogen bonds, polymers with linked mucins or/and hydrophobic interactions. These modified peptide molecules may demonstrate increase drug residence time within the subject, in accordance with a desired feature of the invention. Moreover, targeted mucoadhesive systems may specifically bind to receptors at the enterocytes and M-cell surfaces, thereby further increasing the uptake of particles containing the peptide inhibitor.

[00640] Other embodiments comprise a method for oral delivery of a peptide inhibitor of the present invention, wherein the peptide inhibitor is provided to a subject in combination with permeation enhancers that promote the transport of the peptides across the intestinal mucosa by increasing paracellular or transcellular permeation. Various permeation enhancers and methods for the oral delivery of therapeutic agents is described in Brayden, D.J., Mrsny, R.J., 2011. Oral peptide delivery: prioritizing the leading technologies. Ther. Delivery 2 (12), 1567-1573.

[00641] In certain embodiments, pharmaceutical compositions and formulations of the present invention comprises a peptide inhibitor of the present invention and one or more permeation enhancer. Examples of absorption enhancers may include Bile salts, fatty acids, surfactants (anionic, cationic, and nonanionic) chelators, Zonular OT, esters, cyclodextrin, dextran sulfate, azone, crown ethers, EDTA, sucrose esters, and phosphotidyl choline, for example. Although absorption enhancers are not typically carriers by themselves, they are also widely associated with other carriers to improve oral bioavailability by transporting of peptides and proteins across the intestinal mucosa. Such substances can be added to the formulation as excipients or incorporated to form non specific interactions with the intended peptide inhibitor.

[00642] Dietary components and/or other naturally occurring substances affirmed as enhancing tight junction permeation and as Generally Recognized As Safe (GRAS) include, e.g., asglycerides, acylcarnitines, bile salts, and medium chain fatty acids. Sodium salts of medium

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PCT/US2016/042680 chain fatty acids (MCFAS) were also suggested to be permeation enhancers. The most extensively studied MCFAS is sodium eaprate, a salt of capric acid, which comprises 2-3% of the fatty’ acids in the milk fat fraction. To date, sodium eaprate is mainly used as an excipient in a suppository formulation (Doktacillin™) for improving rectal ampicillin absorption. The permeation properties of another dietary MCFAS, sodium caprylate (8-carbon), were shown in vitro to be lower when compared to sodium eaprate. Sodium caprylate and a peptidic drug were formulated in an admixture with other excipients in oil to generate an oily suspension (OS) that enhanced permeability⁷ (Tuvia, S. etal., Pharmaceutical Research, Vol. 31, No. 8, pp. 2010-2021 (2014).

[00643] For example, in one embodiment, a permeation enhancer is combined with a peptide inhibitor, wherein the permeation enhancer comprises at least one of a medium-chain fatty acid, a long-chain fatty acid, a bile salt, an amphiphilic surfactant, and a chelating agent. In certain embodiments, medium-chain fatty acid salts promote absorption by increasing paracellular permeability of the intestinal epithelium. In one embodiment, a permeation enhancer comprising sodium N-[hydroxybenzoyl)amino] caprylate is used to form a weak noncovalent association with the peptide inhibitor of the instant invention, wherein the permeation enhancer favors membrane transport and further dissociation once reaching the blood circulation. In another embodiment, a peptide inhibitor of the present invention is conjugated to oligoarginine, thereby increasing cellular penetration of the peptide into various cell types. Further, in at least one embodiment a noncovalent bond is provided between a peptide inhibibitor of the present invention and a permeation enhancer selected from the group consisting of a cyclodextrin (CD) and a dendrimers, wherein the permeation enhancer reduces peptide aggregation and increasing stability and solubility for the peptide inhibitor molecule.

[00644] In certain embodiments, a pharmaceutical composition or formulation comprises a peptide inhibitor of the present invention and a transient permeability enhancers (TPEs). Permeation enhancers and TPEs may be used to increase orally bioavailability or the peptide inhibitor. One example of a TPE that may be used is an oily suspension formulation that disperses a powder containing sodioum caprylate and a therapeutic agent (Tuvia, S, et al., Pharmaceutical Research, Vol. 31, No. 8, pp. 2010-2021 (2014).

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PCT/US2016/042680 [00645] In certain embodiments, pharmaceutical composition and formulations may include a peptide inhibitor of the present invention and one or more absorption enhancers, enzyme inhibitors, or mucoso adhesive polymers.

[00646] In particular embodiments, peptide inhibors of the present invention are formulated in a formulation vehicle, such as, e.g., emulsions, liposomes, microsphere or nanoparticles.

[00647] Other embodiments of the invention provide a method for treating a subject with a peptide inhibitor of the present invention having an increased half-life. In one aspect, the present invention provides a peptide inhibitor having a half-life of at least several hours to one day in vitro or in vivo (e.g., when administered to a human subject) sufficient for daily (q.d.) or twice daily (b.i.d.) dosing of a therapeutically effective amount. In another embodiment, the peptide inhibitor has a half-life of three days or longer sufficient for weekly (q.w.) dosing of a therapeutically effective amount. Further, in another embodiment, the peptide inhibitor has a half-life of eight days or longer sufficient for bi-weekly (b.i.w.) or monthly dosing of a therapeutically effective amount. In another embodiment, the peptide inhibitor is derivatized or modified such that is has a longer half-life as compared to the underivatized or unmodified peptide inhibitor. In another embodiment, the peptide inhibitor contains one or more chemical modifications to increase serum half-life.

[00648] When used in at least one of the treatments or delivery systems described herein, a peptide inhibitor of the present invention may be employed in pure form or, where such forms exist, in pharmaceutically acceptable salt form.

[00649] The total daily usage of the peptide inhibitors and compositions of the present invention can be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject will depend upon a variety of factors including: a) the disorder being treated and the severity of the disorder; b) activity of the specific compound employed; c) the specific composition employed, the age, body weight, general health, sex and diet of the patient; d) the time of administration, route of administration, and rate of excretion of the specific peptide inhibitor employed; e) the duration of the treatment; f) drugs used in combination or coincidental with the specific peptide inhibitor employed, and like factors well known in the medical arts.

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PCT/US2016/042680 [00650] In particlar embodiments, the total daily dose of the peptide inhibitors of the invention to be administered to a human or other mammal host in single or divided doses may be in amounts, for example, from 0.0001 to 300 mg/kg body weight daily or 1 to 300 mg/kg body weight daily.

Non-invasive Detection of Intestinal Inflammation [00651] The peptide inhibitors of the invention may be used for detection, assessment and diagnosis of intestinal inflammation by microPET imaging, wherein the peptide inhibitor is labeled with a chelating group or a detectable label, as part of a a non-invasive diagnostic procedure. In one embodiment, a peptide inhibitor is conjugated with a bifunctional chelator. In another embodiment, a peptide inhibitor is radiolabeled. The labeled peptide inhibitor is then administered to a subject orally or rectally. In one embodiment, the labeled peptide inhibitor is included in drinking water. Following uptake of the peptide inhibitor, microPET imaging may be used to visualize inflammation throughout the subject’s bowels and digestive track.

Identification of Peptide Inhibitors that Inhibit IL-23 Signalling [00652] As described herein, in certain embodiments, peptide inhibitors of the present invention preferentially bind to human IL-23R and/or rat IL-23R as compared to mouse IL-23R. Mouse IL-23R contains additional amino acids as compared to human IL-23R or rat IL-23R in the region corresponding to about amino acid residue 315 to about amino acid residue 340 of the mouse IL23R protein, e.g., amino acid region NWQPWSSPFVHQTSQETGKR (see, e.g., Figure 4). In particular embodiments, the peptide inhibitors bind to a region of human IL-23R from about amino acid 230 to about amino acid residue 370.

[00653] The present invention provides a new method to identify an inhibitor (e.g., a peptide inhibitor) of IL-23R, based on identifying an agent (e.g., a peptide) that preferentially binds to human IL-23R or rat IL-23R as compared to mouse IL-23R. In certain embodiments, the method comprises: (a) determining an amount of binding of a candidate agent to a human IL23R polypeptide or a rat IL-23R polypeptide; (b) determining an amount of binding of the candidate agent to the mouse IL-23R polypeptide; and (c) comparing the determined amount of binding to the human IL-23R polypeptide or the rat IL-23R polypeptide to the determined amount of binding to the mouse IL-23R polypeptide, wherein if the determined amount of

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PCT/US2016/042680 binding to the human IL-23R polypeptide or the rat IL-23R polypeptide is greater than the amount of binding to the mouse IL-23R polypeptide, the candidate compound is an inhibitor of IL-23R. In particular embodiments, the candidate compound is identified as an inhibitor of IL23R if the determined amount of binding to the human IL-23R polypeptide or the rat IL-23R polypeptide is at least 1.5-fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 100-fold, at least 200-fold, at least 500-fold, or at least 100-fold the determined amount of binding to the mouse IL-23R polypeptide. In particular embodiments, the candidate compound is a peptide. In particular embodiments, the peptide is a peptide of one of the formulas described herein. In particular embodiments, the human IL-23 polypeptide or rat IL-23R polypeptide comprises or consists of the full length human IL-23R or rat IL-23R protein, respectively. In other embodiments, the human IL-23R polypeptide is a fragment of the full length human IL-23R protein, comprising 8 or more amino acid residues within the region of human IL-23R from about amino acid residue 230 to about amino acid residue 370. In other embodiments, the rat IL23R polypeptide is a fragment of the full length rat IL-23R protein, comprising 8 or more amino acid residues within the region of rat IL-23R from about amino acid residue 245 to about amino acid residue 385.

[00654] In another embodiment, the present invention provides a new method to identify an inhibitor (e.g., a peptide inhibitor) of IL-23R, based on identifying an agent that binds to a region of human IL-23R or rat IL-23 that is disrupted in mouse IL-23R by the presence of additional amino acids from about amino acid residues 315 to about amino acid residue 340 of the mouse IL23R protein, e.g., amino acid region NWQPWSSPFVHQTSQETGKR (see, e.g., Figure 4). In certain embodiments, the method comprises: (a) determining an amount of binding of a candidate agent to a fragment of human IL-23R polypeptide that falls within about amino acid residue 230 to about amino acid residue 370, or to a fragment of rat IL-23R polypeptide that falls within about amino acid residue 245 to about amino acid residue 385; (b) determining an amount of binding of the candidate agent to a negative control (e.g., a negative control peptide unrelated to human IL-23R or rat-IL-23R); and (c) comparing the determined amount of binding to the fragment of human IL-23R polypeptide or the fragment of rat IL-23R polypeptide to the determined amount of binding to the negative control, wherein if the determined amount of binding to the human IL-23R polypeptide fragment or the rat IL-23R polypeptide fragment is

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PCT/US2016/042680 greater than the amount of binding to the negative control, the candidate compound is an inhibitor of IL-23R. In particular embodiments, the candidate compound is identified as an inhibitor of IL-23R if the determined amount of binding to the human IL-23R polypeptide fragment or the rat IL-23R polypeptide fragment is at least 1.5-fold, at least 2-fold, at least 3fold, at least 4-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 30-fold, at least 40fold, at least 50-fold, at least 100-fold, at least 200-fold, at least 500-fold, or at least 100-fold the determined amount of binding to the negative control. In particular embodiments, the candidate compound is a peptide. In particular embodiments, the peptide is a peptide of one of the formulas described herein. In particular embodiments, the fragment of human IL-23R includes at least 8, at least 12, at least 20, at least 50, or at least 100, or all amino acid residues within the region of human IL-23R from about amino acid residue 230 to about amino acid residue 370. In other embodiments, the fragment of rat IL-23R polypeptide includes at least 8, at least 12, at least 20, at least 50, or at least 100, or all amino acid residues within the region of rat IL-23R from about amino acid residue 245 to about amino acid residue 385.

[00655] Methods of determining binding of a candidate compound to an IL-23 polypeptide are known in the art and include but are not limited to in vitro and cell-based binding assays, including those described herein. For example, a labeled candidate compound may be incubated with a recombinantly produced IL-23R polypeptide or negative control bound to a solid support under conditions and for a time sufficient to allow binding, and then binding determined by measuring the amount of label associated with the bound IL-23R polypeptide.

Non-invasive Detection of Intestinal Inflammation [00656] The peptide inhibitors of the invention may be used for detection, assessment and diagnosis of intestinal inflammation by microPET imaging, wherein the peptide inhibitor is labeled with a chelating group or a detectable label, as part of a a non-invasive diagnostic procedure. In one embodiment, a peptide inhibitor is conjugated with a bifunctional chelator. In another embodiment, a peptide inhibitor is radiolabeled. The labeled peptide inhibitor is then administered to a subject orally or rectally. In one embodiment, the labeled peptide inhibitor is included in drinking water. Following uptake of the peptide inhibitor, microPET imaging may be used to visualize inflammation throughout the subject’s bowels and digestive track.

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PCT/US2016/042680

Animal Models of IBP [00657] The present invention includes models of animal disease, including inflammatory diseases and disorders, such as inflammatory bowel diseases, e.g., Crohn’s disease and colitis. As described in the accompanying Examples, several animal models of inflammatory diseases and disorders were developed.

[00658] In one embodiment, the present invention includes a method of assessing the ability of a candidate compound to inhibit or reduce an inflammatory disease disorder, comprising:

[00659] (a) providing to a rat an amount of dextran sulfate sodium (DSS) sufficient to induce IBD;

[00660] (b) providing to the rat an amount of a candidate compound; and [00661] (c) measuring an amount of IBD symptoms present in the rat after being provided with the DSS and the candidate compound;

[00662] wherein if the amount of IBD symptoms measured in (c) are significantly lower than the amount measured in a control rat provided with the amount of DSS and either an amount of a control compound or no peptide (e.g., vehicle control), the candidate compound inhibits or reduces the inflammatory disease or disorder.

[00663]In certain embodiments, the rat is provided with DSS for about 5 to 12 days, e.g., about 9 days. In particular embodiments, the rat is provided with DSS by providing to the rat ad lib exposure to drinking water containing DSS, e.g., about 1% to about 10% DSS, about 2% to about 5% DSS, or about 3% DSS. In particular embodiments, the rat is provided with the test compound at about 5 mg/kg to about 100 mg/kg, or about 10 mg/kg to about 50 mg/kg, or about 20 mg/kg or about 30 mg/kg. In particular embodiments, the rat is provided with test compound orally, e.g., in drinking water. In certain embodiments, the DSS assay is performed as described in the accompanying Examples.

[00664] In another embodiment, the present invention includes a method of assessing the ability of a candidate compound to inhibit or reduce an inflammatory disease disorder, comprising:

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PCT/US2016/042680 [00665] (a) providing to a rat an amount of 2,4,6-Trinitrobenzenesulfonic acid (TNBS) sufficient to induce IBD;

[00666] (b) providing to the rat an amount of a candidate compound; and [00667] (c) measuring an amount of IBD symptoms present in the rat after being provided with the TNBS and the candidate compound;

[00668] wherein if the amount of IBD symptoms measured in (c) are significantly lower than the amount measured in a control rat provided with the amount of TNBS and either an amount of a control compound or no peptide (e.g., vehicle control), the candidate compound inhibits or reduces the inflammatory disease or disorder.

[00669] In certain embodiments, the animals are provided with about lOmg/kg to about 200 mg/kg TNBS, e.g., about 10 mg/kg, about 20 mg/kg, about 30 mg/kg, about 40 mg/kg, about 50 mg/kg, about 60 mg/kg, about 70 mg/kg, about 80 mg/kg, about 90 mg/kg, about 100 mg/kg, about 120 mg/kg, about 150 mg/kg or about 200 mg/kg of TNBS. In certain embodiemnts, the TNBS is in alcohol, e.g., in 45%-5Q% ethanol. In particular embodiments, the TNBS is administered intrarectally. In particular embodiments, the rat is provided with the test compound at about 5 mg/kg to about 100 mg/kg, or about 10 mg/kg to about 50 mg/kg, or about 20 mg/kg or about 30 mg/kg. In particular embodiments, the rat is provided with the test compound orally, e.g., in drinking water. In certain embodiments, the TNBS assay is performed as described in the accompanying Examples.

[00670] In particular embodiments IBD symptoms are measured immediately following provision of the DSS or TNBS and candidate compound (or test compound or no compound), or later, e.g., at about 3 days, 5 days, or 9 days following initial provision of DSS or TNBS and candidate compound (or test compound or no compound). In particular embodiments, the IBD symptoms measured include one or more of percent body weight loss, stool consistency, a quantitative hemoccult score, and ratio of colon weight: colon length. In certain embodiments, the IBD symptoms are measured using a disease activity index (DAI) score and/or ratio of colon weight: colon length, wherein the DAI score consists of ratings from three parameters, including

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PCT/US2016/042680 percent body weight loss, stool consistency, and a quantitative hemoccult score, and can achieve a maximum of three units.

[00671] In certain embodiments, a neutralizing anti-IL-23pl9 antibody is used as a comparator or positive control.

[00672] In certain embodiments, to assess the extent of the inflammatory response, animals are observed, e.g., daily, for clinical signs which included percent body weight loss and signs of loose stools or diarrhea. Following a time period after inoculation of with DSS or TNBS (e.g., 5 days, 6, days, or seven days), rats are sacrificed and their entire colon length and colon weight from cecum to rectum recorded. The severity of colitis may be evaluated by a pathologist blinded to the identity of treatments. In addition to the colon wall thickness, the gross colon damage may be assessed based on a 0-4 scale according to Table 19 below, and histopathological scores were determined based on below parameters (Tables 20 and 21).

[00673] In certain embodiments, IBD symptoms are measured in three groups of rats, each with at least 3 animals, e.g., six animals each, wherein the three groups include: vehicle, DSS or TNBS, and DSS or TNBS with a positive control (e.g., sulfasalazine administered at 100 mg/kg PO, QD).

EXAMPLES

EXAMPLE 1

Synthesis of Peptide Monomers [00674] Peptide monomers of the present invention were synthesized using the Merrifield solid phase synthesis techniques on Protein Technology’s Symphony multiple channel synthesizer. The peptides were assembled using HBTU (O-Benzotriazole-N,N,N’,N’-tetramethyl-uroniumhexafluoro-phosphate), Diisopropylethylamine(DIEA) coupling conditions. For some ammo acid couplings PyAOP(7-Azabenzotriazol-l-yloxy)tripyrrolidinophosponium hexafluorophosphate) and DIEA conditions were used. Rink Amide MBHA resin (100-200 mesh, 0.57 mmol/g) was used for peptide with C-terminal amides and pre-loaded Wang Resin with Ν-α-Fmoc protected amino acid was used for peptide with C-terminal acids. The coupling reagents (HBTU and DIEA premixed) were prepared at lOOmmol concentration. Similarly amino acids solutions were

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PCT/US2016/042680 prepared at 100 mmol concentration. Peptide inhibitors of the present invention were identified based on medical chemistry optimization and/or phage display and screened to identify those having superior binding and/or inhibitory properties.

Assembly [00675] The peptides were assembled using standard Symphony protocols. The peptide sequences were assembled as follows: Resin (250 mg, 0.14 mmol) in each reaction vial was washed twice with 4ml of DMF followed by treatment with 2.5ml of 20% 4-methyl piperidine (Fmoc deprotection) for lOmin. The resin was then filtered and washed two times with DMF (4ml) and re-treated with N-methyl piperifine for additional 30 minute. The resin was again washed three times with DMF (4 ml) followed by addition 2.5ml of amino acid and 2.5ml of HBTU-DIEA mixture. After 45min of frequent agitations, the resin was filtered and washed three timed with DMF (4 ml each). For a typical peptide of the present invention, double couplings were performed. After completing the coupling reaction, the resin was washed three times with DMF (4 ml each) before proceeding to the next amino acid coupling.

Ring Closing Metathesis to form Olefins [00676] The resin (100 pmol) was washed with 2 ml of DCM (3x1 min) and then with 2 ml of DCE (3x1 min) before being treated with a solution of 2 ml of a 6 mM solution of Grubbs' firstgeneration catalyst in DCE (4.94 mg ml-1; 20 mol% with regard to the resin substitution). The solution was refluxed overnight (12 h) under nitrogenbefore being drained. The resin was washed three times with DMF (4 ml each); DCM (4 ml) before being dried and cleavaed.

Cleavage [00677] Following completion of the peptide assembly, the peptide was cleaved from the resin by treatment with cleavage reagent, such as reagent K (82.5% trigluoroacetic acid, 5% water, 5% thioanisole, 5% phenol, 2.5% 1,2-ethanedithiol). The cleavage reagent was able to successfully cleave the peptide from the resin, as well as all remaining side chain protecting groups.

[00678] The cleaved peptides were precipitated in cold diethyl ether followed by two washings with ethyl ether. The filtrate was poured off and a second aliquot of cold ether was added, and the procedure repeated. The crude peptide was dissolved in a solution of acetonitrile:water (7:3

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PCT/US2016/042680 with 1% TFA) and filtered. The quality of linear peptide was then verified using electrospray ionization mass spectrometry (ESI-MS) (Micromass/Waters ZQ) before being purified.

Disulfide Bond Formation via Oxidation [00679] The peptide containing the free thiol (for example diPen) was assembled on a Rink Amide-MBHA resin following general Fmoc-SPPS procedure. The peptide was cleaved from the resin by treatment with cleavage reagent 90% trifluoroacetic acid, 5% water, 2.5% 1,2ethanedithiol, 2.5% tri-isopropylsilane). The cleaved peptides were precipitated in cold diethyl ether followed by two washings with ethyl ether. The filtrate was poured off and a second aliquot of cold ether was added, and the procedure repeated. The crude peptide was dissolved in a solution of acetonitrile:water (7:3 with 1% TFA) and filtered giving the wanted unoxidized peptide crude peptide [00680] The crude, cleaved peptide with X4 and X9 possessing either Cys, Pen, hCys, (D)Pen, (D)Cys or (D)hCys, was dissolved in 20ml of water : acetonitrile. Saturated Iodine in acetic acid was then added drop wise with stirring until yellow color persisted. The solution was stirred for 15 minutes, and the reaction was monitored with analytic HPLC and LCMS. When the reaction was completed, solid ascorbic acid was added until the solution became clear. The solvent mixture was then purified by first being diluted with water and then loaded onto a reverse phase HPLC machine (Luna Cl 8 support, lOu, 100A, Mobile phase A: water containing 0.1% TFA, mobile phase B: Acetonitrile (ACN) containing 0.1% TFA, gradient began with 5% B, and changed to 50% B over 60 minutes at a flow rate of 15ml/min). Fractions containing pure product were then freeze-dried on a lyophilyzer.

Lactam Bond Formation [00681] lOOmg of crude, cleaved peptide (approx. 0.12mmol) is dissolved in 100ml of anhydrous dichloromethane. HOBt (1-Hydroxybenzotriazole hydrate) (0.24mmol, 2 equivalents) is added followed by DIEA (Ν,Ν-Diisopropylethylamine) (1.2mmol, 1 Oequivalents) and TBTU (O(Benzotriazol-l-yl)-N,N,N’,N’-tetramethyluronium tetrafluoroborate)(0.24 mmol, 2 equivalents). The mixture is stirred overnight and followed the reaction by HPLC. When the reaction is completed, dichloromethane is evaporated and diluted with water and Acetonitrile and then loaded onto a reverse phase HPLC machine (Luna Cl8 support, lOu, 100A, Mobile phase A:

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PCT/US2016/042680 water containing 0.1% TFA, mobile phase B: Acetonitrile (ACN) containing 0.1% TFA, gradient begins with 5% B, and is changed to 50% B over 60 minutes at a flow rate of 15ml/min). Fractions containing pure product are then freeze-dried on a lyophilyzer.

Triazole bond formation [00682] The purified peptide containing the relevant amino acids alkyne and azide was stirred at room temperature in a phosphate / MeOH (2 :1) at pH 7.4 (1 mg per 2 ml). CuSO4 -5 H₂O (10 equiv.), and sodium ascorbate (10 equiv.) was added and the mixture was agitated in at room temperature for 36 h. MeOH was removed and the solution was acidified to pH 3 with 1%TFA water mix. The solution was then filtered before being loaded onto HPLC for peptide purification.

Thioether Bond Formation [00683] The peptide containing the free thiol (eg Cys) and hSer(OTBDMS) was assembled on a Rink Amide-MBHA resin following general Fmoc-SPPS procedure. Chlorination was carried out by treating the resin with PPh₃ (10 equiv.) and C1₃CCN (10 equiv.) in DCM for 2 h. The peptide was cleaved from the resin by treatment with cleavage reagent 90% trifluoroacetic acid, 5% water, 2.5% 1,2-ethanedithiol, 2.5% tri-isopropylsilane). The cleaved peptides were precipitated in cold diethyl ether followed by two washings with ethyl ether. The filtrate was poured off and a second aliquot of cold ether was added, and the procedure repeated. The crude peptide was dissolved in a solution of acetonitrile:water (7:3 with 1% TFA) and filtered giving the wanted uncyclized crude peptide [00684] The crude peptide possessing a tree thiol (eg Cys, Pen, hCys, (D)Pen, (D)Cys or (D)hCys) and the alkyl halide (hSer(Cl)) at either the X4 and X9 position or X9 and X4 position was dissolved in 0.1 M TRIS buffer pH 8.5. Cyclization was allowed to take place overnight at RT. The solvent mixture was then purified by first being diluted two-fold with water and then loaded onto a reverse phase HPLC machine (Luna Cl8 support, lOu, 100A, Mobile phase A: water containing 0.1% TFA, mobile phase B: Acetonitrile (ACN) containing 0.1% TFA, gradient began with 5% B, and changed to 50% B over 60 minutes at a flow rate of 15ml/min). Fractions containing pure product were then freeze-dried on a lyophilyzer.

Selenoether Bond Formation

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PCT/US2016/042680 [00685] Crude peptide containing the thiol protected -Selenium amino acid and the alkyl halide at X4 and X9 was dissolved in 0.1 M sodium phosphate buffer pH 5.5 containing DTT (40 equ.). Cyclization was allowed to take place over 24 h at RT. The solution was then diluted two-fold with water, and the final cyclized peptide was purified using RP-HPLC, affording the selenoether.

Diselenide Bond Formation [00686]Diselenide precursor was dissolved in a solution of 0.1 M phosphate buffer pH 6.0 and isopropanolcontaining DTT (40 equiv), and the reaction mixture was incubated at 37°C. After 20h, additional DTT (10 equiv) was added to the reaction. After a total of 32h, the cyclization reaction was then diluted with twofold water, and the final cyclized peptide was purified using RP-HPLC, affording the diselenide.

Purification [00687] Analytical reverse-phase, high performance liquid chromatography (HPLC) was performed on a Gemini Cl 8 column (4.6 mm x 250 mm) (Phenomenex). Semi-Preparative reverse phase HPLC was performed on a Gemini 10 pm Cl8 column (22 mm x 250 mm) (Phenomenex) or Jupiter 10 pm, 300 A ⁰ C18 column (21.2 mm x 250 mm) (Phenomenex). Separations were achieved using linear gradients of buffer B in A (Mobile phase A: water containing 0.15% TFA, mobile phase B: Acetonitrile (ACN) containing 0.1% TFA), at a flow rate of 1 mL/min (analytical) and 15 mL/min (preparative). Separations were achieved using linear gradients of buffer B in A (Mobile phase A: water containing 0.15% TFA, mobile phase B: Acetonitrile (ACN) containing 0.1% TFA), at a flow rate of 1 mL/min (analytical) and 15mL/min (preparative).

Linker Activation and Dimerization [00688] Peptid monomer subunits were linked to form peptide dimer inhibitors as described below.

[006891 Small Scale DIG Linker Activation Procedure: 5mL of NMP was added to a glass vial containing IDA diacid (304.2 mg, 1 mmol), N-hydroxysuccinimide (NHS, 253.2 mg, 2.2 eq. 2.2mmol) and a stirring bar. The mixture was stirred at room temperature to completely dissolve the solid starting materials. N, N’-Dicyclohexylcarbodiimide (DCC, 453.9mg, 2.2 eq., 2.2

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PCT/US2016/042680 mmol) was then added to the mixture. Precipitation appeared within 10 min and the reaction mixture was further stirred at room temperature overnight. The reaction mixture was then filtered to remove the precipitated dicyclohexylurea (DCU). The activated linker was kept in a closed vial prior to use for dimerization. The nominal concentration of the activated linker was approximately 0.20 M.

[00690] For dimerization using PEG linkers, there is no pre-activation step involved. Commercially available pre-activated bi-functional PEG linkers were used.

1006911 Dimerization Procedure: 2mL of anhydrous DMF was added to a vial containing peptide monomer (0.1 mmol). The pH of the peptide was the adjusted to 8~9 with DIEA. Activated linker (IDA or PEG13, PEG 25) (0.48eq relative to monomer, 0.048 mmol) was then added to the monomer solution. The reaction mixture was stirred at room temperature for one hour. Completion of the dimerization reaction was monitored using analytical HPLC. The time for completion of dimerization reaction varied depending upon the linker. After completion of reaction, the peptide was precipitated in cold ether and centrifuged. The supernatant ether layer was discarded. The precipitation step was repeated twice. The crude dimer was then purified using reverse phase HPLC (Luna Cl 8 support, lOu, 100A, Mobile phase A: water containing 0.1% TFA, mobile phase B: Acetonitrile (ACN) containing 0.1% TFA, gradient of 15%B and change to 45%B over 60min, flow rate 15ml/min). Fractions containing pure product were then freeze-dried on a lyophilyzer.

EXAMPLE 2

Characterization of Peptide Inhibition of Binding of Interleukin-23 to the

Interleukin-23 Receptor [00692] Peptide optimization was performed to identify peptide inhibitors of IL-23 signalling that were active at low concentrations (e.g., IC50 <10 nM) while exhibiting gastrointestinal (GI) stability. Certain peptides were tested to identify peptides that inhibit the binding of IL-23 to human IL-23R and inhibit IL-23/IL-23R functional activity, as described below. Peptides tested included peptides containing a variety of different cyclization chemistries, including, e.g., cyclic amides (side chain cyclizations), peptides containing a disulfide linkage, e.g., between two Pen residues, and peptides containing a thioether linkage. Peptide inhibitors of the present invention

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PCT/US2016/042680 include but are not limited to peptides having any of the structures depicted herein. In addition, peptide inhibitors of the present invention include those having the same amino acid sequence of the peptides or structures described herein, without being required to have the same or any N- or C-terminal “capping” groups, such as, e.g., Ac or NH2.

[00693] Assays performed to determine peptide activity are described below, and the results of these assays is provided in Tables E3A-E3H, E4A and E4B, E5A-E5C, E6, E7, and E8. Human ELISA indicates the IL23-IL23R competitive binding assay described below, Rat ELISA indicates the rat IL-23R competitive binding ELISA assay described below, and pStat3HTRF indicates the DB cells IL-23R pSTAT3 cell assay described below. The peptides depicted in Tables E3B-E3E are cyclized via a disulfide bridge formed between two cysteine residues in these peptides. The peptides depicted in Table E3F are dimerized via a linker moiety or through internal cysteine moieties, as indicated. The peptides depicted in Tables E4A and E4B are cyclized via the two Pen residues present in each of these peptides. The peptides depicted in Table E5A are cyclized via a thioether bond between the indicated amino acid residues. Table E5B provides an illustrative structure depicting thioether cyclization, which is indicated in the table by the term “Cyclo,” with the cyclic region bracketed immediately following. The monomer subunits of the peptide dimers shown in Table E5C are cyclized as indicated by the term “Cyclo” and linked to each other via the indicated linker. The peptides shown in Table E6 are cyclized via ring closing metathesis of the indicated residues. Table E7 provides two illustrative structures depicting side chain cyclizations via cyclic amides, and the peptides in this table are cyclized as indicated following the term “Cyclo.” Table E8 depicts peptides cyclized via a cysteine residue and a Pen residue.

[00694] Peptide inhibitors of the present invention include both the cyclized form of the peptides shown herein, as well as the non-cyclized forms. For certain peptides, the residue Abu is present where indicated, whereas in other embodiments related to the non-cyclized form, the Abu may be referred to as a hSer(Cl) or homoSer residue.

IL23-IL23R Competitive Binding ELISA [00695] An Immulon® 4HBX plate was coated with 50 ng/well of IL23R_huFC and incubated overnight at 4°C. The wells were washed four times with PBST, blocked with PBS

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PCT/US2016/042680 containing 3% Skim Milk for 1 hour at room temperature, and washed again four times with PBST. Serial dilutions of test peptides and IL-23 at a final concentration of 2 nM diluted in Assay Buffer (PBS containing 1% Skim Milk) were added to each well, and incubated for 2 hours at room temperature. After the wells were washed, bound IL-23 was detected by incubation with 50 ng/well of goat anti-p40 polyclonal antibodies (R&D Systems #AF309) diluted in Assay Buffer for 1 hour at room temperature. The wells were again washed four times with PBST. The secondary antibodies, HRP conjugated donkey anti-goat IgG (Jackson ImmunoResearch Laboratories #705-035-147) diluted 1:5000 in Assay Buffer was then added, and incubated for 30 minutes at room temperature. The plate was finally washed as above. Signals were visualized with IMB One Component HRP Membrane Substrate, quenched with 2 M sulfuric acid and read spectrophotometrically at 450 nm. IC50 values for various test peptides determined from these data are shown in Tables E3A-E3H, E4A and 4EB, E5A-E5C, E6, E7, and E8.

Rat IL-23R Competitive Binding ELISA [00696] An assay plate was coated with 300 ng/well of Rat IL-23R_huFC and incubated overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions of test peptides and IL-23 at a final concentration of 7 nM were added to each well, and incubated for 2 hours at room temperature. After the wells were washed, bound IL-23 was detected with goat anti-p40 polyclonal antibodies, followed by an HRP conjugated donkey anti-goat IgG. Signals were visualized with TMB One Component HRP Membrane Substrate and quenched with 2 M sulfuric acid. IC50 values for various test peptides determined from these data are shown in Tables E3G, E3H, E4A, E4B, E5B, E5C and E8.

DB Cells IL23R pSTAT3 Cell Assay [00697] IL-23 plays a central role in supporting and maintaining Thl7 differentiation in vivo. This process is thought to mediated primarily through the Signal Transducer and Activator of Transcription 3 (STAT3), with phosphorylation of STAT3 (to yield pSTAT3) leading to upregulation of RORC and pro-inflammatory IL-17. This cell assay examines the levels of pSTAT3 in IL-23R-expressing DB cells when stimulated with IL-23 in the presence of test compounds. DB cells (ATCC #CRL-2289), cultured in RPMI-1640 medium (ATCC #30-2001)

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PCT/US2016/042680 supplemented with 10% FBS and 1% Glutamine, were seeded at 5 X 10E5 cells/well in a 96 well tissue culture plate. Serial dilutions of test peptides and IL-23 at a final concentration of 0.5 nM were added to each well, and incubated for 30 minutes at 37°C in a 5% CO2 humidified incubator. Changes in phospho-STAT3 levels in the cell lysates were detected using the Cisbio HTRF pSTAT3 Cellular Assay Kit, according to manufacturer’s Two Plate Assay protocol. IC50 values determined from these data are shown in Tables E3E, E3G, E3H, E4A, E4B, E5B, E5C, and E8 as absolute values or within ranges. Where not shown, data was not determined.

Table E3A. Illustrative Non-cyclic Peptides and Activities

SEQ ID lllllllll!	Sequence	ELISA iiieiliiiii !!!!!llll!!!l! in nMoles lllBlill!
1	Ac-[ Aib] - [ Aib] - TWQD YWL Y-[ Aib]-R-NH2	>100,000
2	Ac-CAMTWQDYWLYGRC-NH2	7200
3	Ac- [Aib] - [Aib] -TWQD YWL YGR-NH2	>100,000
4	Ac-AMTWQD YWL YGRK-NH2	4100
5	Ac-CAMTWQDYWLYGRCK-NH2	8500
6	Ac-KAMTWQDYWLYGR-NH2	5600
7	Ac-KCAMTWQDYWLYGRC-NH2	10600
8	Ac-AMTWAibDYWLYGR-NH2	>37,500
9	Ac-AMTWQDYWLYGR-NH2	6100
10	Cyclo- [ AMTWQD YWLYGR1	Not active
11	Hy-AATWQDYWLYGR-OH	7785
12	Hy-AMAWQDYWLYGR-OH	24225
13	Hy-AMTAQDYWLYGR-OH	N/A
14	Hy-AMTWADYWLYGR-OH	6248
15	Hy-AMTWQAYWLYGR-OH	9589

Table E3B. Illustrative Peptides Containing the CXXXXC Motif with IC50 >1 uM in IL23IL23R Competitive Binding ELISA

SEQ ID NO.	Sequence
87	Hy-CSDWECYWHIFG-NH2
88	Hy-CETWECYWHSFS-NH2
89	Hy-CQSWECYWHYYG-NH2
90	Hy-CSDWRCYWHVFG-NH2
91	Hy-CHTWVCYWHEFS-NH2
92	Hy-CTDWVCYWHEYS-NH2
93	Hy-CQTWVCYWHTYG-NH2

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SEQ ID NO.	Sequence
94	Hy-CGNWECYWHVYG-NH2
95	Hy-CKDWKCYWHIYG-NH2
96	Hy-CRTWVCYWHVFG-NH2
97	Hy-CAD-[ 1 -Nall - VC YWHTFG-NH2
98	Hy-CAD-[2-Nall-VC YWHTFG-NH2
99	Hy-CAD-[ 1-BIP]-VC YWHTFG-NH2
100	Hy-CAD-[Tic1-VCYWHTFG-NH2
101	Hy-CAD-[ phW]-VCYWHTFG-NH2
102	Hy-CAD WVCY-[ 1 -BIP]-HTFG-NH2
103	Hy-CADWVCY-[Ticl-HTFG-NH2
104	Hy-C AD WVCY- [ ph Wl -HTFG-NH2
105	Hy-CAD WVCYAHTFG-NH2
106	Hy-ACDWVCYWHTFG-NH2
107	Hy-ACDWCCYWCTFG-NH2
108	Hy-AADWCAYWCTFG-NH2
109	Hy-CADWCCYWCTFG-NH2
110	Hy-CADWCCYWCTFG-NH2
111	Hy-CADWCCYWCTFG-NH2
112	Hy-CAD WVCYWHTF-NH2
113	Hy-CAD WVCYWHT-NH2
114	Hv-CADWVCYW-NH2
115	Hy-[p-Alal-SCADWVCYWHTFG-OH
116	Ac-[(D)Lys]-SCADWVCYWHTFG-OH
117	Ac-[(D)Lysl-[p-Alal-CADWVCYWHTFG-OH
118	Hy- [AEA] - C AD WVC YWHTFG-OH
119	Ac-[(D)Lysl-CADWVCYWHTFG-OH
120	Ac-CKDWVCYWHTFG-OH
121	Ac-CADWKCYWHTFG-OH
122	Ac-CADWVCYWKTFG-OH
123	Ac-CADWVCYWHKFG-OH
124	Ac-CADWVCYWHTKG-OH
125	Ac-CADWVCYWHTF-[(D)Lysl-OH
126	Ac-CADWVCYWHTFG-NH2
127	Hy-C AD WVCY- [ 1 -Nal]-HTF-OH
128	Hy-CAD WVC Y- [ 1 -Nal] -HT- [N-Me-Phe] -NH2
129	Hy-CAD WVCY-[l-Nal]-H-[Sarc]-F-OH
130	Hy-CAD WVC Y- [ 1 -Nal] - [N-Me-His]-TF-OH
131	Hy-CAD WVCYWHTFGK-OH
132	Hy-C-[Sarc]-DWVCY-[l-Nal]-HTF-OH
133	Hy-C AD- [N-Me-Trp] - VC Y- [ 1 -Nal] -HTF-OH
134	Hy-CADW-[Sarc]-CY-[l-Nal]-HTF-OH
135	Hy-CAD WVCY-[l-Nal]-HT-[(D)Phe]-OH
136	Hy-CAD WVCY-[l-Nal]-HTF-[Sarc]-OH

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SEQ ID NO.	Sequence
137	Ac-CATWVCYWHTFG-NH2
138	Ac-CADWECYWHTFG-NH2
139	Ac-CADWVCYWHRCGWWGC-NH2
140	Ac-CADWVCY-[l-Nall-H-[(D)Alal-FG-NH2
141	Ac-CADWVCY-[l-Nall-H-[Aibl-FG-NH2
142	Ac-CADWVCY-[l-Nal]-H-[b-Ala]-FG-NH2
143	Ac-CADWVCY-Γ 1-Nall-FTFG-NH2
144	Ac-C AD WVCY-[1-Nal]-[(D) Ala]-TFG-NH2
145	Ac-CADWVCY-[l-Nall-H-[Aibl-[(D)Phel-G-NH2
146	Ac-C ADWVCY- [ 1 -Nal] -HTF- [Aib] -NH2
147	Ac-CADWVCY-[l-Nall-[N-Me-Hisl-[(D)Alal-F-[Aibl-NH2
148	Ac-CADWVCY-[1 -Nal]-H-[AEP]-G-NH2
149	Ac-CADWVCYW-[N-MeHisl-TFG-[AEAl-[(D)Lysl-NH2
150	Ac-CADWVCY-[Aicl-HTFG-[AEAl-[(D)Lysl-NH2
151	Ac-CADWVCY-[Bipl-HTFG-[AEAl-[(D)Lysl-NH2
152	Ac-CQTWQCYW-[N-MeArg]-ENG-[AEA]- [(D)-Lysl -NH2
153	Ac-CQTWQCYWR-[N-MeArg]-NG-[AEA]- [(D)-Lysl -NH2
154	Ac-CQTWQCYWR-[N-MeLysl-NG-[AEAl-[(D)-Lysl -NH2
155	Ac-CQTWQCYWR-[Sarcl-NG-[AEAl- f(D)-Lysl-NH2
156	Ac-CQTWQCYWR-[(D)Glul-NG-[AEAl-[(D)-Lysl-NH2
157	Ac-CQTWQCYW-[(D)Argl-ENG-[AEAl-[(D)-Lysl-NH2
158	Ac-CQTWQCYW-[(D)Argl-[(D)Glul-NG-[AEAl-[(D)Lysl-NH2
159	Ac-CQTWQCYW-[N-MeGlu]-NG-[AEA]-[(D)-Lys]
160	Ac-CADWVC-NH2
161	Ac-CRDWQCYW -[N-MeArgl-KFG-[AEPl-[(D)-Lysl -NH2
162	Ac-CRDWQCYWR-[(D)Lysl-FG-[AEPl-[(D)-Lysl -NH2
163	Ac-CRDWQCYW-[(D)Argl-KFG-[AEPl-[(D)-Lysl -NH2
164	Ac-CRDWQCYW-[(D)Argl-[(D)Lysl-FG-[AEPl-[(D)-Lysl -NH2
165	Ac-CQTWQCYW-[N-MeArg]-ENG-[AEA]-[(D)-Lys] -NH2

Table E3C. Illustrative Peptides Containing the CXXXXC Motif with IC50 of 500nM to lOOOnM in IL23-IL23R Competitive Binding ELISA

SEQ ID NO.	Sequence
166	Hy-CTDWKCYWHEFG-NH2
167	Hy-CRTWTCYWHVYG-NH2
168	Hy-CPNWECYWHRFG-NH2
169	Hy-CADWVCYWHTFG-NH2
170	Hy-CADWMCYWHEYG-NH2
171	Hy-CTTWKCYWHQYG-NH2
172	Hy-CSNWECYWHHYG-NH2
173	Hy-CSDWVCYWHVYG-NH2
174	Hy-CDTWKCYWHRQS-NH2

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175	Hy-C ADWVC Y-[ 1-Nall-HTFG-NH2
176	Hy-CADWVCY-[2-Nal]-HTFG-NH2
177	Hy-CADWVCYWHTFG-NH2
178	Ac-CADWVCYWHTFG-[(D)Lysl-OH
179	Ac-CADWVCYWHTFGAP-[(D)Lysl-OH
180	Ac-CTDWKCYWHTFG-NH2
181	Ac-CRDWVCYWHTFG-NH2
182	Ac-CADWVCYWHEFG-NH2
183	Ac-CADWVCYWHFHQLRDA-NH2
184	Ac-CADWVCYWHEHSERVG-NH2
185	Ac-CADWVCYWHNHSEGSG-NH2
186	Ac-CADWVCYWHRSTGGQH-NH2
187	Ac-[(D)Lysl-CRDWQCY-[l-Nall-HTH-[Sarcl-[AEPl-[(D)Argl-NH2
188	Ac-TQFDCRTWECYWHTFG-NH2
189	Ac-GGVECNDWQCYWHTFG-NH2
190	Ac-REGTCSTWKCYWHTFG-NH2
191	Ac-DTPRCRTWECYWHTFG-NH2
192	Ac-GGGECENWECYWHTFG-NH2
193	Ac-GDHKCS S WECYWHTFG-NH2
194	Ac-GSVHCMTWECYWHTFG-NH2
195	Ac-CADWVCY-[1 -Naf|-VTFG-NH2
196	Ac-CADWVCYW-[(D)Hisl-TFG-[AEAl-[(D)Lysl-NH2

Table E3D. Illustrative Peptides Containing the CXXXXC Motif with IC50 <500nM in IL23IL23R Competitive Binding ELISA

SEQ ID NO.	Sequence
197	Hy-CRDWQCYWHKFG-NH2
198	Hy-CSNWVCYWHTYG-NH2
199	Ac-CADWVCYWHTFG-[3-Alal-[(D)Lysl-OH
200	Ac-CADWVCYWHTFG-[AEAl-[(D)Lysl-OH
201	Ac-CADWVCYWHTFG-OH
202	Ac-C AD WVCYWHTFG- [ AEP] -(D) Arg] -OH
203	Ac-C ADWVCYWHTFG-[AEP1-K-OH
204	Ac-C ADWVC YWHTFG- [Gaba]- [(D)Lys] -OH
205	Ac-CADWVCYWHTFG-[Hexanoicl-[(D)Lysl-OH
206	Ac-C ADWVCYWHTFG- [(PEG)2- [(D)-Lys] -OH
207	Ac-CADWVCYWHTFGP-[(D)Lysl-OH
208	Ac-CADWVCYWHTFG-[Aztl-[(D)-Lysl-OH
209	Ac-CADWVCYWHTFGA-[(D)Lysl-OH
210	Ac-CADWVCYWHTFGAP-[(D)Lysl-OH
211	Ac-CADWVCYWHTFGA[AztH(D)Lysl-OH
212	Ac-CADWVCYWHTFGAA[(D)Lysl-OH
213	Ac-CRDWQC YWHKFG- [ΑΕΡΙ -[(D)Lysl-OH

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SEQ ID NO.	Sequence
214	Ac-CATWQCYWHEYG-NH2
215	Ac-CKTWTCYWHEFG-NH2
216	Ac-CTTWTCYWHQYG-NH2
217	Ac-CRTWECYWHEFG-NH2
218	Ac-CRTWQCYWHEYG-NH2
219	Ac-CQTWQCYWRENG-NH2
220	Ac-CRTWECYWHEYG-NH2
221	Ac-CTTWECYWHEYG-NH2
222	Ac-CRTWECYWHEQS-NH2
223	Ac-CTTWECYWHQFG-NH2
224	Ac-CTTWECYWHEFG-NH2
225	Ac-CQTWECYWHLYG-NH2
226	Ac-CEDWKCYWHKYG-NH2
227	Ac-CTDWVCYWHTFG-NH2
228	Ac-CADWVCYWHTYG-NH2
229	Ac-CADWVCYWHRHADRVK-NH2
230	Ac-CADWVCYWHTFGER-NH2
231	Ac-CADWVCYWHTHGER-NH2
232	Ac-DTPRCRTWECYWHTFG-NH2
233	Ac-CQTWVCYWRENG-FAEAl- [(D)-Lysl -NH2
234	Ac-CQTWQCYWRENG-[AEA1-[(D)-Lysl-NH2
235	Ac-CQTWQCYWRTNG-[AEA1- [(D)-Lysl -NH2
236	Ac-CQTWQCYWRKNG-[AEA1- [(D)-Lysl -NH2
237	Ac-CQTWQCYWRRNG-[AEA1- [(D)-Lysl -NH2
238	Ac-CQTWQCYWR-[Dapal-NG-[AEAl- [(D)-Lysl -NH2
239	Ac-CQTWQCYWR-[Ornl-NG-[AEAl- [(D)-Lysl -NH2
240	Ac-CRTWQCYWRKFG-rAEAl- [(D)-Lysl -NH2
241	Ac-CQTWQCYWRENG-[AEAl-[(D)Argl-NH2
242	Ac-CQTWQCYWRENG-[AEA1-[(D)-Lysl-NH2
243	Ac-CQDWQCYWRENG-rAEAl- [(D)-Lysl -NH2
244	Ac-CQTWQCYWRENG-[AEA1-[(D)-Lysl-NH2
245	Ac-CQTWQCYWRTNG-[AEA1-[(D)-Lysl-NH2
246	Ac-CQTWVCYWRENG-[AEA1-[(D)-Lysl-NH2
247	Ac-CQTWQCYWRKNG-[ AEA1-[(D)-Lysl-NH2
248	Ac-CQTWQCYW-[Cav]-ENG-NH2
249	Ac-CQTWQCYW-[Cpal-ENG-NH2
250	Ac-CQTWQCYWLENG-NH2
251	Ac-CQTWQCYW[-hLeu]-ENG-NH2
252	Ac-CQTWQCYWR-[K-Ac]-NG-NH2
253	Hy-CRTWQCYWRKFG-NH2

Table E3E. IC50 of Illustrative Peptides Containing the CXXXXC Motif with Activities

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SEQ ID NO.	Sequence	ELISA IL23R / IL23 in !!!!!!·111!1	pStat3 HTRF in n Moles
169	Hy-CADWVCYWHTFG-NH2	****	****
178	Ac-CADWVCYWHTFG-[(D)Lysl-OH	****	****
210	Ac-CADWVC YWHTFGAP-[(D)Lysl-OH	****	ND
211	Ac-CADWVCYWHTFGA[Aztl-[(D)Lysl-OH	****	ND
180	Ac-CTDWKCYWHTFG-NH2	****	****
196	Ac-CADWVCYW-[(D)His]-TFG-[AEA]-[(D)Lys]- nh2	****	****
281	DIG dimererisation through N-termina Lysine (Ac-KMTWQDYWLYGR-NH2)2	*****	*****
284	DIG dimererisation through C-terminal Lysine (Ac-AMTWQDYWLYGK-NH2)2	*****	*****

*=<10nM; **=10-25 nM *** = 25-100 nM, **** = 100-1000 nM, *****=1000-10,000 nM.

