UA123772C2 - 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 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.

Description

Cross reference to related applications

ИО001| This application claims priority and is a partial continuation of the US application

Mo14/800627, filed on July 15, 2015, and also claims priority under International Patent Application PCT/O52015/040658, filed on July 15, 2015, US Patent Application Mob2/264820, filed on December 8, 2015. , and US Patent Application Mob2/281123, filed on January 20, 2016, all of which are incorporated herein by reference in their entirety.

List of sequences

I0002| This application contains a Sequence Listing that was submitted in electronic format to the ASIA and is hereby incorporated by reference in its entirety. It is indicated

АЗСИИ copy created on December 26, 2017 is called RKTN-002-ОЗ3УМО 572514ХхЙ and has a size of 808

KB.

The technical field of this invention

I0003)| The present invention relates to novel peptide inhibitors of the interleukin-23 receptor and their use in the treatment or prevention of a variety of diseases and disorders, including inflammatory bowel disease, Crohn's disease and psoriasis.

Technical level

I0004| The cytokine interleukin-23 (IL/-23) has been implicated in the pathogenesis of autoimmune inflammation and related diseases and disorders such as multiple sclerosis, asthma, rheumatoid arthritis, psoriasis, and inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crown. Studies on acute and chronic models of IVI on mice showed the main role of I/-23K and subsequent effector cytokines in the pathogenesis of the disease. 1-238 is expressed in a variety of adaptive and innate immune cells, including cells

T17, T-killer cells, natural killer cells (NK), dendritic cells, macrophages and natural lymphocytes, which are abundant in the intestine. On the surface of the intestinal mucosa, gene expression and levels of II-23E proteins were found to be increased in patients with IVI. IS-23 is thought to mediate this effect by activating the development of the pathogenic cOr4-T cell population, which produces tumor necrosis factor (TNF) 1I-6, 1-17. 0005) 1-23 production increases in the intestine, where it is believed to play a key

A role in regulating the balance between tolerance and immunity through T-cell-dependent and T-cell-independent pathways of intestinal inflammation through effects on T-helper 1 (TA) and TP17-related cytokines, as well as inhibition of regulatory T-cell responses in the digestive tract, which promotes inflammation. In addition, polymorphism in the receptor II -23 (II -23K) was associated with sensitivity to

IVO, also proving the important role of the 1-23 pathway in intestinal homeostasis. 0006) Psoriasis, a chronic skin disease affecting approximately 2-3 95 of the entire population, has been shown to be mediated by the body's T-cell inflammatory response mechanisms. I/-23 is one of several interleukins that play a key role in the pathogenesis of psoriasis, likely through maintenance of chronic autoimmune inflammation through induction of interleukin-17, regulation of memory T cells, and activation of macrophages. Expression of II-23 and I-23E has been shown to be increased in tissues of patients with psoriasis, and antibodies neutralizing 1-23 have shown II-23-dependent inhibition of psoriasis development in animal models of psoriasis.

І0007| I/-23 is a heterodimer consisting of a unique subelement p19 and subelement p40 1/-12, which is a cytokine involved in the development of interferon-y (IEM-y) producing T-helper 1 (TNI) cells. Although both II--23 and 11-12 contain the p40 subelement, they have different phenotypic properties. For example, animals deficient in 1-12 are susceptible to inflammatory autoimmune diseases, whereas animals deficient in II-23 are immune, presumably due to reduced numbers of CO4-producing II-6 T cells. 1-17 and

TME in CM5Z animals with II -23 deficiency. I/-23 binds to II-23E, which is a heterodimeric receptor consisting of subunits I-12KVD1 and 1-23. The binding of 1-23 to I--23K activates signaling pathway molecules Chak-5yai, dak2, Tuk2, and Fan, e8Bai 3, e8ai 4 and na 5, although the activation of 5Ziai4 is much weaker, and various DNA-binding Ziai complexes are formed in response to II/-23 compared to II/-12. II/-23K binds unregulatedly to Chdak2 and ligand-dependently to 5iaiZ3. In contrast to II/-12, which acts mainly on native CO4(t) T-cells, I--23 mainly acts on memory CO4(g) T-cells. 0008) Efforts have been made to identify therapeutic fragments that inhibit the II/-23 pathway for use in the treatment of II/-23-related diseases and disorders. A number of antibodies that bind to II/-23 or II/-23K have been identified, including ustekinumab, a humanized antibody that binds II-23 that has been approved for the treatment of psoriasis. Previously, polypeptide inhibitors that bind to II/-23K and inhibit the binding of 1-23 to 1-23 have been identified (see, for example, the publication of US patent application MeO052013/0029907).