Table E3F. IC50 of Illustrative Peptide Dimers

SEQ ID NO.	Linker Moiety	Sequence	Human IL23R/IL23 lllllllBlllll iiiiiiBBiiiiiii
277	oxidized dimer through the cysteine	(Hy-FPTWEWYWCNRD-NH2)2	*****
278	oxidized dimer through the cysteine	(Hy-ALTWEFYWLCRE-NH2)2	>10,000
291	DIG through Lysine	(Hy-[pAla]SCADWVCYWHTFG-OH) 2DIG	>10,000
292	DIG through Lysine	(Ac-[(D)Lys]-SCADWVCYWHTFG-OH) 2DIG	>10,000
293	DIG through Lysine	(Ac-(D)Ly s- [βΑΗ] -CADWVC YWHTFG0H)2DIG	>10,000
294	DIG through Lysine	(Hy-AEA-CADWVCYWHTFG-OH) 2DIG	>10,000
295	DIG through Lysine	(Ac-[(D)Lys]-CADWVCYWHTFG-OH) 2DIG	>10,000
296	DIG through Lysine	(Ac-CKDWVCYWHTFG-OH) 2dig	>10,000
297	DIG through Lysine	(Ac-CADWKCYWHTFG-OH) 2dig	>10,000
298	DIG through Lysine	(Ac-CADWVCYWKTFG-OH) 2dig
299	DIG through Lysine	(Ac-CADWVCYWHKFG-OH) 2dig	>10,000
300	DIG through Lysine	(Ac-CADWVCYWHTKG-OH) 2dig	*****
301	DIG through Lysine	(Ac-CADWVCYWHTFDK-OH) 2dig	>10,000
302	DIG through Lysine	(Ac-CADWVCYWHTFGDK) 2dig	*****
303	DIG through Lysine	(Ac-CADWVCYWHTFG- [β-Ala] - [(D)Lys] OH)2DIG	***
304	DIG through Lysine	(Ac-CADWVCYWHTFG- [AEA] - [(D)Ly s] OH)2DIG	***
305	DIG through C terminal Lysine	(Hy-CADWVCYWHTFGK-OH) 2DIG	*****
306	PEG25 through Lysine	(Hy-|flAla]-SCADWVCYWHTFG-OH)

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SEQ ID NO.	Linker Moiety	Sequence	Human IL23R/IL23 llliiiillll
		2PEG25
307	PEG25 through Lysine	(Ac-[(D)Lys]-SCADWVCYWHTFG-OH)2
308	PEG25 through Lysine	(Ac-(D)Lys)-[fAla]-CADWVCYWHTFG- OH)2
309	PEG25 through Lysine	(Hy- [AEA] -CADWVC YWHTFG-0H)2
310	PEG25 through Lysine	(Ac- [(D)Ly s] -CAD WVC YWHTFG-0H)2
311	PEG25 through Lysine	(Ac-CKDWVCYWHTFG-OH)2
312	PEG25 through Lysine	(Ac-CADWKCYWHTFG-OH)2
313	PEG25 through Lysine	(Ac-CADWVCYWKTFG-OH)2
314	PEG25 through Lysine	(Ac-CADWVCYWHKFG-OH)2
315	PEG25 through Lysine	(Ac-CAD WVCYWHTKG-OH)2
316	PEG25 through Lysine	(Ac-CADWVCYWHTF- [(D)Ly s] -OH)2
317	PEG25 through Lysine	(Ac-CADWVC YWHTFG- [(D)Ly s] -OH)2
318	PEG25 through Lysine	(Ac-CADWVC YWHTFG- [bAla] -[(D)Ly s] OH)2
319	PEG25 through Lysine	(Ac-CAD WVCYWHTFG- [AEA] - [(D)Ly s] OH)2
320	PEG25 through Cterminal Lysine	(Hy-CADWVCYWHTFGK-OH)2

*=<10nM; **=10-25 nM *** = 25-100 nM, **** = 100-1000 nM, *****=1000-10,000 nM.

Table E3G. IC50 of Illustrative Peptides Containing the CXXWXCXXXXX-[(D)Lys] Motif

SEQ ID NO.	Sequence	Human ELISA I!··!!! IL23R iiiiOiii	lliiiiil! I!··!! IL23R iiiiiliii!	pStat3 HTRF ιιβιι
16	Ac-CQDWQC YWR- [Cha] -FG- [AEA] -[(D)Ly s] -NH2	113
17	Ac-CQT WQCYWR- [Ogl] -FG- [AEA] - [(D)Lys]-NH2	206
18	Ac-CQTWQCYWK- [Dap] -FG-[AEA] -[(D)Ly s] -NH2	32
19	Ac-CQTWQCYWH- [Dap] -FG-[AEA] -[(D)Ly s] -NH2	49		59
20	Ac-CQTWQC YWRLFG- [AEA] - [(D)Lys] -NH2	51		47
21	Ac-CQT WQCYW- [hArg] - [Dap]-FG- [AEA] - [(D)Lys] -NH2	56
22	Ac-CQTWQC YW- [Cit] - [Dap] -FG- [AEA] - [(D)Lys] -NH2	25
23	Ac-CQTWQCYWRVFG-[AEA]-[(D)Lys]-NH2	39	62	14
24	Ac-CQT WQCYWR- [Dap] - [Tic] -G- [AEA] -[(D)Ly s] -NH2	892	65	12
25	Ac-CQTWQCY-[Tic] -[Orn] -KFG- [AEA] - [(D)Lys] -NH2	>30000
26	Ac-CQT WQCYWR- [Dab]-FG- [AEA] - [(D)Ly s] -NH2	37
27	Ac-CQT WQCYW- [Orn] - [Dap] -FG-[AEA] - [(D)Ly s] -NH2	79	276	37
28	Ac-CQTWQCYWHENGA-[(D)Lys]-NH2	220
29	Ac-CRTWQCYWRENGA-[(D)Lys]-NH2	102	86	17
30	Ac-CRTWQCYWREYGA-[(D)Lys]-NH2	78	80	8
31	Ac-C- [N-MeAla] -DWVC YWHTFG-[AEA] -[(D)Lys] -NH2	183

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SEQ ID NO.	Sequence	Human ELISA I!··!!! IL23R iiiieiii	/lliiiii/!! //////////////Hill////////////// IL23R ////////////////Β·/////////////	pStat3 HTRF /11B11
32	Ac-CADWVC YWRKFG- [β Ala] - [(D)Ly s] -NH2	57	33(1)	13
33	Ac-CAD WVC YW- rCitl-KFG-[ β-Alal - i(D)Ly si -NH2	52		29
34	Ac-CAD WVC Y W- [Cit] - [Tie] -FG- [β - Ala] - [(D)Ly s] -NH2	518
35	Ac-CAD WVC YW- [Cit] - [Tba] -FG- [β-Ala] - [(D)Ly s] -NH2	153
36	Ac-CADWVC YW- [Cit] - [Cha] -FG- [β-Ala]- [(D)Ly s] -NH2	223
37	Ac-CADWVC Y- [ 1 -Nal] - [Cit] -VFG- [β-Ala] - [(D)Ly s] -NH2	79		22
38	Ac-CAD WVC YW- [Cit] -VFG-^-Ala] - [(D)Ly s] -NH2	124
39	Ac-CAD WVC YW- [Cit] - [Chg]-FG- [β-Ala] - [(D)Lys] -NH2	>30000
40	Ac-CAD WVC YW- [Cit] - [βΑ13]-FG- [β-Ala]- [(D)Ly s] -NH2	2584
41	Ac-CAD WVC YW- [Tie] - [Tie] -FG- [β-Ala] - [(D)Lys] -NH2	-30000
42	Ac-CADWVC YW- [Tie] -KFG- [β-Ala] - [(D)Lys] -NH2	199
43	Ac-CQTWQC YW- [(D)Ala] -VFG- [AEA] - [(D)Lys] -NH2	232
44	Ac-CQTWQC YW- [βΑΗ]-VFG- [AEA]- [(D)Ly s] -NH2	2207
45	Ac-CQTWQC YW- [(D)Leu] -VFG- [AEA] - [(D)Lys] -NH2	188
46	Ac-CQTWQC YW-[(D)Phe]-VFG- [AEA]- [(D)Lys] -NH2	848
47	Ac-CQTWQC YW- [(D)Asn] -VFG-[AEA] - [(D)Ly s] -NH2	61
48	Ac-CQTWQCYW-[(D)Thr]-VFG-[AEA]-[(D)Lys]-NH2	3662
49	Ac-CQTWQC YW- [(D)Asp] -VFG-[AEA] - [(D)Ly s] -NH2	129
50	Ac-CQTWQC YW- [Cit] - [(D)Leu]-FG- [AEA] - [(D)Ly s] -NH2	709
51	Ac-CQTWQC YW- [Cit] - [(D)Phe]-FG- [AEA] - [(D)Ly s] -NH2	1304
52	Ac-CQT WQ C Y W- [Cit] - [(D) Asn] -FG- [AEA] - [(D)Ly s] -NH2	269
53	Ac-CQTWQCYW- [Cit]- [(D)Thr]-FG- [AEA]- [(D)Lys] -NH2	1214
54	Ac-CQT WQ C YW- [Agp] - VNG- [AEA] - [(D)Ly s] -NH2	241
55	Ac-CQTWQC Y- [oc-MeTrp] -RVNG- [AEA] - [(D)Ly s] -NH2	-6000
56	Ac-CQTWQC Y- [oc-MeTrp] - [Cit] - [hLeu] -NG- [AEA] [(D)Lys]-NH2	-6000
57	Ac-CQTWQCYW- [Cit] -VNG- [AEA]- [(D)Ly s] -NH2	73
58	Ac-CQTWQCYW- [Agp] - [Dap] -NG- [AEA] - [(D)Ly s]-NH2	38
59	Ac-CQTWQC YW-[Cit] -VF- [(D)Ala] - [AEA] - [(D)Ly s] -NH2	397
60	Ac-CQTWQCYW-[Cit] -VF- [(D)Leu] -[AEA] -[(D)Ly s] -NH2	444
61	Ac-CQT WQCYW-[Cit] -VF- [(D)Phe]-[AEA] - [(D)Ly s] -NH2	784
62	Ac-CQTWQCYW- [Cit] -VF- [(D)Asn] - [AEA] - [(D)Lys] -NH2	93
63	Ac-CQT WQCYW-[Cit] -VF- [(D)Thr] - [AEA] - [(D)Lys] -NH2	518
64	Ac-CQTWQCYW- [Cit] -VF- [(D)Asp] - [AEA] - [(D)Lys] -NH2	551
65	Ac-C- [N-MeArg] -TWQC YWRVFG-[AEA] - [(D)Lys] -NH2	149	192	107
66	Ac-C- [N-MeQln] -TWQC YWRVFG-[AEA] - [(D)Ly s] -NH2	69	85	101
67	Ac-C- [Cit] -TWQC YWRVFG- [AEA] -[(D)Ly s]-NH2	50	76	107
68	Ac-CAD WVCYW- [Om]- [Dap] -FG- [AEA] - [(D)Lys]-NH2	382
69	Ac-CAD WVC Y- [1 -Nal] -[Om] - [Dap]-FG- [AEA]- [(D)Ly s] nh2	302
70	Ac-CAD WVC Y- [(D)Trp]-[Om] -[Dap] -FG- [AEA] -	>30000

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SEQ ID NO.	Sequence	Human ELISA I!··!!! IL23R iiiieiii	llliROllli lliiiii!! !!!!! IL23R llllilill!	pStat3 HTRF lliill
	i(D)Lysl-NH2
71	Ac-CAD WVC Y- [hPhe]- [Om]- [Dap] -FG- [AEA]- [(D)Ly s] nh2	-30000
72	Ac-CAD WVC Y- [Bip]- [Om]- [Dap] -FG- [AEA] -[(D)Ly s] nh2	>30000
73	Ac-CAD WVC Y- [Phe(3,5 -F2)] - [Om] -[Dap] -FG- [AEA] [(D)Lys]-NH2	-6000
74	Ac-CAD WVC Y- [Phe(CONH2)] - [Om] - [Dap]-FG- [AEA] [(D)Lys]-NH2	-6000
75	Ac-CADWVC Y- [Phe(4-CF3)] - [Om] - [Dap] -FG- [AEA] [(D)Lys]-NH2	>1000
76	Ac-CADWVC Y- [Phe(2,4-Me2)] - [Om] - [Dap] -FG- [AEA] [(D)Lys]-NH2	1525
77	Ac-CMTWQCYWL YGR- [AEA]- [(D)Lys] -NH2	398
77	Hy-CMT WQC YWL YGR- [AEA] - [(D)Ly s] -NH2	>30000
78	Ac-CADWVC Y-1 βΐι Trp | - [Om] - [Dap]-FG- [AEA] - [(D)Ly s] nh2	-6000
79	Ac-CAD WVC YW- [Om] - [α-MeLeu] -FG- [AEA] -[(D)Ly s] nh2	-6000
80	Ac-CAD WVC YW- [Om] - [β-spiral-pip] -FG-[AEA] [(D)Lys]-NH2	579
81	Ac-CADWVCY-[4-Phenylcylcohexylalanine]- [Om] - [Dap] FG-[AEA]-[(D)Lys]-NH2	>3000
82	Ac-CAD WVC YW-[Om] -[Aib] -FG- [AEA] - [(D)Ly s] -NH2	1085
83	Ac-CAD WVCYW-[Om]-[DiethylGly]-FG-[AEA][(D)Lys]-NH2	-6000
84	Ac-CADWVC Y- [cc-MePhe(4-F)]-[0m]-[Dap]-FG-[AEA] [(D)Lys]-NH2	>30000
85	Ac-CQTWQC Y- [βΙιΡΙιε] -RVNG- [AEA] - [(D)Ly s] -NH2	>30000
86	Ac-CQTWQCY-^(l-Nal)]-RVNG-[AEA]-[(D)Lys]-NH2	>30000
321	Ac-CQTWQC Y- ^hTyr]-RVNG- [AEA] - [(D)Ly s]-NH2	>30000
322	Ac-CQTWQC Y- [phPhe(4-F)l -RVNG- [AEA] - [(D)Lysl-NH2	>30000
323	Ac-CQTWQC Y- [βΝνα(5 -Phenyl)] -RVNG-[AEA] [(D)Lys]-NH2	>30000
324	Ac-CQTWQC Y- [Phe(3,4-Cl2)]-RVNG- [AEA] - [(D)Lys] NH2	>30000
325	Ac-CQTWQC Y- [Tqa] -RVNG- [AEA] - [(D)Ly s] -NH2	>30000
326	Ac-CQTWQC YWR-^hLeu] -NG- [AEA] - [(D)Lys] -NH2	224
327	Ac-CQT WQCYWR- [Aib] -NG- [AEA] - [(D)Lys] -NH2	1065
328	Ac-CQTWQCYWR-^hAla]-NG-[AEA]-[(D)Lys]-NH2	457
329	Ac-CQTWQCYWR-^hVal]-NG-[AEA]-[(D)Lys]-NH2	328
330	Ac-CQTWQCYWR-^-spiral-pip]-NG-[AEA]-[(D)Lys]- NH2	405

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SEQ ID NO.	Sequence	Human ELISA I!··!!! IL23R iiiieiii	lliiiii!! Illilill!:!:!! IL23R !!!lllil!l	pStat3 HTRF !!!1B1!!!
331	Ac-CQTWQCYWR-[pGlu]-NG-[AEA]-[(D)Lys]-NH2	250
332	Ac-CQTWQC YW- [ phLeul -VNG- [AEA]- [(D)Lysl -NH2	311
333	Ac-CQTWQC YW- [β Aib]-VNG- [AEA] - [(D)Ly s] -NH2	2903
334	Ac-CQTWQC YW- [phAla] -VNG- [AEA] - [(D)Ly s] -NH2	355
335	Ac-CQTWQC YW- [phVal] -VNG- [AEA] - [(D)Ly s] -NH2	501
336	Ac-CQTWQC YW- [β-spiral-pip] -VNG-[AEA] -[(D)Ly s] nh2	>6000
337	Ac-CQTWQC YW- [phArg] -VNG- [AEA] -[(D)Ly s] -NH2	922
338	Ac-MRTWQ-[MeCys]-YWRKFG-[AEA]-[(D)Lys]-NH2	4251
339	Ac-ACDWVC YWRKFG- [AEA] - [(D)Ly s] -NH2	630
340	Ac-SRTWQ S YWRKFG-[AEA] - [(D)Ly s] -NH2	2816
341	Ac-CDWVCYWRKFG- [AEA] - [(D)Ly s] -NH2	664
342	Ac-ARTWQ-[MeCys]-YWRKFG-[AEA]-[(D)Lys]-NH2	7571
343	Ac-ARTWQ A YWRKFG- [AEA] - [(D)Ly s] -NH2	3194
344	Ac-CQT WQCYW-[hLeu] -EN- [AEA] -[(D)Ly s] -NH2	132
345	Ac-CQTWQCYW-[hLeu]-ENG-[AEA]-[(D)Lys]-NH2	222
346	Ac-CSTWECYWRVYG-[AEA]-[(D)Lys]-NH2	47
347	Ac-C- [Orn] -TWQC YWRVFG- [AEA] - [(D)Lys] -NH2	22	69	95
348	Ac-CQT WQCYW- [Orn] - [Dap] -FG-[AEA] - [(D)Ly s] -NH2	96
349	Ac-C- [N-MeAsn] -TWQCYWRVFG- [AEA] - [(D)Ly s] -NH2	148
350	Ac-C- [N-MeLys] -TWQC YWRVFG- [AEA] - [(D)Ly s] -NH2	80
351	Ac-C- [Dab] -TWQCYWRVFG-[AEA] -[(D)Ly s] -NH2	23	51	99
352	Ac-CQTWQCY Y- [Orn] - [Dap]-FG- [AEA] - [(D)Ly s] -NH2	710
353	Ac-CSTWQC YW- [Orn]- [Dap] -YG- [AEA] - [(D)Ly s] -NH2	371
354	Ac-CSTWEC YW- [Cit]- [Dap]-YG- [AEA] -[(D)Ly s] -NH2	74
355	Ac-CQTWQCFF- [Orn] - [Dap] -FG- [AEA] - [(D)Lys] -NH2	4274
356	Ac-CPTWQC YWRVFG- [AEA] - [(D)Ly s] -NH2	422
347	Ac-CSTWEC YW- [Orn] - [Dab]-YG- [AEA] -[(D)Ly s] -NH2	338
358	Ac-CSTWEC YWRVFG-[AEA] - [(D)Ly s] -NH2	48
359	Ac-CLTWQCYWRVFG- [AEA] - [(D)Ly s] -NH2	134
360	Ac-CQT WQCYF- [Orn]- [Dap] -FG- [AEA] - [(D)Lys] -NH2	1885
461	Ac-CNTWQCYWRVFG-[AEA]-[(D)Lys]-NH2	21	79	96
362	Ac-C- [Dap] -TWQCYWRVFG-[AEA] -[(D)Ly s] -NH2	31		100
363	Ac-C- [N-Me-Ala] -TWQCYWRVFG- [AEA] - [(D)Ly s] -NH2	139
364	Ac-CKTWQCYWRVFG-[AEA]-[(D)Lys]-NH2	40
365	Ac-CQDWQC YWR- [Cha] -FG- [AEA] -[(D)Ly s] -NH2	113
366	Ac-CQT WQCYWR- [Ogl] -FG- [AEA] - [(D)Lys]-NH2	206
367	Ac-CQTWQCYWK- [Dap] -FG-[AEA] -[(D)Ly s] -NH2	32
368	Ac-CQTWQCYWH- [Dap] -FG-[AEA] -[(D)Ly s] -NH2	49		59
369	Ac-CQTWQC YWRLFG- [AEA] - [(D)Lys] -NH2	51		47
370	Ac-CQT WQCYW- [hArg] - [Dap]-FG- [AEA] - [(D)Lys] -NH2	56

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Table E3H. IC50 of Illustrative Peptides Containing the CXXWXCXXXX Motif

SEQ ID NO.	Sequence	Human I!··!!! IL23R ELISA (nM)	lieill! IL23R ELISA (nM)	pStat3 HTRF (nM)
371	Ac-CSTWECYWRTFG-NH2	252
372	Ac-CDSWECYWRTYG-NH2	366
373	Ac-CSTWECYWHTYG-NH2	181	286	97
374	Ac-CKTWTCYWHTYG-NH2	381
375	Ac-CRTWECYWHEYS-NH2	416
376	Ac-CRTWTCYWHEYG-NH2	434
377	Ac-CFTWQCYWHEYS-NH2	515
378	Ac-CQTWQCYW- [3 -Pal] -ENG-NH2	56	20	101
379	Ac-CQTWQC-NH2	>30000
380	Ac-CRTWQC-NH2	>30000
381	Ac-CADWVCY-NH2	>30000
382	Ac-CADWVCYW-NH2	>30000
383	Ac-CADWVCYWH-NH2	-30000
384	Ac-CADWVCYWHT-NH2	4795
385	Ac-CADWVCYWHTF-NH2	3277
386	Ac-CMTWQCYWLYGR-NH2	613
387	Ac-CRTWQCYWHEFG-NH2
388	Ac-CRTWECYWHTFG-NH2
389	Ac-CQTWQCYWHEFG-NH2
390	Ac-CRTWQCYWQQFGGE-NH2	81
391	Ac-CRSWQCYWLNFGPD-NH2	101
392	Ac-CRTWQCYWLKMGDS-NH2	39
393	Ac-CQTWQCYWIKRDQG-NH2	67
394	Ac-CSTWQCYWLKHGGE-NH2	19	24	2
395	Ac-CSTWECYWSQRADQ-NH2	240
396	Ac-CQTWECYWRTFGPS-NH2	58
397	Ac-CRTWQCYWQEKGTD-NH2	118
398	Ac-CQTWQCYWLDSLGD-NH2	93
399	Ac-CRTWQCYWTKFGSEP-NH2	87		57
340	Ac-CRSWQCYWNKFGADD-NH2	142
341	Ac-CHTWQCYWLNFGDEE-NH2	323
342	Ac-CRTWQCYWLNFGNEQ-NH2	127
343	Ac-CRTWQCYWSEFGTGE-NH2	180	778	103
344	Ac-CRTWQCYWLRLGDEG-NH2	352	483	181
345	Ac-CHTWQCYWSTLGPEA-NH2	222
346	Ac-CSTWQCYWSKQSGGS-NH2	133	204	89
347	Ac-CHTWQCYWLNNGTSQ-NH2	113
348	Ac-CHTWQCYWRANDGRD-NH2	210
349	Ac-SGCRTWQCYWHEFG-NH2	390
350	Ac-NKCRTWQCYWHEYG-NH2	112

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SEQ ID NO.	Sequence	Human I!··!!! IL23R ELISA (nM)	lieill! IL23R ELISA (nM)	pStat3 HTRF (nM)
351	Ac-SGCRTWECYWHEYG-NH2	257
352	Ac-DACRTWECYWHKFG-NH2	165
353	Ac-PECRTWECYWHKFG-NH2	197
354	Ac-QVCQTWECYWREFG-NH2	145
355	Ac-DRCVTWECYWREFG-NH2	217
356	Ac-ADQCRTWQCYWHEFG-NH2	228
357	Ac-KENCRTWECYWREFG-NH2	148
358	Ac-VQECSTWQCYWRTFG-NH2	138
359	Ac-GEECSTWQCYWRKFG-NH2	53		24
360	Ac-DGSCRTWQCYWHQFG-NH2	240
361	Ac-NADCHSWECYWREFG-NH2	872
362	Ac-ERNCSTWECYWRAFG-NH2	855
363	Ac-RVGCSTWECYWREFG-NH2	417
364	Ac-KANCRTWQCYWRKFE-NH2	412
365	Ac-YEDCRTWQCYWENFG-NH2	280
366	Ac-CQTWQCYWRNFGDS-NH2
367	Ac-CQTWQCYWRNFESG-NH2
368	Ac-CQDWQCYWREFGPG-NH2
369	Ac-CQDWQCYWRSFGPQ-NH2
370	Ac-CQTWQCYWRTLGPS-NH2
371	Ac-CRTWQCYWQNFG-NH2	235
372	Ac-CGTWQCYWRTFGPS-NH2	76
373	Ac-CSTWQCYWHKFGNE-NH2	182
374	Ac-CRTWECYWRTYGPS-NH2	116
375	Ac-CRTWQCYWWENSQM-NH2	99
376	Ac-CQTWQCYWREFGGG-NH2	165
377	Ac-CQTWQCYWRTHGDR-NH2	83
378	Ac-CRDWQCYWLSRP-NH2	330
379	Ac-CQTWQCYW- [K(Palm)] -ENG-NH2	4880
380	Ac-CQTWQC YW- [K(PEG8)] -ENG-NH2	153
381	Ac-CQTWQCYW- [hLeu] -EQG-NH2	128
382	Ac-CQTWQABUC- [(D)Tyrl -W-[hLeul -ENG-NH2	>30000
383	Ac-CQTWQC- [(N-MeTyr] -W- [hLeu] -ENG-NH2	>30000
384	Ac-CQTWQC-[Tic-OH] -W- [hLeu] -ENG-NH2	>30000
385	Ac-CQTWQCEW- [hLeu] -ENG-NH2	>30000
386	Ac-CQTWQCTW- [hLeu] -ENG-NH2	>30000
387	Ac-CQTWQC-[Cha]-W-[hLeu]-ENG-NH2	-6000
388	Ac-CQTWQCYW-[oc-MeLeu]-ENG-NH2	22	27	5
389	Ac-CQTWQCYW- [(D)Leu]-ENG-NH2	319
390	Ac-CQTWQCYW- [hLeu] -ENG- [(D)Ly s] -NH2	121
391	Ac-CQTWQCYW- [hLeu] -ENG-OH	317
392	Ac-CQTWQCYW- [hLeu] -ENE-NH2	222	1002	310
393	Ac-CQTWQCYW-[hLeu]-ENR-NH2	93

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SEQ ID NO.	Sequence	Human I!··!!! IL23R ELISA (nM)	lieill! IL23R ELISA (nM)	pStat3 HTRF (nM)
394	Ac-CQTWQC YW- [hLeu] -ENF-NH2	82	182	69
395	Ac-CQTWQC YW- [hLeu] -ENP-NH2	253	114	31
396	Ac-CQTWQC YW- [hLeu] -ENQ-NH2	347
397	Ac-CQTWQC YW- [hLeu] -ENL-NH2	45
398	Ac-CQTWQC YW- [hLeu] -EEG-NH2	135	53	16
399	Ac-CQTWQC YW- [hLeu] -ERG-NH2	647
400	Ac-CQTWQC YW- [hLeu] -EPG-NH2	108	140	27
401	Ac-CQTWQC YW- [hLeu] -ELG-NH2	158
402	Ac-CQTWQC YW- [hLeu] -ETG-NH2	818
403	Ac-CQTWQC YW- [hLeu] -FNG-NH2	395
404	Ac-CQTWQC YW- [hLeu] -PNG-NH2	4828
405	Ac-CQTWQC YW- [hLeu] -NNG-NH2	89		26
406	Ac-CQTWQC YW- [hLeu] -LNG-NH2	78
407	Ac-CQTWQC YW- [hLeu] -TNG-NH2	109
408	Ac-CQTWQCYWFENG-NH2	185
409	Ac-CQTWQCYWPENG-NH2	>30000
410	Ac-CQTWQCYWQENG-NH2	173
411	Ac-CQTWQCYWTENG-NH2	114
412	Ac-CQTWQCYWEENG-NH2	147
413	Ac-CQTWFCYW-[hLeu]-ENG-NH2	1412
414	Ac-CQTWPCYW-[hLeul-ENG-NH2	2735
415	Ac-CQTWNC YW- [hLeu] -ENG-NH2	1849
416	Ac-CQTWRC YW- [hLeu] -ENG-NH2	278
417	Ac-CQTWTCYW-[hLeu]-ENG-NH2	114
418	Ac-CQTWEC YW- [hLeul -ENG-NH2	164
419	Ac-CQTGQCYW-[hLeu]-ENG-NH2	>10,000
420	Ac-CQTPQCYW-[hLeu]-ENG-NH2	>10,000
421	Ac-CQTNQCYW-[hLeu]-ENG-NH2	>10,000
422	Ac-CQTRQCYW-[hLeu]-ENG-NH2	>10,000
423	Ac-CQTTQCYW- [hLeu] -ENG-NH2	>10,000
424	Ac-CQTEQCYW- [hLeu] -ENG-NH2	>10,000
425	Ac-CQFWQCYW-[hLeul-ENG-NH2	1152
426	Ac-CQPWQCYW-[hLeu]-ENG-NH2	>10,000
427	Ac-CQNWQCYW-[hLeu]-ENG-NH2	336
428	Ac-CQRWQCYW-[hLeu]-ENG-NH2	469
429	Ac-CQEWQC YW- [hLeu] -ENG-NH2	773
450	Ac-CFTWQCYW-[hLeu]-ENG-NH2	205
451	Ac-CPTWQCYW-[hLeu]-ENG-NH2	27412
452	Ac-CNTWQC YW- [hLeu] -ENG-NH2	61
453	Ac-CGTWQC YW- [hLeu] -ENG-NH2	167
454	Ac-CTTWQC YW- [hLeu] -ENG-NH2	59	28	10
455	Ac-CETWQC YW- [hLeu] -ENG-NH2	101
456	Ac-CQTWQC YW- [N-MeLeu] -ENG-NH2	>6000

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SEQ ID NO.	Sequence	Human I!··!!! IL23R ELISA (nM)	lieill! IL23R ELISA (nM)	pStat3 HTRF (nM)
457	Ac-CQTWQC YW- [oc-MeOrn] -ENG-NH2	46	64	12
458	Ac-CQTWQC YW- [oc-MeOrn] -ENG-NH2	28	31	7
459	Ac-CQTWQC- [oc-MePhe] -W- [hLeu]-ENG-NH2	-30000
460	Ac-CQTWQCYW-[Aib]-ENG-NH2	31	34	12
461	Ac-CQTWQC- [hTyr] -W- [hLeu] -ENG-NH2	-6000
462	Ac-CQTWQC-[Bip]-W-[hLeu]-ENG-NH2	237
463	Ac-CQTWQCYW-[Ogl]-ENG-NH2	66	163	76
464	Ac-CQTWQC YW- [hLeu] - [Ly s(Ac)] -NG-NH2	19	32	3
465	Ac-CQTWQC YW- [hLeu] -ENGG-NH2	61	140	24
466	Ac-CQTWQCYW-[hLeu]-ENGP-NH2	97
467	Ac-CQTWQC YW- [hLeu] -ENGE-NH2	180
468	Ac-CQTWQCYW-[hLeu]-ENG-(D)Glu-NH2	183
469	Ac-CQTWQC Y- [oc-MePhe] -[hLeu] -ENG-NH2	-30000
470	Ac-CQTWQCYW-[hLeu]-ENGP-NH2	239
471	Ac-CQTWQC YW- [hLeu] -ENGG-NH2	362
472	Ac-CQTWQC YW- [hLeu] -ENGL-NH2	174
473	Ac-CQTWQCYW-[hLeu]-ENGF-NH2	131
474	Ac-CQTWQC YW- [hLeu] -ENGE-NH2	129
475	Ac-CQTWQC YW- [hLeu] -ENGN-NH2	66		23
476	Ac-CQTWQC YW- [hLeu] -ENGT-NH2	160
477	Ac-CQTWQC YW- [hLeu] -ENGR-NH2	>10,000		>1000
478	Ac-PCQTWQCYW-[hLeu]-ENG-NH2	97
479	Ac-LCQTWQCYW-[hLeu]-ENG-NH2	61	26	21
480	Ac-FCQTWQCYW-[hLeu]-ENG-NH2	56	25	16
481	Ac-ECQTWQCYW-[hLeu]-ENG-NH2
482	Ac-NCQT WQC YW- [hLeu] -ENG-NH2
483	Ac-RCQT WQC YW- [hLeu] -ENG-NH2
484	Ac-CQTWQC Y- [2-Nal] - [hLeu] -ENG-NH2
485	Ac-CQTWQC Y- [ 1 -Nal] - [hLeu] -ENG-NH2	18	37	6
486	Ac-CQTWQC- [2-Nall-W- [hLeul -ENG-NH2	48	73	11
487	Ac-CQTWQC- [ 1 -Nal] - [2-Nal] -[hLeu] -ENG-NH2	78	125	17
488	Ac-CQTWQC- [2-Nal] - [ 1 -Nal] -[hLeu] -ENG-NH2	117
489	Ac-CQTWQC- [Aic] -W- [hLeu] -ENG-NH2	126
490	Ac-CQTWQCHW- [hLeu] -ENG-NH2	-6000
491	Ac-CQTWQC YH- [hLeu] -ENG-NH2	398
492	Ac-CQTWQC- [Tyr(OMe)] -W- [hLeu] -ENG-NH2	-30000
493	Ac-CQTWQCY-[Bipl-[hLeul-ENG-NH2	42	51	11
494	Ac-CQTWQC Y- [Tyr(OMe)] - [hLeu] -ENG-NH2	998
495	Ac-CQTWQCHH- [hLeu] -ENG-NH2	148
496	Ac-CQTWQC Y- [oc-MeTrp] - [hLeu] -EQG-NH2	>30000
497	Ac-CQTW-[(K(PEG8)]-CYWLENG-NH2	212
498	Ac-CQTWQCYWZ-LNG-NH2	800
499	Ac-CQTW- [K(PEG8)] C YW- [K(PEG8)] -ENG-NH2	753

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SEQ ID NO.	Sequence	Human I!··!!! IL23R ELISA (nM)	lieill! IL23R ELISA (nM)	pStat3 HTRF (nM)
500	Ac-CQTW-[K(Palm)]-CYWLENG-NH2	-30000
501	Ac-CQTWQCYW-[Om]-[K(Palm)]-NG-NH2	>6000
502	Ac-Gly-[(D)Asn]-(D)Glu-(D)Leu-(D)Trp-(D)Tyr-(D)Cys- (D)Gln-(D)Trp-(D)Thr-(D)Gln-(D)Cys-NH2	>30000
503	Ac-CQTWQC YW-[(0m)] - [K(Peg 8)] -NG-NH2	169
504	Ac-CRTWQCYWHEFG-NH2	166
505	Ac-CRTWECYWHTFG-NH2	333
506	Ac-CQTWQCYWHEFG-NH2	169
507	Ac-CQTWQCYWRNFGDS-NH2	96
508	Ac-CQTWQCYWRNFESG-NH2	315
509	Ac-CQDWQCYWREFGPG-NH2	82
510	Ac-CQDWQCYWRSFGPQ-NH2	117
511	Ac-CQTWQCYWRTLGPSNH2	66
512	Ac-CQTWQC YW- [(D)Prol -ENG-NH2	>30000
513	Ac-CQTWQCYWELNG-NH2	79
514	Ac-CQTWECYWELNG-NH2	154
515	Ac-CQTWQC Y[( 1 -Nal] - [α-MeLeu] -ENG-NH2	22	67	13
516	Ac-CQTWQC Y- [ 1 -Nal] - [(D)Asn]-ENG-NH2	145		98
517	Ac-CQTWQC YWLE- [K(Palm)] -G-NH2	>6000
518	Ac-CQTWQCYWLEN-[K(Palm)l-NH2	2800
519	Ac-CSTWECYWRTFG-NH2	252
520	Ac-CDSWECYWRTYG-NH2	366
521	Ac-CSTWECYWHTYG-NH2	181	286	97

Table E4A. IC50 of Illustrative examples of dimers of Peptides Containing the Ac-[Pen]XXWX-[Pen]-XXXX Motif and analogues

SEQ ID NO.	Sequence	Human ELISA iiiiOii	llOSlll iiiiiii llilll!	pStatJ HTRF iiiiiliii
522	[Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] - [2-Nal] - [α-MeLy s] ENG-NH2]2DIG	**		*
523	[Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] - [2-Nal] - [α-MeLy s] ENG-NH2]2 PEG25	*		**
524	[Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMe-Leu]-QNN-NH2]2 DIG	**		**
525	[Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMe-Leu]-QNN-NH2]2 PEG25	*		**
526	[Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] [Aib]-[Lys(Ac)]-NQ-NH2]2 DIG	***		***
527	[Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] [Aib]-[Lys(Ac)]-NQ-NH2]2 PEG25	**		***

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SEQ ID NO.	Sequence	Human ELISA IlMBl!	lllOllI ELISA llBill!	pStatJ HTRF lllliii!
528	[Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] - [2-Nal] - [cc-MeVal][Lys(Ac)]-NN-[D)Lys]]2 DIG			*
529	[Ac- [Pen] -QTWQ [Pen] - [Phe [4-(2 -acetylaminoethoxy)] - [2 Nal]- [a-MeVal]-[Lys(Ac)]-NN-[D)Lys]]2 DIG			*
530	[Ac- [Pen] -QTWQ [Pen] - [Phe [4-(2 -acetylaminoethoxy)] - [2 Nal]-[a-MeVal]-KNN-NH2]2 DIG		**	*
531	[Ac- [Pen] -QTWQ [Pen] - [Phe [4-(2 -acetylaminoethoxy)] - [2 Nal]-K-[Lys(Ac)]-NN-NH2]2 DIG		***	*
532	[Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] - [2-Nal] - [α-MeLys] [Lys(Ac)]-NN-NH2]2 DIG		**	*
533	[Ac- [a-MeLys] -[Pen] -QTWQ- [Pen]- [Phe(4-CONH2)] - [2-Nal] [a-MeVal]-[Lys(Ac)]-NN-NH2]2 DIG
534	[Ac- [Pen] -QTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [α-MeLys] [Lys(Ac)]-NN-NH2]2 DIG	*	**	*
535	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [Aib] -KNNNH2]2DIG	*	**	*
536	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [4-amino-4carboxy-tetrahydropyran]-KNN-NH2]2 DIG			*
537	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [Achc]KNN-NH2]2 DIG			*
538	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [Acvc]KNN-NH2]2 DIG	*	**	*
539	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [α-MeLeu] KNN-NH2]2 DIG			*
540	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal]- [Aib] -KNNNH2]2 DIG			*
541	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal]- [4-amino-4carboxy-tetrahydropyran] -KNN -NH2]2 DIG			*
542	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal]- [Ache] -KNNNH2]2 DIG			*
543	[Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal]- [Acvc] -KNNNH2]2 DIG			*
544	[Ac- [Pen] -NTWQ- [Pen]- [Phe(4-OMe)] - [2-Nal] - [a-MeLeu]KNN-NH2]2 DIG			*
545	[Ac- [Pen] -QTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [α-MeLys] [Lys(Ac)]-NN-NH2]2 IDA			*
546	[Ac- [Pen] -QTWQ- [Pen] - [Phe(4-CONH2)] - [2-Nal] - [α-MeLys] [Lys(Ac)]-NN-NH2]2 [IDA-pAla]			*
*=<10nl	Vt; **=10-25 nM *** = 25-100 nM, **** = 100-1000 nM, *****=1000-10,000 nM.

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Table E4B. IC50 of Illustrative Peptides Containing the Ac-[Pen]-XXWX-[Pen]-XXXX Motif

and Ana	ogues
SEQ ID NO.	Sequence	Human lliiiliii ΙΙΙΙβΙΙ!	Rat ELISA (nM)	|)Stat3 HTRF iiiii!
547	Ac- [Pen] -RTWQ- [Pen] - YWRKFG- [AEA]- [(D)-Lys] -NH2			***
548	Ac-A- [Pen] -D WV- [Pen] - YWRKFG- [AEA] - [(D)-Lys]-NH2	>30000
549	Ac- [ [Pen] -QT WQ- [Pen] - Y W- [hLeu] -ENG-NH2
550	Ac- [Pen] -QTWQ- [Pen] -YW [N-MeArg] -ENG-NH2	>30000
551	Ac- [Pen] -QTWQ- [Pen]-YW- [hLeu] -ENG-NH2
552	Ac- [Pen] -QTWQ- [Pen]-YW- [N-MeArg] -ENG-NH2	>30000
553	Ac-A- [Pen] -D WV- [Pen] - YW- [Orn]- [Dap] -FG- [AEA] - [(D)-Ly s] - NH2	>30000
554	Ac- [Pen] -QTWQ- [Pen] - YW- [α-MeLeu] -ENG-NH2	***		**
555	Ac- [Pen] -QTWQ- [Pen]-YW- [(D)Asn] -ENG-NH2	*****
556	Ac- [Pen] -QTWQ- [Pen] - Y- [2-Nal] - [α-MeLys] -ENG-NH2	***		*
557	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] -[2-Nal] - [α-MeLys] -ENGNH2	***		**
558	Ac- [Pen] -QTWQ- [Pen] - [2-Nal] - [2-Nal] - [α-MeLys] -ENG-NH2			**
559	Ac- [Pen] -QTWQ- [Pen] - Y- [2-Nal] - [α-MeOm] -ENG-NH2	***		**
560	Ac- [Pen] -QTWQ- [Pen]-YW- [a-MeOm] -ENG-NH2			***
561	Ac- [Pen] -QTWQ- [Pen] - Y- [ 1 -Nal] - [a-MeOm] -ENG-NH2			***
562	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] -[2-Nal] - [a-MeOm] [Lys(Ac)]-NG-NH2			***
563	Ac- [Pen] -QTWQ- [Pen] - YW- [a-MeLys] - [Ly s(Ac)] -NG-NH2			***
564	Ac- [Pen] -QTWQ- [Pen]- [Phe-(4-OMe)]-W- [a-MeLys] [Lys(Ac)]-NG-NH2	***	***	**
565	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] -[2-Nal] - [a-MeLys] [Lys(Ac)]-NG-NH2	***	***	*

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SEQ ID NO.	Sequence	Human lliiiliii ΙΙΙΙβΙΙ!	!! iiiiliiii	pStatJ HTRF iiiii!
566	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] -[ 1 -Nal] - [α-MeLys] [Lys(Ac)]-NG-NH2	***		***
567	Ac- [Pen] -QTWQ- [Pen] - [BIP]- [2-Nal] - [α-MeLys] - [Ly s(Ac)] NG-NH2	>10,000
568	Ac- [Pen] -QTWQ- [Pen] -Phe(3,4-Cl2)- [2-Nal] - [α-MeLys] [Lys(Ac)]-NG-NH2
569	Ac- [Pen] -QTWQ- [Pen] - [Phe(3,5 -F2)] - [2-Nal] - [α-MeLys] [Lys(Ac)]-NG-NH2
570	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-NH2)] -[2-Nal]- [a-MeLy s][Lys(Ac)]-NG-NH2
571	Ac- [Pen] -QTWQ- [Pen] - [2-Nal] - [α-MeLy s] -[Lys(Ac)] -NG-NH2	>10000
572	Ac- [Pen] -QTWQ [Pen]- [Phe(3,4-Cl2)] - [2-Nal] - [α-MeOm] -ENGnh2
573	Ac-[Pen]-QTWQ[Pen]-[Phe(4-CN)]-[2-Nal]-[a-MeOm]-ENG- nh2
574	Ac- [Pen] -QTWQ [Pen]- [Phe(3,5 -F2)] -[2-Nal] - [a-MeOm]-ENGnh2
575	Ac- [Pen] -QTWQ [Pen]- [Phe(4-CH2CO2H)]- [2-Nal] - [α-MeOm] ENG-NH2
576	Ac- [Pen] -QTWQ [Pen]- [Phe(4-CH2COEt2)] - [2-Nal]- [a-MeOm] ENG-NH2
577	Ac- [Pen] -QTWQ [Pen]- [Phe(penta-F)]- [2-Nal] - [α-MeOm] -ENG- nh2
578	Ac- [Pen] -QTWQ [Pen]- [Phe(4-CF3)] - [2-Nal]- [a-MeLy s] -ENGnh2
579	Ac- [Pen] -QTWQ [Pen]- [Phe [4-(2-aminoethoxy)]- [2-Nal] - [aMeLys]-ENG-NH2
580	Ac- [Pen] -QTWQ [Pen]- [Phe [4-(2-aminoethoxy)]- [2-Nal] - [aMeLys]-ENG-NH2
581	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-0Me)] -[2-Nal] - [α-MeLys] K(ivDde)-NG-NH2
582	succinic acid- [Pen] -QTWQ [Pen] -[Phe(4-0Me)] - [2-Nal] - [aMeLys] - [Ly s(Ac)] -NG-NH2	***	***	*
583	glutaric acid- [Pen]-QTWQ [Pen] - [Phe(4-0Me)] -[2-Nal] - [aMeLys] - [Ly s(Ac)] -NG-NH2	***	***	**
584	4-methylmorpholine-2,6-dione- [Pen] -QTWQ [Pen] - [Phe(4OMe)]-[2-Nal] - [α-MeLy s]- [Lys(Ac)] -NG-NH2	***	***	**
585	pyroglutamic acid-[Pen]-QTWQ[Pen]-[Phe(4-OMe)]-[2-Nal]-[aMeLys] - [Ly s(Ac)] -NG-NH2	***	***	*

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SEQ ID NO.	Sequence	Human lliiiliii ΙΙΙΙβΙΙ!	lliilil	pStatJ HTRF lliiii
586	isovaleric acid- [Pen] -QTWQ [Pen] - [Phe(4 -OMe)] - [2 -Nal] - [aMeLys] - [Ly s(Ac)] -NG-NH2	***	***	**
587	gallic acid- [Pen]-QTWQ [Pen] - [Phe(4-OMe)]-[2-Nal]-[aMeLys] - [Ly s(Ac)] -NG-NH2	*****
588	octanoic acid- [Pen] -QTWQ [Pen] -[Phe(4-OMe)] - [2-Nal] -[aMeLys] - [Ly s(Ac)] -NG-NH2
589	4-Biphenylacetic acid- [Pen] -QTWQ [Pen] - [Phe(4-OMe)]- [2 -Nal] - [α-MeLys] - [Lys (Ac)] -NG-NH2
590	4-fluoropheny lacetic acid- [Pen] -QT WQ - [Pen] - [Phe(4 -OMe)] - [2 Nal] - [α-MeLys] - [Lys (Ac)] -NG-NH2	***		*
591	Hy-[Pen]-ADWV-[Pen]-YWHTFG-NH2	>6000
592	Ac- [Pen] -GTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMeLys]-ENG-NH2	**		*
593	Ac-[Pen]-TTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a- MeLys]-ENG-NH2	**		*
594	Ac-[Pen]-STWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a- MeLys]-ENG-NH2	**		*
595	Ac-[Pen]-[Dap]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [a-MeLys]-ENG-NH2	*	***	*
596	Ac- [Pen] - [a-MeOm] -T WQ [Pen] - [Phe [4 -(2 -aminoethoxy)] - [2Nal] - [α-MeLys] -ENG-NH2
597	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMeLys]-ENG-NH2	*		*
598	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMeLys] - [Ly s(Ac)] -NG-NH2	*	***	*
599	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[aMeLys] - [Ly s(Ac)] -NN-NH2	*	**	*
600	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMeLys]-ENG-NH2	**		*
601	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMeLys]-ENA-NH2	*	***	*
602	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMeLeu] - [Lys (Ac)] -NN-NH2	*	*	*
603	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] - [aMeLeu]-QNN-NH2	*	*	*
604	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] enn-nh2	*		*
605	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] -Aib[Lys(Ac)]-NN-NH2	*		*

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SEQ ID NO.	Sequence	Human lliiiliii ΙΙΙΙβΙΙ!	!! lliilil	pStatJ HTRF lliiii
606	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] [Lys(Ac)]-NQ-NH2	*		*
607	Ac- [Pen] -Dap (Ac)TWQ- [Pen] - [Phe [4 -(2 -acetylaminoethoxy)] [2-Nal]-[oc-MeLys(Ac)]-ENG-NH2	**		*
608	Ac- [Pen] - [oc-MeOm(Ac)] -T WQ- [Pen] - [Phe [4-(2acetylaminoethoxy)] -[2-Nal] - [oc-MeLy s(Ac)] -ENG-NH2
609	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal][oc-MeLy s(Ac)] - [Ly s(Ac)]-NG-NH2	*		*
610	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- [oc-MeLys(Ac)]-[Lys(Ac)]-NN-NH2	*		*
611	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- [oc-MeLys(Ac)]-ENG-NH2	**		*
612	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- [oc-MeLys(Ac)]-ENA-NH2	**		*
613	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal][oc-MeLeu]- [Lys(Ac)] -NN-NH2	*		*
614	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- [oc-MeLeu]-QNN-NH2	*		*
615	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- [Aib]-ENN-NH2	**		*
616	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal][Aib] - [Ly s(Ac)]-NN-NH2	*		*
617	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NQ-NH2	*		*
618	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] -[2-Nal] - [Aib] -ENN-NH2			*
619	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] [hLeu]-ENA-NH2			**
620	Ac-[Pen]-TTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			*
621	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]na-nh2			*
622	Ac-[Pen]-TTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NQ-NH2			*
623	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]NQ-NH2			*
624	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] [Lys(Ac)]-NA-NH2			*
625	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]nn-nh2			*

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SEQ ID NO.	Sequence	Human lliiiliii ΙΙΙΙβΙΙ!	!! lliilil	pStatJ HTRF lliiii
626	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] [hLeu]-[Lys(Ac)]-N-[pAla]-NH2			*
627	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)]-[2-Nal] - [hLeu] [Lys(Ac)]-N-[pAla]-NH2			*
628	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] [Lys(Ac)]-N-[pAla]-NH2			*
629	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]Ν-βΑ1α]-ΝΗ2			*
630	Ac- [Pen] -NTWQ- [Pen]- [Phe(4-OMe)] -[2-Nal] - [Aib] -ENN-NH2			*
631	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] [hLeu]-ENA-NH2			*
632	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] [Lys(Ac)]-NN-NH2	*	*	*
633	Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]Ν-[βΑ1α]-ΝΗ2			*
634	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] [Lys(Ac)]-NQ-NH2			*
635	Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]NA-NH2			*
636	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] [Lys(Ac)]-NA-NH2			*
637	Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]NN-NH2			*
638	Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)]NQ-NH2			*
639	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] -[Aib] [Lys(Ac)]-N-[pAla]-NH2		**	*
640	Ac- [Pen] -NTWQ- [Pen] - [Phe(4-OMe)]-[2-Nal] - [hLeu] [Lys(Ac)]-N-[pAla]-NH2			*
641	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal] [hLeu]-[Lys(Ac)]-N-[3Ala]-NH2			*
642	Ac-E-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal][Aib] - [Ly s(Ac)]-NN-NH2			*
643	Ac-(D)Asp- [Pen]-QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2Nal] - [Aib] - [Ly s(Ac)] -NN-NH2			*
644	Ac-R-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal][Aib] - [Ly s(Ac)]-NN-NH2			*
645	Ac-(D)Arg-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2Nal] - [Aib] - [Ly s(Ac)] -NN-NH2			*

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SEQ ID NO.	Sequence	Human lliiiliii ΙΙΙΙβΙΙ!	!! iiiliii	pStatJ HTRF iiiii!
646	Ac-Phe- [Pen] -QTWQ- [Pen]- [Phe [4-(2-aminoethoxy)] - [2-N al] [Aib] - [Ly s(Ac)]-NN-NH2			*
647	Ac-(D)Phe- [Pen]-QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2Nal] - [Aib] - [Ly s(Ac)] -NN-NH2			*
648	Ac-[2-Nal]-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2Nal] - [Aib] - [Ly s(Ac)] -NN-NH2			*
649	Ac-T-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal][Aib] - [Ly s(Ac)]-NN-NH2			*
650	Ac-L-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal][Aib] - [Ly s(Ac)]-NN-NH2			*
651	Ac-(D)Gln- [Pen]-QTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2Nal] - [Aib] - [Ly s(Ac)] -NN-NH2
652	Ac- [(D)Asn] -[Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2Nal] - [Aib] - [Ly s(Ac)] -NN-NH2
653	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] -[2-Nal] - [cc-MeVal] [Lys(Ac)]-NN-[(D)Lys]-NH2			*
654	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- [oc-MeVal]-KNN-NH2			*
655	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]- K-[Lys(Ac)]-NN-NH2			***
666	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-OMe)] -[2-Nal] - [oc-MeLys] [Lys(Ac)]-NN-NH2			*
667	Ac- [(D)Lys] - [Pen] -QTWQ- [Pen] - [Phe(4-CONH2)] -[2-Nal] - [ccMeVal] - [Lys(Ac)] -NN-NH2			*****
668	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-CONH2)] -[2-Nal] - [oc-MeLys] [Lys(Ac)]-NN-NH2		***	*
669	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-CONH2)] -[2-Nal] - [cc-MeVal][Lys(Ac)]-NN-NH2		**	*
670	Ac- [Pen] -QTWQ [Pen]- [Phe(4-CONH2)]- [Phe(3,4-OMe2)]-[ccMeVal] - [Lys(Ac)] -NN-NH2			**
671	Ac- [(D)Phe] -[Pen] -NT WQ [Pen] -[Phe [4-(2-aminoethoxy)] - [2Nal] - [Aib] - [Ly s(Ac)] -NN-NH2
672	Ac- [(D)Phe] - [Pen] -NT WQ - [Pen] - [Phe [4-(2-aminoethoxy)] - [2 Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2
673	Ac- [(D)Phe] -[Pen] -NTWQ [Pen] -[Phe [4-(2-aminoethoxy)] - [2Nal]- [Achc]-[Lys(Ac)]-NN-NH2
674	Ac- [(D)Phe] - [Pen] -NT WQ - [Pen] - [Phe [4-(2-aminoethoxy)] - [2 Nal] - [4-amino-4-carboxy-tetrahydropyran] - [Cit] -NN-NH2
675	Ac- [(D)Phe] - [Pen] -NT WQ - [Pen] - [Phe [4-(2-aminoethoxy)] - [2 Nal] - [Ache] - [Cit] -NN-NH2

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SEQ ID NO.	Sequence	Human lliiiliii ΙΙΙΙβΙΙ!	!! lliilil	pStatJ HTRF iiii!
676	Ac- [(D)Phe] - [Pen] -NT WQ - [Pen] - [Phe [4-(2-aminoethoxy)] - [2 Nal] - [Aib] -[Ly s(Ac)] -N- [pAla] -NH2
677	Ac- [(D)Phe]-[Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [4amino-4-carboxy-tetrahydropyran] - [Lys(Ac)]-NN-NH2
678	Ac- [(D)Phe]-[Pen] -NTWQ- [Pen] - [Phe(4-OMe)]-[2-Nal]- [Ache] [Lys(Ac)]-NN-NH2
679	Ac- [(D)Phe]-[Pen] -NTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [4amino-4-carboxy-tetrahydropyran]-[Cit]-NN-NH2
680	Ac- [(D)Phe]-[Pen] -NTWQ- [Pen] - [Phe(4-OMe)]-[2-Nal]- [Ache] [Cit]-NN-NH2
681	Ac- [(D)Phe]-[Pen] -NTWQ- [Pen] - [Phe(4-OMe)]-[2-Nal]- [Ache] - enn-nh2
682	Ac- [Pen] -NTWQ [Pen]- [Phe(4-CONH2)]- [2-Nal] - [Aib] [Lys(Ac)]-NN-NH2
683	Ac- [Pen] -NTWQ [Pen]- [Phe(4-CONH2)]- [2-Nal]- [4-amino-4carboxy-tetrahydropyran] -Ly s(Ac)] -NN-NH2
684	Ac- [Pen] -NTWQ [Pen]- [Phe(4-CONH2)]- [2-Nal]- [Ache] [Lys(Ac)]-NN-NH2
685	Ac- [Pen] -NTWQ [Pen]- [Phe(4-CONH2)]- [2-Nal]- [Acpc] [Lys(Ac)]-NN-NH2
686	Ac- [Pen] -NTWQ [Pen]- [Phe(4-CONH2)]- [2-Nal] - [oc-MeLeu][Lys(Ac)]-NN-NH2
687	Ac- [Pen] -NTWQ [Pen] -[Phe(4-OMe)]-[2-Nal] - [Aib] -[Ly s(Ac)] nn-nh2
688	Ac- [Pen] -NTWQ [Pen] -[Phe(4-OMe)]- [2-Nal]- [4-amino-4carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2
689	Ac- [Pen] -NTWQ [Pen] -[Phe(4-OMe)]-[2-Nal] - [Ache] -[Ly s(Ac)] nn-nh2
670	Ac- [Pen] -NTWQ [Pen] -[Phe(4-OMe)]-[2-Nal] - [Acpc] -[Ly s(Ac)] nn-nh2
671	Ac- [Pen] -NTWQ [Pen] -[Phe(4-OMe)] - [2-Nal] - [oc-MeLeu] [Lys(Ac)]-NN-NH2

*=<10nM; **=10-25 nM *** = 25-100 nM, **** = 100-1000 nM, *****=1000-10,000 nM.

Table E5A, IC50 of Illustrative Peptide Inhibitors (Thioethers)

SEQ ID NO.	Seq u en ce/S tru ctu re	Human lillli! lillill
672	— [N-MeAla]-DWVCYWHTFG-[AEA]-[(D)Lys] -NH2 s—'	-6000

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SEQ ID iiiiii	Sequeiice/Structure	Human liiiiil lllllll
673	0. — [N-MeAla]-DWV-[Pen]-YWHTFG-[AEA]-[(D)Lys] -NH2	>30000
674	4N-MeAla]-DWV-[(D)Pen]-YWHTFG-[AEA]-[(D)Lys] -NH2	>30000
675	°V- |N-McAla|-D\VV-|liCys|-Y\VHTFG-| AEA|-|(D)Lys| -NH2	-6000
676	‘S— ADWVCYWHTFG-[AEA]-[(D)Lys] -NH2	-3000
677	— ADWV-[Pen]-YWHTFG-[AEA]-[(D)Lys] -NH2	>30000
678	V- ADWV-[(D)Pen]-YWHTFG-[AEA]-[(D)Lys] -NH2	>30000
679	V- ADWV-[hCys]-YWHTFG-[AEA]-[(D)Lys] -NH2 cr—1	-6000
680	ov QDWQCYWRENG-[AEA]-[(D)Lys] -NH2 /s—	>6000
681	c> QDWQCYWRENG-[AEA]-[(D)Lys] -NH2 '-	-30000
682	C> /- QDWQCYWRENG-[AEA]-[(D)Lys] -NH2 '-s-/	-6000
683	ov N~ QDWQCYWRENG-[AEA]-[(D)Lys] -NH2 -SC	-6000
684	S— QDWQCYWRENG-[AEA]-[(D)Lys] -NH2	-30000

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SEQ ID iiiiii	Sequeiice/Structure	Human liiiiil ll·!!
685	°V- QDWQCYWRENG-[AEA]-[(D)Lys] -NH2	>6000
686	ov QDWQ-[hCys]-YWRENG-[AEA]-[(D)Lys] -NH2 s-	>6000
687	c> QDWQ-[hCys]-YWRENG-[AEA]-[(D)Lys] -NH2	>6000
688	°V- QDWQ-[hCys]-YWRENG-[AEA]-[(D)Lys] -NH2 OT''-’	>6000
689	Ok — QDWQ-[hCys]-YWRENG-[AEA]-[(D)Lys] -NH2	-30000
690	v- QDWQCYWRENG-[AEA]-[(D)Lys] -NH,	>30000
691	3— QDWQ-[hCys]-CYWRENG-[AEA]-[(D)Lys] -NH2 o	>30000

Table E5B. IC50 of Illustrative Peptide Inhibitors (Thioethers) -S-

[Phe(4-OMe)]-[2-Nal]-XXXX-NH₂

Ac-Cyclo-[[Abu]-XXWXC]-[Phe(4-OMe)]-[2-Nal]-XXX-NH₂

SEQ ID llBill	Sequence	Human lllllll ιιΙίΒΙιι	Rat ELISA (nM)	pStat3 HTRF (nM
692	Ac-Cyclo-[[Abu]RTWQC]-YWRKFG- [AEA]-[(D)Lys]-NH2	***	****	***

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SEQ ID llBill	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
693	Ac-Cyclo-[CRTWQ-[Abu]]-YWRKFG[AEA]-[(D)Lys]- NH2	****	****	***
694	Ac-Cyclo-[[Abu]-QTWQC]-YWRENG[AEA]-[(D)Lys]- NH2	****	****	***
695	Ac-Cy clo- [ [Abu] -RTWQ- [Pen] ] YWRKFG-[AEA]-[(D)Lys]- NH2	*****
696	Ac- Cyclo-[[Pen]-RTWQ-[Abu]]YWRKFG-[AEA]-[(D) Lys]-NH2	****
697	Ac-Cyclo-[[(D)Cys]-RTWQ-[Abu]]YWRKFG-[AEA]-[(D)-Lys]- NH2	****
698	Ac-Cyclo-[[Abu]-QTWQC]-YW-[Orn][Dap]-NG-[AEA]-[(D) Lys]- NH2	****
699	Ac-Cyclo-[[Abu]-QTWQC]-YW-[hLeu]ENG- NH2	***		**
700	Ac-Cyclo-[Abu]-QTWQ-(D)Cys]]-YW- [hLeu]-ENG-NH2	*****
701	Ac-Cyclo-[[Abu]-QTWQ-[Pen]]-YW- [hLeu]-ENG-NH2	*****
702	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[ot-MeLys]-ENG-NH2	***	****	*
703	Ac-Cyclo-[[Abu]-QTWQC]-YW-[a- MeLeu]-ENG-NH2	**	***	*
704	Ac-Cyclo-[[Abu]-QTWQC]-Y-[2-Nal]- [oc-MeLys]-ENG-NH2	**	**	*
705	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[ot-MeLys]-ENG-NH2	**	**	*
706	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] - [2-Nal] - [ot-MeOrn] -ENG-NH2	**	***	*
707	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] -W- [α-MeOrn] -ENG-NH2	***	***	*
708	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[ot-MeLys]-ENG-NH2	**	***	*

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SEQ ID llBill	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
709	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-W-[a-MeLys]-[Lys(Ac)]-NG-NH2	**	**	**
710	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-W-[a-MeLys]-ENG-NH2	**	***	**
711	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[l-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2	***	***	**
712	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2	*	**	*
713	Ac-Cyclo-[[Abu]-QTWQC]-YW-[a- MeOrn]-[Lys(Ac)]-NG-NH2	***	***	**
714	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] - [2-Nal] - [(D) Asn] - [Ly s(Ac)] -NGnh2	***	****	***
715	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- Phenoxy)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2	****
716	Ac-Cyclo-[[Abu]-QTWQC]-[hPhe(3,4dimethoxy)] - [2-Nal] - [α-MeLy s] [Lys(Ac)l-NG-NH2	*****
717	Ac-Cyclo-[[Abu]-QTWQC]-[DMT]-[2- Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2	*****
718	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- CONH2)]-[2-Nal]-[a-MeLys]- [Lys(Ac)]NG-NH2	*	***	*
719	Ac-Cyclo-[[Abu]-QTWQC]-Phe(3,4Cl2) [2-Nal] - [α-MeLys] - [Ly s(Ac)]NGnh2	****		***
720	Ac-Cyclo- [ [Abu] -QTWQ- [Pen] ] - [Phe(4OMe)]-[2-Nal]-[a-MeLys]-ENG-NH2	****	****	***
721	Ac-Cyclo- [ [Abu] -QTWQ- [Pen] ] - [Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]NG- nh2	***	****	***
722	Ac-Cyclo- [ [Pen] -QTWQ- [Abu] ] - [Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]NG- nh2
723	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] - [Trp(2,5,7-tri-tert-Butyl)] - [a-	>10,000

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SEQ ID llBill	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
	MeLys]-ENG-NH2
724	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] - [Phe(4-0allyl)] - [α-MeLys]-ENGnh2	****
725	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[Tyr(3-tBu)]-[a-MeLys]-ENG- nh2	***	****	**
726	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[Phe(4-tBu)]-[a-MeLys]-ENG- nh2	*****
727	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] - [Phe(4-guanidino)] - [α-MeLys] eng-nh2	****
728	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[Phe(Bzl)]-[a-MeLys]-ENG-NH2	****
729	Ac-Cy clo-[[Abu]-QTWQC]-[Tyr(3-tBu)]W-[a-MeLys]-ENG-NH2	>10,000
780	Ac-Cy clo- [ [ Abu] -QTWQC] - [Phe(4-tBu)]W-[a-MeLys]-ENG-NH2	*****
781	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- guanidino)]-W-[a-MeLys]-ENG-NH2	***	***	***
782	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] -W- [a-MeLys] -ENG-NH2	**	**	*
783	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- CO2H)]-W-[a-MeLys]-ENG-NH2	****
784	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4phenoxy)] -W- [a-MeLy s] -ENG-NH2	***	***	**
785	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-CN)]- W-[a-MeLys]-ENG-NH2	***		***
786	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-Br)]- W-[a-MeLys]-ENG-NH2	***	***	***
787	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- NH2)]-W-[a-MeLys]-ENG-NH2	***	***	*

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SEQ ID iiiiii	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
788	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] -Phe(4-Me)- [α-MeLys] -ENG-NH2	****
789	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)]-[l -Nal]-[a-MeLys]-ENG-NH2	***	***	**
790	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] - [2-Nal] - [α-MeOrn] - [Ly s( Ac)] ng-nh2	**	**	*
791	Ac-Cyclo-[[Abu]-QTWQC]-[2-Nal]-[2- Nal]-[a-MeOrn]-[Lys(Ac)]-NG-NH2	***	****	*
792	Ac-Cyclo-[[Abu]-QTWQC]-[Bip]-[2- Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2	****
793	Ac-Cyclo-[[Abu]-QTWQC]-Cha-[2-Nal]- [a-MeLys]-[Lys(Ac)]-NG-NH2	*****
794	Ac-Cyclo-[[Abu]-QTWQC]-[2-Nal]-[2- Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2	***	***	**
795	Ac-Cyclo-[[Abu]-QTWQC]-[4Pyridylalanine] - [2-Nal] - [α-MeLy s] [Lys(Ac)l-NG-NH2	****
796	Ac-Cyclo-[[Abu]-QTWQC]-[phomoTyr] - [2-Nal] - [α-MeLy s]- [Lys(Ac)] ng-nh2	-10000
797	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- CONH2)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2	**	**	*
798	Ac-Cyclo-[[Abu]-QTWQC]-[2-Nal]-[2- Nal]-[a-MeLys]-ENG-NH2	***	***
799	Ac-Cyclo-[[Abu]-QT-[2-Nal]-QC][Phe(4-OMe)] - [2-Nal] - [α-MeLy s][Lys(Ac)l-NG-NH2	****
800	Ac-Cyclo-[[Abu]-QT-[l-Nal]-QC][Phe(4-OMe)] - [2-Nal] - [α-MeLy s][Lys(Ac)l-NG-NH2	****
801	Ac-Cyclo-[[Abu]-QTYQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2	-10000
802	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2

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SEQ ID iiiiii	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
803	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- NGGE-NHj	***
804	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ngae-nh2
805	Ac-Cyclo-[[Abu]-STWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ngge-nh2
806	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-W-[a-MeLys]-[Lys(Ac)]-NGGE- nh2
807	Ac-Cyclo-[[Abu]-QTWQC]-Y-[2-Nal]- [a-MeLys]-[Lys(Ac)]-NGGE-NH2
808	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] - [2-Nal] - [α-MeLys] - [Ly s(Ac)] -NSnh2	**	**	*
809	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- na-nh2	*	**	*
810	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[Aib]-[Lys(Ac)]-NG-NH2	**	***	*
811	Ac-Cyclo-[[Abu]-QTWQC]-[Phe-4-N3][2-Nal] - [α-MeLys] - [Ly s(Ac)] -NG-NH2	***	***	**
812	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- qg-nh2	***	***	*
813	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- [Cit]-G-NH2
814	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-VNG-NH2	***	***	*
815	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)]-[2-Nal]-[Orn]-[Lys(Ac)]-NG-NH2	****
816	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[Orn]-[Dap]-NG-NH2	****
817	Ac-Cy clo- [ [Abu] -NTWQC] - [Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2	**	***	*

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SEQ ID iiiiii	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
818	Ac-Cyclo-[[Abu]-QT-[Bip]-QC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- ng-nh2	-10000
819	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[Cha]-[Lys(Ac)]-NG-NH2	***	***	*
820	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[Chg]-[Lys(Ac)]-NG-NH2	***
821	Ac-Cyclo-[ [Abu]-QT-[Octgly]-QC][Phe(4-OMe)] - [2-Nal] - [a-MeLy s][Lys(Ac)l-NG-NH2	>10000
822	Ac-Cyclo-[[Abu]-QTWQC]-[Octgly]-[2- Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2	-10000
823	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[Octgly]-[a-MeLys]-[Lys(Ac)]- ng-nh2	-10000
824	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- nge-nh2	***	***	*
825	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- nae-nh2	*	**	*
826	Ac-Cyclo-[[Abu]-STWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]- nge-nh2	***	***	***
827	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4OMe)] -W- [α-MeLys] - [Ly s(Ac)] -NGEnh2	****
828	Ac-Cyclo-[[Abu]-QTWQC]-Y-[2-Nal]- [a-MeLys]-[Lys(Ac)]-NGE-NH2	***
829	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENG- nh2	*	*	*
830	Ac-Cyclo-[[Abu]-QTQQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENG- nh2	>3000
831	Ac-Cyclo-[[Abu]-QTHQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENG- nh2	>3000

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SEQ ID llBill	Sequence	Human liiiil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
832	Ac-Cyclo-[[Abu]-QT-[hPhe]-QC]-[Phe[4(2-aminoethoxy)] ] - [2-Nal] - [α-MeLys] eng-nh2	>3000
833	Ac-Cyclo-[[Abu]-QT-[Glu(Bzl)]-QC]- [Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLysl-ENG-NH2	>3000
834	Ac-Cyclo-[[Abu]-QT-[Bip]-QC]-[Phe[4(2-aminoethoxy)] ] - [2-Nal] - [α-MeLys] eng-nh2	>3000
835	Ac-Cyclo-[[Abu]-QT-[Tic]-QC]-[Phe[4(2-aminoethoxy)] ] - [2-Nal] - [α-MeLys] eng-nh2	>3000
836	Ac-Cy clo-^AbuJ-QT-fPhe^-^aminoethoxyjJJ-QCHPhe^-^aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENGnh2	>3000
837	Ac-Cy clo-[[ Abu]-QT-[Phe(3,4-02)]- QC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-MeLys]-ENG-NH2	>3000
838	Ac-Cyclo-[[Abu]-QT-[Phe(4-OMe)]-QC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENG-NH2	>3000
839	Ac-Cyclo-[[Abu]-QT-[Orn(Benzyl)]-QC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENG-NH2	>3000
840	Ac-Cyclo-[[Abu]-QT[Orn(Benzaldehy de)] -QC] - [Phe[4-(2aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENGnh2
841	Ac-Cyclo-[[Abu]-QTWQC][PheOCH2CH2NHAc] - [2-Nal] - [aMeLysl-ENG-NH2
842	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ά-MeLeu] -ENGnh2
843	Ac-Cyclo-[[Abu]-QT-[5-hydroxyTrp]- QC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-MeLysl-ENG-NH2	-3000
844	Ac-Cy clo-[[Abu]-QT-[6-chloroTrp]-QC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENG-NH2	**	**	*

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SEQ ID /lliilll	Sequence	Human liiliil Iii·!!	Rat ELISA (nM)	pStat3 HTRF (nM
845	Ac-Cy clo-[[Abu]-QT-[N-MeTrp]-QC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENG-NH2	>3000
846	Ac-Cy clo-[[Abu]-QT-[l,2,3,4-tetrahydronorharman]-QC]-[Phe[4-(2aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENGNH2	****
847	Ac-Cyclo-[[Abu]-QT-[Phe(4-CO2H)]- QC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-MeLys]-ENG-NH2	>3000
848	Ac-Cyclo-[[Abu]-QT-[Ph(4-CONH2)]- QC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-MeLys]-ENG-NH2	>3000
849	Ac-Cyclo-[[Abu]-QT-[Ph(4-CONH2)]- QC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [ot-MeLysl-ENG-NH2	>3000
850	Ac-Cy clo- [ [ Abu] -QT- [Phe(3,4-OMe)] - QC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-MeLys]-ENG-NH2	-3000
851	Ac-Cy clo-[[Abu]-QT-[a-MePhe]-QC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENG-NH2	****
852	Ac-Cyclo-[[Abu]-QT-[Phe(4-CF3)]-QC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLysl-ENG-NH2	-3000
853	Ac-Cyclo-[[Abu]-QT-[Phe(4-tBu)]-QC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENG-NH2	>3000
854	Ac-Cy clo- [ [ Abu] -QT- [Phe(2,4-Me2)]- QC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [ot-MeLysl-ENG-NH2	****
855	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] DNG-NH2	*	**	*
856	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] QNG-NH2	*		*
857	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Benzoic acid)]-NG-NH2	*		*

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SEQ ID llBill	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
858	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(succinic acid)]-NG-NH2	*	**	*
859	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(glutaric acid)l-NG-NH2	*		*
860	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(pyroglutamic acid)]-NG-NH2	*		*
861	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(isovaleric acid)l-NG-NH2	*	**	*
862	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Palm)l-NG-NH2	-3000
863	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] Lys[(PEGl)l-NG-NH2
864	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(PEG2)l-NG-NH2
865	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Dap(Benzoic acidjl-NG-NEB
866	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Dap(succinic acidjl-NG-NEE
867	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Dap(glutaric acidjl-NG-NEB
868	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Dap(pyroglutamic acid)]-NG-NH2	**		*
869	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] Dap(IVA)NG-NH2
870	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Dap(PEGl)l-NG-NH2
871	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Dap(PEG2)l-NG-NH2

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SEQ ID lliill	Sequence	Human liiBil llliBil!	Rat ELISA (nM)	pStat3 HTRF (nM
872	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Dap(PEG2-Ac)l-NG-NH2	**		**
873	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Ac)l-NG-[AEAl-[(D)Lysl-NH2	*		*
874	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [a-MeLys][Lys(Ac)l-NG-[(D)Lysl-NH2	*		*
875	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [a-MeLys][Lys(Ac)l-NG-[AEAl-NH2	*		*
876	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Aib] - [Lys (Ac) ] qg-nh2	**		*
877	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ Aib] -QNG-NH2	*	**	*
878	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ Aib]-ENG-NH2	*		*
879	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] -1 -Nal[ Aib] - [Ly s( Ac)] ng-nh2	***		**
880	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Aib] - [Ly s( Ac) ] na-nh2	*	**	*
881	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Aib] -KNG-NH2	*		*
882	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [Phe(4-CO2H)]-[aMeLysl-[Lys(Ac)l-NG-NH2	****
883	Ac-Cy clo- [ [Abu] - [Dap] -TWQC]- [Phe[4(2-aminoethoxy)] ]- [Phe(4-Phenoxy)] - [aMeLysl-[Lys(Ac)l-NG-NH2	****
884	Ac-Cyclo- [ [Abu] -Dap TWQC] - [Phe[4-(2aminoethoxy)] ] - [Phe[4-(2aminoethoxy)] ] - [α-MeLys] - [Ly s( Ac)]ng-nh2	****
885	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [α-MeLys] - [Ly s( Ac)]ng-nh2	>3000

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SEQ ID lliill	Sequence	Human lliMl!	Rat ELISA (nM)	pStat3 HTRF (nM
886	Ac-Cyclo- [ [Abu] -Dab TWQC] - [Phe[4-(2aminoethoxy)] ] - [hPhe] - [α-MeLy s] [Lys(Ac)l-NG-NH2	>1000
887	Ac-Cyclo- [ [Abu] -Dap TWQC] - [Phe[4-(2aminoethoxy) ] ] - [Glu(Bzl)] - [α-MeLys ] [Lys(Ac)l-NG-NH2	>3000
888	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - W - [α-Me-Orn] -EN Gnh2	**		*
889	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-W-[a-MeLys]-[Lys(Ac)]- NG-NH2	*		*
890	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] -W- [α-Me-Orn] [Lys(Ac)l-NG-NH2	**		**
891	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [a-Me-Orn][Lys(Ac)l-NG-NH2	*		*
892	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Ac)l-NG-NH2	*	*	*
893	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Orn] - [Lys(Ac)] NG-NH2	**		**
894	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] -W- [Orn] -ENG-NH2	***
895	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] -W- [Orn] - [Dap] -NG-NH2	****
896	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-W-[Orn]-[Dap(Ac)]-NG- nh2	****
897	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[Orn]-[Dap]-NG- nh2	***		***
898	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Orn] - [Dap(Ac)] NG-NH2	***
899	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy) ] ] - W- [hLeu] -ENG-NH2	**		*

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SEQ ID llBil!	Sequence	Human liiiiil liiiili!	Rat ELISA (nM)	pStat3 HTRF (nM
900	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2(acety 1-aminoethoxy)] ] - [2-Nal] - [aMeLys(Ac)]-[Lys(Ac)l-NG-NH2	*	*	*
901	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - W - [α-Me-Leu] -EN Gnh2	*		*
902	Succicinyl-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] -[2-Nal]-[aMeLysl-[Lys(Ac)l-NG-NH2	*	*	*
903	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-W-[a-MeLys]-[Lys(Ac)]- [Dapl-G-NH2	*****
904	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)]]-W-[a-MeLys]-[Lys(Ac)][6-amino-1,4-diazepane-2,5-dione] -NH2	***		*
905	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] -W-Chg- [Lys(Ac)] -NGnh2	***
906	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2(acety 1-aminoethoxy)] ] - [2-Nal] - [aMeLys(Ac)l-ENG-NH2	*	*	*
907	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [Phe(4-CONH2)]-[aMeLysl-[Lys(Ac)l-NG-NH2	****
908	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [Phe(3,4-OMe2] - [aMeLys]-[Lys(Ac)]-NG-NH2	**	***	*
909	Ac-Cy clo- [ [Abu] - [Dap] -TWQC]- [Phe[4(2-aminoethoxy)] ]- [Tic] - [α-MeLys] [Lys(Ac)l-NG-NH2	>3000
910	Ac-Cyclo- [ [Abu] -Dap TWQC] - [Phe[4-(2- aminoethoxy)]]-[Phe(3,4-Cl2)]-[a- MeLysl-[Lys(Ac)l-NG-NH2	***
911	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s]-ENQnh2	*	*	*
912	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENN- nh2	*	*	*
913	Ac-Cyclo-[[Abu]-TTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENG- nh2	*		*

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SEQ ID iiBiii	Sequence	Human liiBil llliMl!	Rat ELISA (nM)	pStat3 HTRF (nM
914	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [a-MeGly(Ethyl)] Lys(Ac)l-NG-NH2	*		*
915	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeVal] [Lys(Ac)l-NG-NH2	*	*	*
916	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeSer] [Lys(Ac)l-NG-NH2	*		*
917	Ac-Cyclo-[[Abu]-QTDapQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Ac)l-NG-NH2	>3000
918	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ]- [Dap] -[α-MeLy s][Lys(Ac)l-NG-NH2	>3000
919	Ac-Cyclo-[[Abu]-QTRQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Ac)l-NG-NH2	>3000
920	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] -R- [α-MeLy s] - [Lys(Ac)]ng-nh2	>3000
921	Ac-Cyclo-[[Abu]-QTDapQC]-[Phe[4-(2aminoethoxy)] ]-[Dap]-[α-MeLy s][Lys(Ac)l-NG-NH2	>3000
922	Ac-Cyclo-[[Abu]-QTDQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Ac)l-NG-NH2	>3000
923	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ]-D-[α-MeLy s]-[Lys(Ac)]ng-nh2	>3000
924	Ac-Cyclo-[[Abu]-QTDQC]-[Phe[4-(2aminoethoxy)] ]-D-[α-MeLy s]-[Lys(Ac)]ng-nh2	>3000
925	Ac-(D)Lys-[Cyclo-[[Abu]-QTWQC]] - [Phe(4-OMe)]-[2-Nal]-[a-MeLeu]-ENG- nh2	*	**	*
926	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s ] -RNGnh2	**		*
927	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Orn]-NG-NH2	*		*

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SEQ ID iiBiii	Sequence	Human liiBil llliMl!	Rat ELISA (nM)	pStat3 HTRF (nM
928	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] kng-nh2	*		*
929	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] hRNG-NH2	*		*
930	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [hLeu] [Lys(Ac)l-N-[pAlal-NH2	*	*	*
931	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Cit]- [Dap] -NGnh2	**		*
932	Ac-Cy clo-[[Abu]-[a-Me-Orn]-TWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENG-NH2	***		**
933	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] nng-nh2	*		*
934	Ac-Cyclo-[[Abu]-STWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] kngge-nh2	****
935	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2(acety 1-aminoethoxy)] ] - [2-Nal] - [aMeLys(Ac)l-ENQ-NH2	*	*	*
936	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2(acety 1-aminoethoxy)] ] - [2-Nal] - [aMeLys(Ac)l-ENN-NH2	*	*	*
937	Ac-Cyclo-[[Abu]-TWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENG- nh2
938	Ac-Cy clo- [[ Abu] -QTWQC] - [Phe(4-Me)] [2-Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2	*		*
939	Ac-Cy clo- [[Abu] -QTWQC] - [Phe(3 -Me)] [2-Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2	**		*
940	Ac-Cy clo-[[Abu]-QTWQC]-[hTyr]-[2Nal]-[a-MeLys]-[Lys(Ac)]-NG-NH2	*****
941	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[a-MeTrp]-[a-MeLys]- [Lys(Ac)l-NG-NH2	-3000

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SEQ ID llBill	Sequence	Human liiliil llliBil!	Rat ELISA (nM)	pStat3 HTRF (nM
942	Ac-Cyclo- [ [Abu] - [α-MeSer] -TWQC][Phe[4-(2-aminoethoxy)] ] -[2-Nal]-[aMeLysl-[Lys(Ac)l-NG-NH2	***		**
943	Ac-Cyclo-[[Abu]-Q-[a-MeSer]-WQC][Phe[4-(2-aminoethoxy)] ] -[2-Nal]-[aMeLys]-[Lys(Ac)]-NG-NH2	>3000
944	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [a-MePhe]-[a-MeLy s][Lys(Ac)l-NG-NH2	>3000
945	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy) ] ] - W - [Aib] -EN G-NH2	**		*
946	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Aib] - [Lys (Ac) ] ng-nh2	*		*
947	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ Aib]-E[Dap(Ac)l-G-NH2	**		*
948	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ Aib]-E[Dab(Ac)l-G-NH2	*	*	*
949	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ Aib]-E[Lys(Ac)l-G-NH2	**		*
950	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy) ] ] - W - [Aib] -ENN-NH2	**		*
951	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLeu]-ENNnh2	*	*	*
952	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [Phe(3,4-OMe2)] - [ Aib] ENG-NH2	***		**
953	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [Phe(3,4-Cl2)] - [ Aib] ENN-NH2	***		*
954	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLeu)- [Cit] nn-nh2	*	*	*
955	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLeu] [Lys(Ac)l-NN-NH2	*	*	*

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SEQ ID llBill	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
956	Ac-Cy clo- [[Abu] -QTWQC] - [Phe(4-Me)][2-Nal]-[Aib]-ENG-NH2	**		*
957	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(3,4- F2)]-[2-Nal]-[Aib]-ENG-NH2	***		**
958	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(3- CONH2)]-[2-Nal]-[Aib]-ENG-NH2	****
959	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(2,4- Cl2)]-[2-Nal]-[Aib]-ENG-NH2	****
960	Ac-Cy clo- [[Abu] -QTWQC] - [Phe(3 -Me)][2-Nal]-[Aib]-ENG-NH2	**		*
961	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-Cl)]- [2-Nal]-[Aib]-ENG-NH2	**		*
962	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-F)]- [2-Nal]-[Aib]-ENG-NH2	****
963	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(2,4-Cl2, 4-OBz)]-[2-Nal]-[Aib]-ENG-NH2	*****
964	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4- OMe)]-[2-Nal]-[a-MeLeu]-ENG- [(D)Lys]-NH2	***		**
965	Ac-E-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENN- nh2	*	*	*
966	Ac-(D)Glu-[Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENN-NH2	*	*	*
967	Ac-Arg-Cyclo-[[Abu]-QTWQC]-[Phe[4(2-aminoethoxy)] ] - [2-Nal] - [α-MeLys] enn-nh2	*		*
968	Ac-[(D)Arg]-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENN-NH2	*	*	*
969	Ac-F-Cyclo-[[Abu]-QTWQC]]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENN- nh2	*	*	*
970	Ac-[(D)Phe]-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENN-NH2	*	*	*

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SEQ ID llBill	Sequence	Human liiBil llliBill	Rat ELISA (nM)	pStat3 HTRF (nM
971	Ac-[2-Nal]-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLys]-ENN-NH2	*	**	*
972	Ac-T-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENN- nh2	*	*	*
973	Ac-Leu-Cy clo- [ [Abu] -QTWQC] - [Phe[4(2-aminoethoxy)] ] - [2-Nal] - [α-MeLys] enn-nh2	*	*	*
974	Ac-[(D)Gln]-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [aMeLysl-ENN-NH2	*	*	*
975	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Acpc] -ENNnh2			**
976	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Acbc] -ENNnh2		*	*
977	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Ache] - ENN nh2		*	*
978	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Acvc] -ENN-NH2		*	*
979	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [4-amino-4carboxy-piper idine] -ENN-NH2			*
980	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [4-amino-4carboxy-tetrahy dropy ran] -ENN-NH2	*	*	*
981	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ά-MeLeu] [Lys(Ac)l-NG-NH2			*
982	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ά-MeLeu] -ENGnh2			*
983	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ά-MeLeu] qng-nh2			*
984	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [ά-MeLeu] - QN[pAlal-NH2			*

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SEQ ID llBill	Sequence	Human ELISA llliBil!	Rat ELISA (nM)	pStat3 HTRF (nM
985	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLeu] qdg-nh2			***
986	Ac-Cyclo-[[Abu]-QTWQC]- cyclo([Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-MeLeul-QDl-G-NH2			****
987	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [Aib] -QN- [PAla] nh2			*
988	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)]]-[l,2,3,4-tetrahydronorharman] - [ Aibl - QNG-NH2
989	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy) ] ] - [ 5 -hy droxy T rp] - [ Aib] qng-nh2			**
990	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Ac)] - [ Asn(isobutyl)] -G-N-NH2			***
991	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ] - [2-Nal] - [α-MeLy s] [Lys(Ac)]-[Asp(l,4-diaminoethane)]-G- nh2			***
992	Ac-(D)Phe-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [4amino-4-carboxy-tetrahydropyran]-ENNnh2
993	Ac-[(D)Arg]-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [4amino-4-carboxy-tetrahydropyran]-ENNnh2
*=<10n	M; **=10-25 nM *** = 25-100 nM, **** =	100-1000 nM, *****	=>1000r

Table E5C. IC50 of Illustrative Thioether Peptide Dimers Synthesized

SEQ ID NO.

Linker

Sequence

Human llBlil lllllill

Rat ELIS A (nlVI)

pStat3 HTRF

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994	DIG through (D)Lys	[Ac-[(D)Lys]-Cyclo-[[Abu]- QTWQC]-[Phe(4-OMe)]-[2- Nal]-[a-MeLeu]-ENG-NH2]2 DIG	*	***	*
995	DIG through Phe[4-(2- aminoethox y)]	[Ac-Cyclo-[[Abu]-QTWQC][Phe[4-(2-aminoethoxy)] ] - [2Nal]-[Aib]-QNG-NH2]2 DIG	***		**
996	DIG through a-MeLys	[Ac-Cyclo-[[Abu]-QTWQC][Phe(4-OMe)]-[2-Nal]-[aMeLys]-ENG-NH2]2 DIG	*	**	*
997	PEG25 through aMeLys	[Ac-[(D)Lys]-Cyclo-[[Abu]- QTWQC]-[Phe(4-OMe)]-[2- Nal]-[a-MeLys]-ENG-NH2]2 PEG25	*	**	*
998	DIG through (D)Lys	[Ac-Cyclo-[[Abu]-QTWQC][Phe(4-OBzl)] -W- [a-MeLys] ENG-NH2]2DIG			*
999	PEG25 through (D)Lys	[Ac-Cyclo-[[Abu]-QTWQC]Y(Bzl)-W- [a-MeLys] -ENGNH2]2PEG25			*
	Alexa488PEG4 through [D- Arg]	[D-Arg]-Cyclo-[[Abu] - QTWQC]-[Phe(4-2ae)]-[2- Nal]-[THP]-ENN-NH2			*

*=<10nM; **=10-25 nM *** = 25-100 nM, **** = 100-1000 nM, *****=>1000 nM.

Table E5D, Illustrative Thioether Peptides

SEQ ID NO.	Sequence	Human IL23R / IL23 ELISA (nM)
993	Ac-[D-Arg]- Cyclo-[[Abu]-QTWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-ENN-NH2	*
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWQC]-[Phe(4-2ae)]-[2Nal]-[THP]]-END-NH2	**
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-EDN-NH2	***
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWEC]-[Phe(4-2ae)]-[2Nal]-[THP]-ENN-NH2	**
	Ac-[D-Arg]- Cyclo-[[Abu]-ETWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-ENN-NH2	**

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	Ac-[D-Arg]- Cyclo-[[Abu]-QTWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-EDD-NH2	***
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWEC]-[Phe(4-2ae)]-[2Nal]-[THP]-END-NH2	**
	Ac-[D-Arg]- Cyclo-[[Abu]-ETWQC]-[Phe(4-2ae)]-[2Nal]-[Tetrahydropyran-A]-END-NH2	**
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWEC]-[Phe(4-2ae)]-[2Nal]-[THP]-EDN-NH2	***
	Ac-[D-Arg]- Cyclo-[[Abu]-ETWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-EDN-NH2	***
	Ac-[D-Arg]- Cyclo-[Abu-ETWEC]-[Phe(4-2ae)]-[2-Nal][THP]-ENN-NH2	**
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-ENN-OH	**
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-END-OH	***
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-EDN-OH	***
	Ac-[D-Arg]- Cyclo-[[Abu]-QTWEC]-[Phe(4-2ae)]-[2Nal]-[THP]-ENN-OH	**
	Ac-[D-Arg]- Cyclo-[[Abu]ETWQC]-[Phe(4-2ae)]-[2Nal]-[THP]-ENN-OH	**

* = < 1 nM; ** = 1 nM- 10nM; *** = 10 nM- 100 nM

Table E6, IC50 of Peptide Inhibitors (Ring Closing Metathesis)

SEQ ID NO.	Seq u en ce/S tru ctu re	IT ii mail ELISA llilil
1000	O ui θ NH2\ il n X V^ADWV- Jf* YWHTFG-NH2	~20000
1001	O ui θ Ac-NH. η Π Ji y^-ADWV^ YWHTFG-NH2	-30000
1002	O kl 0 Ac-NHL U N X yy RTWQ YWRKFG-[AEA]-[(D)Lys] -NH2	*****

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*=<10nM; **=10-25 nM *** = 25-100 nM, **** = 100-1000 nM, *****=1000-10,000 nM.

Table E7. IC50 of Illustrative Peptides Containing Cyclic amides (side chain cyclizations)

SEQ ID NO.	Sequence	Human lliilil iilhiiii
1009	Ac-Cyclo-[[Dap]-QTWQE]-YWRENG-[AEA]-[(D)Lys]-NH2	-6000
1010	Ac-Cyclo-[EQTWQ-[Dab]]-YWRENG-[AEA]-[(D)Lys]-NH2	>6000
1011	Ac-Cyclo-[EQTWQ-[Dap]]-YWRENG-[AEA]-[(D)Lys]-NH2	-6000
1012	Ac-Cyclo-[[Dab]QTWQE]-YWRENG-[AEA]-[(D)Lys]-NH2	-30000
1013	Ac-Cyclo-[[Dap]-QTWQ-[(D)Asp]-YWRENG-[AEA]-[(D)Lys]-NH2	>30000
1014	Ac-Cyclo-[[Dap]-QTWQD]-YWRENG-[AEA]-[(D)Lys]-NH2	>30000

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1015	Ac-Cyclo-[[DQTWQ-[Dab]]-YWRENG-[AEA]-[(D)Lys]-NH2	-6000
1016	Ac-Cyclo-[[Dab]QTWQD]-YWRENG-[AEA]-[(D)Lys]-NH2	>6000
1017	Ac-Cyclo-[[(D)Dab]-QTWQ-[(D)Asp]]-YWRENG-[AEA]-[(D)Lys]- nh2	-6000
1018	Ac-Cyclo-[[(D)Asp]-QTWQ-[(D)Dab]]-YWRENG-[AEA]-[(D)Lys]- nh2	-1400
1019	Ac-Cyclo-[[(D)Asp]-QTWQ-[(D)Dap]]-YWRENG-[AEA]-[(D)Lys]- nh2	-30000

Table E8. IC50 of Illustrative Peptides Containing the Ac-[Pen]-XXWXXXXXX Motif and Ac-XXXWX-[Pen]-XXXX analogues

SEQ ID NO.	Sequence	Human llllil!!	///Raf/// llllil!	pStatd HTRF
1020	Ac- [Pen] -AD WVC YWHTFG-NH2	*****
1021	Ac-CADWV-[Pen]-YWHTFG-NH2	*****
1022	Ac- [(D)Pen]-AD WVCYWHTFG- [AEA] -[(D)-Ly s] -NH2		*****
1023	Ac-CADWV- [(D)Pen] - YWHTFG- [AEA] - [(D)-Ly s] -NH2	>30000	*****
1024	Ac- [Pen] -RT WQCYWRKFG- [AEA] - [(D)-Ly s] -NH2
1025	Ac-ACDWV-[Pen]-YWRKFG-[AEA]-[(D)-Lys]-NH2	*****
1026	Ac-A- [Pen] -DWVC YWRKFG- [AEA] -[(D)-Ly s] -NH2
1027	Ac-A- [hCys] -DWV- [Pen] - YWRKFG- [AEA] -[(D)-Ly s] -NH2	-30000
1028	Ac-CQTWQ- [Pen] - YW- [α-MeLeu] -ENG-NH2
1029	Ac-CQTWQ- [Pen] - YW- [(D)Asn]-ENG-NH2	*****

*=<10nM; **=10-25 nM *** = 25-100 nM, **** = 100-1000 nM, *****=1000-10,000 nM.

[00698] SAR analysis of the activities of the peptide inhibitors tested indicated that the CXXXXC disulphide is associated with high activity. The two Trp residues and the Phe residue are also associated with high activity, but it is recognized that these amino acids can be readily exchanged with similar homologs (e.g., 1-Nal substitued for Trp and/or Phe substituted for Tyr). In addition, the data suggested that the presence of one or more basic residues at the C-terminus

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2 3 4 5 6 7 8 9 10 11 12 13 14

Cys-Xxx-Xxx-Trp-Xxx-Cys-Tyr-Trp-His-Xxx-Phe-Xxx-Xxx-(D)Lys-OH

I_I

EXAMPLE 3

Stability of Peptide Inhibitors in Simulated Intestinal Fluid (SIF), Simulated Gastric Fluid (SGF) and Redox Conditions [00699] Studies were carried out in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) to evaluate gastric stability of the peptide inhibitors of the present invention. In addition, studies were carried out to assess redox stability of the peptide inhibiotrs of the present invention.

[00700] SIF was prepared by adding 6.8 g of monobasic potassium phosphate and 10.0 g of pancreatin to 1.0 L of water. After dissolution, the pH was adjusted to 6.8 using NaOH. DMSO stocks (2 mM) were first prepared for the test compounds. Aliquots of the DMSO solutions were dosed into 6 individual tubes, each containing 0.5 mL of SIF, which is pre-warmed to 37°C. The final test compound concentration was 20 μΜ. The vials were kept in a benchtop Thermomixer® for the duration of the experiment. At each timepoint (0, 5, 10, 20, 40, 60, or 360 minutes or 24 hours), 1.0 mL of acetonitrile containing 1% formic acid was added to one vial to terminate the reaction. Samples were stored at 4°C until the end of the experiment. After the final timepoint is sampled, the tubes were mixed and then centrifuged at 3,000 rpm for 10 minutes. Aliquots of the supernatant were removed, diluted 1:1 into distilled water containing internal standard, and analyzed by LCMS/MS. Percent remaining at each timepoint was calculated based on the peak area response ratio of test to compound to internal standard. Time 0 was set to 100%, and all later timepoints were calculated relative to time 0. Half-lives were calculated by fitting to a firstorder exponential decay equation using Graphpad. Stablity in SIF assays is shown in Tables E9 and E10.

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PCT/US2016/042680 [00701] SGF was prepared by adding 20 mg NaCI, 32 mg porcine pepsin (MP Biochemicals, catalog 02102599), and 70μ1 HC1 to 10ml water (final pH=2). Aliquots of SGF (0.5ml each) were pre-warmed at 37°C. To start the reaction, 1 μΐ of peptide stock solution (lOmM in DMSO) was added to 0.5ml SGF and thoroughly mixed such that the final peptide concentration was 20μΜ. The reactions were incubated at 37°C with gentle shaking. At each time point (0, 15, 30, 60 min) 50μ1 aliquots were removed and added to 200 ul acetonitrile containing 0.1% formic acid to quench the reaction. Samples are stored at 4°C until the end of the experiment and centrifuged at 10,000 rpm for 5 minutes. Aliquots of the supernatant were removed, diluted 1:1 into distilled water containing internal standard, and analyzed by LCMS/MS. Percent remaining at each timepoint was calculated based on the peak area response ratio of test to compound to internal standard. Time 0 was set to 100%, and all later timepoints were calculated relative to time 0. Half-lives were calculated by fitting to a first-order exponential decay equation using GraphPad. Stability in SGF assays in shown in Tables E9 and E10.

Table E9. Stability of Illustrative Peptides containing the Ac-[Pen]-XXWX-[Pen]-XXXX Motif and Analogues in Simulated Intestinal Fluid (SIF) and Simulated Gastric Fluid (SGF)

SEQ ID NO:	Sequence	iiiiiiii llllill (min)	lllllBlll llllill! (min)
549	Ac- [[Pen] -QTWQ- [Pen] - YW- [hLeu] -ENG-NH2
1030	Ac- [Pen] -QTWQ- [Pen] -YWN-Me-RENG-NH2
551	Ac- [Pen] -QTWQ- [Pen] -YW- [hLeu] -ENG-NH2
552	Ac- [Pen] -QTWQ- [Pen] - YW- [N-MeArg] -ENG-NH2		***
554	Ac- [Pen] -QTWQ - [Pen] - YW- [α-MeLeu] -ENG-NH2		**
1028	Ac-CQTWQ- [Pen] - YW- [α-MeLeu] -ENG-NH2		*****
555	Ac- [Pen] -QTWQ- [Pen] -YW- [(D)Asn] -ENG-NH2		**
1029	Ac-CQTWQ- [Pen]-YW- [(D)Asn] -ENG-NH2		*****
556	Ac- [Pen] -QTWQ- [Pen] -Y-[2-Nal] -[a-MeLy s] -ENG-NH2		**
557	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)]-[2-Nal] - [a-MeLy s] -ENG-NH2	***	**
558	Ac- [Pen] -QTWQ- [Pen] - [2-Nal] - [2-Nal] - [α-MeLy s] -ENG-NH2		**

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SEQ ID NO:	Sequence	lllliill lllliii (min)	lllliBlll lllliii! (min)
559	Ac- [Pen] -QTWQ- [Pen] -Y-[2-Nal] -[oc-MeOrn] -ENG-NH2		**
560	Ac- [Pen] -QTWQ-[Pen] - YW- [oc-MeOm]-ENG-NH2		**
561	Ac- [Pen] -QTWQ- [Pen] -Y-[ 1 -Nal] -[oc-MeOrn] -ENG-NH2		**
1031	Ac- [Pen] -QTWQ- [Pen] - [[Phe(4-OMe)](OMe)]- [2-Nal]- [α-MeOm] [Lys(Ac)]-NG-NH2		*
563	Ac- [Pen] -QTWQ-[Pen] - YW- [a-MeLys] - [Ly s(Ac)] -NG-NH2	*	*
1032	Ac-[Pen]-QTWQ-[Pen]- [Phe(4-OMe)]-W-[a-MeLys]-[Lys(Ac)]-NG-NH2		*
565	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)]-[2-Nal] - [a-MeLys] - [Ly s(Ac)] -NGnh2	*	*
566	Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)]-[ 1 -Nal] - [a-MeLys] - [Ly s(Ac)] -NGnh2		*
1033	succinic anhydride- [Pen] -QTWQ [Pen] - [Phe(4-OMe)] - [2-Nal] - [α-MeLys] [Lys(Ac)]-NG-NH2	**	*
585	pyroglutamic acid-[Pen]-QTWQ[Pen]-[Phe(4-OMe)]-[2-Nal]-[a-MeLys][Lys(Ac)]-NG-NH2	**	*
1034	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]- [Lys(Ac)]-NN-NH2	*	*
601	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]- ENA-NH2	*	*
602	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]- [Lys(Ac)]-NN-NH2	**	***
603	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]- QNN-NH2	*	*
604	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] - [Aib] -ENNnh2	*	*
605	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-Aib-[Lys(Ac)]- nn-nh2	**	***
606	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NQ-NH2	*	*
607	Ac-[Pen]-Dap(Ac)TWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[a-	*	*

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SEQ ID NO:	Sequence	/lllliill lllllll (min)	I///////:·///////// /lllllll! (min)
	MeLys(Ac)]-ENG-NH2
608	Ac- [Pen] - [oc-MeOm(Ac)] -TWQ- [Pen]- [Phe [4-(2-acetylaminoethoxy)] - [2Nal]-[oc-MeLys(Ac)]-ENG-NH2	**	****
609	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[oc- MeLys(Ac)]-[Lys(Ac)]-NG-NH2	*	*
610	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[oc- MeLys(Ac)]-[Lys(Ac)]-NN-NH2	*	*
611	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[oc- MeLys(Ac)]-ENG-NH2	*	**
612	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[oc- MeLys(Ac)]-ENA-NH2	*	*
613	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[ocMeLeu] - [Ly s(Ac)]-NN-NH2	*	*
614	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[oc- MeLeu]-QNN-NH2	*	*
615	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[Aib]- enn-nh2	*	*
616	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2	*	*
617	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NQ-NH2	*	*
522	[Ac-[Pen]-QTWQ-[Pen]-[Phe(4-OMe)]-[2-Nal]-[oc-MeLys]-ENG-NH2]2 DIG		*
618	Ac- [Pen] -QTWQ-[Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib]-ENN-NH2	*	***
619	Ac- [Pen] -QTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] - [hLeu] -ENAnh2	*****	*****
620	Ac- [Pen] -TT WQ- [Pen] - [Phe [4 -(2 -aminoethoxy)] - [2-Nal] - [Aib] [Lys(Ac)]-NN-NH2	*	*
625	Ac- [Pen] -QTWQ-[Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib]- [Ly s(Ac)]-NN-NH2	*	**
628	Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-N-[pAla]-NH2	*	*

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SEQ ID NO:	Sequence	lllliill lllllll (min)	llllilill!!!!!! lllllll! (min)
630	Ac- [Pen] -NTWQ-[Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib]-ENN-NH2	*	***
631	Ac- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] - [2-Nal] - [hLeu] -ΕΝΑnh2	*****
632	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2	*	*
633	Ac- [Pen] -NTWQ-[Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib] - [Ly s(Ac)] -Ν- [βAla] nh2	*	**
634	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NQ-NH2	*	*
636	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NA-NH2	*	*
637	Ac- [Pen] -NTWQ-[Pen] - [Phe(4-OMe)] - [2-Nal] - [Aib]- [Ly s(Ac)]-NN-NH2	*	*
638	Ac-[Pen]-NTWQ-[Pen]-[Phe(4-OMe)]-[2-Nal]-[Aib]-[Lys(Ac)]-NQ-NH2	*	*
639	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-N-^Ala]-NH2	*	*
640	Ac- [Pen] -NTWQ-[Pen] - [Phe(4-OMe)] -[2-Nal] - [hLeu] - [Lys(Ac)] -Ν[βΑ1η]-ΝΗ2	*****	*****
641	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[hLeu]- [Lys(Ac)]-N-^Ala]-NH2	*****	*****
669	Ac- [Pen] -QTWQ- [Pen]- [Phe(4-CONH2)] - [2-Nal] -[oc-MeVal] - [Lys(Ac)] nn-nh2	**	*
534	[Ac-[Pen]-QTWQ-[Pen]-[Phe(4-CONH2)]-[2-Nal]-[oc-MeLys]-[Lys(Ac)]NN-NH2]2 DIG	**	*
1035	Ac- [(D)Phe]- [Pen] -NTWQ- [Pen] - [Phe [4-(2-aminoethoxy)] -[2-Nal]- [Aib][Lys(Ac)]-NN-NH2	*	*
676	Ac- [(D)Phe]- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] -[2-Nal] - [Aib][Lys(Ac)]-N-^Ala]-NH2	**	*
682	Ac- [Pen] -NTWQ [Pen] - [Phe(4-CONH2)] - [2-Nal] - [Aib]- [Ly s(Ac)]-ΝΝ- nh2	**
683	Ac- [Pen] -NTWQ [Pen] - [Phe(4-CONH2)] - [2-Ν al] -[4-amino-4-carboxytetrahydropyran]-Lys(Ac)]-NN-NH2	**	*

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SEQ ID NO:	Sequence	lllliill! llilll!! (min)	IIIIIIBII!!!! llilll!! (min)
684	Ac- [Pen] -NTWQ [Pen] - [Phe(4-CONH2)] - [2-Nal] -[Ache]- [Ly s(Ac)] -NNNH2	*	*
1036	Ac-[Pen]-NTWQ[Pen]-[Phe(4-CONH2)]-[2-Nal]-[Acvc]- [Lys(Ac)]-NNNH2	*	*
686	Ac- [Pen] -NTWQ [Pen] - [Phe(4-CONH2)] - [2-Nal] -[α-MeLeu] -[Ly s(Ac)] NN-NH2	*	*
688	Ac-[Pen]-NTWQ[Pen]-[Phe(4-OMe)]-[2-Nal]-[4-amino-4-carboxytetrahydropyran]- [Ly s(Ac)] -NN -NH2	*	*
689	Ac- [Pen] -NTWQ [Pen] - [Phe(4-OMe)] -[2-Nal] - [Ache] - [Ly s(Ac)]-NN-NH2	*	**
1037	Ac- [Pen] -NTWQ [Pen] - [Phe(4-OMe)] - [2-Nal] - [Acvc] - [Ly s(Ac)] -NN-NH2	**	*
671	Ac- [Pen] -NTWQ [Pen] - [Phe(4-OMe)] - [2-Nal]- [α-MeLeu] - [Ly s(Ac)] -NNNH2	*	*
535	[Ac-[Pen]-NTWQ- [Pen]- [Phe(4-CONH2)] - [2-Nal] - [Aib] -KNN-NH2]2 DIG	**	**
536	[Ac-[Pen]-NTWQ-[Pen]-[Phe(4-CONH2)]-[2-Nal]-[4-amino-4-carboxytetrahydropyran]-KNN-NH2]2 DIG	*	*
537	[Ac-[Pen]-NTWQ-[Pen]-[Phe(4-CONH2)]-[2-Nal]-[Achc]-KNN-NH2]2 DIG	**	***
539	[Ac-[Pen]-NTWQ-[Pen]-[Phe(4-CONH2)]-[2-Nal]-[a-MeLeu]-KNNNH2]2 DIG	**	**

§ the matrix used is 100 fold dilution of standard SIF concentration *=>360min; **=180-360minn; ***=120-180min; ****=<60-120min; *****=<60min

Table E10. Stability of Illustrative Peptides Containing Thioethers Motif and Analogues Within

Simulated Intestinal Fluid (SIF) and Simulated Gastric Fluid (SGF)

SEQ ID NO:	Sequence	llilll!!! lllliill! (min)	llllil!!!! Illlllilllllll (min)
692	Ac-Cyclo-[[Abu]RTWQC]-YWRKFG-[AEA]-[(D)Lys]-NH2	*****
694	Ac-Cyclo-[[Abu]-QTWQC]-YWRENG-[AEA]-[(D)Lys]-NH2	*****
699	Ac-Cyclo-[[Abu]-QTWQC]-YW-[hLeu]-ENG-NH2	*****	ND
700	Ac-Cyclo-[Abu]-QTWQ-(D)Cys]]-YW-[hLeu]-ENG-NH2

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SEQ ID NO:	Sequence	llllBllll lillllll (min)	llllillll lillllll (min)
701	Ac-Cyclo-[[Abu]-QTWQ-[Pen]]-YW-[hLeu]-ENG-NH2	*****
703	Ac-Cyclo-[[Abu]-QTWQC]-YW-[ot-MeLeu]-ENG-NH2	*****
704	Ac-Cyclo-[[Abu]-QTWQC]-Y-[2-Nal]-[a-MeLys]-ENG-NH2	*****
702	Ac-Cyclo- [ [Abu]-QTWQC] - [Phe(4-OMe)] - [2-Nal] - [aMeLysl-ENG-NH2		*****
706	Ac-Cyclo- [ [Abu]-QTWQC] - [Phe(4-OMe)] - [2-Nal] - [aMeOrn]-ENG-NH2		*****
707	Ac-Cyclo- [ [ Abu]-QTWQC] - [Phe(4-OMe)] - W- [α-MeOrn] ENG-NH2	**	*****
702	Ac-Cyclo- [ [Abu]-QTWQC] - [Phe(4-OMe)] - [2-Nal] - [aMeLys]-ENG-NH2	**	*****
709	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-OMe)]-W-[a-MeLys]- [Lys(Ac)l-NG-NH2	φ	*****
710	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-OMe)]-W-[a-MeLys]- ENG-NH2	φ	*****
711	Ac-Cyclo- [ [ Abu]-QTWQC] - [Phe(4-OMe)] - [ 1 -Nal] - [aMeLysl-[Lys(Ac)l-NG-NH2	φ	*****
712	Ac-Cyclo- [ [Abu]-QTWQC] - [Phe(4-OMe)] - [2-Nal] - [aMeLysl-[Lys(Ac)l-NG-NH2	**	*****
713	Ac-Cyclo-[[Abu]-QTWQC]-YW-[a-MeOrn]-[Lys(Ac)]-NG- nh2	**
714	Ac-Cyclo- [ [Abu] -QTWQC] - [Phe(4-OMe)] - [2-Nal] - [(D) Asn] [Lys(Ac)l-NG-NH2	φ
715	Ac-Cyclo- [ [ Abu] -QTWQC]- [Phe(4-Phenoxy)] - [2-Nal] - [aMeLysl-[Lys(Ac)l-NG-NH2	φ
716	Ac-Cyclo- [ [Abu]-QTWQC] - [hPhe(3,4-dimethoxy)] - [2-Nal] -[aMeLysl-[Lys(Ac)l-NG-NH2	**
717	Ac-Cyclo-[[Abu]-QTWQC]-[DMT]-[2-Nal]-[a-MeLys]- [Lys(Ac)l-NG-NH2	φ
718	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-CONH2)]-[2-Nal]-[a- MeLysl-[Lys(Ac)lNG-NH2		*****
719	Ac-Cyclo-[[Abu]-QTWQC]-Phe(3,4-Cl2)[2-Nal]-[a-MeLys]- [Lys(Ac)]NG-NH2
720	Ac-Cyclo-[[Abu]-QTWQ-[Pen]]-[Phe(4-OMe)]-[2-Nal]-[a- MeLysl-ENG-NH2	**
721	Ac-Cyclo-[[Abu]-QTWQ-[Pen]]-[Phe(4-OMe)]-[2-Nal]-[a- MeLys]-[Lys(Ac)lNG-NH2	**
782	Ac-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] -W- [aMeLys]-ENG-NH2	φ

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SEQ ID NO:	Sequence	lIllBllll llllillll (min)	llllillll llllillll (min)
790	Ac-Cyclo- [ [Abu]-QTWQC] - [Phe(4-OMe)] - [2-Nal] - [aMeOrn]-[Lys(Ac)]-NG-NH2		*****
791	Ac-Cyclo-[[Abu]-QTWQC]-[2-Nal]-[2-Nal]-[a-MeOrn]- [Lys(Ac)l-NG-NH2		ND
794	Ac-Cyclo-[[Abu]-QTWQC]-[2-Nal]-[2-Nal]-[a-MeLys]- [Lys(Ac)l-NG-NH2	**	ND
797	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-CONH2)]-[2-Nal]-[ot- MeLysl-[Lys(Ac)l-NG-NH2		*****
798	Ac-Cyclo-[[Abu]-QTWQC]-[2-Nal]-[2-Nal]-[a-MeLys]-ENG- nh2	**	ND
810	Ac-Cyclo- [ [Abu] -QTWQC] - [Phe(4-OMe)] - [2-Nal] - [Aib] [Lys(Ac)l-NG-NH2	φ
815	Ac-Cyclo- [ [Abu] -QTWQC] - [Phe(4-OMe)] - [2-Nal] - [Orn] [Lys(Ac)l-NG- NH2	φ
820	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-OMe)]-[2-Nal]-[Chg]- [Lys(Ac)l-NG-NH2
822	Ac-Cyclo-[[Abu]-QTWQC]-[Octgly]-[2-Nal]-[a-MeLys]- [Lys(Ac)l-NG-NH2	*****
823	Ac-Cyclo- [ [Abu]-QTWQC] - [Phe(4-OMe)] - [Octgly]-[aMeLysl-[Lys(Ac)l-NG-NH2
823	Ac-Cyclo- [ [Abu]-QTWQC] - [Phe(4-OMe)] - [Octgly]-[aMeLys]-[Lys(Ac)]-NG-NH2	*****
829	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-MeLys]-ENG-NH2	φ	Φ
857	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][a-MeLysl-[Lys(Benzoic acid)l-NG-NH2	**	φ
861	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][oc-MeLysl-[Lys(isovaleric acid)l-NG-NH2	φ	φ
876	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [Aibl-[Lys(Ac)l-QG-NH2		*****
877	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [Aibl-QNG-NH2		**
878	Ac-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [Aib]-ENG-NH2	*****
879	Ac-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] -1 Nal[Aib]-[Lys(Ac)]-NG-NH2	φ	φ
880	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][ Aib]- [Ly s(Ac)] -NA-NH2		*****
891	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]- [a-Me-Orn]-[Lys(Ac)l-NG-NH2	**	**
892	Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-	φ	φ

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SEQ ID NO:	Sequence	IlllBllll lliilil (min)	lliilil!!!! 111111111 (min)
	[a-MeLys]-[Lys(Ac)]-NG-NH2
893	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][Orn]-[Lys(Ac)]-NG-NH2	*****
894	Ac-Cy clo- [ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] -W[Orn]-ENG-NH2	*****
895	Ac-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] -W[Ornl-[Dapl-NG-NH2	*****
896	Ac-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] -W[Orn]-[Dap(Ac)l-NG-NH2	*****
897	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][Ornl-[Dapl-NG-NH2	*****
898	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][Orn]-[Dap(Ac)]-NG-NH2	*****
899	Ac-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] -W[hLeu]-ENG-NH2	*****	*****
900	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-(acetyl-aminoethoxy)]][2-Nall-[a-MeLys(Ac)l-[Lys(Ac)l-NG-NH2	**	*****
901	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-W-[aMe-Leu]-ENG-NH2	φ	**
902	Succiciny 1-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] [2-Nall-[a-MeLysl-[Lys(Ac)l-NG-NH2	φ	**
906	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-(acetyl-aminoethoxy)]][2-Nal]-[a-MeLys(Ac)]-ENG-NH2		*****
820	Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-OMe)]-[2-Nal]-[Chg]- [Lys(Ac)l-NG-NH2	φ	**
911	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][ot-MeLysl-ENQ-NH2	**	**
912	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][ot-MeLys]-ENN-NH2	**	**
913	Ac-Cy clo- [ [ Abu]-TTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [ot-MeLysl-ENG-NH2	**	**
914	Ac-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [a-Me-Gly(Ethyl)] Lys(Ac)]-NG-NH2		*****
915	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][a-MeVal]-[Lys(Ac)]-NG-NH2
916	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][a-MeSer]-[Lys(Ac)l-NG-NH2	*****
925	Ac-(D)Lys-[Cyclo-[[Abu]-QTWQC]]-[Phe(4-OMe)]-[2-Nal]- [a-MeLeu]-ENG-NH2		*****
1039	[ Ac- [(D)Lys] -Cyclo- [ [Abu] -QTWQC] - [Phe(4-OMe)]- [2-Nal] [a-MeLeu]-ENG-NH2]2 DIG : dimerization through (D)Lys		*****

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SEQ ID NO:	Sequence	lIllBllll llllillll (min)	llllillll llllillll (min)
930	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][hLeu] - [Ly s(Ac)] -N- [ β Ala] -NH2	*****	ND
933	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][a-MeLysl-NNG-NH2	**	**
946	Ac-Cy clo- [ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [Aibl-[Lys(Ac)l-NG-NH2
955	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][a-MeLeu]-[Lys(Ac)]-NN-NH2		*****
1040	[Ac-Cyclo-[[Abu]-QTWQC]-Y(Bzl)-W-[a-MeLys]-ENGNH2]2;PEG25 through [a-MeLys]	**	*****
965	Ac-E-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2Nall-[ot-MeLysl-ENN-NH2	φ
966	Ac-(D)Glu-[Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ]-[2-Nal] - [α-MeLys]-ENN-NH2	φ
967	Ac-Arg-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2Nall-[a-MeLysl-ENN-NH2	*****
1041	Ac-[(D)Arg-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)l 1-[2-Nall - [a-MeLy si-ENN-NH2	φ	**
969	Ac-F-Cyclo-[[Abu]-QTWQC]]-[Phe[4-(2-aminoethoxy)]]-[2- Nall-[a-MeLysl-ENN-NH2
970	Ac-[(D)Phe]-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)] ]-[2-Nal] - [a-MeLy s]-ENN-NH2	**	φφφ
972	Ac-T-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2Nal]-[a-MeLys]-ENN-NH2	φ	φφφ
973	Ac-Leu-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2Nall-[a-MeLysl-ENN-NH2	φ	φφφ
1042	Ac-[(D)Qln]-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2aminoethoxy)l 1-[2-Nall - [a-MeLy si-ENN-NH2	φ	φφφ
975	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][Acpcl-ENN-NH2	*****	φ
976	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][Acbcl-ENN-NH2	*****
1043	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][Acpc]- ENN-NH2	**	φ
978	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][Acvc]-ENN-NH2		φ
979	Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]-[2-Nal][4-amino-4-carboxy-piperidine]-ENN-NH2	φ	φ
972	Ac-T-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2Nall-[a-MeLysl-ENN-NH2	φ	φ

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PCT/US2016/042680 § the matrix used is 100 fold dilution of standard SIF concentration *=>360min; **=180-360minn; ***=120-180min; ****=<60-120min; *****=<60min [00702] For each peptide tested, the DTT stability assay was conducted by adding 5μ1 of a lOmM peptide stock solution in DMSO to 1ml of lOOmM Tris-Cl, pH 7.5 (final peptide concentration is 50μΜ). At time 0 min, 5ul of a freshly thawed lOOmM DTT solution was added to the incubation tube containing the peptide, such that the final DTT concentration was 0.5mM. The reactions were incubated at room temperature. At different time points up to 120 minutes (20 min, 40 min, 80 min, 120 min), 50μ1 aliquots were removed, and the reaction was quenched by adding 10μ1 of 5M acetic acid. To measure disappearance of the parent peptide, the quenched samples (30μ1) were analyzed by reverse phase HPLC and UV absorbance at 220nm. The fraction oxidized remaining was graphed versus time, and half-lives were calculated by fitting to a first-order exponential decay equation using Excel. The results of these studies are shown in Table Ell. The peptides having half-life >120 min are all considered stable.

Table El 1. Stability of Illustrative Peptides in DTT Assay

Sequence	DTT Stability (min)
Ac-CRTWECYWHEFG-NH2	<10
Ac-CQTWQCYW-[hLeu]-ENG-NH2	Φ
Ac-CADWVWCYWHTFGA-[Azt]-[(D)Lys]-NH2	φ
Ac-Cyclo-[[Abu]-RTWQC]-YWRKFG-[AEA]-[(D)Lys]-NH2	>120
Ac-[[Pen]-QTWQ- [Pen] - YW- [hLeu] -ENG-NH2	>120
Ac-[Pen] -QTWQ- [Pen] - YW- [α-MeLeu] -ENG-NH2	>120
Ac-Cy clo-[[Abu]-QTWQC]-[Phe(4-OMe)]-[2-Nal]-[a-MeLys]eng-nh2	>120
Ac-[Pen] -QTWQ- [Pen] - [Phe(4-Ome)] -[2-Nal] - [α-MeLys] -ENG-NH2	>120
Ac-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] -W- [aMeLys]-ENG-NH2	>120
Ac-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] - [4amino-4-carboxy-tetrahydropyran]-ENN-NH2	>120
[Ac- [Pen] -QTWQ- [Pen]- [Phe(4-CONH2)] - [2-Nal]- [α-MeLy s] - [Ly s(Ac)]NN-NH2]2 DIG	>120

*=10-120 min

EXAMPLE 4

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Cross-Reactivity of Peptide Inhibitors [00703] The amino acids of the extracellular domain of the human IL-23R are 95%, 77% and 70% identical to the cyno IL-23R, rat IL-23R and mouse IL-23R, respectively. Interestingly, the mouse receptor contains an insertion of 21 residues that are absent in human, mouse, chimp, dog and cow receptor. These additional amino acids are located in a region where human IL-23R is thought to bind to IL-23.

[00704] To identify peptide inhibitors that cross-reacted with species other than human IL-23R, the ability of certain peptide inhibitors to inhibit human IL-23R, cyno IL-23R, rat IL-23R and mouse IL-23R by ELISA assay. In line with the observation regarding the sequence differences between human IL-23R and mouse IL-23R, the peptide antagonists tested showed a lack of or very weak inhibitory activities in the mouse IL-23R ELISA (see Table E12). In contrast, the antagonists tested to date displayed comparable potency towards the rat receptor and slightly less activity towards the cyno receptor.

[00705] Various bioassays performed to determine the potency, cross reactivity and the selectivity of IL-23R antagonists are described below.

Assays for Selectivity of specific IL-23R Antagonists

Human IL-12R31 ELISA [00706] An assay plate was coated with 100 ng/well of human IL-12Rpi_huFC and incubated overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions of test peptides and IL-23 at a final concentration of 2.5 nM were added to each well, and incubated for 2 hours at room temperature. After the wells were washed, bound IL-23 was detected with goat anti-p40 polyclonal antibodies, followed by an HRP conjugated donkey anti-goat IgG. Signals were visualized with TMB One Component HRP Membrane Substrate and quenched with 2 M sulfuric acid.

Mouse IL-23R Competitive Binding ELISA [00707] An assay plate was coated with 50 ng/well of Mouse IL-23R_huFC and incubated overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions of test

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PCT/US2016/042680 peptides and IL-23 at a final concentration of 4 nM were added to each well, and incubated for 2 hours at room temperature. After the wells were washed, bound IL-23 was detected with goat anti-p40 polyclonal antibodies, followed by an HRP conjugated donkey anti-goat IgG. Signals were visualized with TMB One Component HRP Membrane Substrate and quenched with 2 M sulfuric acid.

Rat IL-23R Competitive Binding ELISA [00708] An assay plate was coated with 300 ng/well of Rat IL-23R_huFC and incubated overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions of test peptides and IL-23 at a final concentration of 7 nM were added to each well, and incubated for 2 hours at room temperature. After the wells were washed, bound IL-23 was detected with goat anti-p40 polyclonal antibodies, followed by an HRP conjugated donkey anti-goat IgG. Signals were visualized with TMB One Component HRP Membrane Substrate and quenched with 2 M sulfuric acid.

Cyno IL-23R Competitive Binding ELISA [00709] An assay plate was coated with 50 ng/well of Cyno IL-23R_huFC and incubated overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions of test peptides and IL-23 at a final concentration of 2 nM were added to each well, and incubated for 2 hours at room temperature. After the wells were washed, bound IL-23 was detected with goat anti-p40 polyclonal antibodies, followed by an HRP conjugated donkey anti-goat IgG. Signals were visualized with TMB One Component HRP Membrane Substrate and quenched with 2 M sulfuric acid.

Table El 2. Cross-Reactivity of Illustrative Peptide Inhibitors

Cmpd. Number	Human IL-23R Activity (nM)	Rodent and Cyno IL-23R Cross Reactivity (nM)
ELISA hulL23R IL23	Cell Assay pSTAT3 HTRF	ELISA mouse IL23R IL23	ELISA rat IL23R IL23	ELISA cyno IL23R IL23
22	+	+	-	+	+
197	++	ND	-	++	ND
169	++	++	-	++	+

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198	+++	+++	ND	+++	+++
213	+++	+++	ND	+++	ND
219	+++	+++	ND	+++	ND
230	+++	+++	ND	+++	ND

+++ indicates 0-250 nM ++ indicates 251-1000 nM + indicates 1001-10,000 nM - indicates > 25,000 nM

EXAMPLE 5

NK Cell Assay [00710] Natural killer (NK) cells, purified from human peripheral blood of healthy donors by negative selection (Miltenyi Biotech, Cat # 130-092-657), were cultured in complete media (RPMI 1640 containing 10% FBS, L-glutamine and penicillin-streptomycin) in the presence of IL-2 (RnD, Cat # 202-IL-010/CF) at 25 ng/mL. After 7 days, cells were centrifuged, and resuspended in complete media at 1E6 cells/mL. Recombinant IL-23 at predetermined EC50 to EC75 and IL-18 (RnD, Cat # B003-5) at 10 ng/mL were mixed with varying concentrations of peptides, and added to NK cells seeded at 1E5 cells per well. After 20 to 24 hours, IFNy in the supernatant was quantified using Quantikine ELISA (RnD, Cat # DIF50).

Table El 3, IC50 of Illustrative Peptide Inhibitors in Primary Cell dne (NK Cell Assay)

Sequence	NK cell assay (nM)
Ac-Cyclo-[[Abu]-QTWQC]-Y-[2-Nal]-[ot-MeLys]-ENG-NH2	*
Ac-Cyclo-[[Abu]-QTWQC]-[Phe(4-OMe)]-[2-Nal]-[a-MeLys]- eng-nh2	*
Ac-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] -W- [aMeLys]-ENG-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] -[2-Nal][a-MeLys]-[Lys(isovaleric acid)]-NG-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [Aib]-QNG-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [Aib] - [Lys (Ac) ] -NA-NH2	*

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Ac-Cy clo-[[Abu]-QTWQC]-[Phe[4-(2-(acetyl-aminoethoxy)]][2-Nal] - [oc-MeLys(Ac)] - [Ly s( Ac)]-NG- NIL	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [Phe(3,4OMe2] - [α-MeLys] - [Ly s(Ac)] -NG-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [α-MeLys]-ENQ-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [α-MeLys]-ENN-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] -[2-Nal][a-MeVal]-[Lys(Ac)]-NG-NH2	*
[Ac-Cy clo-[[Abu]-QTWQC]-[Phe(4-OMe)]-[2-Nal]-[a-MeLys]ENG-NH2]2; DIG through a-MeLys	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [a-MeLeu)-[Cit]-NN-NH2	*
Ac-[(D)Phe]-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[a-MeLys]-ENN-NH2	*
Ac-T-Cy clo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2Nal]-[a-MeLys]-ENN-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [Acbc]-ENN-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [Acpc]- ENN-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [Achc]-ENN-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] - [2-Nal] [4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	*
Ac-Cyclo- [ [Abu]-QTWQC] - [Phe[4-(2-aminoethoxy)] ] -[2-Nal][a-MeLeu]-QN-[pAla]-NH2	*
Ac-(D)Phe-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	*
Ac-[(D)Arg]-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- ENN-NH2	*

*=<25nM

Table 14. IC50 of Illustrative Peptides Containing the Ac-[Pen]-XXWX-[Pen]-XXXX Motif and analogues (NK cell assay)

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Sequence	NK Cell assay (nM)
Ac-[Pen]-QTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[oc-MeLeu]- [Lys(Ac)]-NN-NH2	*
Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]- nn-nh2	*
Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]- N-[f5Ala]-NH2	*
Ac-[Pen]-QTWQ-[Pen]-[Phe(4-OMe)]-[2-Nal]-[oc-MeLys]-[Lys(Ac)]-NN- nh2	*
Ac- [Pen] -QTWQ- [Pen] -[Phe(4-CONH2)] - [2-Nal] -[oc-MeLys]- [Lys(Ac)] nn-nh2	*
Ac- [Pen] -QTWQ- [Pen] -[Phe(4-CONH2)] - [2-Nal] -[oc-MeVal] -[Lys(Ac)] nn-nh2	**
[Ac- [Pen] -QTWQ [Pen] - [Phe [4-(2-acetylaminoethoxy)] - [2-Nal] - [aMeVal]-KNN-NH2]2 DIG	*
[Ac-[Pen]-QTWQ[Pen]-[Phe[4-(2-acetylaminoethoxy)]-[2-Nal]-K[Lys(Ac)]-NN-NH2]2 DIG	*
[Ac- [Pen] -QTWQ- [Pen] - [Phe(4-OMe)] - [2-Nal] - [oc-MeLys] - [Lys(Ac)] -NNNH2]2 DIG	*
[Ac- [Pen] -QTWQ- [Pen]- [Phe(4-CONH2)] - [2-Nal]- [oc-MeLys] - [Ly s(Ac)] NN-NH2]2 DIG	*
Ac- [(D)Phe]-[Pen] -NTWQ [Pen] - [Phe(4-OMe)] - [2-Nal] - [4-amino-4carboxy-tetrahy dropyran] - [Cit] -NN-NH2	*
Ac- [(D)Phe]-[Pen] -NTWQ [Pen] - [Phe(4-OMe)] - [2-Nal] - [Ache] -ENN-NH2	*
Ac-[Pen] -NTWQ [Pen] - [Phe(CONH2)] - [2-Nal] -[Aib] - [Ly s(Ac)]-NN-NH2	*
[Ac-[Pen]-NTWQ-[Pen]-[Phe(4-CONH2)]-[2-Nal]-[Aib]-KNN-NH2]2 DIG	*

*=<10nM; **=10-25nM

EXAMPLE 6

Bioassay Characterization of Peptide Inhibitors [00711] The potency, cross reactivity, and selectivity of certain peptide inhibitors was determined using various bioassays developed for this purpose and described below.

Rat Splenocvte Assay

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PCT/US2016/042680 [00712] A new assay developed was the rat splenocyte assay. This assay examined the levels of IL-17A in activated rat splenocytes following stimulation with IL-23 in the presence of test compound.

[00713] Briefly, splenocytes freshly isolated from rat were seeded in 96-well tissue culture plates in complete medium containing IL-Ιβ. Serial dilutions of test compounds were distributed to each well along with rat IL-23 at a final concentration that is between EC50 to EC80 values; plates then were incubated for 3 days at 37 °C in a 5% CCE humidified incubator. Changes in IL17A levels in the supernatants were detected using an ELISA.

Rat Colitis Model: 9 Days of 3% DSS-Containing Drinking Water [00714] There is a body of evidence in the literature supporting the pathogenic role of IL-23/IL23R signaling in animal models of colitis. For the IL-23 ligand, this requirement has been shown in multiple models, including an IL-10 spontaneous colitis model, a Helicobacter hepaticusdriven colitis model, the anti-CD40 innate colitis model, and the chronic CD45RB^hlgh CD4⁺ Tcell transfer model. For the IL-23 receptor, the requirement for colitis development has been shown in the acute models of colitis induced by DSS or by anti-CD40, as well as the chronic CD45RB^hlgh CD4⁺ T-cell transfer model. Since certain peptide inhibitors of the present invention do not cross react with the IL-23 receptor from mouse but do recognize that from the rat, a rat model of IBD relevant to the IL-23 pathway was developed.

[00715] In this model, colitis was induced in SD rats by 9 days of ad lib exposure to drinking water containing 3% DSS. The disease activity index (DAI) score and ratio of colon weight:colon length were compared between three study groups (n=6 rats/group): vehicle, 3% DSS, and 3% DSS with positive control (sulfasalazine administered at 100 mg/kg PO, QD). The DAI score consisted of ratings from three parameters, including percent body weight loss, stool consistency, and a quantitative hemoccult score, and could achieve a maximum value of 3 units. DSS-exposed animals displayed significantly elevated DAI score (compared to vehicle control) from Day 4 onward, with DAI values peaking at approximately 2.5 by the end of the study (Day 9). Treatment of the DSS-exposed rats with the positive control (sulfasalazine) attenuated the disease score (compared to DSS alone) from Day 5. The differences observed in the terminal

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PCT/US2016/042680 ratio of colon weight:colon length also were significant for DSS-induced disease animals with and without sulfasalazine treatment.

Ex Vivo Activity and Stability [00716] Two peptides (Compound A and Compound B) were selected for use in further biological studies (shown below). One contained a thioether linkage and the other contained a Pen-Pen disulfide bond. The activity, selectivity and ex vivo stability profiles of the two compounds are provided herein.

[00717] Assays for selectivity of peptide inhibitors included a human IL-12Rbl ELISA and measurement of the production of IL-12 in PHA activated human PBMC, which are described briefly below.

Human IL-12R31 ELISA [00718] An assay plate was coated with 100 ng/well of human IL-12Rbl_huFC and incubated overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions of test peptides and IL-23 at a final concentration of 2.5 nM were added to each well, and incubated for 2 hours at room temperature. After the wells were washed, bound IL-23 was detected with goat anti-p40 polyclonal antibodies, followed by an HRP conjugated donkey anti-goat IgG. Signals were visualized with TMB One Component HRP Membrane Substrate and quenched with 2 M sulfuric acid. Data from these assays is provided herein.

Production of IFNy by IL-12 in PHA Activated Human PBMC [00719] This assay examined the ability of IL-23R antagonists to neutralize production of IFNy proteins in IL-12-stimulated human PBMCs. IL-23R peptide inhibitors specific to the IL-23/IL23R pathway are not expected to alter the levels of IFNy produced. Compound A and Compound B were tested in this assay, and a graph showing that they do not alter the levels of IFNy produced at most concentrations tested is provided in Figure 2.

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Compound A

Compound B

In Vivo Activity [00720] Acute colitis was induced by feeding female Sprague Dawley rats with 3% (wt/vol) DSS dissolved in drinking water. For nine days starting at the same day as DSS, Compounds A or B was administered orally three times per day at 20 mg/kg or 30 mg/kg. Compounds A was also administered intraperitoneally three times per day at 30 mg/kg. A neutralizing anti-IL-23pl9 antibody was used as a comparator, and was administered intraperitoneally at 4 mg/kg on the same day and fifth day after starting DSS. To quantify colitis with clinical activity, disease activity index (DAI) was determined daily for each animal as an average of three parameters: body weight change (scale 0-3), stool consistency (scale 0-3) and hemoccult blood (scale 0-3), as shown in Table El5. At necropsy, the entire colon was removed from the cecum to the rectum. The colon was measured for length, flushed with PBS to remove feces, weighed, and opened

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PCT/US2016/042680 longitudinally to determine macroscopic score. The visible damage of the colon was scored on a scale from 0-3, as shown in Table E16.

[00721] Table El7 shows that at Day 7, treatment with Compound A and B significantly improved DAI scores compared to vehicle treated group. FIG. 1 shows results for DAI values from Day 7. In addition, a significant reduction was also observed in the colon weight to colon length ratios, and colon macroscopic scores (FIG. 3). The reduction in inflammation observed with orally delivered peptides was similar to the effects observed from neutralizing anti-IL23pl9 monoclonal antibody. Statistical analysis for significance was compared to the vehicle treated group and was determined using Student’s T-test (GraphPad Prism). Differences were noted as signficant *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Table El 5. Scoring of the Disease Activity Index

Score	Percent Body Weight Change	Stool Consistency	Hemoccult Score
0	None	Normal	Normal
1	1 to 7	Semi solid	Guaiac+
2	8 to 15	Loose	Bleeding+
3	> 15	Diarrhea	Bleeding++

Table El 6. Scoring of Gross Morphologic Damage of the Colon

Score	Gross morphology
0	Normal
1	Erythemia
2	Erythemia, slight edema, small erosions
3	Two are more bleeding ulcers, inflammation, moderate adhesions
4	Severe ulceration, stenosis with dilations, severe adhesions

Table El7. Disease activity index scores and the individual parameters scores at Day 7, colon weight to length ratios and colon macroscopic scores at Day 9.

Day 7

Day 9 Necropsy

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	Percent Body Weight Change	Stool Consistency	Hemoccult Score	DAI	Colon Weight/Length (g/cm)	Colon Macrosopic Score
Group	Mean	SD	Mean	SD	Mean	SD	Mean	SD	Mean	SD	Mean	SD
NoDSS	11.00	2 08****	0	Q****	0	Q****	0	Q****	75.51	7 03***	ND	ND
3%DSS, Vehicle	-6.39	1.11	2.00	0.58	1.50	0.50	1.72	0.45	124.36	17.11	1.00	1.00
Anti- IL23pl9 mAh	-0.05	1 92****	1.00	0.58*	0.50	0.5*	0.67	0.43**	99.96	16.19*	0.00	o**
Compound A, PO	3.18	2 09****	1.17	0.90	0.50	0.5*	0.56	0.46**	98.38	6.91*	0.00	o**
Compound B, PO	0.13	1 24****	0.83	0.69*	0.67	0.47*	0.61	Q 2***	97.36	9.32*	0.00	o**
Compound A, IP	-0.50	1.88***	1.17	0.69	0.83	0.69	0.83	0.54*	104.32	12.45	0.33	0.47

EXAMPLE 7

In Vitro ASSays and Surface Plasmon Resonance (SPR) Analysis [00722] In vitro assays and SPR were performed to further characterize an illustrative compound, Compound C:

Ac-Cyclo-[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-W-[a-MeLys]-ENG-NH2

Compound C.

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PCT/US2016/042680 [00723] Assays described in previous examples were performed to demonstrate that Compound C is a potent, selective and competitive inhibitor of IL-23R, showing potent inhibition of IL-23dependent upregulation of phosphor-STAT3 (pSTAT3) in human DB cells and IFNy production in human peripheral blood natural killer (PB NK) cells. In adition, Compound C was selective, showing little inhibition in a cell free ELISA for human IL6R, or in IL-12-dependent production of IFNg in PBMC. Data is shown below in Table E18A. Compound C also cross-reacted with cynomolgus IL-23R (IC50 7 nM) and rat IL-23R (IC50 17 nM), and inhibited IL-23-dependent IL-17A production in rat splenocytes (IC50 130 nM) (data not shown).

Table El 8A In vitro Characterization of Compound C

	IC50	KD
	pSTAT3 DB Cell Assay	IFNy/PB NK Primary Cell Assay	IL-6/IL-6R ELISA	IFNy/IL-12 PBMC Cell Assay	IL-23R Surface	IL- 12Rpl Surface
Compound C	4nM	27nM	>100 uM	>100 uM	2.4nM	None

[00724] Compound C exposure was also restricted to the GI following oral administration to rats does PO at 20 mg/kg, with AUC values of 355 ug.h/g for small intestine mucosa; 77 ug.h/g for colon mucosa; and 0.3 ug.h/mL for plasma, with a 40% recovery in feces.

[00725] Compound C was also stable in a variety of GI fluids and reducing environment, having a SIF half-life of > 24 h; a SGF half-life of > 24 h; a human intestinal fluid half-life of > 24 h, and a half-life of > 2 h in a DTT assay.

[00726] SPR experiments were carried out using a Biacore 2000 instrument and T100 optical biosensors equipped with Biacore CM4 and Xantec HCI 500m sensor chips. Recombinant human IL-23R_huFC (RnD), or recombinant human IL-12Rpi_huFC (RnD) or a mixture of the two receptor subunits were captured on an anti-human IgG surface. Recombinant human IL-23

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PCT/US2016/042680 (Humanzyme) or Compound C was used as the analyte. SPR sensorgrams were fitted to a one to one interaction model, giving rise to a rough estimate of the association rate constant (k_on), dissociation rate constant (k_Off) and dissociation constant (Kd) of the complexes, as shown in Table Ell. The data show that Compound C does not bind to IL-12RP1, and binds to IL-23R and the mixed surface of IL-12RP1 and IL-23R with similar potency, at 2.42nM and 2.56nM, respectively. This affinity for IL-23R is comparable to that from IL-23. In contrast, the affinity of IL-23 to the mixed surface is approximately 14x faster than that from Compound C.

Table E18B. Binding characteristics of IL-23 and Compound C for IL-12RP1, IL-23R or mixed IL-12RP1 and IL-23R as determined by SPR.

	IL-23	Compound C
Surface	ka(M-l sec-1)	kd(sec-1)	KD (nM)	ka(M-l sec-1)	kd(sec-1)	KD (nM)
IL-12Rbl huFC	5.01E+05	4.38E-04	0.87	does not bind up to 16.7 uM
IL-23R huFC	7.82E+05	0.00132	1.69	1.37E+07	0.033	2.42
IL-12Rbl huFC/IL23R huFC	6.31E+05	1.15E-04	0.18	1.59E+07	0.041	2.56

EXAMPLE 8

Efficacy of IL-23R Antagonists in TNBS Induced Colitis in Rat [00727] To further evaluate the efficacy of IL-23R antagonists in an animal model of disease, acute colitis was induced by providing 7-week-old female Sprague-Dawley rats with 60 mg/kg 2,4,6-Trinitrobenzenesulfonic acid (TNBS) in 45%-50% ethanol (TNBS/ethanol) administered intrarectally at Day 0. Compound C (described in Example 7) was administered orally three times a day at 20 mg/kg or 6.7 mg/kg and was provided in drinking water at 0.6 mg/mL or 0.2 mg/mL, respectively, for 8 days starting approximately 24 hours (Day -1) prior TNBS inoculation. A neutralizing anti-IL-23pl9 antibody was used as a comparator, and was administered intraperioneally at 4 mg/kg on Day -1 and again on Day 3. All animals received orally PBS (pH 7.4) vehicle which was used to formulate Compound C. The study design in shown in Figure 5.

[00728] To assess the extent of the inflammatory response, animals were observed daily for clinical signs which included percent body weight loss and signs of loose stools or diarrhea. Six days after inoculation of TNBS, rats were sacrificed and the entire colon length and colon weight

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PCT/US2016/042680 from cecum to rectum from each animal were recorded. The severity of colitis was evaluated by a pathologist blinded to the identity of treatments. In addition to the colon wall thickness, the gross colon damage was scored on a 0-4 scale according to Table El9 below, and histopathological scores were determined based on below parameters (Tables E20 and E21).

Table El 9. Definitions for colon macroscopic scores

Score	Colon Gross Morphology
0	Normal
1	Erythema
2	Erythema, slight edema, small erosions
3	Two or more bleeding ulcers, inflammation, moderate adhesions
4	Severe ulceration, stenosis with dilations, severe adhesions

Table E20. Definitions for histopathology

Parameter	Definition
Inflammation	Extent and severity of inflammatory cells infiltration, localized and/or diffuse involving full thickness of the colon section (transmural). Inflammatory cells include polymorpho-nuclear leukocytes (neutrophils), mononuclear cells (macrophages + lymphopcytes), fibroplasia and neovascularization.
Mucosal Necrosis	Necrosis in the mucosa with loss of surface epithelium, hemorrhage and cellular debris; measured as the length of the lesion on the total length of the colon section to determine % area affected
Gland Loss	% crypt epithelial degeneration with or without superficial mucosal erosion
Colon Thickness	the average thickness of the colon measured transmurally (full thickness) from the mucosal surface to the serosa

Table E21. Scoring criteria

Score	Inflammation
0	Normal tissue, no inflammation
0.5	Very minimal localized infiltrates in the superficial mucosa affecting <2% of the colon section
1	Minimal degree of multifocal infiltrates in the mucosa affecting approximately 2 - 10% of the colon section
2	Mild degree of multifocal infiltrates in the mucosa, submucosa, outer muscle band, and serosa affecting approximately 11 - 25% of the colon section
3	Moderate degree of multifocal infiltrates in the mucosa submucosa, outer muscle band and serosa affecting approximately 26 - 50% of the colon section
4	Marked degree of multifocal to diffuse infiltrates in the mucosa submucosa, outer muscle band and serosa affecting approximately 51- 75% of the colon

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	section
5	Sever degree of multifocal to diffuse infiltrates in the mucosa submucosa, outer muscle band and serosa affecting approximately >75% of the colon section

Score	Mucosal Necrosis
0	No Necrosis
0.5	Very minimal and localized region affecting <2% of the total colon section
1	Minimal focal to multifocal regions affecting 2 - 10% of the total colon section
2	Mild focal to multifocal regions affecting 11 - 25% of the total colon section
3	Moderate focal to multifocal regions affecting 26 - 50% of the total colon section
4	Marked focal to multifocal regions affecting 51 - 75% of the total colon section
5	Severe focal to multifocal regions affecting >75% of the total colon section

Score	Gland Loss
0	No loss, normal crypt epithelium and mucosa
0.5	Very minimal loss not exceeding 1-2 regions of mucosa/gland affected
1	Minimal, 1-10% regions of mucosa/gland affected
2	Mild, 11 -25% regions of mucosa/gland affected
3	Moderate, 26-50% regions of mucosa/gland affected
4	Marked, 51-75% regions of mucosa/gland affected
5	Severe, >75% regions of mucosa/gland affected

Score	Colon Thickness
0	Normal = <350 microns or less
0.5	Very Minimal = 351-400 microns
1	Minimal = 400- 500 microns
2	Mild = 501 - 600 microns
3	Moderate = 601 - 700 microns
4	Marked = 701 - 800 microns
5	Severe = >801 microns

[00729] Compared to the sham group, rats challenged with TNBS suffered acute weight loss, displayed increased incidence of loose stools, and increased colon weight to length ratio. These data were confirmed by the macroscopic examination of colon which revealed mild colonic injury characterized by erythema, edema and small erosions. Treatment with Compound C attenuated these changes as compared to the TNBS colitis group. At the high dose, Compound C was significantly effective in reducing the colon weight to length ratio, diminishing the thickness of the colon walls, and more importantly, improving the colon gross pathology scores to normal

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PCT/US2016/042680 in 70% of the animals. Statistical significances were observed at the low dose in all above indications except colon wall thickness although a trend was evident. The reduction in inflammation observed with orally delivered Compound C was similar to the effect observed from the neutralizing anti-IL-23pl9 monoclonal antibody (Figure 6).

[00730] Histological examination of H&E stained distal colons show that the majority of the lesions observed from the vehicle group are transmural, characterized by necrosis with inflammatory cells transversing the entire thickness of the colon, presence of necrotic tissue debris on the lumen surface, and mucosa devoid of crypts. The animals treated with Compound C generally showed localized lesions limited in the mucosa and submucosa regions, with colon tissues showed potential signs of healing at sites of necrosis. Specifically, the animals treated with 160 mg/kg/d Compound C showed a significant reduction in inflammation, mucosal necrosis and colon wall thickness leading to a significant reduction in the overall histological score, comparable to that from the anti-IL-23pl9 antibody control (FIG. 7).

[00731] Concentration analysis of samples collected 1 hour post the last PO dose show that the plasma concentrations of Compound C detected from all animals are <=2X below the IC75 of the compounds as determined in the rat splenocyte/IL-17A cell based assay or the rat IL-23R ELISA, suggesting that the efficacies observed from oral treatment are most likely due to its local activity at the colon (see FIG. 8). Collectively, these data highlights the protective effect of an IL-23R antagonist in the development of TNBS colitis.

[00732] These studies demonstrate that peptides of the present invention are potent, selective and orally efficacious IL-23R peptide antagonists that are promising therapeutics for the treatment of IBD and other disorders. As shown herein, the present invention provides petpides that are: potent blockers of IL-23/IL-23R signaling in a human cell line and in human primary cells; selective for IL-23R, and do not inhibit binding to IL-6R or signaling through IL-12R; crossreactive towards rat and cynomolgus but not mouse homologs, enabling in vivo studies in these species; resistant to proteolytic and reducing environments of the GI, resulting in high drug levels in the intestinal tissues and limited drug concentrations in the circulation, offering potential safety advantages over systemically delivered therapeutics; and effective and

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PCT/US2016/042680 comparable to an anti-IL23pl9 monoclonal antibody in attenuating colitis in a TNBS-induced rat colitis model, most like through Gl-restricted activities.

EXAMPLE 9

In Vitro Characterization of an Illustrative IL-23R Antagonists [00733] To evaluate the properties of efficacy the IL-23R peptide antagonist of SEQ ID NOS: 980 (Peptide 980), 993 (Peptide 993), and 1185 (Peptide 1185) experiments to determine potency, selectivity, and stability of the peptides were performed as described above. The IC50 values of the peptides as measured by quantitative ELISA for IL-23/IL-23R competitive binding assays (performed as described above in Example 2) for human (Hu), cynomolgus monkey (Cyno), and rat (Rat) IL-23 and IL-23R binding are shown in Table E22. The potencies of the peptides were also evaluated by IL-23R activity assays as described above. The IC50 values of the peptides as determined by the reduction of phospho-STAT3 (pSTAT3) levels in human DB cells exposed to IL-23 (Hu DB Cell (pSTAT3); performed as described above in Example 2); by the reduction of IFNy produced by human NK cells exposed to IL-23 (Hu NK cell; performed as described above n Example 5); and by the reduction of IL-17A produced by activated splenocytes exposed to IL-23 (Rat(spleen); performed as described above in Example 6). Selectivity was evaluated by measuring the IC50 of the peptides for inhibiting human IL-23/IL12R betal interactions (see Example 4) or human IL-6/IL-6R interactions (see Example 6). The stabilities of the peptides were determined by measuring the half-life of the peptides exposed to simulated intestinal fluid (SIF), simulated gastric fluid (SGF), or human intestinal fluid (SIF).

Table E22. Properties of illustrative IL-23R antagonists Peptide

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	lllil!!!!!!!!!!!!!! !ΐβ:!!!!!!!!!!!!!!1	Cell assa\ !/Bl!!!!!!!!/!!	Sclectix it\ /lillia!!!!!!!!!!!!!	Stabili t\ ////lllil////////////////////////////////////////////////////
Peptide	/111!!	/////ilii////////	//00//////	Hu DB Cell	Hu NK	Rai	////1/10/////////////////////////////	/:/:110:/:/:/:/:/:/:/:/:/:/:/:	/////11/////////	/////111/////	HIF
lllllllll!	//β///////////		!l!ili!!l!	1L-6R
Peptide 993	2.0	2.0	2.0	0.6	2.2	18.3	>100,000	>100,000	12	6	24
Peptide 980	1	1.3	3	0.6	2.8	11.5	>100,000	>100,000	11	10
Peptide 1185	2	3	3	2	3.9	35	>100,000	>100,000	33	12	24

The structure of Peptide 993 is shown below:

χ·'*' •H_:+T' Ob

Ac-[(D)-Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahydropyran]-ENN-NH₂ (SEQ ID NO: 993)

The structure of Peptide 1185 is shown below:

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PCT/US2016/042680 eu.

S¹¹

Q I

X Y Y S ,ΑΗ ' δ — 'y s^- χ

O

I A v wt ~ I M

Jk ,0

ii :3

Y,A ;f.> X f 1

A U'f.

r r.....

» , $

''Mi» £5 Of o' '

8sfS ’

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran][Lys(Ac)]-NN-NH₂ (SEQ ID NO: 1185)

The structure of Peptide 980 is shown below:

x-i,·

CU w

x XA XI

Al··

I f

it χ y x «·' ••N 0

·%
ί		λ	0
u X v..u..	Λ	I « .,A. ,α.,.	A

ill 1 *1

X X·%... Q

A | HO '0 x>,,a

I ftjf Ύ

Ac-Cyclo- [ [Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] ]- [2-Nal] - [4-amino-4-carboxytetrahydropyran]-ENN-NH₂ (SEQ ID NO: 980) [00734] The results summarized in Table E22 indicate that the peptides potently and selectively inhibit IL-23/IL-23R binding as compared to IL-23/IL-12R betal or IL-6/IL-6R interactions. This inhibition was confirmed with cell culture assays that measure the IL-23R-dependent such

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PCT/US2016/042680 as STAT3 phosphorylation, IFNy production, and IL-17A production. The peptides were also determined to have a high degree of stability when exposed to simulated intestinal fluid, simulated gastric fluid, or human intestinal fluid.

[00735] Data from the Human DB Cell (pSTAT3) experiment were used for Schild analysis (see FIG. 17). For Schild analysis, concentrations of 0.3nM, InM, 3nM, ΙΟηΜ, 30nM, lOOnM of Peptide 993 were tested. The Schild slope was determined to be 1.068, indicating that Peptide 993 behaves as a simple competitive antagonist. Schild analysis was also performed on a peptide with the structure of SEQ ID NO: 1169, which is highly similar to the stuctures of Peptide 1185. The Schild slope was determined to be 0.91, indicating that peptides with similar structure, including Petide 1185, are likely behave as a simple competitive antagonist. Schild analysis was also performed on the peptide of SEQ ID NO: 1211, which has a structure similar to to Peptide 980. The Schild slope was determined to be 0.76. However, when the slop was fixed to 1, the R² value was 0.975. These data suggest that peptides with similar structure, including Petide 1185, could behave as a simple competitive antagonist.

EXAMPLE 10

In Vivo Pharmacokinetics of Illustrative IL-23R Antagonists [00736] Pharmacokinetic properties of example peptides were measured in vivo. Sprague Dawley rats were administered Peptide 993 at 10 mg/kg P.O.

[00737] A single oral dose of Peptide 933 was administered to normal female Sprague-Dawley rats (N=3 rats per time point) either with or without a drinking water dose that was provided ad libitum (see FIG. 11). Following the oral dose, the exposure of Peptide 993 was determined in the plasma at 0.25, 0.5, 1, 3, 6, 8, and 24 hours post-dose. The levels of Peptide 993 were also determined in small intestine, colon, small intestine mucosa, colon mucosa, small intestine mucus, Peyer’s patch and Mesenteric Lymph Node (MLN) at 1, 3, 6, 8 and 24 hours post-dose. Urine and feces were collected at 6 and 24 hours to determine the excretion of Peptide 993. Plasma, feces, and tissue samples were stored at -80 ± 10 °C prior to analysis. For plasma, 50 pL of the sample was used to extract compound by means of protein precipitation using a quench solution (MeOH:ACN w/ 0.1% formic acid, 50:50 volume) with internal standard. For feces, samples were homogenized with 0.1% Formic acid in water (water:feces ratio of 4:1) prior to

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PCT/US2016/042680 extraction. 50 pL of fecal homogenate was used to extract compound by means of protein precipitation using a quench solution (MeOH:ACN w/ 0.1% formic acid, 50:50 volume) with internal standard. For tissues such as colon or small intestine, samples were homogenized with 0.1% Formic acid in water (water:tissue ratio of 3:1) prior to extraction. For tissue such as Peyer’s Patch and Mesenteric Lymph Nodes, samples were homogenized with 0.1% Formic acid in water (water:tissue ratio of 20:1) prior to extraction. 50 pL of tissue homogenate was used to extract compound by means of protein precipitation using a quench solution (MeOH:ACN w/ 0.1% formic acid, 50:50 volume) with internal standard. The precipitated protein was removed by filter plate and the collected supernatant was dried and reconstituted. Processed samples were analyzed on an AB/MDS Sciex API 4000 mass spectrometer. Positive ions were monitored in the multiple reaction-monitoring (MRM) mode. Quantitation was by peak area ratio.

[00738] No detectable levels of Peptide 993 were observed in rat plasma between 0 and 24 hours following administration (see FIG. 11 A). In contrast, detectable levels of Peptide 993 were present in the Peyer’s Patch and small intestine for at least six hours (see FIGS. 11B and 11C), and for at least 8 hours in the colon post-dose administration (see FIG 1 ID). Levels greater than 5% of the total administered dose of Peptide 993 were detected in the rat feces at 24 hours following administration, further indicating that Peptide 993 has a high degree of oral stability. Taken together, these results demonstrate that Peptide 993 is an orally stabile GI restricted peptide, that demonstrates a high GI content and limited systemic distribution following oral administration.

[00739] Sprague Dawley rats were administered Peptide 1185 at 10 mg/kg P.O. A single oral dose of Peptide 1185 was administered to normal female Sprague-Dawley rats (N=3 rats per time point). Following the oral dose, the exposure of Peptide 1185 was determined in the plasma in samples taken up to 8 hours post-dose. Urine and feces were collected to hours to determine the excretion of Peptide 1185 (FIG 18).

[00740] Sprague Dawley rats were administered Peptide 980 at 10 mg/kg P.O. A single oral dose of Peptide 980 was administered to normal female Sprague-Dawley rats (N=3 rats per time point). Following the oral dose, the exposure of Peptide 980 was determined in the plasma in

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PCT/US2016/042680 samples taken up to 8 hours post-dose. Urine and feces were collected to hours to determine the excretion of Peptide 980 (FIG 19).

EXAMPLE 11

Saftey Profile of Illustrative IL-23R Antagonists [00741] Saftey profiles of illustrative peptide inhibitors were characterized. Peptide 993 and Peptide 1185 were evaluated in a safety panel examining binding to a panel of 44 targets. The targets included G protein coupled receptors (GPCRs), transporters, e.g., dopamine transporter (DAT), and ion channels. For all targets, these peptides displayed no activity, as defined by a change (inhibitory or stimulatory) in the target’s activity of greater than 25%. The targets tested in the safety panel are listed in Table E24. For each target, Peptide 993 and Peptide 1185 was determined to be inactive at concentrations of up to 10 μΜ. The safety profile of Peptide 980 was evaluated by testing compounds selected from Table E24. For all compounds tested, Peptide 980 showed only moderate activity in the acetylcholinesterase assay (33%), and otherwise did not display any activity, as defined by by a change in the target’s activity of greater than 25%.

Table E24, Peptide 993 and Peptide 1185 are Inactive in a Safety Panel

Panel of 44 targets

A	M	5-HT
2A	3	3
alphaiA	delta2 (DOP)	2+ Cei chsinnel (L, dihydropyridine site)
alpha2A	ksippsi (KOP)	hERG (membrane prepsiration)
beta 1	mu (MOP)	K chsinnel V
beta2	5-HTia	+ Nei chsinnel (site 2)
CB 1	5-HT IB	AR
CB 2	5-HT 2A	GR
CCK1 (CCKA)	5-HT 2B	Lck kinsise
D	V	COX
1	la	1
D2S	dopsimine transporter (DAT)	COX2
ETa	norepinephrine transporter (NET)	acetylcholinesterase

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Panel of 44 targets
H 1	5-HT transporter (SERT)	MAO-A
H2	BZD (central)	PDE3A
M 1	NMDA	PDE4D 2
M 2	N neuronal α4β2

EXAMPLE 12

Effects of An Illustrative Peptide Inhibitor in a Rat Model of Acute Colitis [00742] To evaluate the efficacy of the illustrative peptide inhibitor Peptide 1185 in an animal model of disease, acute colitis was induced by providing 7-week-old female Sprague-Dawley rats with 64 mg/kg TNBS in 50% ethanol administered intrarectally at Day 0. Peptide 1185 was administered orally 37mg/kg/day (combined PO and in drinking water), PO BID, day -1 to day 7. A sham group that was not exposed to TNBS and a TNBS treated group that received treatment with vehicle were used as control groups. For comparators, neutralizing anti-IL-23pl9 antibody was administered intraperioneally at 4 mg/kg on Day -1 and again on Day 3, and prednisolone was administered at 10 mg/day P.O. All animals received orally water as the vehicle which was used to formulate Peptide 993.

[00743] As described above, animals were observed daily for clinical signs which included percent body weight loss and signs of loose stools or diarrhea. Six days after inoculation of TNBS, rats were sacrificed and the entire colon length and colon weight from each animal were recorded. The severity of colitis was evaluated by a pathologist. In addition to the colon wall thickness, the gross colon damage was scored on a 0-5 scale according to Table E29, and histopathological scores were determined based on the parameters listed in Table E30.

[00744] Treatment with Peptide 1185 significantly reduced some of the disease parameters that were observed in the TNBS rat model of acute colitis. While rats in the sham group continued to gain weight over the course of the study, rats exposed to TNBS and treated with vehicle experienced weight loss. Oral treatment with prednisolone or systemic treatment with anti-IL23pl9 prevented the weight loss in TNBS exposed rats. Treatment with orally administered

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Peptide 1185 did not significantly prevent the weight loss in TNBS challenged rats (see FIG. 13). A significant reduction was also observed in the colon weight to colon length ratios following treatment with prednisolone or anti-IL-23pl9 as compared to treatment with vehicle. Oral administration of Peptidell85 resulted in similar reductions of colon weight to colon length ratios and colon macroscopic scores in TNBS exposed rats. Higher colon macroscopic scores indicated a higher degree of colon pathology. The colon macroscopic score was determined by adding the scores for adhesion, strictures, ulcer, and colon wall thickness, all of which were significantly reduced by treatment with prednisolone, anti-IL-23pl9, or Peptide 1185, as compared to vehicle treated controls. These data demonstrate that oral administration of Peptide 1185 has comparable efficacy to systemic administration of anti-IL-23pl9 monoclonal antibody.

[00745] The pathological features of tissue sections from colon taken from rats in the sham, vehicle, anti-IL-23pi9, and Peptide 1185 groups were examined. Mucosal inflammation, transmural inflammation, gland loss, and erosion were scored according to the criteria listed in Table E29 For all of these features, treatment with anti-IL-23pl9 or Prednisolone reduced the histopathology scores associated with TNBS exposure. Treatment with Peptide 1185 did not significantly reduce the histopathology scores.

EXAMPLE 13

Effects of An Illustrative Peptide Inhibitor in a Rat Model of Acute Colitis [00746] To evaluate the efficacy of the illustrative IL-23R peptide inhibitor Peptide 993 in an animal model of disease, acute colitis was induced by providing 7-week-old female SpragueDawley rats with 64 mg/kg TNBS in 50% ethanol administered intrarectally at Day 0. Peptide 993 was administered orally two times a day at 10 mg/kg, for a total of 42 mg/kg per day, for 8 days starting approximately 24 hours (Day -1) prior TNBS inoculation. A sham group that was not exposed to TNBS and a TNBS treated group that received treatment with vehicle were used as control groups. All animals received orally water as the vehicle which was used to formulate Peptide 993.

[00747] As described above, animals were observed daily for clinical signs which included percent body weight loss and signs of loose stools or diarrhea. Six days after inoculation of

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TNBS, rats were sacrificed and the entire colon length and colon weight from each animal were recorded. The severity of colitis was evaluated by a pathologist. In addition to the colon wall thickness, the gross colon damage was scored on a 0-5 scale according to Table E29, and histopathological scores were determined based on the parameters listed in Table E30.

[00748] Treatment with Peptide 993 significantly reduced all disease parameters that were observed in the TNBS rat model of acute colitis. While rats in the sham group continued to gain weight over the course of the study, rats exposed to TNBS and treated with vehicle experienced weight loss. Treatment with orally administered Peptide 993 also prevented the weight loss in TNBS challenged rats (see FIG. 12). In addition, a significant reduction was also observed in the colon weight to colon length ratios following treatment with oral administration of Peptide 993. Higher colon macroscopic scores indicated a higher degree of colon pathology and was significantly reduced by treatment with Peptide 993, as compared to vehicle treated controls. Oral administration of Peptide 993 has comparable efficacy to systemic administration of antiIL-23pl9 monoclonal antibody, which served as a positive control. Histopathological scores were significantly reduced in colons from Peptide 993 treated rats as compared to vehicle group.

EXAMPLE 14

Effects of An Illustrative Peptide Inhibitor in a Rat Model of Acute Colitis [00749] To evaluate the efficacy of the illustrative IL-23R peptide inhibitor Peptide 980 in an animal model of disease, acute colitis was induced by providing 7-week-old female SpragueDawley rats with 64 mg/kg TNBS in 50% ethanol administered intrarectally at Day 0. Peptide 980 was administered orally 37mg/kg/day (combined PO and in drinking water), PO BID, day -1 to day 7. A sham group that was not exposed to TNBS and a TNBS treated group that received treatment with vehicle were used as control groups. All animals received orally PBS as the vehicle which was used to formulate Peptide 980.

[00750] As described above, animals were observed daily for clinical signs which included percent body weight loss and signs of loose stools or diarrhea. Six days after inoculation of TNBS, rats were sacrificed and the entire colon length and colon weight from each animal were recorded. The severity of colitis was evaluated by a pathologist. In addition to the colon wall thickness, the gross colon damage was scored on a 0-5 scale according to Table E29, and

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PCT/US2016/042680 histopathological scores were determined based on the parameters listed in Table E30. Treatment with Peptide 980 significantly reduced all disease parameters that were observed in the TNBS rat model of acute colitis.

[00751] Treatment with orally administered Peptide 980 prevented the weight loss in TNBS challenged rats (see FIG. 14). In addition, a significant reduction was also observed in the colon weight to colon length ratios following treatment with oral administration of Peptide 980. Higher colon macroscopic score indicates a higher degree of colon pathology, and was significantly reduced by treatment with Peptide 980, as compared to vehicle treated controls (see FIG. 14).

[00752] Pathological features of tissue sections from colon taken from rats in the sham, vehicle, and Peptide 980 treated groups were examined. Mucosal inflammation, transmural inflammation, gland loss, and erosion (see FIG. 14D) were scored according to the criteria listed in Table E30. The sum of the histopathology score was significantly reduced by Peptide 980 treatment as compared to vehicle.

EXAMPLE 15

Levels of BioMarkers Following Treatment with Peptide Inhibitors in a Rat Model of Acute Colitis [00753] Levels of inflammatory markers were examined in the colons. The distal colon tissue samples, designated for protein expression analysis, were flash frozen after collection. For protein extraction, the samples were thawed, weighed and homogenized in the extraction buffer (PBS pH 7.2 supplemented with Protease Inhibitors, 3x volume:weight). The homogenates were centrifuged at 13krpm at 4°C for 15 minutes, a total of two times to remove the debris. The supernatants were saved in multiple aliquots in -80°C and subsequently used for protein expression analysis on ELISA. The total protein in each sample was quantified using BCA assay. MPO, IL-Ιβ, IL-6, IL-17A and IL-22 protein expression in the distal colon samples were analyzed using commercially available rat ELISA kits.

[00754] Treatment with Peptide 993 reduced levels of inflammatory markers present in the colon. The disease defining (MPO, IL-6 and IL-1 beta) and IL-23 directed biomarkers (IL-22, and IL312

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17A) were reduced by treatment with Peptide 993 as compared to vehicle treated controls (see FIG. 15). These data demonstrate that administration of Peptide 993 in amounts that can reduce pathology in vivo also decrease levels of biomarkers present in the colon that are associated with IL-23R activity. Treatment with Peptide 980 reduced levels MPO and IL-22 as compared to vehicle treated controls (see FIG. 16). Treatment with Peptide 1185 at the dose tested did not significantly reduce levels of MPO, IL-22, or IL-17A.

Table E29. Colon Macroscopic Score

Colonic Score Parameters: the values for each animal was summed to obtain the colonic score (maximum value = 12),_

Adhesions: none = 0 minimal = 1 involving several bowel loops = 2_

Strictures: none = 0 minimal = 1 mild = 2 severe, proximal dilatation = 3_

Ulcers:

none focal hyperemia, no ulcers = 1 ulcer without significant inflammation (hyperemia and bowel wall thickening = 2 ulceration of 1 - <3 cm = 3 ulceration 3- <6 cm = 4 ulceration > 6 cm = 5_

Wall thickness:

Wall thickness: less than 1 mm = 0 1-3 mm = 1 > 3 mm = 2

Table E30a. Histopathology - Mucosal/Submucosal Inflammation Score

Mucosal/Submucosal Inflammation Score

The extent of macrophage, lymphocyte, neutrophil and other inflammatory infiltrateswas assigned severity scores according to the following criteria:

0=Normal

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PCT/US2016/042680 l=Minimal, larger focal area with MIMIC and neutrophils or minimal diffuse,no separation of glands, may be mostly in areas of submucosal edema or mesentery

2=Mild, diffuse mild, or multifocal affecting 11-25% of mucosa with minor focal ormultifocal gland separation, no separation in most areas

3=Moderate, 26-50% of mucosa affected with minimal to mild focal ormultifocal separation of glands by inflammatory cell infiltrate, milder in remaining areasof mucosa with some areas having no gland separation by inflammation

4=Marked, 51-75% of mucosa affected with mild to moderate separation of glandsby inflammatory cell infiltrate, minimal to mild in remaining areas of mucosa but allglands have some separation by infiltrate

5=Severe, 76-100% of mucosa affected with moderate to marked areas of gland separation by inflammatory cell infiltrate, mild to moderate in remaining areas of mucosa

Table E30b.

Mucosal Thickness Score

Mucosal thickness was scored in the colon in a non-tangential area ofthe section that best represented the overall mucosal thickness. This parameter is indicative of gland elongation and mucosal hyperplasia. A hyperplasia score was determined as follows.

- =No mucosa present

0=IMormal

1= Minimal, 5-10% thicker than control mucosa

2=Mild, 11-25% thicker than control mucosa

3=Moderate, 26-50% thicker than control mucosa

4=Marked, 51-75% thicker than control mucosa

Table E30c.

Transmural Inflammation

Presence of inflammatory cell infiltrates within the tunica muscularis mucosa and increased fibroblasts/fibrocytes with perpendicularly arranged blood vessels (granulation tissue), possibly extending to the serosa.

0=IMormal

l=Minimal, 5-10% infiltration

2=Mild, 11-25% infiltration

3=Moderate, 26-50% infiltration

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4=Marked, 51-75% infiltration

5=Severe, infiltrates reach the serosa and mesentery

Table E30d.

Gland Loss Score

Crypt epithelial and remaining gland epithelial loss was scored based on the approximate percent

of the mucosa that was affected as follows:

0=None

l=Minimal, 1-10% of the mucosa affected

2=Mild, 11-25% of the mucosa affected

3=Moderate, 26-50% of the mucosa affected

4=Marked, 51-75% of the mucosa affected

5=Severe, 76-100% of the mucosa affected

Table E30e.

Erosion Score

The loss of surface epithelium was scored based on the approximate percent of the mucosa thatwas affected as follows.

0=None

l=Minimal, 1-10% of the mucosa affected

2=Mild, 11-25% of the mucosa affected

3=Moderate, 26-50% of the mucosa affected

4=Marked, 51-75% of the mucosa affected

5=Severe, 76-100% of the mucosa affected

Table E30f.

Histopathology Sum

A sum of inflammation, gland loss, erosion, and transmural inflammation scores was calculated.

EXAMPLE 16

Characterization of Additional Peptide Inhibition of Binding of Interleukin-23

TO THE INTERLEUKIN-23 RECEPTOR

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PCT/US2016/042680 [00755] Peptide optimization was performed to identify additional peptide inhibitors of IL-23 signalling that were active at low concentrations (e.g., IC50 <10 nM) while exhibiting gastrointestinal (GI) stability. Certain peptides were tested to identify peptides that inhibit the binding of IL-23 to human IL-23R and inhibit IL-23/IL-23R functional activity, as described below. Peptides tested included peptides containing a variety of different cyclization chemistries, including, e.g., peptides containing a disulfide linkage, e.g., between two Pen residues, and peptides containing a thioether linkage. Peptide inhibitors of the present invention include but are not limited to peptides having any of the structures depicted herein. In addition, peptide inhibitors of the present invention include those having the same amino acid sequence of the peptides or structures described herein, without being required to have the same or any N- or C-terminal “capping” groups, such as, e.g., Ac or NIL.

[00756] Assays performed to determine peptide activity were performed as described in Example 2 above. Human ELISA indicates the IL23-IL23R competitive binding assay, Rat ELISA indicates the rat IL-23R competitive binding ELISA assay, and pStat3HTRF indicates the DB cells IL-23R pSTAT3 cell assay. The peptides depicted in Table E31 are cyclized via a disulfide bridge formed between two residues in these peptides. The peptides depicted in Table E32 are cyclized via a thioether bond between the indicated amino acid residues. Table E32 provides an illustrative structure depicting thioether cyclization, which may also be indicated in the table by the term “Cyclo,” with the cyclic region bracketed immediately following.

Table E31. Illustrative Peptides Containing the Ac-[Pen]-XXWX-[Pen]-XXXX Motif and Analogues

SEQ ID NO:	Sequence	Human ELISA (nM)	Rat ELISA (nM)	pStat3 HTRF (nM)
1115	[Palm]-[isoGlu]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]- [2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2			**
1116	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(PEG4-isoGlu-Palm)]-NN-NH2			*
1117	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(Ac)]- [Lys(Ac)]-NN-NH2		**	*
1118	[Octanyl]-[lsoGlu]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2- aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2		**	*
1119	[Octanyl]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2- Nal]-[Aib]-[Lys(Ac)]-NN-NH2		**	*

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1120	[Palm]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2			*
1121	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(PEG4-Octanyl)]-NN-NH2		**	*
1122	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(PEG4-Palm)]-NN-NH2			*
1123	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-Palm)]-[2- Nal]-[Aib]-[Lys(Ac)]NN-NH2			***
1124	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-Lauryl)]-[2- Nal]-[Aib]-[Lys(Ac)]-NN-NH2			**
1125	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(PEG4-Palm)- [Lys(Ac)]-NN-NH2			*
1126	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(PEG4- Lauryl)]-[Lys(Ac)]-NN-NH2			*
1127	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-lsoGlu- Palm)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2			***
1128	Ac-[Pen]-NTWQ-[Pen]- [Phe[4-(2-aminoethoxy)-(PEG4-lsoGLuLauryl)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2			***
1129	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(PEG4- lsoGlu-Palm)]-[Lys(Ac)]-NN-NH2		**	*
1130	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-a-Me-K(PEG4-lsoGlu- Lauryl)]-[Lys(Ac)]-NN-NH2			*
1131	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(IVA)]- [Lys(Ac)]-NN-NH2		**	*
1132	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(Biotin)]- [Lys(Ac)]-NN-NH2	*	**	*
1133	Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH2)-[2-Nal]-[a-MeLys(Octanyl)]- [Lys(Ac)]-NN-NH2		**	*
1134	Ac-[Pen]-[Lys(IVA)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2		**	*
1135	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Lys(IVA)]-N-NH2			*
1136	Ac-[Pen]-[Lys(Biotin)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2		**	*
1137	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Lys(Biotin)]-N-NH2			**
1138	Ac-[Pen]-[Lys(Octanyl)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2- Nal]-[Aib]-[Lys(Ac)]-NN-NH2			**
1139	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Lys(octanyl)]-N-NH2			**
1140	Ac-[Pen]-[Lys(Palm)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-- [Aib]-[Lys(Ac)]-NN-NH2			>1000

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1141	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-Lys(Palm)]-N-NH2			>1000
1142	Ac-[Pen]-[Lys(PEG8)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]— [Aib]-[Lys(Ac)]-NN-NH2			**
1143	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Lys(PEG8)]-N-NH2			**
1144	Ac-[Pen]-K(Pegll-Palm)TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2- Nal]-[Aib]-[Lys(Ac)]-NN-NH2			**
1145	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Lys(Pegll-palm)]-N-NH2			**
1146	Ac-[Pen]-[Cit]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2		*	*
1147	Ac-[Pen]-[Lys(Ac)]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2		**	*
1148	Ac-[Pen]-NT-[Phe(3,4-OCH3)2]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2- Nal]-[Aib]-[Lys(Ac)]-NN-NH2			-1000
1149	Ac-[Pen]-NT-[Phe(2,4-CH3)2]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2- Nal]-[Aib]-[Lys(Ac)]-NN-NH2			***
1150	Ac-[Pen]-NT-[Phe(3-CH3)]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2			***
1151	Ac-[Pen]-NT-[Phe(4-CH3)]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2			***
1152	Ac[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-N-[pAla]-NH2	*	*	*
1153	Ac-[(D)Tyr]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-N-[pAla]-NH2	*	*	*
1154	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-QN-NH2			*
1155	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Lys(Ac)]-N-NH2			*
1156	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-N-[Lys(Ac)]-NH2			*
1157	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-QQ-NH2		**	*
1158	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-Q-[pAla]-NH2		**	*
1159	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-N-[Cit]-NH2			*
1160	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Cit]-NNH2		**	*
1161	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Cit]-Q-NH2			*
1162	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Cit]-[Lys(Ac)]-NH2			**

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1163	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Lys(Ac)]-[Cit]-NH2			**
1164	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QN- [βΑΐ3]-ΝΗ2	*	*	*
1165	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-E-[Cit]- q-nh2			*
1166	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- CitNCitNH2		*	*
1167	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Cit]- Q-[Cit]-NH2			*
1168	Ac-[Pen]-[Cit]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2		*	*
1169	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2
1170	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QNN- nh2		*	*
1171	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-ENQ- nh2		**	*
1172	Ac-[Pen]-GPWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			>1000
1173	Ac-[Pen]-PGWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			-1000
1174	Ac-[Pen]-NTWN-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			**
1175	Ac-[Pen]-NSWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			*
1176	Ac-[Pen]-N-[Aib]-WQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			>1000
1177	Ac-[Pen]-NTW-[Aib]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]N-[Aib]-NH2			**
1178	Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2		*	*
1179	Ac-[Pen]-[Lys(Ac)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]— [Aib]-[Lys(Ac)]NNNH2			*
1180	Ac-[Pen]-QVWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			*
1181	Ac-[Pen]-NT-[2-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			**
1182	Ac-[Pen]-NT-[l-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2			**
1183	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]- [Lys(Ac)]-NN-NH2	*	*	*
1184	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]- [Lys(Ac)]-NN-NH2	*	*	*

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1185	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4- carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	*	*	*
1186	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]- [Lys(Ac)]-N-[pAla]-NH2	*	*	*
1187	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]- [Lys(Ac)]-N-[pAla]-NH2	*	*	*
1188	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4- carboxy-tetrahydropyran]-[Lys(Ac)]-N-[pAla]-NH2	*	*	*
1189	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-LN-NH2			*
1190	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-GN-NH2			*
1191	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-SN-NH2		**	*
1192	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Aib]-N-NH2			*
1193	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-FN-NH2			*
1194	Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2	*	*	*
1195	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[Tic]-[pAla]-NH2			***
1196	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[nLeu]-[pAla]-NH2			*
1197	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-G-[pAla]-NH2			*
1198	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-R-[pAla]-NH2			*
1199	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]- [Lys(Ac)]-W-[pAla]-NH2			**
1200	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]- [Lys(Ac)]-S-[pAla]-NH2			*
1201	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]- [Lys(Ac)]-L-[pAla]-NH2			*
1202	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]- [Lys(Ac)]-[AIB]-[pAla]-NH2			*
1203	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]- [Lys(Ac)]-[N-MeAla]-[pAla]-NH2			***
1204	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-[2-Nap]-[pAla]-NH2		**	*
1205	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-F-[pAla]-NH2		**	*
1206	Ac-[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[ 4amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]NN-NH2			*

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Table E32. IC50 of Illustrative Peptide Inhibitors (Thioethers)

[Phe(4-OMe)]-[2-Nal]-XXXX-NHu o

Ac-Cyclo-[[Abu]-XXWXC]-[Phe(4-OMe)]-[2-Nal]-XXX-NH ₂

SEQ ID NO:	Sequence	Human ELISA (nM)	Rat ELISA (nM)	pStat3 HTRF (nM)
1207	Biotin-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	TBC	*	*
1208	Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino- 4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	TBC	*	*
1209	Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	TBC	*	*
1210	Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	*	*	*
1211	Ac-E-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-ENN-NH2
1212	Ac-[(D)Asp]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2
1213	Ac-R-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	*	*	*
1214	Ac-[(D)Arg]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	TBC	*	*
1215	Ac-F-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-ENN-NH2			*
1216	Ac-[(D)Phe]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2
1217	Ac-[2-Nal]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2			*
1218	Ac-T-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-ENN-NH2			*
1219	Ac-L-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [4-amino-4-carboxy-tetrahydropyran]-ENN-NH2			*
1220	Ac-[(D)Gln]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	TBC	*	*
1221	Ac-[(D)Asn]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2		*	*

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1222	Ac-cyclo[[Abu]-Q.TWQC]-[Phe[4-(2-aminoethoxy)-(PEG4-Alexa488)]- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2			*
1223	[Alexa488]-[PEG4]-cyclo[[Abu]-Q.TWQC]-[Phe[4-(2-aminoethoxy)]-- [2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	*	*	*
1224	[Alexa647]-[PEG4]-cyclo[[Abu]-Q.TWQC]-[Phe[4-(2-aminoethoxy)]-[2- Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	*		TBC
1225	[Alexa-647]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2	*
1226	[Alexa647]-[PEG12]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2	*
1227	[Alexa488]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- [Lys(Ac)]-NN-NH2	*		*

* < 10 nM; ** > 10 and < 100 nM; *** >100 and < 1,000 nM

EXAMPLE 17

Stability of Additional Peptide Inhibitors in Simulated Intestinal Fluid (SIF), Simulated Gastric Fluid (SGF) and Redox Conditions [00757] Studies were carried out in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) to evaluate gastric stability of additional peptide inhibitors of the present invention. In addition, studies were carried out to assess redox stability of the additional peptide inhibitors of the present invention.

Table E33. Thioethers and Dipens

SEQ ID NO:	Sequence	SIF tl/2 (min)	SGF tl/2 (min)
1228	Biotin-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4- amino-4-carboxy-tetrahydropyran]-ENN-NH2	>90	>180
1229	Ac-cyclo[[Abu]-Q.TWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4- carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	>180	>180
1230	Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4- amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	>180	<180
1231	Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-	>180,	>180
amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	>180	>180

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1232	[Octanyl]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2	>180	>180
1233	[Palm]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]- [Aib]-[Lys(Ac)]-NN-NH2	>180	>10
1234	Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)-(PEG4-Alexa488)]-[2- Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	>180	>90
1235	[Alexa488]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]—[2Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	>180	> 180
1236	[Alexa647]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2- Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH2	>180	>180
1237	Ac[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib][Lys(Ac)]-N-[pAla]-NH2	>180	>180
1238	Ac-[(D)Tyr]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-N-[pAla]-NH2	>180	>180
1239	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QN-[pAla]- nh2	Stable	>180
1240	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]- [Lys(Ac)]-NN-NH2	>180 >180	>180, >180
1241	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4- carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	>180, >180	>180, >180
1242	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]- [Lys(Ac)]-N-[pAla]-NH2	Stable	>180
1243	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4- carboxy-tetrahydropyran]-[Lys(Ac)]-N-[pAla]-NH2	>180	>180
1244	Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]- [Lys(Ac)]-NN-NH2	>180	>180
1245	Ac-[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4- AMINO-4-CARBOXY-TETRAHYDROPYRAN]-[Lys(Ac)]NNNH2	>180	>180
1246	[Alexa488]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2- aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]- nn-nh2	>180	>180
>90 = less t	ian or equal to 180 min and greater than 90 min; >45 min = less than or equal to 90

min and greater than 45 min; >10 = less than or equal to 45 min and greater than 10 min; <10 = less than 10 min.

EXAMPLE 18

NK Cell Assay [00758] Natural killer (NK) cells, purified from human peripheral blood of healthy donors by negative selection (Miltenyi Biotech, Cat # 130-092-657), were cultured in complete media (RPMI 1640 containing 10% FBS, L-glutamine and penicillin-streptomycin) in the presence of

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IL-2 (RnD, Cat # 202-IL-010/CF) at 25 ng/mL. After 7 days, cells were centrifuged, and resuspended in complete media at 1E6 cells/mL. Recombinant IL-23 at predetermined EC50 to EC75 and IL-18 (RnD, Cat # B003-5) at 10 ng/mL were mixed with varying concentrations of peptides, and added to NK cells seeded at 1E5 cells per well. After 20 to 24 hours, IFNy in the supernatant was quantified using Quantikine ELISA (RnD, Cat # DIF50). Results are shown in Table E34. Multiple results shown for a single peptide are from separate assays.

Table E34. Primary Cell Assay (Thioethers and Dipens)

SEQ ID NO:	Sequence	NK cell Assay (nM)
1247	Ac-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahyd ropyran]-[Lys(Ac)]-NN-NH2	* * * ? ?
1248	Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4- carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2	? ?
1249	[Alexa647]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4- amino-4-carboxy-tetrahydropyran]-ENN-NH2	* * * ?
1250	Ac[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]--[Aib]- [Lys(Ac)]-N-[pAla]-NH2	**
1251	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QN-[pAla]-NH2	**
1252	Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]- nn-nh2	**
1253	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]-[Lys(Ac)]- nn-nh2	*
1254	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahyd ropyran]-[Lys(Ac)]-NN-NH2	*
1255	Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahyd ropyran]-[Lys(Ac)]-N-[pAla]-NH2	*
1256	Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN- nh2	*

[00759]All of the above U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, are incorporated herein by reference, in their entirety.

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PCT/US2016/042680 [00761] From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.

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Claims (29)

1. What is claimed is:

   1. A peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Xa):

   XI-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Xa) wherein

   XI is any amino acid or absent;

   X2 is any amino acid or absent;

   X3 is any amino acid or absent;

   X4 is any amino acid or chemical moiety capable of forming a bond with X9;

   X5 is any amino acid;

   X6 is any amino acid;

   X7 is any amino acid;

   X8 is any amino acid;

   X9 is any amino acid or chemical moiety capable of forming a bond with X4;

   XI0 is any amino acid;

   XII is any amino acid;

   XI2 is any amino acid;

   XI3 is any amino acid;

   XI4 is any amino acid;

   XI5 is any amino acid,

   XI6 is any amino acid or absent;

   XI7 is any amino acid or absent;

   XI8 is any amino acid or absent;

   XI9 is any amino acid or absent; and

   X20 is any amino acid or absent, wherein the peptide inhibitor is cyclized via a bond between X4 and X9, and

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   PCT/US2016/042680 wherein the peptide inhibitor inhibits the binding of an interleukin-23 (IL-23) to an IL-23 receptor.
2. 2. The peptide inhibitor of claim 1, wherein the bond between X4 and X9, is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefin bond.
3. 3. The peptide inhibitor of claim 1, wherein X4 is Cys and X9 is Cys, and the bond is a disulfide bond.
4. 4. The peptide inhibitor of claim 1, wherein X4 is Pen and X9 is Pen, and the bond is a disulfide bond.
5. 5. The peptide inhibitor of claim 1, wherein the peptide inhibitor comprises an amino acid sequence of any one of SEQ ID NOS: 365-370, 857-1029.
6. 6. The peptide inhibitor of claim 1, wherein the peptide inhibitor comprises an amino acid sequence set forth in any of Formulas (Va), (Vb), (Vc), (Vd), (Ve), (Vf), (Vg) and (Vh).
7. 7. The peptide inhibitor of claim 1, wherein the peptide inhibitor comprises any of the following amino acid sequences:

   [Pa1m] - [isoGlu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] NNNH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-isoGlu-Palm)]-NNNH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[ot-MeLys(Ac)]-[Lys(Ac)]-NN-NH₂;

   [Octany 1] - [IsoGlu] - [PEG4] - [Pen]-NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]- [Aib] [Lys(Ac)]-NN-NH₂;

   [Octanyl]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

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   PCT/US2016/042680 [Palm] - [PEG4]- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -NN NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-Octanyl)]-NN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(PEG4-Palm)]-NN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-Palm)]-[2-Nal]-[Aib]-[Lys(Ac)]NNNH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)-(PEG4-Lauryl)] - [2-Nal] - [ Aib]- [Lys(Ac)]-NNNH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[ot-MeLys(PEG4-Palm)-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[ot-MeLys(PEG4-Lauryl)]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-IsoGlu-Palm)]-[2-Nal]-[Aib][Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]- [Phe[4-(2-aminoethoxy)-(PEG4-IsoGLu-Lauryl)]-[2-Nal]-[Aib][Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[ot-MeLys(PEG4-IsoGlu-Palm)]-[Lys(Ac)]NN-NH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(PEG4-IsoGlu-Lauryl)]-[Lys(Ac)]NN-NH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(IVA)]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(Biotin)]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH₂)-[2-Nal]-[a-MeLys(Octanyl)]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-[Lys(IVA)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(IVA)]-N-NH₂;

   Ac-[Pen]-[Lys(Biotin)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Biotin)]-NNH₂;

   Ac-[Pen]-[Lys(Octanyl)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

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   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(octanyl)]-NNH₂;

   Ac-[Pen]-[Lys(Palm)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]~ [Aib]-[Lys(Ac)]-NN-NH₂; Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -Ly s(Palm)] -N-NH₂; Ac-[Pen]-[Lys(PEG8)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂; Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(PEG8)]-N-NH₂; Ac- [Pen] -K(Peg 11 -Palm)TWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] -NNNH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]—[Aib] - [Lys(Ac)] - [Ly s(Peg 11 -palm)]N-NH₂;

   Ac-[Pen]-[Cit]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-[Lys(Ac)]-TW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NNNH₂;

   Ac- [Pen] -NT- [Phe(3,4-OCH3 )2] -Q- [Pen] - [Phe[4-(2-aminoethoxy)]- [2-Nal]- [ Aib] - [Ly s(Ac)] NN-NH₂;

   Ac- [Pen] -NT - [Phe(2,4-CH3 )2] -Q- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] -NNNH₂;

   Ac- [Pen] -NT- [Phe(3 -CH3)] -Q- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib]- [Ly s(Ac)] -NNNH₂;

   Ac- [Pen] -NT- [Phe(4-CH3)] -Q- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib]- [Ly s(Ac)] -NNNH₂;

   Ac[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[PAla]NH₂;

   Ac-[(D)Tyr]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[PAla]NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-QN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-N-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[Lys(Ac)]-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-QQ-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-Q-[PAla]-NH2;

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   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[Cit]-NH2;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-NNH2;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-Q-NH2;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Cit]-[Lys(Ac)]-NH2;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-[Cit]-NH2;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-QN-[PAla]-NH2;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] -E- [Cit]-Q-NH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -N- [Cit] -NH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -Q- [Cit] -N H₂;

   Ac-[Pen]-[Cit]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib] -QNN-NET;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [ Aib]-ENQ-NH₂;

   Ac-[Pen]-GPWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac-[Pen]-PGWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac-[Pen]-NTWN-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac-[Pen]-NSWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac-[Pen]-N-[Aib]-WQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac-[Pen]-NTW-[Aib]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]N-[Aib]-NH2;

   Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac-[Pen]-[Lys(Ac)]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]NNNH2;

   Ac-[Pen]-QVWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-NT-[2-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-NT-[l-Nal]-Q-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH2;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [α-MeLeu]- [Lys(Ac)] -NN-NH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [α-MeLys] - [Lys(Ac)]-N N-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran][Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLeu]-[Lys(Ac)]-N-[PAla]-NH2;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[a-MeLys]-[Lys(Ac)]-N-[PAla]-NH₂;

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   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran][Lys(Ac)]-N-[pAla]-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-LN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-GN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-SN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Aib]-N-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-FN-NH₂;

   Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[Tic]-[PAla]-NH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Ly s(Ac)] - [nLeu] - [ β A la] -NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-G-[PAla]-NH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -R- [ β Ala] -NH₂; Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-W-^Ala]-NH₂;

   Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]—[Aib] - [Lys(Ac)] -S - [ β A la] -NH₂; Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]~ [Aib]-[Lys(Ac)]-L-^Ala]-NH₂; Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]—[Aib]-[Lys(Ac)]-[AIB]-^Ala]-NH₂; Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal]—[Aib] - [Ly s(Ac)] - [N-MeAla] - [β Ala] NH₂;

   Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[2-Nap]-^Ala]-NH₂; Ac- [Pen] -NTWQ- [Pen] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys(Ac)] -F - [β Ala] -NH₂; Ac-[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[ 4-amino-4-carboxytetrahydropyran]-[Lys(Ac)]NNNH₂;

   Biotin-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahy dropyran] -ENN-NH₂;

   Ac-cy clo [ [ Abu] -QTWQC]- [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4-carboxytetrahy dropyran] - [Ly s(Ac)] -NN-NH₂;

   Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahy dropyran] - [Ly s(Ac)] -NN-NH₂;

   Ac-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxytetrahy dropyran] - [Ly s(Ac)] -NN-NH₂;

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   Ac-E-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahy dropyran] -ENN-NEB;

   Ac-[(D)Asp]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahy dropyran]-ENN-NEB;

   Ac-R-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahy dropyran] -ENN-NEB;

   inoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NEB;

   Ac-F-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy· tetrahy dropyran] -ENN-NEB;

   Ac- [(D)Phe] - [(D) Arg] -cyclo[ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4carboxy-tetrahydropyran]-ENN-NEB;

   Ac- [2-Nal] - [(D) Arg] -cy clo[ [ Abu] -QTWQC] - [Phe[4-(2-aminoethoxy)] - [2-Nal] - [4-amino-4carboxy-tetrahydropyran]-ENN-NEB;

   Ac-T-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahy dropyran] -ENN-NEB;

   Ac-L-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy tetrahy dropyran] -ENN-NEB;

   Ac-[(D)Gln]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahy dropyran]-ENN-NEB;

   Ac-[(D)Asn]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahy dropyran]-ENN-NEB;

   Ac-cy clo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)-(PEG4-Alexa488)]-[2-Nal]-[4-amino-4carboxy-tetrahy dropyran]-ENN-NEB;

   [Alexa488]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]—[2-Nal]-[4-amino-4carboxy-tetrahydropyran]-ENN-NEB;

   [Alexa647]-[PEG4]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4carboxy-tetrahy dropyran]-ENN-NEB;

   [Alexa-647]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2;

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   PCT/US2016/042680 [Alexa647]-[PEG12]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2; and [Alexa488]-[PEG4]-[(D)Arg]-cyclo[[Abu]-QTWQC]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4amino-4-carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH2, wherein the peptide inhibitor is cyclized via a disulfide bond between two Pen residues or by a thioether bond between Abu and a Cys residue, and wherein the peptide inhibitor inhibits the binding of an interleukin-23 (IL-23) to an IL-23 receptor.
8. 8. The peptide inhibitor of any one of claims 1-7, further comprising one or more half-life extension moiety and/or one or more linker moiety conjugated to the peptide inhibitor.
9. 9. The peptide inhibitor of claim 8, wherein the half-life extension moiety is conjugated to the peptide inhibitor via one or more linker moieties.
10. 10. The peptide inhibitor of any one of claims 1-9, wherein the peptide inhibitor comprises the structure of Formula I:

    R'-X-R² (I) or a pharmaceutically acceptable salt or solvate thereof, wherein

    R¹ is a bond, hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C6-C12 aryl, a C1-C6 alkyl, a C1-C20 alkanoyl, and including PEGylated versions alone or as spacers of any of the foregoing; X is the amino acid sequence; and

    R² is OH or NH₂.
11. 11. A peptide dimer inhibitor of an interleukin-23 receptor, wherein the peptide dimer inhibitor comprises two peptide monomer subunits connected via one or more linker moieties, wherein each peptide monomer subunit has a sequence or structure set forth in any one of claims 1-10.
12. 12. The peptide dimer inhibitor of claim 11, wherein one or both peptide monomer subunit is cyclized via an intramolecular bond between X4 and X9.

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13. 13. The peptide dimer inhibitor of claim 12, wherein one or both intramolecular bond is a disulfide bond, a thioether bond, a lactam bond, a selenoether, diselenide, or an olefin bond.
14. 14. The peptide dimer inhibitor of any one of claims 11-13, wherein the linker moiety is a diethylene glycol linker, an iminodiacetic acid (IDA) linker, a β-Ala-iminodiaceticacid (β-AlaIDA) linker, or a PEG linker.
15. 15. The peptide dimer inhibitor of any one of claims 11-14, wherein the N-terminus of each peptide monomer subunit is connected by the linker moiety or wherein the C-terminus of each peptide monomer subunit is connected by the linker moiety.
16. 16. The peptide inhibitor of any one of claims 1-10 or the peptide dimer of any of claims 11-15 further comprising a conjugated chemical substituent.
17. 17. The peptide inhibitor or the peptide dimer of claim 16, wherein the conjugated chemical substituent is a lipophilic substituent or a polymeric moiety.
18. 18. The peptide inhibitor or the peptide dimer of claim 16, wherein the conjugated chemical substituent is Ac, Palm, gamaGlu-Palm, isoGlu-Palm, PEG2-Ac, PEG4-isoGlu-Palm, (PEG)sPalm, succinic acid, glutaric acid, pyroglutaric acid, benzoic acid, IVA, octanoic acid, 1,4 diaminobutane, isobutyl, or biotin.
19. 19. The peptide inhibitor or the peptide dimer of claim 16, wherein the conjugated chemical substituent is a polyethylene glycol with a molecular mass of 400 Da to 40,000 Da.
20. 20. A polynucleotide comprising a sequence encoding the peptide inhibitor of any one of claims

    I- 10 or one or both peptide monomer subunit of the peptide dimer inhibitor of any one of claims

    II- 15.
21. 21. A vector comprising the polynucleotide of claim 20.

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22. 22. A pharmaceutical composition comprising the peptide inhibitor or the peptide dimer inhibitor of any one of claims 1-19, and a pharmaceutically acceptable carrier, excipient, or diluent.
23. 23. The pharmaceutical composition of claim 22, further comprising an enteric coating.
24. 24. The pharmaceutical composition of claim 23, wherein the enteric coating protects and releases the pharmaceutical composition within a subject’s lower gastrointestinal system.
25. 25. A method for treating an Inflammatory Bowel Disease (IBD), ulcerative colitis, Crohn’s disease, Celiac disease (nontropical Sprue), enteropathy associated with seronegative arthropathies, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, chronic granulomatous disease, glycogen storage disease type lb, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Wiskott-Aldrich Syndrome, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, psoriasis, psoriatic arthritis, or graft versus host disease in a subject, comprising providing to the subject an effective amount of the peptide inhibitor or peptide dimer inhibitor of any one of claims 1-19, or the pharmaceutical composition of any one of claims 22-24.
26. 26. The method of claim 25, wherein the pharmaceutical composition is provided to the subject by an oral, parenteral, intravenous, peritoneal, intradermal, subcutaneous, intramuscular, intrathecal, inhalation, vaporization, nebulization, sublingual, buccal, parenteral, rectal, intraocular, inhalation, topically, vaginal, or topical route of administration.
27. 27. The method of claim 25 for treating Inflammatory Bowel Disease (IBD), ulcerative colitis, Crohn’s disease, wherein the pharmaceutical composition is provided to the subject orally.

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28. 28. The method of claim 25 for treating psoriasis, wherein the pharmaceutical composition is provided to the subject orally, topically, parenterally, intravenously, subcutaneously, peritonealy, or intravenously.
29. 29. The method of any one claims 25-28, wherein the peptide inhibitor or the peptide dimer inhibitor inhibits binding of an interleukin-23 (IL-23) to the interleukin-23 receptor (IL-23R).

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    3.0ι **

    2.5

    Ί

    Compound A jp

    3% DSS

    FIG. 1

    SUBSTITUTE SHEET (RULE 26)

    WO 2017/011820

    PCT/US2016/042680

    IL-12 Stimulation of IFNy Release From Human PBMCs

    OD (450 nm)

    2.4

    2.01.6

    1.20.80.4 *♦·* Compound A Compound B

    0.0 0.0001

    *.......r-r-r-rrrq-r......-,......

    0.01 1 Compound (uM)

    100

    FIG. 2

    SUBSTITUTE SHEET (RULE 26)

    WO 2017/011820

    PCT/US2016/042680 £

    fifS o

    Q, o

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    « a> a o a. o Ξ a. a, < CL ffi φ > T 8, O c » 8. fi a UL s o 0 s o fi o 0

    3% DSS

    FIG. 3 A

    0 Normal .........1......... ferythema 111111111 Trythema^ slight edaraa, small erosions lie Two or more bleeding ulcers, inflammation, moderate adhesions I 4 Severe ulceration, stenosis with dilations, severe adhesions FIG. 3B

    SUBSTITUTE SHEET (RULE 26)

    WO 2017/011820

    PCT/US2016/042680

    I

    I

    I i

    ΞΖ5

    IL23RJi uman IL23R„mouse

    IL23R_jrat

    IL23R_chimp

    IL23R„dog

    IL23R„cow !L23R_human !L23R_mouse !L23R_rat !L23R„chimp !L23R_dog

    IL23R_cow !L23R_human

    IL23R mouse

    IL23R_rat !L23R_chimp

    IL23R_dog !L23R_cow !L23R_human

    IL23R_mouse !L23R_rat

    IL23R_chimp !L23R_dog !L23R_cow

    IL23R_h liman iL23R,...mouse !L23R_rat !L23R_chimp !L23R_dog !L23R_cow !L23R_h liman iL23Rjnouse

    SL23R_rat

    IL23R chimp

    IL23R....dog

    IL23R.__.cow

    1 10 20 J__________________X______________________1_______________________L______________________J_______________________JL__

    ---------------MNQVT I Q WD A V

    MKREREMRGFYYIWDMSHLTLQLHVV

    MRREREMRGFYYIWDMSHVALQLHVV

    ---------------MNQVT I Q W D A V

    ---------------_{M N} q | _T | q w D V V

    ---------------MNQVTIHWDVV

    130 140 150

    ...I______________________jl______________________1.1______________________L

    G K D 1 S S G Y P P D 1 P D Ε V TG V 1 Y E Y S G K D 1 S S GH P P D A P S N L TC V 1 Y E Y S G K D 1 S S G Y P P D A P S N M T C V 1 Y E Y S G K D 1 s s G Y P P D 1 P D Ε V TC V 1 Y E Y S G K D 1 s s G Y P P D V P D K V TC V 1 Y E Y S G K D 1 s s G Y P P D V P D K V AC V 1 Y E Y S

    260 270 280

    WDSQTT IEKVSCEMRYKATTNQTWNV WKSKTM IEKVFCEMRYKTTTNQTWSV W K S K IMTGKVFCEMRYKATTNQTWNV WDSQTT IEKVSCEMRYKATTNQTWNV WNSQTT IEKVSCEMRHKTTTNQTWKV WDSQTS IEKVSCEMRYKDTTNQTWNV ___________1______________________JL__

    ALYiLFSWO

    ALYVLFRWd

    ALYALFRWG

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    160

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    GNMTCTWNAq

    GNMTCTWNTG

    GNMTCTWNTG

    GNMTCTWNAG

    GNMTCTWNSG

    GNMTCTWNPG

    290 kTfd't n7 ty'V

    K F F D A N F T Y V KEFDTNYTYV K E F D T N F T Y V KEFDTNFPYE KEFDTNFTYS

    NRG- D G L L L G M i V F A V M L S L S L G F N R S F R T G N H Q - D G L L S G Μ V F L A 1 M L P F S L G F N R S L R 1 G N SQ- D G L L S G Μ V F L A i L L P F S L G F N R S L R 1 G NRG- D G L L L G Μ IV F A V M L S L S L. G F N R S L R T G N RQQ D G L L L G M IF F A A M L S L S L G F N R S 1 R T G N R K Q D G L L L G Μ V F F A V M L S V L S L G F N R S L R T G

    P D L N T G YK PQ 1 s N F L P E G S H L S N N N E I T S L T L P D L N T G YK PQ V s N V P P b u N L F 1 N R D E R D P T S L P D L N T G YK P Q V s N V p p Ε Ε N H F I N R D E R D P M S L P D L N T G YK P Q 1 s N F L P E G S H L ς N N N r 1 T S L T L P G L S T G YK P Q 1 s N F L T Λ Λ b υ N H L ς K K D r TS S S T L P D L N T G YK P Q 1 s S F L P GG N H L S N D D E T A S S I L

    K A

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    E L P S 1 N T Y FP QN 1 L E S H F NR 1 S L L Ε K DLRS 1 N S Y F P Q N V L E S H F SR I S L F Q K DIPS 1 N S Y F P Q N V L E S H F SG 1 P L L Q K E L P S 1 N T Y F P Q N 1 L E S H F NR 1 S L L Ε K E L P S 1 N S Y F P Q N 1 L Ε N H F NT 1 S L L Ε K E L P S 1 N S Y F P G N 1 L E S H F NR 1 S L L Ε K

    SUBSTITUTE SHEET (RULE 26)

    WO 2017/011820

    PCT/US2016/042680

    ! H G G 1 T N H G G 1 T S 1 H G G i A T H G G 1 T N H G G 1 T N i H G G 1 T N

    _!_1_L

    NCSGHIWVEPAT

    NCSGDMWVERGE NCSGNMWVEPGE NCSGHIWVEPAT NCSGHIWVEPAT NCSGHIWVEPAT

    K M G Μ N 1 S 1 Y CQ AA I K Q M GM NV S 1 Y C Q E A L K Q M GMNVSVYCQEALK K M G Μ N 1 S 1 Y CQ AA 1 K K M G Μ N 1 S 1 Y CQ AA 1 K K M G Μ N 1 S 1 Y CQ AA i K

    K L T Y 1 D K Y V V Η V K P T Y 1 D K V I V Η V K P T Y 1 D K Y T V Η V K L I Y * D “ K V V V Η V K P T Y 1 D K Y V V Η V R P T ¥ 1 D • K Y V V Η V

    KSLETEEEQQYLTSSYIN KSLETEEEQQYLASSYVK KSLETEEQQQYLASNYVN K8LETEEEQQYLTSSY I N KSLEKEEEQQYLSSSYIN KSLETEEEQEYLTSSY I N _I_I_

    NCQPRKLHFYK

    NCRPRNLYFYK

    NCRPRNLHFYK

    NCQPRKLHFYK

    NCQPRKLYFYK

    NCQPSKLYFYK

    I STDS LQGGKKYLVWV I STDS LQGGRKYLVWV I STDS LQGGRKYLVWV I STDS LQGGKKYLVWV I STDS LQGGKKYLVWV I STDS LQKGKKYLVWV

    300 310 320 330 3H0 iQQSEFYLEPDSKYVFQVRCQETGKRNWQPWSSPFVHQTSQETGKRNW

    QQSEFYLEPNSKYVFQVRCQGTGKR--------------------NW jQQSEFYLEPNIKYVFQVRCQETGKR--------------------YW iQQSEFYLEPNTKYlFQVRCQETGKR--------------------YW | Q Q S E F Y L Q P N A Μ Y V F Q V R C Q E T G K K...............................................................Y W

    K R R 1 L L L K R K V L L M K R K V L L M K R R 1 L L L K R R 1 L L L K R R 1 L L L

    I P K W L Y E D f P K W L Y E D I P K W L Y E D I P K W L Y E D

    I P K W L Η E D I P K W L Y E D

    PNMKNSNVVKMLQENSELMN NNSSEQVLYVD PNMENSNVAKLLQEKSVFEN DNASEQALYVD

    P N Μ E N S N IAKLLQEKSVFEN ENASEQALYVD PNMKNSNVVKMLQENSELMNNNSSEQVLYVD PNMENSKVVEI LQKQSEFMN NNSSEQVLYAD PNMENSKVVKILQERNEFMNNNSSEQVLYVD

    I_I_I_I_I_I_I_I_I_I_L

    P V D S L D S G N N P R L Q K HP N F A F S V S S V N S L S N T 1 F L G t L S L 1 L N Q G EC T D D - --- H F A R L K T YP N F Q F S A S S M A L L N K T L 1 L D r· L C L V L N Q G E F T G D - — -- H F A R L K T YP N F T F S A S S MT S L S K T L 1 L D p L S L V L N Q G E F P V D S L D S G N N P R L Q K HP N F A F S V S S V N S L s N T 1 F L G p L S L I L N Q G EC L A D S S D L G G N A R F K K Y P N F A F S V S S MN S L s N T L F L E L S L 1 L N Q G E R P A D S L N L G N N A R F K K YP D F A F S V S S T N S L s N T 1 F L E P L N L I L N Q G EC

    680 690 700 710 720

    J!I!I.I.L

    SUBSTITUTE SHEET (RULE 26)

    WO 2017/011820

    PCT/US2016/042680

    100

    110

    120

    G F K E G I K E G I K E G I K E

    T R T R T R T R

    NKTTARLWYKNFLEPHASMYCTAECPKHFGETL

    NRTTAR1WYKGFSEPHAYMHCTAECPGHFGETL VWYKGF S EP HASMYCTAECPGRFQE TL YCTAECPKHFQETL YCTAECPGYFQE TL

    N R T T

    NKTTARLWYKNFLEPHAS

    NKTTARLWYSNFLEPHAS

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    R F Η I TRI NKTTARLWYNNFVEPQAFVYCTAECSRYFPETL

    220

    L

    230

    240

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    Compound C

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    SUBSTITUTE SHEET (RULE 26)

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    PRTH_002_03WO_ST25 SEQUENCE LISTING

    <110> PROTAGONIST THERAPEUTICS, INC. <120> ORAL PEPTIDE INHIBITORS OF INTERLEUKIN-23 RECEPTOR AND THEIR USE TO TREAT INFLAMMATORY BOWEL DISEASES <130> PRTH-002/03WO <150> PCT/US2015/040658 <151> 2015-07-15 <150> US 14/800,627 <151> 2015-07-15 <150> US 62/264,820 <151> 2015-12-08 <150> US 62/281,123 <151> 2016-01-20 <160> 1114 <170> PatentIn version 3.5 <210> 1 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Aib <220> <221> MOD_RES <222> (2)..(2) <223> Aib <220> <221> MOD_RES <222> (11)..(11) <223> Aib <400> 1 Xaa Xaa Thr Trp Gln Asp Tyr Trp Leu Tyr Xaa Arg 1 5 10 <210> 2 <211> 14 <212> PRT <213> Artificial Sequence

    <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 1

    PRTH_002_03WO_ST25

    <400> 2 Cys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Cys 1 5 10 <210> 3 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <220> <221> MOD RES <222> (1)..(1) <223> Aib <220> <221> MOD_RES <222> (2)..(2) <223> Aib <400> 3

    Xaa Xaa Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 4 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 4

    Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Lys 1 5 10 <210> 5 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 5

    Cys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Cys Lys 1 5 10 15

    <210> 6 <211> 13 <212> PRT <213> Artificial Sequence

    Page 2

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 6

    Lys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 7 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 7

    Lys Cys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Cys 1 5 10 15 <210> 8 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> Aib <400> 8

    Ala Met Thr Trp Xaa Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 9 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 9

    Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 10 <211> 12 <212> PRT <213> Artificial Sequence

    Page 3

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 10

    Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 11 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 11

    Ala Ala Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 12 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 12

    Ala Met Ala Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 13 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 13

    Ala Met Thr Ala Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 14 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 14

    Ala Met Thr Trp Ala Asp Tyr Trp Leu Tyr Gly Arg 1 5 10

    Page 4

    PRTH_002_03WO_ST25 <210> 15 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 15

    Ala Met Thr Trp Gln Ala Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 16 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Cha <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 16

    Cys Gln Asp Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 17 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Octgly <220>

    <221> MOD_RES

    Page 5

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 17

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Gly Phe Gly Xaa Lys 1 5 10 <210> 18 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 18

    Cys Gln Thr Trp Gln Cys Tyr Trp Lys Xaa Phe Gly Xaa Lys 1 5 10 <210> 19 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid

    Page 6

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 19

    Cys Gln Thr Trp Gln Cys Tyr Trp His Xaa Phe Gly Xaa Lys 1 5 10 <210> 20 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 20

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Leu Phe Gly Xaa Lys 1 5 10 <210> 21 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hArg <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14)

    Page 7

    PRTH_002_03WO_ST25 <223> D-Lys <400> 21

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 22 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 22

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 23 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 23

    Page 8

    PRTH_002_03WO_ST25

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 24 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (11)..(11) <223> Tic <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 24

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Xaa Gly Xaa Lys 1 5 10 <210> 25 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Tic <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid

    Page 9

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 25

    Cys Gln Thr Trp Gln Cys Tyr Xaa Xaa Lys Phe Gly Xaa Lys 1 5 10 <210> 26 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 26

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 27 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES

    Page 10

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 27

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 28 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 28

    Cys Gln Thr Trp Gln Cys Tyr Trp His Glu Asn Gly Ala Lys 1 5 10 <210> 29 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 29

    Cys Arg Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Ala Lys 1 5 10 <210> 30 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 11

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 30

    Cys Arg Thr Trp Gln Cys Tyr Trp Arg Glu Tyr Gly Ala Lys 1 5 10 <210> 31 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> N-MeAla <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 31

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 32 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 32

    Cys Ala Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Ala Lys 1 5 10

    Page 12

    PRTH_002_03WO_ST25 <210> 33 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 33

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Lys Phe Gly Ala Lys 1 5 10 <210> 34 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> Tle <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 34

    Page 13

    PRTH_002_03WO_ST25

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 35 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> t-butyl-Ala <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 35

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Ala Phe Gly Ala Lys 1 5 10 <210> 36 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> Cha <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala

    Page 14

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 36

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 37 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 37

    Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Val Phe Gly Ala Lys 1 5 10 <210> 38 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES

    Page 15

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 38

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Val Phe Gly Ala Lys 1 5 10 <210> 39 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> Chg <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 39

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 40 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit

    Page 16

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Beta-Ala <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 40

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Ala Phe Gly Ala Lys 1 5 10 <210> 41 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Tle <220>

    <221> MOD_RES <222> (10)..(10) <223> Tle <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 41

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 42 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 17

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Tle <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 42

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Lys Phe Gly Ala Lys 1 5 10 <210> 43 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Ala <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 43

    Cys Gln Thr Trp Gln Cys Tyr Trp Ala Val Phe Gly Xaa Lys 1 5 10 <210> 44 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 18

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> Beta-Ala <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 44

    Cys Gln Thr Trp Gln Cys Tyr Trp Ala Val Phe Gly Xaa Lys 1 5 10 <210> 45 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Leu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 45

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Val Phe Gly Xaa Lys 1 5 10 <210> 46 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Phe

    Page 19

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 46

    Cys Gln Thr Trp Gln Cys Tyr Trp Phe Val Phe Gly Xaa Lys 1 5 10 <210> 47 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Asn <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 47

    Cys Gln Thr Trp Gln Cys Tyr Trp Asn Val Phe Gly Xaa Lys 1 5 10 <210> 48 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Thr <220>

    <221> MOD_RES

    Page 20

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 48

    Cys Gln Thr Trp Gln Cys Tyr Trp Thr Val Phe Gly Xaa Lys 1 5 10 <210> 49 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Asp <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 49

    Cys Gln Thr Trp Gln Cys Tyr Trp Asp Val Phe Gly Xaa Lys 1 5 10 <210> 50 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Leu

    Page 21

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 50

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Leu Phe Gly Xaa Lys 1 5 10 <210> 51 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Phe <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 51

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Phe Phe Gly Xaa Lys 1 5 10 <210> 52 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9)

    Page 22

    PRTH_002_03WO_ST25 <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Asn <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 52

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Asn Phe Gly Xaa Lys 1 5 10 <210> 53 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Thr <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 53

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Thr Phe Gly Xaa Lys 1 5 10 <210> 54 <211> 14 <212> PRT <213> Artificial Sequence <220>

    Page 23

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Agp <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 54

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 55 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MeTrp <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 55

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Asn Gly Xaa Lys 1 5 10 <210> 56 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 24

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MeTrp <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10) <223> hLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 56

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Leu Asn Gly Xaa Lys 1 5 10 <210> 57 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 57

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 58 <211> 14

    Page 25

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Agp <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 58

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Asn Gly Xaa Lys 1 5 10 <210> 59 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (12)..(12) <223> D-Ala <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys

    Page 26

    PRTH_002_03WO_ST25 <400> 59

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Ala Xaa Lys 1 5 10 <210> 60 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (12)..(12) <223> D-Leu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 60

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Leu Xaa Lys 1 5 10 <210> 61 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (12)..(12) <223> D-Phe <220>

    <221> MOD_RES <222> (13)..(13)

    Page 27

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 61

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Phe Xaa Lys 1 5 10 <210> 62 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (12)..(12) <223> D-Asn <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 62

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Asn Xaa Lys 1 5 10 <210> 63 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    Page 28

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (12)..(12) <223> D-Thr <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 63

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Thr Xaa Lys 1 5 10 <210> 64 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (12)..(12) <223> D-Asp <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 64

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Asp Xaa Lys 1 5 10 <210> 65 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 29

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (2)..(2) <223> N-MeArg <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 65

    Cys Arg Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 66 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> N-MeGln <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 66

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 67 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 30

    PRTH_002_03WO_ST25 <222> (2)..(2) <223> Cit <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 67

    Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 68 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 68

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 69 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 31

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 69

    Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 70 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> D-Trp <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14)

    Page 32

    PRTH_002_03WO_ST25 <223> D-Lys <400> 70

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 71 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> hPhe <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 71

    Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 72 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Bip <220>

    Page 33

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 72

    Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 73 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(3,5-F2) <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 73

    Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10

    Page 34

    PRTH_002_03WO_ST25 <210> 74 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(CONH2) <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 74

    Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 75 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-CF3) <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES

    Page 35

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 75

    Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 76 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(2,4-Me2) <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 76

    Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 77 <211> 14 <212> PRT <213> Artificial Sequence

    Page 36

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 77

    Cys Met Thr Trp Gln Cys Tyr Trp Leu Tyr Gly Arg Xaa Lys 1 5 10 <210> 78 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Beta-hTrp <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 78

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 79 <211> 14 <212> PRT

    Page 37

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 79

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Leu Phe Gly Xaa Lys 1 5 10 <210> 80 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Beta-spiral-pip <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 80

    Page 38

    PRTH_002_03WO_ST25

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 81 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 4-Phenylcyclohexylalanine <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 81

    Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 82 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib

    Page 39

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 82

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 83 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Diethyl-Gly <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 83

    Cys Ala Asp Trp Val Cys Tyr Trp Xaa Gly Phe Gly Xaa Lys 1 5 10 <210> 84 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 40

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> Beta-MePhe(4-F) <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 84

    Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 85 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Beta-hPhe <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 85

    Cys Gln Thr Trp Gln Cys Tyr Phe Arg Val Asn Gly Xaa Lys

    1 5 10 <210> 86 <211> 14 <212> PRT <213> Artificial Sequence

    Page 41

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial peptide Sequence : Synthetic <220> <221> MOD RES <222> (8)..(8) <223> Beta-1-Nal <220> <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220> <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 86 Cys Gln Thr Trp Gln Cys Tyr Xaa Arg Val Asn Gly Xaa Lys 1 5 10 <210> 87 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic <400> 87 Cys Ser Asp Trp Glu Cys Tyr Trp His Ile Phe Gly 1 5 10 <210> 88 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic <400> 88 Cys Glu Thr Trp Glu Cys Tyr Trp His Ser Phe Ser 1 5 10 <210> 89 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic

    <400> 89

    Page 42

    PRTH_002_03WO_ST25

    Cys Gln Ser Trp Glu Cys Tyr Trp His Tyr Tyr Gly 1 5 10 <210> 90 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 90

    Cys Ser Asp Trp Arg Cys Tyr Trp His Val Phe Gly 1 5 10 <210> 91 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 91

    Cys His Thr Trp Val Cys Tyr Trp His Glu Phe Ser 1 5 10 <210> 92 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 92

    Cys Thr Asp Trp Val Cys Tyr Trp His Glu Tyr Ser 1 5 10 <210> 93 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 93

    Cys Gln Thr Trp Val Cys Tyr Trp His Thr Tyr Gly

    1 5 10 <210> 94 <211> 12 <212> PRT

    Page 43

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 94

    Cys Gly Asn Trp Glu Cys Tyr Trp His Val Tyr Gly 1 5 10 <210> 95 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 95

    Cys Lys Asp Trp Lys Cys Tyr Trp His Ile Tyr Gly 1 5 10 <210> 96 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 96

    Cys Arg Thr Trp Val Cys Tyr Trp His Val Phe Gly 1 5 10 <210> 97 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <210> 98 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <221> MOD_RES <222> (4)..(4) <223> 1-Nal <400> 97

    Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly

    1 5 10

    Page 44

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (4)..(4) <223> 2-Nal <400> 98

    Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 99 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (4)..(4) <223> 1-Bip <400> 99

    Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 100 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (4)..(4) <223> Tic <400> 100

    Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 101 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 45

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (4)..(4) <223> Beta-hTrp <400> 101

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 102 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Bip <400> 102

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 103 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Tic <400> 103

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 104 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 46

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> Beta-hTrp <400> 104

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 105 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 105

    Cys Ala Asp Trp Val Cys Tyr Ala His Thr Phe Gly 1 5 10 <210> 106 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 106

    Ala Cys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 107 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 107

    Ala Cys Asp Trp Cys Cys Tyr Trp Cys Thr Phe Gly 1 5 10 <210> 108 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 108

    Ala Ala Asp Trp Cys Ala Tyr Trp Cys Thr Phe Gly Page 47

    1 5 <210> 109 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 109 Cys Ala Asp Trp Cys Cys Tyr Trp 1 5 <210> 110 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 110 Cys Ala Asp Trp Cys Cys Tyr Trp 1 5 <210> 111 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 111 Cys Ala Asp Trp Cys Cys Tyr Trp 1 5 <210> 112 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 112 Cys Ala Asp Trp Val Cys Tyr Trp 1 5 <210> 113 <211> 10 <212> PRT <213> Artificial Sequence

    PRTH_002_03WO_ST25

    Sequence: Synthetic

    Cys Thr Phe Gly 10

    Sequence: Synthetic

    Cys Thr Phe Gly 10

    Sequence: Synthetic

    Cys Thr Phe Gly 10

    Sequence: Synthetic

    His Thr Phe 10

    Page 48

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 113

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr

    1 5 10 <210> 114 <211> 8 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 114

    Cys Ala Asp Trp Val Cys Tyr Trp

    1 5 <210> 115 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Beta-Ala <400> 115

    Ala Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 116 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <400> 116

    Lys Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10

    Page 49

    PRTH_002_03WO_ST25 <210> 117 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (2)..(2) <223> Beta-Ala <400> 117

    Lys Ala Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 118 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> (2-aminoethoxy)acetic acid <400> 118

    Xaa Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 119 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <400> 119

    Lys Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Page 50

    PRTH_002_03WO_ST25

    1 5 10 <210> 120 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 120

    Cys Lys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 121 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 121

    Cys Ala Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 122 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 122

    Cys Ala Asp Trp Val Cys Tyr Trp Lys Thr Phe Gly 1 5 10 <210> 123 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 123

    Cys Ala Asp Trp Val Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 124 <211> 12 <212> PRT <213> Artificial Sequence

    Page 51

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial peptide Sequence: Synthetic <400> 124 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Lys Gly 1 5 10 <210> 125 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (12)..(12) <223> D-Lys <400> 125 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Lys 1 5 10 <210> 126 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <400> 126 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 127 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic

    <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <400> 127

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10

    Page 52

    PRTH_002_03WO_ST25 <210> 128 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (11)..(11) <223> N-Me-Phe <400> 128

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 129 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Sarc <400> 129

    Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Phe 1 5 10 <210> 130 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 53

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> N-Me-His <400> 130

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 131 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 131

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 132 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Sarc <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <400> 132

    Cys Xaa Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 133 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 54

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (4)..(4) <223> N-Me-Trp <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <400> 133

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 134 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> Sarc <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <400> 134

    Cys Ala Asp Trp Xaa Cys Tyr Xaa His Thr Phe 1 5 10 <210> 135 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (11)..(11) <223> D-Phe <400> 135

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10

    Page 55

    PRTH_002_03WO_ST25 <210> 136 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (12)..(12) <223> Sarc <400> 136

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Xaa 1 5 10 <210> 137 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 137

    Cys Ala Thr Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 138 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 138

    Cys Ala Asp Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 139 <211> 16 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 56

    PRTH_002_03WO_ST25 <400> 139

    Cys Ala Asp Trp Val Cys Tyr Trp His Arg Cys Gly Trp Trp Gly Cys 1 5 10 15 <210> 140 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Ala <400> 140

    Cys Ala Asp Trp Val Cys Tyr Xaa His Ala Phe Gly 1 5 10 <210> 141 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <400> 141

    Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Phe Gly 1 5 10 <210> 142 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 57

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> beta-Ala <400> 142

    Cys Ala Asp Trp Val Cys Tyr Xaa His Ala Phe Gly 1 5 10 <210> 143 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <400> 143

    Cys Ala Asp Trp Val Cys Tyr Xaa Phe Thr Phe Gly 1 5 10 <210> 144 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Ala <400> 144

    Cys Ala Asp Trp Val Cys Tyr Xaa Ala Thr Phe Gly 1 5 10 <210> 145

    Page 58

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> D-Phe <400> 145

    Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Phe Gly 1 5 10 <210> 146 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (12)..(12) <223> Aib <400> 146

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Xaa 1 5 10 <210> 147 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 59

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> N-Me-His <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Ala <220>

    <221> MOD_RES <222> (12)..(12) <223> Aib <400> 147

    Cys Ala Asp Trp Val Cys Tyr Xaa His Ala Phe Xaa 1 5 10 <210> 148 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> AEP <400> 148

    Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Gly 1 5 10 <210> 149 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 60

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> N-MeHis <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 149

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 150 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Aic <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 150

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly Xaa Lys 1 5 10 <210> 151 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Bip

    Page 61

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 151

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly Xaa Lys 1 5 10 <210> 152 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> N-MeArg <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 152

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 153 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> N-MeArg <220>

    <221> MOD_RES <222> (13)..(13)

    Page 62

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 153

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Arg Asn Gly Xaa Lys 1 5 10 <210> 154 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> N-MeLys <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 154

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly Xaa Lys 1 5 10 <210> 155 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Sarc <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    Page 63

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 155

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 156 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Glu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 156

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 157 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Arg <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys

    Page 64

    PRTH_002_03WO_ST25 <400> 157

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 158 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Arg <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Glu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 158

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 159 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> N-MeGlu <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES

    Page 65

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> D-Lys <400> 159

    Cys Gln Thr Trp Gln Cys Tyr Trp Glu Asn Gly Xaa Lys 1 5 10 <210> 160 <211> 6 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 160

    Cys Ala Asp Trp Val Cys

    1 5 <210> 161 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> N-MeArg <220>

    <221> MOD_RES <222> (13)..(13) <223> AEP <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 161

    Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 162 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 66

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (10)..(10) <223> D-Lys <220>

    <221> MOD_RES <222> (13)..(13) <223> AEP <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 162

    Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 163 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Arg <220>

    <221> MOD_RES <222> (13)..(13) <223> AEP <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 163

    Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 164 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Arg

    Page 67

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Lys <220>

    <221> MOD_RES <222> (13)..(13) <223> AEP <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 164

    Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 165 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> N-MeArg <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 165

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 166 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 166

    Cys Thr Asp Trp Lys Cys Tyr Trp His Glu Phe Gly 1 5 10

    Page 68

    PRTH_002_03WO_ST25 <210> 167 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide <400> 167

    Cys Arg Thr Trp Thr Cys Tyr Trp

    Sequence: Synthetic

    1 5 <210> 168 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 168 Cys Pro Asn Trp Glu Cys Tyr Trp 1 5 <210> 169 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 169 Cys Ala Asp Trp Val Cys Tyr Trp 1 5 <210> 170 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 170 Cys Ala Asp Trp Met Cys Tyr Trp 1 5 <210> 171 <211> 12 <212> PRT <213> Artificial Sequence

    His Val Tyr Gly 10

    Sequence: Synthetic

    His Arg Phe Gly 10

    Sequence: Synthetic

    His Thr Phe Gly 10

    Sequence: Synthetic

    His Glu Tyr Gly 10

    Page 69

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 171

    Cys Thr Thr Trp Lys Cys Tyr Trp His Gln Tyr Gly 1 5 10 <210> 172 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 172

    Cys Ser Asn Trp Glu Cys Tyr Trp His His Tyr Gly 1 5 10 <210> 173 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 173

    Cys Ser Asp Trp Val Cys Tyr Trp His Val Tyr Gly 1 5 10 <210> 174 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 174

    Cys Asp Thr Trp Lys Cys Tyr Trp His Arg Gln Ser 1 5 10 <210> 175 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 70

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> 1-Nal <400> 175

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 176 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <400> 176

    Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 177 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 177

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 178 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 178

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 179

    Page 71

    PRTH_002_03WO_ST25 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (15)..(15) <223> D-Lys <400> 179 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Pro Lys 1 5 10 15 <210> 180 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <400> 180 Cys Thr Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 181 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <400> 181 Cys Arg Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 182 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic

    <400> 182

    Cys Ala Asp Trp Val Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 183 <211> 16

    Page 72

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 183

    Cys Ala Asp Trp Val Cys Tyr Trp His Phe His Gln Leu Arg Asp Ala 1 5 10 15 <210> 184 <211> 16 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 184

    Cys Ala Asp Trp Val Cys Tyr Trp His Glu His Ser Glu Arg Val Gly 1 5 10 15

    <210> <211> <212> <213> 185 16 PRT Artificial Sequence <220> <223> Description peptide of Artificial <400> 185

    Cys Ala Asp Trp Val Cys Tyr Trp 1 5

    Sequence: Synthetic

    His Asn His Ser Glu Gly Ser Gly 10 15 <210> 186 <211> 16 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 186

    Cys Ala Asp Trp Val Cys Tyr Trp His Arg Ser Thr Gly Gly Gln His

    1 5 10 15 <210> <211> <212> <213> 187 15 PRT Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic

    Page 73

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (9)..(9) <223> 1-Nal <220>

    <221> MOD_RES <222> (13)..(13) <223> Sarc <220>

    <221> MOD_RES <222> (14)..(14) <223> AEP <220>

    <221> MOD_RES <222> (15)..(15) <223> D-Arg <400> 187

    Lys Cys Arg Asp Trp Gln Cys Tyr 1 5

    Xaa His Thr His Xaa Xaa Arg 10 15 <210> 188 <211> 16 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide <400> 188

    Thr Gln Phe Asp Cys Arg Thr Trp 1 5

    Sequence: Synthetic

    Glu Cys Tyr Trp His Thr Phe Gly 10 15

    <210> <211> <212> <213> 189 16 PRT Artificial Sequence <220> <223> Description of Artificial <400> peptide 189 Gly Gly Val Glu Cys Asn Asp Trp 1 5 <210> 190 <211> 16 <212> PRT <213> Artificial Sequence

    Sequence: Synthetic

    Gln Cys Tyr Trp His Thr Phe Gly 10 15

    Page 74

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial peptide <400> 190

    Arg Glu Gly Thr Cys Ser Thr Trp

    Sequence: Synthetic

    1 5 <210> 191 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 191 Asp Thr Pro Arg Cys Arg Thr Trp 1 5 <210> 192 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 192 Gly Gly Gly Glu Cys Glu Asn Trp 1 5 <210> 193 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 193 Gly Asp His Lys Cys Ser Ser Trp 1 5 <210> 194 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 194

    Gly Ser Val His Cys Met Thr Trp

    Lys Cys Tyr Trp His Thr Phe Gly 10 15

    Sequence: Synthetic

    Glu Cys Tyr Trp His Thr Phe Gly 10 15

    Sequence: Synthetic

    Glu Cys Tyr Trp His Thr Phe Gly 10 15

    Sequence: Synthetic

    Glu Cys Tyr Trp His Thr Phe Gly 10 15

    Sequence: Synthetic

    Glu Cys Tyr Trp His Thr Phe Gly Page 75

    PRTH_002_03WO_ST25

    1 5 10 15 <210> 195 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <400> 195

    Cys Ala Asp Trp Val Cys Tyr Xaa Val Thr Phe Gly 1 5 10 <210> 196 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-His <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 196

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 197 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 197

    Page 76

    PRTH_002_03WO_ST25

    Cys Arg Asp Trp Gln Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 198 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 198

    Cys Ser Asn Trp Val Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 199 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 199

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 200 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys

    Page 77

    PRTH_002_03WO_ST25

    <400> 200 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> <211> <212> <213> 201 12 PRT Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic <400> 201

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 202 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> AEP <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Arg <400> 202

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Arg 1 5 10 <210> 203 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> AEP <400> 203

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10

    Page 78

    PRTH_002_03WO_ST25 <210> 204 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> Gaba <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 204

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 205 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> Hexanoic-D-Lys <400> 205

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 206 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (PEG)2-D-Lys <400> 206

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys Page 79

    PRTH_002_03WO_ST25

    1 5 10 <210> 207 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 207

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Pro Lys 1 5 10 <210> 208 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> Azt <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 208

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 209 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys

    Page 80

    PRTH_002_03WO_ST25

    <400> 209 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 210 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <220> <221> MOD_RES <222> (15)..(15) <223> D-Lys <400> 210

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Pro Lys 1 5 10 15 <210> 211 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (14)..(14) <223> Azt <220>

    <221> MOD_RES <222> (15)..(15) <223> D-Lys <400> 211

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Xaa Lys

    1 5 10 15 <210> <211> <212> <213> 212 15 PRT Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> <222> MOD_RES (15)..(15) Page 81

    PRTH_002_03WO_ST25 <223> D-Lys <400> 212

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Ala Lys 1 5 10 15 <210> 213 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> AEP <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 213

    Cys Arg Asp Trp Gln Cys Tyr Trp His Lys Phe Gly Xaa Lys 1 5 10 <210> 214 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 214

    Cys Ala Thr Trp Gln Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 215 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 215

    Cys Lys Thr Trp Thr Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 216 <211> 12 <212> PRT

    Page 82

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 216

    Cys Thr Thr Trp Thr Cys Tyr Trp His Gln Tyr Gly 1 5 10 <210> 217 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 217

    Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 218 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 218

    Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 219 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 219

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 220 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 220

    Page 83

    PRTH_002_03WO_ST25

    Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 221 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 221

    Cys Thr Thr Trp Glu Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 222 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 222

    Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Gln Ser 1 5 10 <210> 223 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 223

    Cys Thr Thr Trp Glu Cys Tyr Trp His Gln Phe Gly 1 5 10 <210> 224 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 224

    Cys Thr Thr Trp Glu Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 225 <211> 12 <212> PRT

    Page 84

    <213> Artificial Sequence <220> <223> Description peptide of Artificial <400> 225 Cys Gln Thr Trp Glu Cys Tyr Trp 1 5 <210> 226 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description peptide of Artificial <400> 226

    Cys Glu Asp Trp Lys Cys Tyr Trp 1 5

    PRTH_002_03WO_ST25

    Sequence: Synthetic

    His Leu Tyr Gly 10

    Sequence: Synthetic

    His Lys Tyr Gly 10 <210> 227 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 227

    Cys Thr Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 228 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 228

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 229 <211> 16 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 229

    Page 85

    PRTH_002_03WO_ST25

    Cys Ala Asp Trp Val Cys Tyr Trp His Arg His Ala Asp Arg Val Lys 1 5 10 15

    <210> 230 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Synthetic peptide <400> 230 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Glu Arg 1 5 10 <210> 231 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Synthetic peptide <400> 231 Cys Ala Asp Trp Val Cys Tyr Trp His Thr His Gly Glu Arg 1 5 10 <210> 232 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Synthetic peptide <400> 232 Asp Thr Pro Arg Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe 1 5 10 15 <210> 233 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Synthetic peptide

    <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES

    Page 86

    PRTH_002_03WO_ST25 <222> (14)..(14) <223> D-Lys <400> 233

    Cys Gln Thr Trp Val Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 234 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 234

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 235 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 235

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Asn Gly Xaa Lys 1 5 10 <210> 236 <211> 14 <212> PRT <213> Artificial Sequence

    Page 87

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 236

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly Xaa Lys 1 5 10 <210> 237 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 237

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Arg Asn Gly Xaa Lys 1 5 10 <210> 238 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Dapa <220>

    <221> MOD_RES <222> (13)..(13)

    Page 88

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 238

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 239 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Orn <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 239

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 240 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 240

    Page 89

    PRTH_002_03WO_ST25

    Cys Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 241 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Arg <400> 241

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Arg 1 5 10 <210> 242 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 242

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 243 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 90

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 243

    Cys Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 244 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 244

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 245 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 245

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Asn Gly Xaa Lys Page 91

    PRTH_002_03WO_ST25

    1 5 10 <210> 246 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 246

    Cys Gln Thr Trp Val Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 247 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 247

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly Xaa Lys 1 5 10 <210> 248 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 92

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Cav <400> 248

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 249 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cpa <400> 249

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 250 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 250

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 251 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 251

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10

    Page 93

    PRTH_002_03WO_ST25 <210> 252 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys-Ac <400> 252

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly 1 5 10 <210> 253 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 253

    Cys Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly 1 5 10 <210> 254 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8)

    Page 94

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Lys <400> 254

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 255 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 255

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 256 <211> 12 <212> PRT <213> Artificial Sequence <220>

    Page 95

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 256

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 257 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2)

    Page 96

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 257

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 258 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 258

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 259 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 97

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-(2-aminoethoxy)) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 259

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 260 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 260

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 261 <211> 20 <212> PRT <213> Mus sp.

    Page 98

    PRTH_002_03WO_ST25 <400> 261

    Asn Trp Gln Pro Trp Ser Ser Pro Phe Val His Gln Thr Ser Gln Glu 1 5 10 15

    Thr Gly Lys Arg 20 <210> 262 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 262

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 263 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 99

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 263

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 264 <211> 8 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> <222> <223> MOD_RES (2). Any .(2) amino acid <220> <221> MOD_ RES <222> (3). .(3) <223> Any amino acid <220> <221> MOD_ RES <222> (5). .(5) <223> Any amino acid <400> 264

    Cys Xaa Xaa Trp Xaa Cys Tyr Trp

    Page 100

    PRTH_002_03WO_ST25 <210> 265 <211> 4 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: peptide

    Synthetic <220>

    <221> MOD_RES <222> (1)..(1) <223> alpha-MeLys <400> 265 Lys Glu Asn Gly 1 <210> 266 <211> 4 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: peptide

    Synthetic <220>

    <221> MOD_RES <222> (1)..(1) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (2)..(2) <223> Lys(Ac) <400> 266 Lys Lys Asn Asn 1 <210> 267 <211> 4 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: peptide

    Synthetic <220>

    <221> MOD_RES <222> (1)..(1) <223> alpha-MeLeu

    Page 101

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (2)..(2) <223> Lys(Ac) <400> 267 Leu Lys Asn Asn 1 <210> 268 <211> 4 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> alpha-MeLeu <400> 268 Leu Glu Asn Gly 1 <210> 269 <211> 4 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> alpha-MeLeu <400> 269 Leu Glu Asn Gly 1 <210> 270 <211> 4 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1)

    Page 102

    PRTH_002_03WO_ST25 <223> alpha-MeLys <400> 270 Lys Glu Asn Asn 1 <210> 271 <211> 6 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> 2-Nal <220>

    <221> MOD_RES <222> (6)..(6) <223> alpha-MeLys <400> 271

    Trp Gln Cys Tyr Xaa Lys 1 5 <210> 272 <211> 6 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: peptide

    Synthetic

    Synthetic <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (5)..(5) <223> 2-Nal <220>

    <221> MOD_RES <222> (6)..(6) <223> alpha-MeLys <400> 272

    Trp Gln Cys Phe Xaa Lys 1 5 <210> 273

    Page 103

    PRTH_002_03WO_ST25 <211> 6 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (5)..(5) <223> 2-Nal <220>

    <221> MOD_RES <222> (6)..(6) <223> Aib <400> 273

    Trp Gln Cys Phe Xaa Xaa 1 5 <210> 274 <211> 6 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (3)..(3) <223> Pen <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (5)..(5) <223> 2-Nal <220>

    <221> MOD_RES <222> (6)..(6) <223> alpha-MeLys <400> 274

    Trp Gln Xaa Phe Xaa Lys 1 5

    Page 104

    PRTH_002_03WO_ST25 <210> 275 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Any amino acid <220>

    <221> MOD_RES <222> (3)..(3) <223> Any amino acid <220>

    <221> MOD_RES <222> (5)..(5) <223> Any amino acid <220>

    <221> MOD_RES <222> (10)..(10) <223> Any amino acid <220>

    <221> MOD_RES <222> (12)..(12) <223> Any amino acid <220>

    <221> MOD_RES <222> (13)..(13) <223> Any amino acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 275

    Cys Xaa Xaa Trp Xaa Cys Tyr Trp His Xaa Phe Xaa Xaa Lys 1 5 10 <210> 276 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 105

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Tyr(OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 276

    Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Glu Asn Gly 1 5 10 <210> 277 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 277

    Phe Pro Thr Trp Glu Trp Tyr Trp Cys Asn Arg Asp 1 5 10 <210> 278 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 278

    Ala Leu Thr Trp Glu Phe Tyr Trp Leu Cys Arg Glu 1 5 10 <210> 279 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 106

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Tyr(OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 279

    Xaa Gln Thr Trp Gln Xaa Tyr Xaa Lys Glu Asn Gly 1 5 10 <210> 280 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 280

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 281 <211> 12 <212> PRT <213> Artificial Sequence

    Page 107

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 281

    Lys Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 282 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Lys <400> 282

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 283 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 108

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 283

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 284 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 284

    Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Lys 1 5 10 <210> 285 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6)

    Page 109

    PRTH_002_03WO_ST25 <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 285

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 286 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    Page 110

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 286

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 287 <400> 287 000 <210> 288 <400> 288 000 <210> 289 <400> 289 000 <210> 290 <400> 290 000 <210> 291 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Beta-Ala <400> 291

    Ala Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 292 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 111

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <400> 292

    Lys Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 293 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (2)..(2) <223> Beta-Ala <400> 293

    Lys Ala Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 294 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> (2-aminoethoxy)acetic acid <400> 294

    Xaa Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 295 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 112

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <400> 295

    Lys Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 296 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 296

    Cys Lys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 297 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 297

    Cys Ala Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 298 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 298

    Cys Ala Asp Trp Val Cys Tyr Trp Lys Thr Phe Gly 1 5 10 <210> 299 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 113

    PRTH_002_03WO_ST25 <400> 299

    Cys Ala Asp Trp Val Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 300 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 300

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Lys Gly 1 5 10 <210> 301 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 301

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Asp Lys 1 5 10 <210> 302 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 302

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Asp Lys 1 5 10 <210> 303 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    Page 114

    PRTH_002_03WO_ST25

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 303 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 304 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Synthetic peptide <220> <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220> <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 304

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 305 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 305

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 306 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Beta-Ala

    Page 115

    PRTH_002_03WO_ST25

    <400> 306 Ala Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe 1 5 10 <210> 307 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> D-Lys <400> 307

    Lys Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 308 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (2)..(2) <223> Beta-Ala <400> 308

    Lys Ala Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly

    1 5 10 <210> <211> <212> <213> 309 13 PRT Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> <222> MOD_RES (1)..(1) Page 116

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <400> 309

    Xaa Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 310 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <400> 310

    Lys Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 311 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 311

    Cys Lys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 312 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 312

    Cys Ala Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 313 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 117

    PRTH_002_03WO_ST25 <400> 313

    Cys Ala Asp Trp Val Cys Tyr Trp Lys Thr Phe Gly

    1 5 10 <210> 314 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <400> 314 Cys Ala Asp Trp Val Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 315 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <400> 315 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Lys Gly 1 5 10 <210> 316 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD RES <222> (12)..(12) <223> D-Lys <400> 316 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Lys 1 5 10 <210> 317 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic

    Page 118

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 317

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 318 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 318

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 319 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 319

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 320 <211> 13

    Page 119

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 320

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 321 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Beta-hTyr <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 321

    Cys Gln Thr Trp Gln Cys Tyr Tyr Arg Val Asn Gly Xaa Lys 1 5 10 <210> 322 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Beta-hPhe(4-F) <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    Page 120

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 322

    Cys Gln Thr Trp Gln Cys Tyr Phe Arg Val Asn Gly Xaa Lys 1 5 10 <210> 323 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Beta-Nva(5-Phenyl) <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 323

    Cys Gln Thr Trp Gln Cys Tyr Xaa Arg Val Asn Gly Xaa Lys 1 5 10 <210> 324 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(3,4-Cl2) <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys

    Page 121

    PRTH_002_03WO_ST25 <400> 324

    Cys Gln Thr Trp Gln Cys Tyr Phe Arg Val Asn Gly Xaa Lys 1 5 10 <210> 325 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Tqa <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 325

    Cys Gln Thr Trp Gln Cys Tyr Xaa Arg Val Asn Gly Xaa Lys 1 5 10 <210> 326 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Beta-hLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 326

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Leu Asn Gly Xaa Lys Page 122

    PRTH_002_03WO_ST25

    1 5 10 <210> 327 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 327

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 328 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Beta-hAla <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 328

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Ala Asn Gly Xaa Lys

    1 5 10

    Page 123

    PRTH_002_03WO_ST25 <210> 329 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Beta-hVal <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 329

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Asn Gly Xaa Lys 1 5 10 <210> 330 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Beta-spiral-pip <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 330

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 331 <211> 14 <212> PRT

    Page 124

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Beta-Glu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 331

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 332 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Beta-hLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 332

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Val Asn Gly Xaa Lys 1 5 10 <210> 333 <211> 14 <212> PRT <213> Artificial Sequence <220>

    Page 125

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Beta-Aib <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 333

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 334 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Beta-hAla <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 334

    Cys Gln Thr Trp Gln Cys Tyr Trp Ala Val Asn Gly Xaa Lys 1 5 10 <210> 335 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 126

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Beta-hVal <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 335

    Cys Gln Thr Trp Gln Cys Tyr Trp Val Val Asn Gly Xaa Lys 1 5 10 <210> 336 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Beta-spiral-pip <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 336

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 337 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 127

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> Beta-hArg <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 337

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Asn Gly Xaa Lys 1 5 10 <210> 338 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> MeCys <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 338

    Met Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 339 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid

    Page 128

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 339

    Ala Cys Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 340 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 340

    Ser Arg Thr Trp Gln Ser Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 341 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 341

    Cys Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 342 <211> 14 <212> PRT

    Page 129

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> MeCys <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 342

    Ala Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 343 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 343

    Ala Arg Thr Trp Gln Ala Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 344 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 130

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 344

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Xaa Lys 1 5 10 <210> 345 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 345

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Xaa Lys 1 5 10 <210> 346 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid

    Page 131

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 346

    Cys Ser Thr Trp Glu Cys Tyr Trp Arg Val Tyr Gly Xaa Lys 1 5 10 <210> 347 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Orn <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 347

    Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 348 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES

    Page 132

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 348

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 349 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> N-MeAsn <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 349

    Cys Asn Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 350 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> N-MeLys <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid

    Page 133

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 350

    Cys Lys Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 351 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 351

    Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 352 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13)

    Page 134

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 352

    Cys Gln Thr Trp Gln Cys Tyr Tyr Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 353 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 353

    Cys Ser Thr Trp Gln Cys Tyr Trp Xaa Xaa Tyr Gly Xaa Lys 1 5 10 <210> 354 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    Page 135

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 354

    Cys Ser Thr Trp Glu Cys Tyr Trp Xaa Xaa Tyr Gly Xaa Lys 1 5 10 <210> 355 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 355

    Cys Gln Thr Trp Gln Cys Phe Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 356 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 136

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 356

    Cys Pro Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 357 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 357

    Cys Ser Thr Trp Glu Cys Tyr Trp Xaa Xaa Tyr Gly Xaa Lys 1 5 10 <210> 358 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 137

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 358

    Cys Ser Thr Trp Glu Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 359 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 359

    Cys Leu Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 360 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid

    Page 138

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 360

    Cys Gln Thr Trp Gln Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 361 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 361

    Cys Asn Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 362 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 362

    Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10

    Page 139

    PRTH_002_03WO_ST25 <210> 363 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> N-Me-Ala <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 363

    Cys Ala Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 364 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 364

    Cys Lys Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 365 <211> 14 <212> PRT <213> Artificial Sequence <220>

    Page 140

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Cha <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 365

    Cys Gln Asp Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 366 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Ogl <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 366

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 367 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 141

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 367

    Cys Gln Thr Trp Gln Cys Tyr Trp Lys Xaa Phe Gly Xaa Lys 1 5 10 <210> 368 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 368

    Cys Gln Thr Trp Gln Cys Tyr Trp His Xaa Phe Gly Xaa Lys 1 5 10 <210> 369 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 142

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 369

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Leu Phe Gly Xaa Lys 1 5 10 <210> 370 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hArg <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 370

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 371 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 371

    Cys Ser Thr Trp Glu Cys Tyr Trp Arg Thr Phe Gly 1 5 10 <210> 372

    Page 143

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 372

    Cys Asp Ser Trp Glu Cys Tyr Trp Arg Thr Tyr Gly 1 5 10 <210> 373 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 373

    Cys Ser Thr Trp Glu Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 374 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 374

    Cys Lys Thr Trp Thr Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 375 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 375

    Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Tyr Ser 1 5 10 <210> 376 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 144

    PRTH_002_03WO_ST25 <400> 376

    Cys Arg Thr Trp Thr Cys Tyr Trp His Glu Tyr Gly

    1 5 10 <210> 377 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 377

    Cys Phe Thr Trp Gln Cys Tyr Trp His Glu Tyr Ser 1 5 10 <210> 378 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> 3-Pal <400> 378

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 379 <211> 6 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 379

    Cys Gln Thr Trp Gln Cys

    1 5 <210> 380 <211> 6 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 145

    PRTH_002_03WO_ST25 <400> 380

    Cys Arg Thr Trp Gln Cys

    1 5 <210> 381 <211> 7 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 381

    Cys Ala Asp Trp Val Cys Tyr

    1 5 <210> 382 <211> 8 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 382

    Cys Ala Asp Trp Val Cys Tyr Trp

    1 5 <210> 383 <211> 9 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 383

    Cys Ala Asp Trp Val Cys Tyr Trp His

    1 5 <210> 384 <211> 10 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 384

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr

    1 5 10 <210> 385 <211> 11

    Page 146

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 385

    Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe 1 5 10 <210> 386 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 386

    Cys Met Thr Trp Gln Cys Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 387 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 387

    Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 388 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 388

    Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 389 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 147

    PRTH_002_03WO_ST25 <400> 389

    Cys Gln Thr Trp Gln Cys Tyr Trp His Glu Phe Gly

    1 5 10 <210> 390 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 390

    Cys Arg Thr Trp Gln Cys Tyr Trp Gln Gln Phe Gly Gly 1 5 10 <210> 391 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 391

    Cys Arg Ser Trp Gln Cys Tyr Trp Leu Asn Phe Gly Pro 1 5 10 <210> 392 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 392

    Cys Arg Thr Trp Gln Cys Tyr Trp Leu Lys Met Gly Asp 1 5 10

    Glu

    Asp

    Ser <210> 393 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 393

    Cys Gln Thr Trp Gln Cys Tyr Trp Ile Lys Arg Asp Gln

    1 5 10

    Gly <210> 394 <211> 14

    Page 148

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 394

    Cys Ser Thr Trp Gln Cys Tyr Trp Leu Lys His Gly Gly Glu 1 5 10 <210> 395 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 395

    Cys Ser Thr Trp Glu Cys Tyr Trp Ser Gln Arg Ala Asp Gln 1 5 10 <210> 396 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 396

    Cys Gln Thr Trp Glu Cys Tyr Trp Arg Thr Phe Gly Pro Ser 1 5 10 <210> 397 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 397

    Cys Arg Thr Trp Gln Cys Tyr Trp Gln Glu Lys Gly Thr Asp

    1 5 10 <210> 398 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic

    Page 149

    PRTH_002_03WO_ST25

    <400> 398 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Asp Ser Leu Gly Asp 1 5 10 <210> <211> <212> <213> 399 15 PRT Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <400> 399

    Cys Arg Thr Trp Gln Cys Tyr Trp Thr Lys Phe Gly Ser Glu Pro 1 5 10 15

    <210> 400 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 400

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Pro Gly 1 5 10 <210> 401 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <210> 402 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 401

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Leu Gly

    1 5 10

    Page 150

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 402

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Thr Gly 1 5 10 <210> 403 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 403

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Phe Asn Gly 1 5 10 <210> 404 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 404

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Pro Asn Gly 1 5 10 <210> 405 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 151

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 405

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Asn Asn Gly 1 5 10 <210> 406 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 406

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Leu Asn Gly 1 5 10 <210> 407 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 407

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Thr Asn Gly 1 5 10 <210> 408 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 408

    Page 152

    PRTH_002_03WO_ST25

    Cys Gln Thr Trp Gln Cys Tyr Trp Phe Glu Asn Gly

    1 5 10 <210> 409 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 409

    Cys Gln Thr Trp Gln Cys Tyr Trp Pro Glu Asn Gly 1 5 10 <210> 410 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 410

    Cys Gln Thr Trp Gln Cys Tyr Trp Gln Glu Asn Gly 1 5 10 <210> 411 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 411

    Cys Gln Thr Trp Gln Cys Tyr Trp Thr Glu Asn Gly 1 5 10 <210> 412 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 412

    Cys Gln Thr Trp Gln Cys Tyr Trp Glu Glu Asn Gly 1 5 10 <210> 413 <211> 12 <212> PRT

    Page 153

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 413

    Cys Gln Thr Trp Phe Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 414 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 414

    Cys Gln Thr Trp Pro Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 415 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 415

    Cys Gln Thr Trp Asn Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 416 <211> 12 <212> PRT <213> Artificial Sequence <220>

    Page 154

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 416

    Cys Gln Thr Trp Arg Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 417 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 417

    Cys Gln Thr Trp Thr Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 418 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 418

    Cys Gln Thr Trp Glu Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 419 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 155

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 419

    Cys Gln Thr Gly Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 420 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 420

    Cys Gln Thr Pro Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 421 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 421

    Cys Gln Thr Asn Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 422 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 156

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> hLeu <400> 422

    Cys Gln Thr Arg Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 423 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 423

    Cys Gln Thr Thr Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 424 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 424

    Cys Gln Thr Glu Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 425 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu

    Page 157

    PRTH_002_03WO_ST25 <400> 425

    Cys Gln Phe Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 426 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 426

    Cys Gln Pro Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 427 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 427

    Cys Gln Asn Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 428 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 428

    Cys Gln Arg Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10

    Page 158

    PRTH_002_03WO_ST25 <210> 429 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 429

    Cys Gln Glu Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 430 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 430

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 431 <211> 12 <212> PRT <213> Artificial Sequence <220>

    Page 159

    <223> Description of Artificial PRTH_002_03WO_ST25 Sequence: Synthetic peptide <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 431 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly

    1 5 10 <210> 432 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CO2H) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac)

    Page 160

    PRTH_002_03WO_ST25 <400> 432

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 433 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 433

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 434 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES

    Page 161

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 434

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 435 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 435

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala 1 5 10

    Page 162

    PRTH_002_03WO_ST25 <210> 436 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 436

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala Glu 1 5 10 <210> 437 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8)

    Page 163

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 437

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 438 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-(2-aminoethoxy)) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 438

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 439 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 164

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 439

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Asp Asn Gly 1 5 10 <210> 440 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(succinic acid) <400> 440

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 441 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 165

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(glutaric acid) <400> 441

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 442 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES

    Page 166

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Lys(pyroglutamic acid) conjugated through side chain <400> 442

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly

    1 5 10 <210> 443 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(isovaleric acid) <400> 443

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 444 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 167

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 444

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Lys 1 5 10 <210> 445 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10)

    Page 168

    PRTH_002_03WO_ST25 <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <400> 445

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Xaa 1 5 10 <210> 446 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 446

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly 1 5 10 <210> 447 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    Page 169

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 447

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 448 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 448

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 449 <211> 12 <212> PRT <213> Artificial Sequence

    Page 170

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 449

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 450 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 450

    Cys Phe Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 451 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 171

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 451

    Cys Pro Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 452 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 452

    Cys Asn Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 453 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 453

    Cys Gly Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 454 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 172

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 454

    Cys Thr Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 455 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 455

    Cys Glu Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 456 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> N-MeLeu <400> 456

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 457 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9)

    Page 173

    PRTH_002_03WO_ST25 <223> alpha-MeOrn <400> 457

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 458 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 458

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 459 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> alpha-MePhe <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 459

    Cys Gln Thr Trp Gln Cys Phe Trp Leu Glu Asn Gly 1 5 10 <210> 460 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 174

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> Aib <400> 460

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 461 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> hTyr <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 461

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 462 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> Bip <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 462

    Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 463 <211> 12 <212> PRT <213> Artificial Sequence

    Page 175

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Ogl <400> 463

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 464 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 464

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Lys Asn Gly 1 5 10 <210> 465 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 465

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Gly 1 5 10 <210> 466 <211> 13

    Page 176

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 466

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Pro 1 5 10 <210> 467 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 467

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Glu 1 5 10 <210> 468 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Glu <400> 468

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Glu

    1 5 10

    Page 177

    PRTH_002_03WO_ST25 <210> 469 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MePhe <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 469

    Cys Gln Thr Trp Gln Cys Tyr Phe Leu Glu Asn Gly 1 5 10 <210> 470 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 470

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Pro 1 5 10 <210> 471 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 471

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Gly

    1 5 10

    Page 178

    PRTH_002_03WO_ST25 <210> 472 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 472

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Leu 1 5 10 <210> 473 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 473

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Phe 1 5 10 <210> 474 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <210> 475 <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 474

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Glu

    1 5 10

    Page 179

    PRTH_002_03WO_ST25 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 475

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Asn 1 5 10 <210> 476 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 476

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Thr 1 5 10 <210> 477 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 477

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Arg 1 5 10 <210> 478 <211> 13 <212> PRT <213> Artificial Sequence

    Page 180

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> hLeu <400> 478

    Pro Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 479 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> hLeu <400> 479

    Leu Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 480 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> hLeu <400> 480

    Phe Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 481 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 181

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> hLeu <400> 481

    Glu Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 482 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> hLeu <400> 482

    Asn Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 483 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (10)..(10) <223> hLeu <400> 483

    Arg Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 484 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 182

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 484

    Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 485 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 485

    Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 486 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 486

    Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10

    Page 183

    PRTH_002_03WO_ST25 <210> 487 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> 1-Nal <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 487

    Cys Gln Thr Trp Gln Cys Xaa Xaa Leu Glu Asn Gly 1 5 10 <210> 488 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 488

    Cys Gln Thr Trp Gln Cys Xaa Xaa Leu Glu Asn Gly 1 5 10 <210> 489

    Page 184

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> Aic <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 489

    Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 490 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 490

    Cys Gln Thr Trp Gln Cys His Trp Leu Glu Asn Gly 1 5 10 <210> 491 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 491

    Cys Gln Thr Trp Gln Cys Tyr His Leu Glu Asn Gly 1 5 10

    Page 185

    PRTH_002_03WO_ST25 <210> 492 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> Tyr(OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 492

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 493 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> Bip <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 493

    Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 494 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 186

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> Tyr(OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 494

    Cys Gln Thr Trp Gln Cys Tyr Tyr Leu Glu Asn Gly 1 5 10 <210> 495 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 495

    Cys Gln Thr Trp Gln Cys His His Leu Glu Asn Gly 1 5 10 <210> 496 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MeTrp <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 496

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Gln Gly 1 5 10 <210> 497 <211> 12 <212> PRT <213> Artificial Sequence

    Page 187

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> Lys(PEG8) <400> 497

    Cys Gln Thr Trp Lys Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 498 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Any amino acid <400> 498

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Leu Asn Gly 1 5 10 <210> 499 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> Lys(PEG8) <220>

    <221> MOD_RES <222> (9)..(9) <223> Lys(PEG8) <400> 499

    Cys Gln Thr Trp Lys Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 500 <211> 12 <212> PRT

    Page 188

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> Lys(Palm) <400> 500

    Cys Gln Thr Trp Lys Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 501 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Palm) <400> 501

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Lys Asn Gly 1 5 10 <210> 502 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> D-Asn <220>

    <221> MOD_RES <222> (3)..(3) <223> D-Glu <220>

    Page 189

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (4)..(4) <223> D-Leu <220>

    <221> MOD_RES <222> (5)..(5) <223> D-Trp <220>

    <221> MOD_RES <222> (6)..(6) <223> D-Tyr <220>

    <221> MOD_RES <222> (7)..(7) <223> D-Cys <220>

    <221> MOD_RES <222> (8)..(8) <223> D-Gln <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Trp <220>

    <221> MOD_RES <222> (10)..(10) <223> D-Thr <220>

    <221> MOD_RES <222> (11)..(11) <223> D-Gln <220>

    <221> MOD_RES <222> (12)..(12) <223> D-Cys <400> 502

    Gly Asn Glu Leu Trp Tyr Cys Gln Trp Thr Gln Cys 1 5 10 <210> 503 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn

    Page 190

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(PEG8) <400> 503

    Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Lys Asn Gly 1 5 10 <210> 504 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 504

    Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 505 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 505

    Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 506 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 506

    Cys Gln Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 507 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 507

    Page 191

    PRTH_002_03WO_ST25

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Gly Asp Ser 1 5 10 <210> 508 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 508

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Glu Ser 1 5 10 <210> 509 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 509

    Cys Gln Asp Trp Gln Cys Tyr Trp Arg Glu Phe Gly Pro 1 5 10 <210> 510 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 510

    Cys Gln Asp Trp Gln Cys Tyr Trp Arg Ser Phe Gly Pro 1 5 10

    Gly

    Gly

    Gln <210> 511 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 511

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Leu Gly Pro Ser 1 5 10 <210> 512 <211> 12 <212> PRT

    Page 192

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Pro <400> 512

    Cys Gln Thr Trp Gln Cys Tyr Trp Pro Glu Asn Gly 1 5 10 <210> 513 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 513

    Cys Gln Thr Trp Gln Cys Tyr Trp Glu Leu Asn Gly 1 5 10 <210> 514 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 514

    Cys Gln Thr Trp Glu Cys Tyr Trp Glu Leu Asn Gly 1 5 10 <210> 515 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9)

    Page 193

    PRTH_002_03WO_ST25 <223> alpha-MeLeu <400> 515

    Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 516 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Asn <400> 516

    Cys Gln Thr Trp Gln Cys Tyr Xaa Asn Glu Asn Gly 1 5 10 <210> 517 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Palm) <400> 517

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Lys Gly 1 5 10 <210> 518 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 194

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (12)..(12) <223> Lys(Palm) <400> 518

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Lys 1 5 10 <210> 519 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 519

    Cys Ser Thr Trp Glu Cys Tyr Trp Arg Thr Phe Gly 1 5 10 <210> 520 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 520

    Cys Asp Ser Trp Glu Cys Tyr Trp Arg Thr Tyr Gly 1 5 10 <210> 521 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 521

    Cys Ser Thr Trp Glu Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 522 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 195

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 522

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 523 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys

    Page 196

    PRTH_002_03WO_ST25 <400> 523

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 524 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Leu <400> 524

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 525 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6)

    Page 197

    PRTH_002_03WO_ST25 <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Leu <400> 525

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 526 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 526

    Page 198

    PRTH_002_03WO_ST25 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 527 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 527 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 528 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 199

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 528

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 529 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES

    Page 200

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 529

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 530 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <400> 530

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10

    Page 201

    PRTH_002_03WO_ST25 <210> 531 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 531

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 532 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7)

    Page 202

    PRTH_002_03WO_ST25 <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 532

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 533 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeVal <220>

    Page 203

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 533

    Lys Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 534 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 534

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 535 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 204

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 535

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 536 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES

    Page 205

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 536

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 537 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Achc <400> 537

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 538 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 206

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acvc <400> 538

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 539 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 539

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10

    Page 207

    PRTH_002_03WO_ST25 <210> 540 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 540

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 541 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    Page 208

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 541

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 542 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <220> <221> MOD_RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Achc <400> 542 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10

    <210> 543 <211> 12 <212> PRT <213> Artificial Sequence

    Page 209

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acvc <400> 543

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 544 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES

    Page 210

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 544

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 545 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 545

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 546 <211> 12 <212> PRT <213> Artificial Sequence

    Page 211

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 546

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 547 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (13)..(13)

    Page 212

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 547

    Xaa Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 548 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 548

    Ala Xaa Asp Trp Val Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 549 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    Page 213

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 549

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 550 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> N-MeArg <400> 550

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 551 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen

    Page 214

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 551

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 552 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> N-MeArg <400> 552

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 553 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES

    Page 215

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 553

    Ala Xaa Asp Trp Val Xaa Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 554 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 554

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 555 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 216

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Asn <400> 555

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Asn Glu Asn Gly 1 5 10 <210> 556 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 556

    Xaa Gln Thr Trp Gln Xaa Tyr Xaa Lys Glu Asn Gly

    1 5 10 <210> 557 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 217

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 557

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 558 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    Page 218

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 558

    Xaa Gln Thr Trp Gln Xaa Xaa Xaa Lys Glu Asn Gly 1 5 10 <210> 559 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 559

    Xaa Gln Thr Trp Gln Xaa Tyr Xaa Xaa Glu Asn Gly 1 5 10 <210> 560 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen

    Page 219

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 560

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 561 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 561

    Xaa Gln Thr Trp Gln Xaa Tyr Xaa Xaa Glu Asn Gly 1 5 10 <210> 562 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 220

    PRTH_002_03WO_ST25 <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 562

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 563 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 563 Xaa Gln Thr Trp Gln Xaa Tyr Trp Lys Lys Asn Gly 1 5 10

    Page 221

    PRTH_002_03WO_ST25 <210> 564 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe-(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 564

    Xaa Gln Thr Trp Gln Xaa Phe Trp Lys Lys Asn Gly 1 5 10 <210> 565 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7)

    Page 222

    PRTH_002_03WO_ST25 <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 565

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 566 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 566

    Page 223

    PRTH_002_03WO_ST25

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly

    1 5 10 <210> 567 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Bip <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 567

    Xaa Gln Thr Trp Gln Xaa Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 568 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 224

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3,4-Cl2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 568

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 569 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3,5-F2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES

    Page 225

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 569

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 570 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-NH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 570

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 571 <211> 11 <212> PRT <213> Artificial Sequence

    Page 226

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (9)..(9) <223> Lys(Ac) <400> 571

    Xaa Gln Thr Trp Gln Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 572 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3,4-Cl2) <220>

    <221> MOD_RES <222> (8)..(8)

    Page 227

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 572

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 573 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CN) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 573

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 574 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 228

    <221> MOD_RES <222> (1)..(1) <223> Pen PRTH_002_03WO_ST25 <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe(3,5-F2) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 574 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly

    1 5 10 <210> 575 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CH2CO2H) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn

    Page 229

    PRTH_002_03WO_ST25 <400> 575

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 576 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CH2COEt2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 576

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 577 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES

    Page 230

    <222> (6)..(6) <223> Pen PRTH_002_03WO_ST25 <220> <221> MOD RES <222> (7)..(7) <223> Phe(penta-F) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 577 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly

    1 5 10 <210> 578 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-CF3) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 578 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10

    Page 231

    PRTH_002_03WO_ST25 <210> 579 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 579

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 580 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7)

    Page 232

    PRTH_002_03WO_ST25 <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 580

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 581 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(ivDde) <400> 581

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 582

    Page 233

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 582

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 583 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen

    Page 234

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 583

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 584 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES

    Page 235

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Lys(Ac) <400> 584

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 585 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> PyroGlu <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 585

    Glu Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 586 <211> 12 <212> PRT <213> Artificial Sequence

    Page 236

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 586

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 587 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7)

    Page 237

    PRTH_002_03WO_ST25 <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 587

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 588 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 588

    Page 238

    PRTH_002_03WO_ST25

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly

    1 5 10 <210> 589 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 589

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 590 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 239

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 590

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 591 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <400> 591

    Xaa Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly 1 5 10 <210> 592 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 240

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 592

    Xaa Gly Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 593 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 241

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 593

    Xaa Thr Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 594 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 594

    Xaa Ser Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 595 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1)

    Page 242

    PRTH_002_03WO_ST25 <223> Pen <220>

    <221> MOD_RES <222> (2)..(2) <223> Dap <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 595

    Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 596 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (2)..(2) <223> alpha-MeOrn <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 243

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 596

    Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 597 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 597

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 598 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 244

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 598

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 599 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES

    Page 245

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 599

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 600 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 600

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 601 <211> 12 <212> PRT <213> Artificial Sequence

    Page 246

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 601

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Ala 1 5 10 <210> 602 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8)

    Page 247

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 602

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 603 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 603

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 604 <211> 12 <212> PRT <213> Artificial Sequence <220>

    Page 248

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 604

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 605 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 249

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 605

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 606 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 606

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 607 <211> 12

    Page 250

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (2)..(2) <223> Dap(Ac) <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 607

    Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 608 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (2)..(2) <223> alpha-MeOrn(Ac)

    Page 251

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 608

    Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 609 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <220>

    <221> MOD_RES <222> (10)..(10)

    Page 252

    PRTH_002_03WO_ST25 <223> Lys(Ac) <400> 609

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 610 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 610

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 611 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 253

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 611

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 612 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac)

    Page 254

    PRTH_002_03WO_ST25 <400> 612

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Ala 1 5 10 <210> 613 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 613

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 614 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 255

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 614

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 615 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib

    Page 256

    PRTH_002_03WO_ST25 <400> 615

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 616 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 616

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 617 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1)

    Page 257

    PRTH_002_03WO_ST25 <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 617

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 618 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    Page 258

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> Aib <400> 618

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 619 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 619

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Glu Asn Ala 1 5 10 <210> 620 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 259

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 620

    Xaa Thr Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 621 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES

    Page 260

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac)

    <400> 621 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 622 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Syntheti peptide <220> <221> MOD RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 622 Xaa Thr Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 623 <211> 12 <212> PRT <213> Artificial Sequence

    Page 261

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 623

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 624 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7)

    Page 262

    PRTH_002_03WO_ST25 <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 624

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 625 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 625

    Page 263

    PRTH_002_03WO_ST25

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn

    1 5 10 <210> 626 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 626

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 627 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 264

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 627

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 628 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES

    Page 265

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 628

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 629 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib

    Page 266

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 629

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala

    1 5 10 <210> 630 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <220> <221> MOD_RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <400> 630 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 631 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 267

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 631

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Glu Asn Ala 1 5 10 <210> 632 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    Page 268

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 632

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 633 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220> <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 633 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10

    Page 269

    PRTH_002_03WO_ST25

    <210> 634 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Syntheti peptide <220> <221> MOD RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 634 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 635 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Syntheti peptide <220> <221> MOD_RES <222> (1)..(1) <223> Pen

    <220>

    <221> MOD_RES

    Page 270

    PRTH_002_03WO_ST25 <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 635

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala

    1 5 10 <210> 636 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib

    Page 271

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 636

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 637 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 637

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn

    1 5 10 <210> 638 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 272

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 638

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln

    1 5 10 <210> 639 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)]

    <220>

    Page 273

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 639

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 640 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac)

    Page 274

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 640

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 641 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 641

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 642 <211> 13

    Page 275

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 642

    Glu Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 643 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Asp <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen

    Page 276

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 643

    Asp Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 644 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10)

    Page 277

    PRTH_002_03WO_ST25 <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 644

    Arg Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 645 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Arg <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 645

    Arg Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 646

    Page 278

    PRTH_002_03WO_ST25 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 646

    Phe Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 647 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen

    Page 279

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 647

    Phe Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 648 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> 2-Nal <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES

    Page 280

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 648

    Xaa Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 649 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 649

    Thr Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10

    Page 281

    PRTH_002_03WO_ST25 <210> 650 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 650

    Leu Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 651 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Gln <220>

    <221> MOD_RES <222> (2)..(2)

    Page 282

    PRTH_002_03WO_ST25 <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 651

    Gln Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 652 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Asn <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 283

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 652

    Asn Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 653 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys

    Page 284

    PRTH_002_03WO_ST25 <400> 653

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 654 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <400> 654

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 655 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES

    Page 285

    PRTH_002_03WO_ST25 <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 655

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 656 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 656

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10

    Page 286

    PRTH_002_03WO_ST25 <210> 657 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 657

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 658 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9)

    Page 287

    PRTH_002_03WO_ST25 <223> 4-amino-4-carboxy-tetrahydropyran <400> 658

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 659 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 659

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 660 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 288

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 660

    Xaa Gln Thr Trp Gln Cys Phe Xaa Val Lys Asn Gly 1 5 10 <210> 661 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 661

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Ala 1 5 10

    Page 289

    PRTH_002_03WO_ST25 <210> 662 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)]] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 662

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 663 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES

    Page 290

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 663

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 664 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 664

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Asn 1 5 10 <210> 665 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)]

    Page 291

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Cit <400> 665

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Xaa Asn Asn 1 5 10 <210> 666 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 666

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10

    Page 292

    PRTH_002_03WO_ST25 <210> 667 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 667

    Lys Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 668 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 293

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 668

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 669 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 294

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 669

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 670 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220> <221> MOD_RES <222> (8)..(8) <223> Phe(3,4-OMe2) <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 670 Xaa Gln Thr Trp Gln Xaa Phe Phe Val Lys Asn Asn 1 5 10 <210> 671 <211> 13

    Page 295

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 671

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 672 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe

    Page 296

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> 4-amino-4-carboxy-tetrahydropyran <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 672

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 673 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8)

    Page 297

    PRTH_002_03WO_ST25 <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Achc <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 673

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 674 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> 4-amino-4-carboxy-tetrahydropyran <220>

    Page 298

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (11)..(11) <223> Cit <400> 674

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 675 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Achc <220>

    <221> MOD_RES <222> (11)..(11) <223> Cit <400> 675

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 676 <211> 13 <212> PRT <213> Artificial Sequence

    Page 299

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> Beta-Ala <400> 676

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 677 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 300

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> 4-amino-4-carboxy-tetrahydropyran <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 677

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 678 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen

    Page 301

    PRTH_002_03WO_ST25

    <220> <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220> <221> MOD RES <222> (9)..(9) <223> 2-Nal <220> <221> MOD_RES <222> (10)..(10) <223> Achc <220> <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 678 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 679 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence : Synthetic peptide <220> <221> MOD_RES <222> (1)..(1) <223> D-Phe <220> <221> MOD_RES <222> (2)..(2) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> Pen <220> <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220> <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220> <221> MOD_RES <222> (10)..(10)

    Page 302

    PRTH_002_03WO_ST25 <223> 4-amino-4-carboxy-tetrahydropyran <220>

    <221> MOD_RES <222> (11)..(11) <223> Cit <400> 679

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 680 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Achc <220>

    <221> MOD_RES <222> (11)..(11) <223> Cit <400> 680

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn

    1 5 10 <210> 681

    Page 303

    PRTH_002_03WO_ST25 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Achc <400> 681

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 682 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen

    Page 304

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 682

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 683 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> 4-amino-4-carboxy-tetrahydropyran <220>

    <221> MOD_RES

    Page 305

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Lys(Ac) <400> 683

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 684 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Achc <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 684

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 685 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 306

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acpc <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 685

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 686 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8)

    Page 307

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 686

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 687 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 687

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 688

    Page 308

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> 4-amino-4-carboxy-tetrahydropyran <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 688

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 689 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen

    Page 309

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Achc <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 689

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 690 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 690

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 691 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 310

    PRTH_002_03WO_ST25 <222> (5)..(5) <223> hCys <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 691

    Gln Asp Trp Gln Cys Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 692 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 692

    Xaa Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 693 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> Abu

    Page 311

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 693

    Cys Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 694 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 694

    Xaa Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 695 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (6)..(6)

    Page 312

    PRTH_002_03WO_ST25 <223> Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 695

    Xaa Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 696 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Abu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 696

    Xaa Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 697 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 313

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (1)..(1) <223> D-Cys <220>

    <221> MOD_RES <222> (6)..(6) <223> Abu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 697

    Cys Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 698 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 698

    Xaa Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Asn Gly Xaa Lys 1 5 10

    Page 314

    PRTH_002_03WO_ST25 <210> 699 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 699

    Xaa Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 700 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> <222> <223> MOD_RES (1). Abu .(1) <220> <221> MOD_ RES <222> (6). .(6)

    <223> D-Cys <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 700

    Xaa Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 701 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 315

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 701

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 702 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 702

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 703 <211> 12 <212> PRT <213> Artificial Sequence

    Page 316

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 703

    Xaa Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 704 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 704

    Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Glu Asn Gly 1 5 10 <210> 705 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1)

    Page 317

    PRTH_002_03WO_ST25 <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 705

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 706 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 706 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 707 <211> 12 <212> PRT <213> Artificial Sequence

    <220>

    Page 318

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <400> 707

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 708 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 708

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 709 <211> 12 <212> PRT <213> Artificial Sequence

    Page 319

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 709

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly 1 5 10 <210> 710 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 710

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 711 <211> 12

    Page 320

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 711

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 712 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 321

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 712

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 713 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 713

    Xaa Gln Thr Trp Gln Cys Tyr Trp Xaa Lys Asn Gly 1 5 10 <210> 714 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7)

    Page 322

    PRTH_002_03WO_ST25 <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Asn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 714

    Xaa Gln Thr Trp Gln Cys Phe Xaa Asn Lys Asn Gly 1 5 10 <210> 715 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-Phenoxy) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 715 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10

    <210> 716

    Page 323

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> hPhe(3,4-dimethoxy) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 716

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 717 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> DMT <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 324

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 717

    Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 718 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 718

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 719 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 325

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3,4-Cl2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 719

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 720 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 326

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 720

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 721 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 721

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly

    1 5 10 <210> 722 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 327

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 722

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 723 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> Trp(2,5,7-tri-tert-Butyl) <220>

    Page 328

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 723

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 724 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-Oallyl) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 724

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 725 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe)

    Page 329

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> Tyr(3-tBu) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 725

    Xaa Gln Thr Trp Gln Cys Phe Tyr Lys Glu Asn Gly 1 5 10 <210> 726 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-tBu) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 726

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 727 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 330

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-guanidino) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 727

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 728 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(Bzl) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 728

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 729 <211> 12 <212> PRT <213> Artificial Sequence

    Page 331

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Tyr(3-tBu) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 729

    Xaa Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 730 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acpc <220>

    <221> MOD_RES <222> (10)..(10)

    Page 332

    PRTH_002_03WO_ST25 <223> Lys(Ac) <400> 730

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 731 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 731

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 732 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 333

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (1)..(1) <223> N-MeAla <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 732

    Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 733 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> N-MeAla <220>

    <221> MOD_RES <222> (5)..(5) <223> Pen <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 733

    Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 734 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 334

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> N-MeAla <220>

    <221> MOD_RES <222> (5)..(5) <223> D-Pen <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 734

    Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 735 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> N-MeAla <220>

    <221> MOD_RES <222> (5)..(5) <223> hCys <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 735

    Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 736 <211> 13

    Page 335

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 736

    Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 737 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> Pen <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 737

    Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 738 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 336

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (5)..(5) <223> D-Pen <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 738

    Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 739 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> hCys <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 739

    Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 740 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12)

    Page 337

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 740

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 741 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 741

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 742 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 742

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 743

    Page 338

    PRTH_002_03WO_ST25 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 743

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 744 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 744

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 745 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid

    Page 339

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 745

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 746 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> hCys <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 746

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 747 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> hCys <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES

    Page 340

    PRTH_002_03WO_ST25 <222> (13)..(13) <223> D-Lys <400> 747

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 748 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> hCys <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 748

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 749 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (5)..(5) <223> hCys <220>

    <221> MOD_RES <222> (12)..(12) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys

    Page 341

    PRTH_002_03WO_ST25 <400> 749

    Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 750 <400> 750 000 <210> 751 <400> 751 000 <210> 752 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 752

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asn Ala 1 5 10 <210> 753 <211> 12 <212> PRT <213> Artificial Sequence <220>

    Page 342

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acbc <400> 753

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 754 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Achc <400> 754

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10

    Page 343

    PRTH_002_03WO_ST25 <210> 755 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)]] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acvc <400> 755

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 756 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES

    Page 344

    PRTH_002_03WO_ST25 <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 756

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 757 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac)

    Page 345

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 757

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 758 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-acetylaminoethoxy)]] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <400> 758

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 759 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1)

    Page 346

    PRTH_002_03WO_ST25 <223> Pen

    <220> <221> MOD_RES <222> (6). .(6) <223> Pen <220> <221> MOD_ RES <222> (7). .(7)

    <223> Phe[4-(2-acetylaminoethoxy)]] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 759

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 760 <211> 629 <212> PRT <213> Homo sapiens

    <400> 760 Met 1 Asn Gln Val Thr 5 Ile Gln Trp Asp Ala 10 Val Ile Ala Leu Tyr 15 Ile Leu Phe Ser Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly 20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile 35 40 45 Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Arg Lys Leu 50 55 60 His Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe Gln Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Lys Asn Phe Leu Glu Pro His 85 90 95 Ala Ser Met Tyr Cys Thr Ala Glu Cys Pro Lys His Phe Gln Glu Thr 100 105 110 Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ile Pro 115 120 125

    Page 347

    PRTH_002_03WO_ST25

    Asp Glu 130 Val Thr Cys Val Ile Tyr 135 Glu Tyr Ser Gly 140 Asn Met Thr Cys Thr Trp Asn Ala Gly Lys Leu Thr Tyr Ile Asp Thr Lys Tyr Val Val 145 150 155 160 His Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Gln Tyr Leu Thr Ser 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr 180 185 190 Leu Val Trp Val Gln Ala Ala Asn Ala Leu Gly Met Glu Glu Ser Lys 195 200 205 Gln Leu Gln Ile His Leu Asp Asp Ile Val Ile Pro Ser Ala Ala Val 210 215 220 Ile Ser Arg Ala Glu Thr Ile Asn Ala Thr Val Pro Lys Thr Ile Ile 225 230 235 240 Tyr Trp Lys Ser Gln Thr Thr Ile Glu Lys Val Ser Cys Glu Met Arg 245 250 255 Tyr Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr 260 265 270 Asn Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Ile 275 280 285 Lys Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Tyr Trp 290 295 300 Gln Pro Trp Ser Ser Leu Phe Phe His Lys Thr Pro Glu Thr Val Pro 305 310 315 320 Gln Val Thr Ser Lys Ala Phe Gln His Asp Thr Trp Asn Ser Gly Leu 325 330 335 Thr Val Ala Ser Ile Ser Thr Gly His Leu Thr Ser Asp Asn Arg Gly 340 345 350 Asp Ile Gly Leu Leu Leu Gly Met Ile Val Phe Ala Val Met Leu Ser 355 360 365 Ile Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Phe Arg Thr Gly Ile

    Page 348

    PRTH_002_03WO_ST25

    370 375 380

    Lys Arg Arg 385 Ile Leu Leu 390 Leu Ile Pro Lys Trp 395 Leu Tyr Glu Asp Ile 400 Pro Asn Met Lys Asn Ser Asn Val Val Lys Met Leu Gln Glu Asn Ser 405 410 415 Glu Leu Met Asn Asn Asn Ser Ser Glu Gln Val Leu Tyr Val Asp Pro 420 425 430 Met Ile Thr Glu Ile Lys Glu Ile Phe Ile Pro Glu His Lys Pro Thr 435 440 445 Asp Tyr Lys Lys Glu Asn Thr Gly Pro Leu Glu Thr Arg Asp Tyr Pro 450 455 460 Gln Asn Ser Leu Phe Asp Asn Thr Thr Val Val Tyr Ile Pro Asp Leu 465 470 475 480 Asn Thr Gly Tyr Lys Pro Gln Ile Ser Asn Phe Leu Pro Glu Gly Ser 485 490 495 His Leu Ser Asn Asn Asn Glu Ile Thr Ser Leu Thr Leu Lys Pro Pro 500 505 510 Val Asp Ser Leu Asp Ser Gly Asn Asn Pro Arg Leu Gln Lys His Pro 515 520 525 Asn Phe Ala Phe Ser Val Ser Ser Val Asn Ser Leu Ser Asn Thr Ile 530 535 540 Phe Leu Gly Glu Leu Ser Leu Ile Leu Asn Gln Gly Glu Cys Ser Ser 545 550 555 560 Pro Asp Ile Gln Asn Ser Val Glu Glu Glu Thr Thr Met Leu Leu Glu 565 570 575 Asn Asp Ser Pro Ser Glu Thr Ile Pro Glu Gln Thr Leu Leu Pro Asp 580 585 590 Glu Phe Val Ser Cys Leu Gly Ile Val Asn Glu Glu Leu Pro Ser Ile 595 600 605 Asn Thr Tyr Phe Pro Gln Asn Ile Leu Glu Ser His Phe Asn Arg Ile

    610 615 620

    Page 349

    PRTH_002_03WO_ST25

    Ser Leu Leu Glu Lys

    625 <210> 761 <211> 659 <212> PRT <213> Mus musculus

    <400> 761 Tyr Tyr Ile Trp Asp 15 Met Met 1 Lys Arg Glu Arg 5 Glu Met Arg Gly Phe 10 Ser His Leu Thr Leu Gln Leu His Val Val Ile Ala Leu Tyr Val Leu 20 25 30 Phe Arg Trp Cys His Gly Gly Ile Thr Ser Ile Asn Cys Ser Gly Asp 35 40 45 Met Trp Val Glu Pro Gly Glu Ile Phe Gln Met Gly Met Asn Val Ser 50 55 60 Ile Tyr Cys Gln Glu Ala Leu Lys His Cys Arg Pro Arg Asn Leu Tyr 65 70 75 80 Phe Tyr Lys Asn Gly Phe Lys Glu Glu Phe Asp Ile Thr Arg Ile Asn 85 90 95 Arg Thr Thr Ala Arg Ile Trp Tyr Lys Gly Phe Ser Glu Pro His Ala 100 105 110 Tyr Met His Cys Thr Ala Glu Cys Pro Gly His Phe Gln Glu Thr Leu 115 120 125 Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ala Pro Ser 130 135 140 Asn Leu Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys Thr 145 150 155 160 Trp Asn Thr Gly Lys Pro Thr Tyr Ile Asp Thr Lys Tyr Ile Val His 165 170 175 Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Gln Tyr Leu Ala Ser Ser 180 185 190 Tyr Val Lys Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr Leu 195 200 205 Val Trp Val Gln Ala Val Asn Ser Leu Gly Met Glu Asn Ser Gln Gln Page 350

    PRTH_002_03WO_ST25

    210 215 220

    Leu 225 His Val His Leu Asp Asp 230 Ile Val Ile Pro 235 Ser Ala Ser Ile Ile 240 Ser Arg Ala Glu Thr Thr Asn Asp Thr Val Pro Lys Thr Ile Ile Tyr 245 250 255 Trp Lys Ser Lys Thr Met Ile Glu Lys Val Phe Cys Glu Met Arg Tyr 260 265 270 Lys Thr Thr Thr Asn Gln Thr Trp Ser Val Lys Glu Phe Asp Ala Asn 275 280 285 Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asp Ser Lys 290 295 300 Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Asn Trp Gln 305 310 315 320 Pro Trp Ser Ser Pro Phe Val His Gln Thr Ser Gln Glu Thr Gly Lys 325 330 335 Arg Asn Trp Gln Pro Trp Ser Ser Pro Phe Val His Gln Thr Ser Gln 340 345 350 Thr Val Ser Gln Val Thr Ala Lys Ser Ser His Glu Pro Gln Lys Met 355 360 365 Glu Met Leu Ser Ala Thr Ile Phe Arg Gly His Pro Ala Ser Gly Asn 370 375 380 His Gln Asp Ile Gly Leu Leu Ser Gly Met Val Phe Leu Ala Ile Met 385 390 395 400 Leu Pro Ile Phe Ser Leu Ile Gly Ile Phe Asn Arg Ser Leu Arg Ile 405 410 415 Gly Ile Lys Arg Lys Val Leu Leu Met Ile Pro Lys Trp Leu Tyr Glu 420 425 430 Asp Ile Pro Asn Met Glu Asn Ser Asn Val Ala Lys Leu Leu Gln Glu 435 440 445 Lys Ser Val Phe Glu Asn Asp Asn Ala Ser Glu Gln Ala Leu Tyr Val

    450 455 460

    Page 351

    PRTH_002_03WO_ST25

    Asp 465 Pro Val Leu Thr Glu 470 Ile Ser Glu Ile Ser 475 Pro Leu Glu His Lys 480 Pro Thr Asp Tyr Lys Glu Glu Arg Leu Thr Gly Leu Leu Glu Thr Arg 485 490 495 Asp Cys Pro Leu Gly Met Leu Ser Thr Ser Ser Ser Val Val Tyr Ile 500 505 510 Pro Asp Leu Asn Thr Gly Tyr Lys Pro Gln Val Ser Asn Val Pro Pro 515 520 525 Gly Gly Asn Leu Phe Ile Asn Arg Asp Glu Arg Asp Pro Thr Ser Leu 530 535 540 Glu Thr Thr Asp Asp His Phe Ala Arg Leu Lys Thr Tyr Pro Asn Phe 545 550 555 560 Gln Phe Ser Ala Ser Ser Met Ala Leu Leu Asn Lys Thr Leu Ile Leu 565 570 575 Asp Glu Leu Cys Leu Val Leu Asn Gln Gly Glu Phe Asn Ser Leu Asp 580 585 590 Ile Lys Asn Ser Arg Gln Glu Glu Thr Ser Ile Val Leu Gln Ser Asp 595 600 605 Ser Pro Ser Glu Thr Ile Pro Ala Gln Thr Leu Leu Ser Asp Glu Phe 610 615 620 Val Ser Cys Leu Ala Ile Gly Asn Glu Asp Leu Pro Ser Ile Asn Ser 625 630 635 640 Tyr Phe Pro Gln Asn Val Leu Glu Ser His Phe Ser Arg Ile Ser Leu 645 650 655

    Phe Gln Lys <210> 762 <211> 639 <212> PRT <213> Rattus norvegicus <400> 762

    Met Arg Arg Glu Arg Glu Met Arg Gly Phe Tyr Tyr Ile Trp Asp Met 1 5 10 15

    Ser His Val Ala Leu Gln Leu His Val Val Ile Ala Leu Tyr Ala Leu Page 352

    20 PRTH_002_03WO_ST25 25 30 Phe Arg Trp Gly His Gly Gly Ile Ala Thr Ile Asn Cys Ser Gly Asn 35 40 45 Met Trp Val Glu Pro Gly Glu Ile Phe Gln Met Gly Met Asn Val Ser 50 55 60 Val Tyr Cys Gln Glu Ala Leu Lys Asn Cys Arg Pro Arg Asn Leu His 65 70 75 80 Phe Tyr Lys Asn Gly Phe Lys Glu Arg Phe His Ile Thr Arg Ile Asn 85 90 95 Arg Thr Thr Ala Arg Val Trp Thr Lys Gly Phe Ser Glu Pro His Ala 100 105 110 Ser Met Tyr Cys Thr Ala Glu Cys Pro Gly Arg Phe Gln Glu Thr Leu 115 120 125 Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ala Pro Ser 130 135 140 Asn Met Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys Thr 145 150 155 160 Trp Asn Thr Gly Lys Pro Thr Tyr Ile Asp Thr Lys Tyr Thr Val His 165 170 175 Val Lys Ser Leu Glu Thr Glu Glu Gln Gln Gln Tyr Leu Ala Ser Asn 180 185 190 Tyr Val Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr Leu 195 200 205 Val Trp Val Gln Ala Val Asn Ala Leu Gly Met Glu Asn Ser Gln Gln 210 215 220 Leu Gln Val His Leu Asp Asp Ile Val Ile Pro Ser Pro Ser Ile Ile 225 230 235 240 Ser Arg Ala Glu Thr Thr Asn Ala Asn Val Pro Lys Thr Ile Ile Tyr 245 250 255 Trp Lys Ser Lys Ile Met Thr Gly Lys Val Phe Cys Glu Met Arg Tyr 260 265 270

    Page 353

    Lys Ala Thr 275 Thr Asn PRTH_002_03WO_ST25 Gln Thr Trp 280 Asn Val Lys Glu Phe 285 Asp Thr Asn Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Ser Lys 290 295 300 Tyr Val Phe Gln Val Arg Cys Gln Gly Thr Gly Lys Arg Tyr Trp Gln 305 310 315 320 Pro Trp Ser Ser Pro Phe Val His Gln Thr Pro Gln Thr Ala Ser Gln 325 330 335 Val Thr Ser Lys Pro Pro His Glu Pro Gln Lys Ile Glu Met Leu Thr 340 345 350 Ala Thr Ile Phe Lys Gly His Ser Thr Ser Asp Asn Ser Gln Asp Ile 355 360 365 Gly Leu Leu Ser Gly Met Val Phe Leu Ala Ile Met Leu Pro Ile Phe 370 375 380 Ser Leu Ile Gly Ile Phe Asn Arg Ser Leu Arg Ile Gly Ile Lys Arg 385 390 395 400 Lys Val Leu Leu Met Ile Pro Lys Trp Leu Tyr Glu Asp Ile Pro Asn 405 410 415 Met Glu Asn Ser Asn Ile Ala Lys Leu Leu Gln Glu Lys Ser Val Phe 420 425 430 Glu Asn Glu Asn Ala Ser Glu Gln Ala Leu Tyr Val Asp Pro Ile Leu 435 440 445 Thr Glu Ile Ser Glu Ile Ser Pro Leu Glu His Lys Pro Thr Asp Tyr 450 455 460 Lys Lys Asp Arg Leu Thr Gly Phe Leu Glu Thr Arg Asp Cys Pro Leu 465 470 475 480 Thr Thr Leu Ser Thr Ser Ser Ser Val Val Tyr Ile Pro Asp Leu Asn 485 490 495 Thr Gly Tyr Lys Pro Gln Val Ser Asn Val Pro Pro Glu Glu Asn His 500 505 510 Phe Ile Asn Arg Asp Glu Arg Asp Pro Met Ser Leu Glu Ala Thr Gly 515 520 525

    Page 354

    PRTH_002_03WO_ST25

    Asp His 530 Phe Ala Arg Leu Lys 535 Thr Tyr Pro Asn Phe 540 Thr Phe Ser Ala Ser Ser Met Thr Ser Leu Ser Lys Thr Leu Ile Leu Asp Glu Leu Ser 545 550 555 560 Leu Val Leu Asn Gln Gly Glu Phe Asn Ser Leu Asp Ile Gln Asn Ser 565 570 575 Arg Gln Glu Glu Thr Ser Met Ile Leu Gln Asn Asp Ser Pro Ser Glu 580 585 590 Thr Ile Pro Val Gln Thr Leu Leu Pro Asp Glu Phe Val Ser Cys Leu 595 600 605 Ala Ile Gly Ser Glu Asp Leu Pro Ser Ile Asn Ser Tyr Phe Pro Gln 610 615 620 Asn Val Leu Glu Ser His Phe Ser Gly Ile Pro Leu Leu Gln Lys

    625 630 635 <210> 763 <211> 629 <212> PRT <213> Pan sp. <400> 763

    Met 1 Asn Gln Val Thr 5 Ile Gln Trp Asp Ala Val 10 Ile Ala Leu Tyr 15 Ile Leu Phe Ser Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly 20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile 35 40 45 Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Arg Lys Leu 50 55 60 His Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe Gln Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Lys Asn Phe Leu Glu Pro His 85 90 95 Ala Ser Met Tyr Cys Thr Ala Glu Cys Pro Lys His Phe Gln Glu Thr 100 105 110

    Page 355

    Leu Ile Cys 115 Gly Lys Asp Ile Ser 120 PRTH_002_03WO_ST25 Asp Ile Pro Ser Gly Tyr Pro Pro 125 Asp Glu Val Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys 130 135 140 Thr Trp Asn Ala Gly Lys Leu Thr Tyr Met Asp Thr Lys Tyr Val Val 145 150 155 160 His Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Gln Tyr Leu Thr Ser 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr 180 185 190 Leu Val Trp Val Gln Ala Ala Asn Ala Leu Gly Met Glu Glu Ser Lys 195 200 205 Gln Leu Gln Ile Tyr Leu Asp Asp Ile Val Ile Pro Ser Ala Ser Val 210 215 220 Ile Ser Arg Ala Glu Thr Ile Asn Ala Thr Val Pro Lys Thr Ile Ile 225 230 235 240 Tyr Trp Asp Ser Gln Thr Thr Ile Glu Lys Val Ser Cys Glu Met Arg 245 250 255 Tyr Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr 260 265 270 Asn Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Ile 275 280 285 Lys Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Tyr Trp 290 295 300 Gln Pro Trp Ser Ser Pro Phe Phe His Lys Thr Pro Glu Thr Val Pro 305 310 315 320 Gln Val Thr Ser Lys Ala Phe Gln His Asp Thr Trp Asn Ser Gly Leu 325 330 335 Thr Val Ala Ser Ile Ser Thr Gly His Leu Thr Ser Asp Asn Arg Gly 340 345 350 Asp Ile Gly Leu Leu Leu Gly Met Ile Val Phe Ala Val Met Leu Ser 355 360 365

    Page 356

    PRTH_002_03WO_ST25

    Ile Leu 370 Ser Leu Ile Gly Ile 375 Phe Asn Arg Ser Leu 380 Arg Thr Gly Ile Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu Tyr Glu Asp Ile 385 390 395 400 Pro Asn Met Lys Asn Ser Asn Val Val Lys Met Leu Gln Glu Asn Ser 405 410 415 Glu Leu Met Asn Asn Asn Ser Ser Glu Gln Val Leu Tyr Val Asp Pro 420 425 430 Met Ile Thr Glu Ile Lys Glu Ile Phe Ile Pro Glu His Lys Pro Thr 435 440 445 Asp Tyr Lys Lys Leu Asn Thr Gly Pro Leu Glu Thr Arg Asp Thr Leu 450 455 460 Gln Asn Ser Leu Phe Asp Asn Thr Thr Val Val Tyr Ile Pro Asp Leu 465 470 475 480 Asn Thr Gly Tyr Lys Pro Gln Ile Ser Asn Phe Leu Pro Glu Gly Ser 485 490 495 His Leu Ser Asn Asn Asn Glu Ile Thr Ser Leu Thr Leu Lys Pro Pro 500 505 510 Val Asp Ser Leu Asp Ser Gly Asn Asn Pro Arg Leu Gln Lys His Pro 515 520 525 Asn Phe Ala Phe Ser Val Ser Ser Val Asn Ser Leu Ser Asn Thr Ile 530 535 540 Phe Leu Gly Glu Leu Ser Leu Ile Leu Asn Gln Gly Glu Cys Ser Ser 545 550 555 560 Pro Asp Ile Gln Asn Ser Val Glu Glu Glu Thr Thr Thr Leu Leu Glu 565 570 575 Asn Asp Ser Pro Ser Glu Thr Ile Pro Glu Gln Thr Leu Leu Pro Asp 580 585 590 Glu Phe Val Ser Cys Leu Gly Ile Val Asn Glu Glu Leu Pro Ser Ile 595 600 605 Asn Thr Tyr Phe Pro Gln Asn Ile Leu Glu Ser His Phe Asn Arg Ile

    610 615 620

    Page 357

    PRTH_002_03WO_ST25

    Ser Leu Leu Glu Lys 625 <210> 764 <211> 631 <212> PRT <213> Canis familiaris <400> 764

    Met Asn 1 Gln Ile Thr 5 Ile Gln Trp Asp Val 10 Val Ile Ala Leu Tyr 15 Ile Phe Phe Asn Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly 20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile 35 40 45 Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Arg Lys Leu 50 55 60 Tyr Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe Gln Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Ser Asn Phe Leu Glu Pro His 85 90 95 Ala Ser Met Tyr Cys Thr Ala Glu Cys Pro Gly Tyr Pro Gln Glu Thr 100 105 110 Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Val Pro 115 120 125 Asp Lys Val Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys 130 135 140 Thr Trp Asn Ser Gly Lys Pro Thr Tyr Ile Asp Thr Lys Tyr Val Val 145 150 155 160 Tyr Val Lys Ser Leu Glu Lys Glu Glu Glu Gln Gln Tyr Leu Ser Ser 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr 180 185 190 Leu Val Trp Val Gln Ala Ala Asn Ala Leu Gly Met Glu Lys Ser Lys 195 200 205

    Page 358

    PRTH_002_03WO_ST25

    Gln Leu Gln 210 Ile Asn Leu Asp Asp Ile 215 Val Ile Pro 220 Ser Ala Ala Ile Ile Ser Arg Ala Glu Asp Ile Asn Thr Thr Ile Pro Lys Thr Ile Ile 225 230 235 240 His Trp Asn Ser Gln Thr Thr Ile Glu Asn Val Ser Cys Glu Met Arg 245 250 255 His Lys Thr Thr Thr Asn Gln Thr Trp Lys Val Lys Glu Phe Asp Thr 260 265 270 Asn Phe Pro Tyr Glu Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Thr 275 280 285 Lys Tyr Ile Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Tyr Trp 290 295 300 Gln Pro Trp Ser Ser Pro Phe Phe His Lys Thr Ala Glu Thr Val Pro 305 310 315 320 Gln Val Thr Val Lys Ser Phe Gln His Asp Thr Gln Asn Ser Glu Leu 325 330 335 Leu Ile Ala Ser Ile Phe Lys Gly His Leu Thr Ser Asp Asn Arg Gln 340 345 350 Gln Asp Ile Gly Leu Leu Leu Gly Met Ile Phe Phe Ala Ala Met Leu 355 360 365 Ser Ile Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Ile Arg Thr Gly 370 375 380 Ile Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu His Glu Asp 385 390 395 400 Ile Pro Asn Met Glu Asn Ser Lys Val Val Glu Met Leu Gln Lys Gln 405 410 415 Ser Glu Phe Met Asn Asn Asn Ser Ser Glu Gln Val Leu Tyr Ala Asp 420 425 430 Pro Val Ile Thr Glu Ile Glu Ile Phe Leu Pro Glu Glu His Lys Pro 435 440 445 Thr Asp Tyr Lys Ala Glu Lys Asn Thr Gly Ser Leu Glu Thr Arg Asp

    450 455 460

    Page 359

    PRTH_002_03WO_ST25

    Cys 465 Leu Gln Asn Ser Leu 470 Leu Thr Asn Thr Thr Val 475 Val Tyr Ile Pro 480 Gly Leu Ser Thr Gly Tyr Lys Pro Gln Ile Ser Asn Phe Leu Thr Gly 485 490 495 Gly Asn His Leu Ser Lys Lys Asp Glu Thr Ser Ser Ser Thr Leu Lys 500 505 510 Pro Leu Ala Asp Ser Ser Asp Leu Gly Gly Asn Ala Arg Phe Lys Lys 515 520 525 Tyr Pro Asn Phe Ala Phe Ser Val Ser Ser Met Asn Ser Leu Ser Asn 530 535 540 Thr Leu Phe Leu Glu Glu Leu Ser Leu Ile Leu Asn Gln Gly Glu Arg 545 550 555 560 Ser Pro Leu Asp Met Gln Asn Ser Val Glu Gly Glu Thr Thr Met Leu 565 570 575 Leu Glu Asn Ala Ser Pro Asn Glu Thr Ile Pro Glu Gln Thr Leu Leu 580 585 590 Pro Asp Glu Phe Val Ser Cys Leu Gly Ile Met Asn Glu Glu Leu Pro 595 600 605 Ser Ile Asn Ser Tyr Phe Pro Gln Asn Ile Leu Glu Asn His Phe Asn 610 615 620 Thr Ile Ser Leu Leu Glu Lys

    625 630 <210> 765 <211> 630 <212> PRT <213> Bos sp. <400> 765

    Met Asn Gln Val Thr Ile His Trp Asp Val Val Ile Ala Leu Tyr Il e 1 5 10 15 Phe Phe Ser Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gl ^y 20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Il e

    35 40 45

    Page 360

    PRTH_002_03WO_ST25

    Ser Ile 50 Tyr Cys Gln Ala Ala Ile 55 Lys Asn Cys Gln 60 Pro Ser Lys Leu Tyr Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe His Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Asn Asn Phe Val Glu Pro Gln 85 90 95 Ala Phe Met Tyr Cys Thr Ala Glu Cys Ser Arg Tyr Phe Pro Glu Thr 100 105 110 Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Val Pro 115 120 125 Asp Lys Val Ala Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys 130 135 140 Thr Trp Asn Pro Gly Arg Pro Thr Tyr Ile Asp Thr Lys Tyr Val Val 145 150 155 160 Tyr Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Glu Tyr Leu Thr Ser 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Lys Gly Lys Lys Tyr 180 185 190 Leu Val Trp Val Gln Ala Ser Asn Val Leu Gly Met Glu Lys Ser Lys 195 200 205 Gln Leu Gln Ile His Leu Asp Asp Ile Val Ile Pro Ser Ala Ser Ile 210 215 220 Ile Ser Arg Ala Glu Asp Ile Asn Thr Thr Val Ser Lys Thr Val Ile 225 230 235 240 His Trp Asp Ser Gln Thr Ser Ile Glu Lys Val Ser Cys Glu Met Arg 245 250 255 Tyr Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr 260 265 270 Asn Phe Thr Tyr Glu Gln Gln Ser Glu Phe Tyr Leu Gln Pro Asn Ala 275 280 285 Met Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Lys Tyr Trp 290 295 300

    Page 361

    PRTH_002_03WO_ST25

    Gln 305 Pro Trp Ser Ser Pro 310 Phe Phe His Lys Thr 315 Pro Glu Ile Val Pro 320 Gln Val Thr Met Lys Ser Phe Gln His Asp Thr Gln Asn Ser Gly Leu 325 330 335 Leu Ile Ala Ser Ile Phe Lys Lys His Leu Thr Ser Asp Asn Arg Lys 340 345 350 Gln Asp Ile Gly Leu Leu Leu Gly Met Val Phe Phe Ala Val Met Leu 355 360 365 Ser Val Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Leu Arg Thr Gly 370 375 380 Ile Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu Tyr Glu Asp 385 390 395 400 Ile Pro Asn Met Glu Asn Ser Lys Val Val Lys Ile Leu Gln Glu Arg 405 410 415 Asn Glu Phe Met Asn Asn Asn Ser Ser Glu Gln Val Leu Tyr Val Asp 420 425 430 Pro Val Ile Thr Glu Ile Glu Ile Ile Leu Pro Glu Glu Lys Pro Met 435 440 445 Gly Tyr Lys Lys Glu Asn Asn Thr Gly Cys Leu Glu Arg Lys Glu Ser 450 455 460 Leu Glu Lys Ser Leu Leu Thr Asp Thr Thr Val Val Tyr Ile Pro Asp 465 470 475 480 Leu Asn Thr Gly Tyr Lys Pro Gln Ile Ser Ser Phe Leu Pro Gly Gly 485 490 495 Asn His Leu Ser Asn Asp Asp Glu Thr Ala Ser Ser Ile Leu Glu Pro 500 505 510 Pro Ala Asp Ser Leu Asn Leu Gly Asn Asn Ala Arg Phe Lys Lys Tyr 515 520 525 Pro Asp Phe Ala Phe Ser Val Ser Ser Thr Asn Ser Leu Ser Asn Thr 530 535 540 Leu Phe Leu Glu Glu Leu Asn Leu Ile Leu Asn Gln Gly Glu Cys Ser

    Page 362

    560

    545

    550

    PRTH_002_03WO_ST25

    555

    Pro Pro Asp Met Gln Asn Ser Ile Glu Gly Gl u Thr Ala Met Leu Leu 565 570 575 Glu Asp Asp Leu Leu Asn Glu Thr Ile Pro Gl u Gln Thr Leu Leu Pro 580 585 590 Asp Glu Phe Val Ser Cys Leu Gly Ser Met As n Lys Glu Leu Pro Ser 595 600 605 Ile Asn Ser Tyr Phe Pro Gln Asn Ile Leu Gl u Ser His Phe Asn Arg 610 615 620 Ile Ser Leu Leu Glu Lys

    625 630 <210> 766 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 766

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Asn 1 5 10

    Page 363

    PRTH_002_03WO_ST25 <210> 767 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 767

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10

    <210> 768 <400> 000 768 <210> 769 <400> 000 769 <210> 770 <400> 000 770 <210> 771 <400> 000 771

    Page 364

    PRTH_002_03WO_ST25 <210> 772 <400> 772 000 <210> 773 <400> 773 000 <210> 774 <400> 774 000 <210> 775 <400> 775 000 <210> 776 <400> 776 000 <210> 777 <400> 777 000 <210> 778 <400> 778 000 <210> 779 <400> 779 000 <210> 780 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 365

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-tBu) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 780

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 781 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-guanidino) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 781

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 782 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES

    Page 366

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 782

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 783 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CO2H) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 783

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 784 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-phenoxy)

    Page 367

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 784

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 785 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CN) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 785

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 786 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-Br) <220>

    <221> MOD_RES <222> (9)..(9)

    Page 368

    PRTH_002_03WO_ST25 <223> alpha-MeLys <400> 786

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 787 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-NH2) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 787

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 788 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-Me) <220>

    Page 369

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 788

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 789 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 789

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 790 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe)

    Page 370

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 790

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 791 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 791 Xaa Gln Thr Trp Gln Cys Xaa Xaa Xaa Lys Asn Gly 1 5 10 <210> 792 <211> 12

    Page 371

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Bip <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 792

    Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 793 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Cha <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 372

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 793

    Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 794 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 794

    Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly

    1 5 10 <210> 795 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 373

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> 4-Pyridylalanine <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 795

    Xaa Gln Thr Trp Gln Cys Ala Xaa Lys Lys Asn Gly 1 5 10 <210> 796 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Beta-homoTyr <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    Page 374

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 796

    Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly 1 5 10 <210> 797 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 797

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 798 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 375

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 798

    Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Glu Asn Gly 1 5 10 <210> 799 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> 2-Nal <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 799

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly Page 376

    PRTH_002_03WO_ST25

    1 5 10 <210> 800 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> 1-Nal <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 800

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 801 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 377

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 801

    Xaa Gln Thr Tyr Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 802 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 802

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10

    Page 378

    PRTH_002_03WO_ST25 <210> 803 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 803

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Gly Glu 1 5 10 <210> 804 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    Page 379

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 804

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Ala Glu 1 5 10 <210> 805 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 805

    Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Gly Glu 1 5 10 <210> 806 <211> 14 <212> PRT <213> Artificial Sequence

    Page 380

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 806

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly Gly Glu 1 5 10 <210> 807 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 807

    Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly Gly Glu Page 381

    PRTH_002_03WO_ST25

    1 5 10 <210> 808 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 808

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ser 1 5 10 <210> 809 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe)

    Page 382

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 809

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala 1 5 10 <210> 810 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 810 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 811 <211> 12 <212> PRT

    Page 383

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe-4-N3 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 811

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 812 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    Page 384

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 812

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Gln Gly 1 5 10 <210> 813 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (11)..(11) <223> Cit <400> 813

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Xaa Gly 1 5 10 <210> 814 <211> 12 <212> PRT <213> Artificial Sequence

    Page 385

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 814

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Val Asn Gly 1 5 10 <210> 815 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES

    Page 386

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Lys(Ac) <400> 815

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 816 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <400> 816

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 817 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 387

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 817

    Xaa Asn Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 818 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Bip <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10)

    Page 388

    PRTH_002_03WO_ST25 <223> Lys(Ac) <400> 818

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 819 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Cha <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 819

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 820 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    Page 389

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Chg <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 820

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 821 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Octgly <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac)

    Page 390

    PRTH_002_03WO_ST25 <400> 821

    Xaa Gln Thr Gly Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 822 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Octgly <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 822

    Xaa Gln Thr Trp Gln Cys Gly Xaa Lys Lys Asn Gly 1 5 10 <210> 823 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES

    Page 391

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> Octgly <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 823

    Xaa Gln Thr Trp Gln Cys Phe Gly Lys Lys Asn Gly 1 5 10 <210> 824 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 824

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Glu 1 5 10

    Page 392

    PRTH_002_03WO_ST25 <210> 825 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 825

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala Glu 1 5 10 <210> 826 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8)

    Page 393

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 826

    Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Glu 1 5 10 <210> 827 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 827

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly Glu 1 5 10 <210> 828 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 394

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 828

    Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly Glu 1 5 10 <210> 829 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 829

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 830 <211> 12 <212> PRT <213> Artificial Sequence

    Page 395

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 830

    Xaa Gln Thr Gln Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 831 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 831

    Xaa Gln Thr His Gln Cys Phe Xaa Lys Glu Asn Gly Page 396

    PRTH_002_03WO_ST25

    1 5 10 <210> 832 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> hPhe <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 832

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 833 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Glu(Bzl)

    Page 397

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 833

    Xaa Gln Thr Glu Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 834 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Bip <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 834

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 835 <211> 12 <212> PRT

    Page 398

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Tic <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 835

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 836 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 399

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 836

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 837 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(3,4-Cl2) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 837

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 838 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 400

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 838

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 839 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Orn(Benzyl) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES

    Page 401

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> alpha-MeLys <400> 839

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 840 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Orn(Benzaldehyde) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 840

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 841 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 402

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe-OCH2CH2NHAc <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 841

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 842 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 842

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly

    1 5 10 <210> 843 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 403

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> 5-hydroxyTrp <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 843

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 844 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> 6-chloroTrp <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    Page 404

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 844

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 845 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> N-MeTrp <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 845

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 846 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 405

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (4)..(4) <223> 1,2,3,4-tetrahydro-norharman <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 846

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 847 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-CO2H) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys] <400> 847

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly Page 406

    PRTH_002_03WO_ST25

    1 5 10 <210> 848 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 848

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 849 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-CONH2)

    Page 407

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 849

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 850 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(3,4-OMe) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 850

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 851 <211> 12 <212> PRT

    Page 408

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> alpha-MePhe <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 851

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 852 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-CF3) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 409

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 852

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 853 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(4-tBu) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys] <400> 853

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 854 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 410

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Phe(2,4-Me2) <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 854

    Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 855 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 855

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Asp Asn Gly Page 411

    PRTH_002_03WO_ST25

    1 5 10 <210> 856 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 856

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Gln Asn Gly 1 5 10 <210> 857 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 412

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Benzoic acid) <400> 857

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 858 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(succinic acid) <400> 858

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly

    1 5 10 <210> 859 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 413

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(glutaric acid) <400> 859

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 860 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    Page 414

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (10)..(10) <223> Lys(pyroglutamic acid) conjugated through side chain <400> 860

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly

    1 5 10 <210> 861 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(isovaleric acid) <400> 861

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 862 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 415

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Palm) <400> 862

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 863 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(PEG1) <400> 863

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Page 416

    PRTH_002_03WO_ST25

    1 5 10 <210> 864 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(PEG2) <400> 864

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 865 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)]

    Page 417

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(Benzoic acid) <400> 865

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 866 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(succinic acid) <400> 866

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 867 <211> 12 <212> PRT

    Page 418

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(glutaric acid) <400> 867

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 868 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    Page 419

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(pyroglutamic acid) conjugated through side chain <400> 868

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly

    1 5 10 <210> 869 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(IVA) <400> 869

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 870 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 420

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(PEG1) <400> 870

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 871 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES

    Page 421

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Dap(PEG2) <400> 871

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 872 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(PEG2-Ac) <400> 872

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 873 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 422

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 873

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Xaa Lys 1 5 10 <210> 874 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9)

    Page 423

    PRTH_002_03WO_ST25 <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 874

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Lys 1 5 10 <210> 875 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <400> 875

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Xaa 1 5 10 <210> 876

    Page 424

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 876 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Gln Gly 1 5 10 <210> 877 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 425

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 877

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly 1 5 10 <210> 878 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 878

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 879 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES

    Page 426

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 1-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 879

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 880 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 880

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Ala 1 5 10

    Page 427

    PRTH_002_03WO_ST25 <210> 881 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <400> 881 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 882 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> Phe(4-CO2H) <220> <221> MOD_RES <222> (9)..(9) Page 428

    PRTH_002_03WO_ST25 <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 882

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 883 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (2)..(2) <223> Dap <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-Phenoxy) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 883

    Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 884 <211> 12 <212> PRT <213> Artificial Sequence <220>

    Page 429

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (2)..(2) <223> Dap <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 884

    Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 885 <211> 11 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MeLys

    Page 430

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Lys(Ac) <400> 885

    Xaa Gln Thr Trp Gln Cys Phe Lys Lys Asn Gly 1 5 10 <210> 886 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (2)..(2) <223> Dab <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> hPhe <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 886

    Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 887 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic Page 431

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (2)..(2) <223> Dap <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Glu(Bzl) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 887

    Xaa Xaa Thr Trp Gln Cys Phe Glu Lys Lys Asn Gly 1 5 10 <210> 888 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Orn

    Page 432

    PRTH_002_03WO_ST25 <400> 888

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 889 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 889

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly 1 5 10 <210> 890 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9)

    Page 433

    PRTH_002_03WO_ST25 <223> alpha-Me-Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 890

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Lys Asn Gly 1 5 10 <210> 891 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 891

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 892 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 434

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 892

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 893 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac)

    Page 435

    PRTH_002_03WO_ST25 <400> 893

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 894 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <400> 894

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 895 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES

    Page 436

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Dap <400> 895

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Xaa Asn Gly 1 5 10 <210> 896 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap(Ac) <400> 896

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Xaa Asn Gly 1 5 10 <210> 897 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)]

    Page 437

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Orn <220>

    <221> MOD_RES <222> (10)..(10) <223> Dap <400> 897

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 898 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Orn <220> <221> MOD_RES <222> (10)..(10) <223> Dap(Ac) <400> 898 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 899 <211> 12 <212> PRT

    Page 438

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 899

    Xaa Gln Thr Trp Gln Cys Phe Trp Leu Glu Asn Gly 1 5 10 <210> 900 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 900

    Page 439

    PRTH_002_03WO_ST25

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly

    1 5 10 <210> 901 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Leu <400> 901

    Xaa Gln Thr Trp Gln Cys Phe Trp Leu Glu Asn Gly 1 5 10 <210> 902 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys

    Page 440

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 902

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 903 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (11)..(11) <223> Dap <400> 903

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Xaa Gly 1 5 10 <210> 904 <211> 10 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 441

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 904

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys

    1 5 10 <210> 905 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> Chg <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 905

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Lys Asn Gly 1 5 10 <210> 906 <211> 12 <212> PRT <213> Artificial Sequence

    Page 442

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 906

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 907 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10)

    Page 443

    PRTH_002_03WO_ST25 <223> Lys(Ac) <400> 907

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 908 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(3,4-OMe2) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 908

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 909 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    Page 444

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (2)..(2) <223> Dap <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Tic <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 909

    Xaa Xaa Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 910 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (2)..(2) <223> Dap <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(3,4-Cl2) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys

    Page 445

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 910

    Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 911 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 911

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 912 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES

    Page 446

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 912

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 913 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 913

    Xaa Thr Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 914 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 447

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-Me-Gly(Ethyl) <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 914

    Xaa Gln Thr Trp Gln Cys Phe Xaa Gly Lys Asn Gly 1 5 10 <210> 915 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeVal <220>

    <221> MOD_RES <222> (10)..(10)

    Page 448

    PRTH_002_03WO_ST25 <223> Lys(Ac) <400> 915

    Xaa Gln Thr Trp Gln Cys Phe Xaa Val Lys Asn Gly 1 5 10 <210> 916 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeSer <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 916

    Xaa Gln Thr Trp Gln Cys Phe Xaa Ser Lys Asn Gly 1 5 10 <210> 917 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    Page 449

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (4)..(4) <223> Dap <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 917

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 918 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Dap <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac)

    Page 450

    PRTH_002_03WO_ST25 <400> 918

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 919 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 919

    Xaa Gln Thr Arg Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 920 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES

    Page 451

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 920

    Xaa Gln Thr Trp Gln Cys Phe Arg Lys Lys Asn Gly 1 5 10 <210> 921 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (4)..(4) <223> Dap <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Dap <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 921

    Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10

    Page 452

    PRTH_002_03WO_ST25 <210> 922 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 922

    Xaa Gln Thr Asp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 923 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9)

    Page 453

    PRTH_002_03WO_ST25 <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 923

    Xaa Gln Thr Trp Gln Cys Phe Asp Lys Lys Asn Gly 1 5 10 <210> 924 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 924

    Xaa Gln Thr Asp Gln Cys Phe Asp Lys Lys Asn Gly 1 5 10 <210> 925 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    Page 454

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLeu <400> 925

    Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 926 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 926

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Arg Asn Gly 1 5 10 <210> 927 <211> 12 <212> PRT <213> Artificial Sequence

    Page 455

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Orn <400> 927

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 928 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES

    Page 456

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> alpha-MeLys <400> 928

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 929 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> hArg <400> 929

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Arg Asn Gly 1 5 10 <210> 930 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 457

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 930

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 931 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Cit <220>

    <221> MOD_RES <222> (10)..(10)

    Page 458

    PRTH_002_03WO_ST25 <223> Dap <400> 931

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 932 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (2)..(2) <223> alpha-Me-Orn <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 932

    Xaa Xaa Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 933 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    Page 459

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 933

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Asn Asn Gly 1 5 10 <210> 934 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 934

    Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Gly Glu 1 5 10 <210> 935 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 460

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 935

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 936 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-(acetyl-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys(Ac) <400> 936

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 937 <211> 11

    Page 461

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (6)..(6) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (7)..(7) <223> 2-Nal <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MeLys <400> 937

    Xaa Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 938 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-Me) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys

    Page 462

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 938

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 939 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3-Me) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 939

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 940 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1)

    Page 463

    PRTH_002_03WO_ST25 <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> hTyr <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 940

    Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly 1 5 10 <210> 941 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MeTrp <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 941

    Page 464

    PRTH_002_03WO_ST25

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly 1 5 10 <210> 942 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (2)..(2) <223> alpha-MeSer <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 942

    Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 943 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 465

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (3)..(3) <223> alpha-MeSer <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 943

    Xaa Gln Ser Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 944 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> alpha-MePhe <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES

    Page 466

    PRTH_002_03WO_ST25 <222> (10)..(10) <223> Lys(Ac) <400> 944

    Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 945 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 945

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 946 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 467

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 946

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 947 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Dap(Ac) <400> 947

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Xaa Gly 1 5 10 <210> 948 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 468

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Dab(Ac) <400> 948

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Xaa Gly

    1 5 10 <210> 949 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib

    <220>

    Page 469

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 949

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Lys Gly 1 5 10 <210> 950 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 950

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Asn 1 5 10 <210> 951 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 470

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 951

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Asn 1 5 10 <210> 952 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(3,4-OMe2) <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 952

    Xaa Gln Thr Trp Gln Cys Phe Phe Xaa Glu Asn Gly 1 5 10 <210> 953 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES

    Page 471

    PRTH_002_03WO_ST25 <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(3,4-Cl2) <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 953

    Xaa Gln Thr Trp Gln Cys Phe Phe Xaa Glu Asn Asn 1 5 10 <210> 954 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Cit <400> 954

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Xaa Asn Asn 1 5 10 <210> 955 <211> 12 <212> PRT <213> Artificial Sequence

    Page 472

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 955

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 956 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-Me) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9)

    Page 473

    PRTH_002_03WO_ST25 <223> Aib <400> 956

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 957 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3,4-F2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 957

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 958 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3-CONH2) <220>

    Page 474

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 958

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 959 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(2,4-Cl2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 959

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 960 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu

    Page 475

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(3-Me) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 960

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 961 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe(4-Cl) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> Aib <400> 961 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10

    <210> 962 <211> 12 <212> PRT <213> Artificial Sequence

    <220>

    <223> Description of Artificial Sequence: Synthetic Page 476

    PRTH_002_03WO_ST25 peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-F) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 962

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 963 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(2,4-Cl2, 4-OBz) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 963

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10

    Page 477

    PRTH_002_03WO_ST25 <210> 964 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 964

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly Lys 1 5 10 <210> 965 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9)

    Page 478

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 965

    Glu Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 966 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Glu <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 966

    Glu Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 967 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 479

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 967

    Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 968 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Arg <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 968

    Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10

    Page 480

    PRTH_002_03WO_ST25 <210> 969 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 969

    Phe Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 970 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES

    Page 481

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 970

    Phe Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 971 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> 2-Nal <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 971

    Xaa Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 972 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 482

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 972

    Thr Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 973 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 973

    Leu Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 974 <211> 13 <212> PRT

    Page 483

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Gln <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 974

    Gln Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 975 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    Page 484

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> Acpc <400> 975

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 976 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acbc <400> 976

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 977 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)]

    Page 485

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Achc <400> 977

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 978 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acvc <400> 978

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 979 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 486

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> 4-amino-4-carboxy-piperidine <400> 979

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 980 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 980

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 981 <211> 12 <212> PRT <213> Artificial Sequence

    Page 487

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 981

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Gly 1 5 10 <210> 982 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9)

    Page 488

    PRTH_002_03WO_ST25 <223> alpha-MeLeu <400> 982

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 983 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 983

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asn Gly 1 5 10 <210> 984 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 489

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 984

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asn Ala 1 5 10 <210> 985 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 985

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asp Gly 1 5 10 <210> 986 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 490

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 986

    Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asp Gly 1 5 10 <210> 987 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (12)..(12) <223> Beta-Ala <400> 987

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Ala Page 491

    PRTH_002_03WO_ST25

    1 5 10 <210> 988 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 1,2,3,4-tetrahydro-norharman <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 988

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly

    1 5 10 <210> 989 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence: Synthetic <220> <221> MOD_RES <222> (1)..(1) <223> Abu <220> <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220> <221> MOD_RES <222> (8)..(8) <223> 5-hydroxyTrp

    Page 492

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 989

    Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Gln Asn Gly 1 5 10 <210> 990 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (11)..(11) <223> Asn(isobutyl) <400> 990

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Asn

    1 5 10 <210> 991 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 493

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <220>

    <221> MOD_RES <222> (11)..(11) <223> Asp(1,4-diaminoethane) <400> 991

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asp Gly 1 5 10 <210> 992 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    Page 494

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> 4-amino-4-carboxy-tetrahydropyran <400> 992

    Phe Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 993 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Arg <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> 4-amino-4-carboxy-tetrahydropyran <400> 993

    Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 994 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 495

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLeu <400> 994

    Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 995 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <400> 995

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly Page 496

    PRTH_002_03WO_ST25

    1 5 10 <210> 996 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 996

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 997 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe)

    Page 497

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 997

    Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 998 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OBzl) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 998

    Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 999 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7)

    Page 498

    PRTH_002_03WO_ST25 <223> Tyr(Bzl) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 999

    Xaa Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 1000 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> allylGly <220>

    <221> MOD_RES <222> (6)..(6) <223> allylGly <400> 1000

    Gly Ala Asp Trp Val Gly Tyr Trp His Thr Phe Gly 1 5 10 <210> 1001 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> allylGly <220>

    <221> MOD_RES <222> (6)..(6) <223> allylGly <400> 1001

    Gly Ala Asp Trp Val Gly Tyr Trp His Thr Phe Gly 1 5 10 <210> 1002

    Page 499

    PRTH_002_03WO_ST25 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> 2-(3'-butenyl)Gly <220>

    <221> MOD_RES <222> (6)..(6) <223> 2-(4'-pentenyl)Gly <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1002

    Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1003 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> 2-(4'-pentenyl)Gly <220>

    <221> MOD_RES <222> (6)..(6) <223> 2-(3'-butenyl)Gly <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys

    Page 500

    PRTH_002_03WO_ST25 <400> 1003

    Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1004 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> allylGly <220>

    <221> MOD_RES <222> (6)..(6) <223> 2-(4'-pentenyl)Gly <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1004

    Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1005 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> 2-(4'-pentenyl)Gly <220>

    <221> MOD_RES <222> (6)..(6) <223> allylGly <220>

    <221> MOD_RES <222> (13)..(13)

    Page 501

    PRTH_002_03WO_ST25 <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1005

    Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1006 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> 2-(3'-butenyl)Gly <220>

    <221> MOD_RES <222> (6)..(6) <223> 2-(3'-butenyl)Gly <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1006

    Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1007 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> 2-(3'-butenyl)Gly <220>

    Page 502

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (6)..(6) <223> allylGly <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1007

    Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1008 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> allylGly <220>

    <221> MOD_RES <222> (6)..(6) <223> 2-(3'-butenyl)Gly <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1008

    Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1009 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 503

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1009

    Xaa Gln Thr Trp Gln Glu Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1010 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1010

    Glu Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1011 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 504

    PRTH_002_03WO_ST25 <222> (6)..(6) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1011

    Glu Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1012 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1012

    Xaa Gln Thr Trp Gln Glu Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1013 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Dap

    Page 505

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> D-Asp <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1013

    Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1014 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1014

    Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1015 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6)

    Page 506

    PRTH_002_03WO_ST25 <223> Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1015

    Asp Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1016 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1016

    Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1017 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Dab <220>

    Page 507

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (6)..(6) <223> D-Asp <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1017

    Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1018 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Asp <220>

    <221> MOD_RES <222> (6)..(6) <223> D-Dab <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1018

    Asp Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1019 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 508

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Asp <220>

    <221> MOD_RES <222> (6)..(6) <223> D-Dap <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1019

    Asp Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1020 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <400> 1020

    Xaa Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 1021 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <400> 1021

    Cys Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Page 509

    PRTH_002_03WO_ST25

    1 5 10 <210> 1022 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1022

    Xaa Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 1023 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> D-Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1023

    Cys Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys

    1 5 10

    Page 510

    PRTH_002_03WO_ST25 <210> 1024 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1024

    Xaa Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1025 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1025

    Ala Cys Asp Trp Val Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys

    1 5 10 <210> 1026 <211> 14 <212> PRT

    Page 511

    PRTH_002_03WO_ST25 <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1026

    Ala Xaa Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1027 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (2)..(2) <223> hCys <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1027

    Ala Cys Asp Trp Val Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys

    1 5 10 <210> 1028

    Page 512

    PRTH_002_03WO_ST25 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 1028

    Cys Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1029 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Asn <400> 1029

    Cys Gln Thr Trp Gln Xaa Tyr Trp Asn Glu Asn Gly 1 5 10 <210> 1030 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen

    Page 513

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (9)..(9) <223> N-Me-Arg <400> 1030

    Xaa Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 1031 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    <220> <221> MOD RES <222> (1)..(1) <223> Pen <220> <221> MOD_RES <222> (6)..(6) <223> Pen <220> <221> MOD_RES <222> (7)..(7) <223> [Phe(4-OMe)](OMe) <220> <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeOrn <220> <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 1031 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 1032 <211> 12

    Page 514

    PRTH_002_03WO_ST25 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 1032

    Xaa Gln Thr Trp Gln Xaa Phe Trp Lys Lys Asn Gly 1 5 10 <210> 1033 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe)

    Page 515

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 1033

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 1034 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 1034

    Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10

    Page 516

    PRTH_002_03WO_ST25 <210> 1035 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Aib <220>

    <221> MOD_RES <222> (11)..(11) <223> Lys(Ac) <400> 1035

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1036 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    Page 517

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acvc <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 1036

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1037 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal

    Page 518

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> Acvc <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 1037

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1038 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 1038

    Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 1039 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 519

    PRTH_002_03WO_ST25 <222> (1)..(1) <223> D-Lys <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLeu <400> 1039

    Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 1040 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Tyr(Bzl) <220>

    <221> MOD_RES <222> (9)..(9) <223> alpha-MeLys <400> 1040

    Xaa Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 1041 <211> 13 <212> PRT <213> Artificial Sequence

    Page 520

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Arg <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 1041

    Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 1042 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Gln <220>

    <221> MOD_RES <222> (2)..(2) <223> Abu <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (9)..(9)

    Page 521

    PRTH_002_03WO_ST25 <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> alpha-MeLys <400> 1042

    Gln Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 1043 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Acpc <400> 1043

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 1044 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1044

    Page 522

    PRTH_002_03WO_ST25

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly

    1 5 10 <210> 1045 <211> 16 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (15)..(15) <223> Azt <220>

    <221> MOD_RES <222> (16)..(16) <223> D-Lys <400> 1045

    Cys Ala Asp Trp Val Trp Cys Tyr Trp His Thr Phe Gly Ala Xaa Lys 1 5 10 15 <210> 1046 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (13)..(13) <223> (2-aminoethoxy)acetic acid <220>

    <221> MOD_RES <222> (14)..(14) <223> D-Lys <400> 1046

    Xaa Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys

    1 5 10 <210> 1047 <211> 12 <212> PRT <213> Artificial Sequence

    Page 523

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Abu <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe[4-(2-aminoethoxy)] <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Achc <400> 1047

    Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 1048 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES

    Page 524

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> 4-amino-4-carboxy-tetrahydropyran <220>

    <221> MOD_RES <222> (11)..(11) <223> Cit <400> 1048

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 1049 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> D-Phe <220>

    <221> MOD_RES <222> (2)..(2) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Pen <220>

    <221> MOD_RES <222> (8)..(8) <223> Phe(4-OMe) <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-Nal <220>

    <221> MOD_RES <222> (10)..(10) <223> Achc <400> 1049

    Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10

    Page 525

    PRTH_002_03WO_ST25 <210> 1050 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(1) <223> Pen <220>

    <221> MOD_RES <222> (6)..(6) <223> Pen <220>

    <221> MOD_RES <222> (7)..(7) <223> Phe(CONH2) <220>

    <221> MOD_RES <222> (8)..(8) <223> 2-Nal <220>

    <221> MOD_RES <222> (9)..(9) <223> Aib <220>

    <221> MOD_RES <222> (10)..(10) <223> Lys(Ac) <400> 1050

    Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1051 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1051

    Cys Arg Ser Trp Gln Cys Tyr Trp Asn Lys Phe Gly Ala Asp Asp

    1 5 10 15 <210> 1052 <211> 15 <212> PRT <213> Artificial Sequence

    Page 526

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial peptide <400> 1052

    Cys His Thr Trp Gln Cys Tyr Trp

    Sequence: Synthetic

    1 5 <210> 1053 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 1053 Cys Arg Thr Trp Gln Cys Tyr Trp 1 5 <210> 1054 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 1054 Cys Arg Thr Trp Gln Cys Tyr Trp 1 5 <210> 1055 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 1055 Cys Arg Thr Trp Gln Cys Tyr Trp 1 5 <210> 1056 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide <400> 1056

    Cys His Thr Trp Gln Cys Tyr Trp

    Leu Asn Phe Gly Asp Glu Glu 10 15

    Sequence: Synthetic

    Leu Asn Phe Gly Asn Glu Gln 10 15

    Sequence: Synthetic

    Ser Glu Phe Gly Thr Gly Glu 10 15

    Sequence: Synthetic

    Leu Arg Leu Gly Asp Glu Gly 10 15

    Sequence: Synthetic

    Ser Thr Leu Gly Pro Glu Ala Page 527

    1 5 PRTH_002_03WO_ST25 10 15 <210> 1057 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <400> 1057 Cys Ser Thr Trp Gln Cys Tyr Trp Ser Lys Gln Ser Gly Gly Ser 1 5 10 15 <210> 1058 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <400> 1058 Cys His Thr Trp Gln Cys Tyr Trp Leu Asn Asn Gly Thr Ser Gln 1 5 10 15 <210> 1059 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <400> 1059 Cys His Thr Trp Gln Cys Tyr Trp Arg Ala Asn Asp Gly Arg Asp 1 5 10 15 <210> 1060 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide

    <400> 1060

    Ser Gly Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Phe Gly

    1 5 10 <210> 1061 <211> 14 <212> PRT <213> Artificial Sequence

    Page 528

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1061

    Asn Lys Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 1062 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1062

    Ser Gly Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 1063 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1063

    Asp Ala Cys Arg Thr Trp Glu Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 1064 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1064

    Pro Glu Cys Arg Thr Trp Glu Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 1065 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1065

    Gln Val Cys Gln Thr Trp Glu Cys Tyr Trp Arg Glu Phe Gly Page 529

    1 5

    PRTH_002_03WO_ST25 <210> 1066 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1066

    Asp Arg Cys Val Thr Trp Glu Cys Tyr Trp Arg Glu Phe 1 5 10 <210> 1067 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1067

    Ala Asp Gln Cys Arg Thr Trp Gln Cys Tyr Trp His Glu 1 5 10 <210> 1068 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1068

    Lys Glu Asn Cys Arg Thr Trp Glu Cys Tyr Trp Arg Glu 1 5 10

    Gly

    Phe Gly 15

    Phe Gly 15 <210> 1069 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1069

    Val Gln Glu Cys Ser Thr Trp Gln Cys Tyr Trp Arg Thr

    1 5 10

    Phe Gly <210> 1070 <211> 15 <212> PRT <213> Artificial Sequence

    Page 530

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial peptide <400> 1070

    Gly Glu Glu Cys Ser Thr Trp Gln 1 5

    Sequence: Synthetic

    Cys Tyr Trp Arg Lys Phe Gly 10 15 <210> 1071 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide <400> 1071

    Asp Gly Ser Cys Arg Thr Trp Gln 1 5

    Sequence: Synthetic

    Cys Tyr Trp His Gln Phe Gly 10 15 <210> 1072 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide <400> 1072

    Asn Ala Asp Cys His Ser Trp Glu 1 5

    Sequence: Synthetic

    Cys Tyr Trp Arg Glu Phe Gly 10 15 <210> 1073 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide <400> 1073

    Glu Arg Asn Cys Ser Thr Trp Glu 1 5

    Sequence: Synthetic

    Cys Tyr Trp Arg Ala Phe Gly 10 15 <210> 1074 <211> 15 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial peptide <400> 1074

    Arg Val Gly Cys Ser Thr Trp Glu

    Sequence: Synthetic

    Cys Tyr Trp Arg Glu Phe Gly Page 531

    1 5 PRTH_002_03WO_ST25 10 15 <210> 1075 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic <400> 1075 Lys Ala Asn Cys Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gl 1 5 10 15 <210> 1076 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic <400> 1076 Tyr Glu Asp Cys Arg Thr Trp Gln Cys Tyr Trp Glu Asn Phe Gl 1 5 10 15 <210> 1077 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic <400> 1077 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Gly Asp Ser 1 5 10 <210> 1078 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial peptide Sequence : Synthetic <400> 1078 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Glu Ser Gly 1 5 10

    <210> 1079 <211> 14 <212> PRT <213> Artificial Sequence

    Page 532

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1079

    Cys Gln Asp Trp Gln Cys Tyr Trp Arg Glu Phe Gly Pro Gly 1 5 10 <210> 1080 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1080

    Cys Gln Asp Trp Gln Cys Tyr Trp Arg Ser Phe Gly Pro Gln 1 5 10 <210> 1081 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1081

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Leu Gly Pro Ser 1 5 10 <210> 1082 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1082

    Cys Arg Thr Trp Gln Cys Tyr Trp Gln Asn Phe Gly 1 5 10 <210> 1083 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1083

    Cys Gly Thr Trp Gln Cys Tyr Trp Arg Thr Phe Gly Pro Ser Page 533

    PRTH_002_03WO_ST25

    1 5 10 <210> 1084 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1084

    Cys Ser Thr Trp Gln Cys Tyr Trp His Lys Phe Gly Asn 1 5 10 <210> 1085 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1085

    Cys Arg Thr Trp Glu Cys Tyr Trp Arg Thr Tyr Gly Pro 1 5 10 <210> 1086 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1086

    Cys Arg Thr Trp Gln Cys Tyr Trp Trp Glu Asn Ser Gln 1 5 10 <210> 1087 <211> 14 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1087

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Phe Gly Gly 1 5 10

    Glu

    Ser

    Met

    Gly <210> 1088 <211> 14 <212> PRT <213> Artificial Sequence

    Page 534

    PRTH_002_03WO_ST25 <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1088

    Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr His Gly Asp Arg 1 5 10 <210> 1089 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <400> 1089

    Cys Arg Asp Trp Gln Cys Tyr Trp Leu Ser Arg Pro 1 5 10 <210> 1090 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Lys(Palm) <400> 1090

    Cys Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 1091 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> Lys(PEG8) <400> 1091

    Cys Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10

    Page 535

    PRTH_002_03WO_ST25 <210> 1092 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1092

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Gln Gly 1 5 10 <210> 1093 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> D-Tyr <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1093

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1094 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> N-MeTyr <220>

    <221> MOD_RES

    Page 536

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> hLeu <400> 1094

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1095 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (7)..(7) <223> Tic-OH <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1095

    Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 1096 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1096

    Cys Gln Thr Trp Gln Cys Glu Trp Leu Glu Asn Gly 1 5 10 <210> 1097 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 537

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1097

    Cys Gln Thr Trp Gln Cys Thr Trp Leu Glu Asn Gly

    1 5 10 <210> 1098 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <220> <221> MOD_RES <222> (7)..(7) <223> Cha <220> <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1098 Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 1099 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <220> <221> MOD_RES <222> (9)..(9) <223> alpha-MeLeu <400> 1099 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1100 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide Page 538

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> D-Leu <400> 1100

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1101 <211> 13 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <220>

    <221> MOD_RES <222> (13)..(13) <223> D-Lys <400> 1101

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Lys 1 5 10 <210> 1102 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1102

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1103 <211> 12 <212> PRT <213> Artificial Sequence <220>

    Page 539

    PRTH_002_03WO_ST25 <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1103

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Glu 1 5 10 <210> 1104 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1104

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Arg 1 5 10 <210> 1105 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1105

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Phe 1 5 10 <210> 1106 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide

    Page 540

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1106

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Pro 1 5 10 <210> 1107 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1107

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gln 1 5 10 <210> 1108 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1108

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Leu 1 5 10 <210> 1109 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES

    Page 541

    PRTH_002_03WO_ST25 <222> (9)..(9) <223> hLeu <400> 1109

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Glu Gly 1 5 10 <210> 1110 <211> 12 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (9)..(9) <223> hLeu <400> 1110

    Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Arg Gly 1 5 10 <210> 1111 <211> 20 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(3) <223> Any amino acid or absent <220>

    <221> MOD_RES <222> (4)..(4) <223> 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, or 2-(5'-hexenyl)glycine <220>

    <221> MOD_RES <222> (5)..(5) <223> Ala, Arg, Sarc, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln <220>

    <221> MOD_RES <222> (6)..(6) <223> Asp, Thr or Asn <220>

    <221> MOD_RES <222> (8)..(8)

    Page 542

    PRTH_002_03WO_ST25 <223> Val, Gln or Glu <220>

    <221> MOD_RES <222> (9)..(9) <223> 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine or 2-(5'-hexenyl)glycine <220>

    <221> MOD_RES <222> (11)..(11) <223> Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu) <220>

    <221> MOD_RES <222> (13)..(13) <223> Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Beta-hAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln <220>

    <221> MOD_RES <222> (15)..(15) <223> Gly, Ser, Thr, Gln, Ala, Sarc, Beta-Ala, Glu, Arg or Asn <220>

    <221> MOD_RES <222> (16)..(20) <223> Any amino acid or absent <400> 1111

    Xaa Xaa Xaa Gly Xaa Xaa Trp Xaa Gly Tyr Xaa His Xaa Phe Xaa Xaa 1 5 10 15

    Xaa Xaa Xaa Xaa 20 <210> 1112 <211> 20 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(3) <223> Any amino acid or absent <220>

    <221> MOD_RES <222> (5)..(5) <223> Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln <220>

    Page 543

    PRTH_002_03WO_ST25 <221> MOD_RES <222> (6)..(6) <223> Asp, Thr, Asn or Phe <220>

    <221> MOD_RES <222> (8)..(8) <223> Val, Gln, Glu or Lys <220>

    <221> MOD_RES <222> (11)..(11) <223> Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2), 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu) <220>

    <221> MOD_RES <222> (13)..(13) <223> Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Beta-hAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn,

    Gln or absent <220>

    <221> MOD_RES <222> (14)..(14) <223> Phe, Tyr, Asn, Arg, Gln, Lys(Ac), His, Dap(Ac), Dab(Ac),

    Asp or absent <220>

    <221> MOD_RES <222> (15)..(15) <223> Gly, Ser, Thr, Gln, Ala, Sarc, beta-Ala, Glu, Arg, Asn or absent <220>

    <221> MOD_RES <222> (16)..(20) <223> Any amino acid or absent <400> 1112

    Xaa Xaa Xaa Cys Xaa Xaa Trp Xaa Cys Tyr Xaa His Xaa Xaa Xaa Xaa 1 5 10 15

    Xaa Xaa Xaa Xaa 20 <210> 1113 <211> 20 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(3) <223> Any amino acid or absent

    Page 544

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (5)..(5) <223> Ala, Arg, Sarc, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab, Dap(Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln <220>

    <221> MOD_RES <222> (6)..(6) <223> Asp, Thr or Asn <220>

    <221> MOD_RES <222> (8)..(8) <223> Val, Gln or Glu <220>

    <221> MOD_RES <222> (11)..(11) <223> Trp, 1-Nal, 2-Nal, Phe(3,4-OMe2), 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu) <220>

    <221> MOD_RES <222> (13)..(13) <223> Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta-hAla, Val, Aib, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn,

    Gln or absent <220>

    <221> MOD_RES <222> (15)..(15) <223> Gly, Ser, Thr, Gln, Ala, Sarc, beta-Ala, Glu, Arg, Asn or absent <220>

    <221> MOD_RES <222> (16)..(20) <223> Any amino acid or absent <400> 1113

    Xaa Xaa Xaa Cys Xaa Xaa Trp Xaa Cys Tyr Xaa His Xaa Phe Xaa Xaa 1 5 10 15

    Xaa Xaa Xaa Xaa 20 <210> 1114 <211> 19 <212> PRT <213> Artificial Sequence <220>

    <223> Description of Artificial Sequence: Synthetic peptide <220>

    <221> MOD_RES <222> (1)..(3) <223> Any amino acid or absent

    Page 545

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (5)..(6) <223> Any amino acid <220>

    <221> MOD_RES <222> (8)..(8) <223> Any amino acid <220>

    <221> MOD_RES <222> (10)..(10) <223> Tyr, 1-Nal, 2-Nal, Phe(3,4-F2), Phe(3,4-Cl2), Phe(3-Me), Phe[4-(2-aminoethoxy)], Phe[4-(2-(acetyl-aminoethoxy)], Phe(4-Br), Phe(4-CONH2), Phe(4-Cl), Phe(4-CN),

    Phe(4-guanidino) Phe(4-Me), Phe(4-NH2), Phe(4-N3), <220>

    <221> MOD_RES <222> (10)..(10) <223> continued from above; Phe(4-OMe) or Phe(4-OBzl) <220>

    <221> MOD_RES <222> (11)..(11) <223> Trp, 1-Nal, Phe(3,4-OMe2), 5-Hydroxy-Trp, Phe(3,4-Cl2) or Tyr(3-t-Bu) <220>

    <221> MOD_RES <222> (12)..(12) <223> Arg, Lys, His, hArg, Cit, Orn, 1-Nal, D-Ala, D-Leu, D-Phe,

    D-Asn, D-Asp, Agp, Leu, Beta-hLeu, Aib, Beta-hAla, Beta-hVal, Beta-hArg, hLeu, Dap, 4-amino-4-carboxy-tetrahydropyran, Achc, Acpc, Acbc, Acvc, Agp, Aib, alpha-DiethylGly, alpha-MeLys, <220>

    <221> MOD_RES <222> (12)..(12) <223> continued from above; alpha-MeLys(Ac), alpha-Me-Leu, alpha-MeOrn, alpha-MeSer, alpha-MeVal, Cha, Cit, Cpa,

    D-Asn, Glu, hArg or Lys <220>

    <221> MOD_RES <222> (13)..(13) <223> Cha, Ogl, Aib, Leu, Val, Dab, Glu, Lys, Beta-hLeu, Beta-hAla, Beta-hVal, Beta-Glu, Lys(Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Lys(Ac) or Gln <220>

    <221> MOD_RES <222> (14)..(14) <223> Phe, Tic, Asn, Tyr, Asn, Arg, Gln, Lys(Ac), His, Dap(Ac), Dab(Ac) or Asp <220>

    <221> MOD_RES <222> (16)..(16) <223> Any amino acid

    Page 546

    PRTH_002_03WO_ST25 <220>

    <221> MOD_RES <222> (17)..(17) <223> D-Lys <220>

    <221> MOD_RES <222> (18)..(19) <223> Any amino acid or absent <400> 1114

    Xaa Xaa Xaa Cys Xaa Xaa Trp Xaa Cys Xaa Xaa Xaa Xaa Xaa Gly Xaa 1 5 10 15

    Lys Xaa Xaa

    Page 547