Crohn's disease or psoriasis clinical trials with ustekinumab and briakinumab (which target a common p40 subunit) and tildrakizumab, guzelkumab, ME0I2070, and VI-655066 (which target a unique p19 1-23 subunit) have highlighted the likely blockade of 1-23 signaling in the treatment of inflammatory diseases a person Although these data are promising, challenges remain in identifying stable and selective agents that preferentially target the 1-23 pathway in the intestine that can be used to treat intestinal inflammation such as bowel diseases including Crohn's disease, ulcerative colitis, and related disorders .

I0009| Clearly, there remains a need in this area for new therapeutic agents targeting the 1-23 pathway that can be used to treat and prevent I-23-related diseases, including those associated with autoimmune inflammation in the intestinal tract. In addition, compounds and methods of specifically targeting 1-23 from the luminal side of the digestive tract may provide a therapeutic effect for IVI patients suffering from local inflammation of intestinal tissue. The present invention addresses these needs by introducing novel peptide inhibitors that bind II-23E to inhibit 1-23 binding and signaling and are suitable for oral administration.

Brief Description of the Invention The present invention provides novel peptide inhibitors of II-23B and related methods of use.

In the first aspect, the present invention provides a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, and the peptide inhibitor contains the amino acid sequence of the formula (Xa): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10 -X11-X12-X13-X14-

X15-X16-X17-X18-X19-X20 (Xa) (ZEO IU MO: 1354), where:

X1, X2 and X3 represent any amino acid or are absent, xX4 represents any amino acid or a chemical fragment capable of forming a bond with

HO;

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

ХУ is any amino acid or chemical fragment capable of forming a bond with

Ha;

Co) X10, X11, X12, X13, X14 and X15 represent any amino acid; and

X16, X17, X18, X19 and X20 represent any amino acid or are absent; and the peptide inhibitor is looped through the connection between XA and XO, and the peptide inhibitor inhibits the connection of interleukin-23 (II-23) with the I-23 receptor. 0011) In some variants of implementation of Xa: 0012) X1 is absent; X2 is absent; HZ is absent; X4 is Su, Aby or Rep; X5 is Aa, a-MeOt, a-Mezeg, Sii, Oar, OSabr, bar(As), Stpu, Guv, Avp, M-Mesip, M-MeAgo9, Opt, ap,

Agud, Zeg or Tig; Xb is Ar or Tig; X7 is Tgr or b-chloro-Tgr; X8 represents Sim, SiIp or Mai; ХУ represents Su, Aby or Rep; X10 is 2-May, an analogue of Rie,

Tug, or an analogue of Tug; X11 is 1-Mai, 2-Mai, Pne(3,4-dimethoxy), 5-hydroxyTgr, Ppe(3,4-

Sig2), Ttr or Tug(3-IVy); X12 is 3-Rai, Asrs, Asbs, Asms, Asps, Aar, Aib, a-Diethylose, a-

Me" uz, a-Mei! uz(As), a-Mei ey, o-MeOgp, a-Mezeg, o-Memai, Sam, Sa, Sii, Sra, O-Azp, Sim, Niv,

NG ey, pAga, GG uv, I ey, Osidiu, Ot, 4-amino-4-carboxypiperidine, Ago, 5eg, Tig or TNR; X13 is Sii, Azr, bab, bar, Re, Nih, bar (Red2-Ac), YuBar (pyroglutaric acid), Sim, NotoAgo,

Huz, Huz(Ac), I uz(benzoic acid), I uz(glutaric acid), GU5(IMA), Huz(Reda-isoStpy-Rait),

Guz (pyroglutaric acid), I uh (succinic acid), Azp, Ogp, Sp, Agu, TAg or Mai; X14 is Azr, Bab(As), Bar(As), Rie, Ni, Iuz(As), Mei, Azp(isobutyl), Sp, Ago, Tug or Azvr(1,4-diaminobutane); and X15 is Aa, VAia, sim, Su, Avp, Sp, Agud or Zeg. 0013) In some embodiments, Xa: X1 is absent; X2 is absent; HZ is absent; X4 represents Suz, Aby or Rep; X5 is Aa, a-MeOt, o-Mezeg, Sii, Yuar, ab, OSar(As), Spu, GG uv,

BO Azp, Ogp, SiIp, Agou, Zeg or TNyg; Xb is Ar or Tpg; X7 is Tgr or b-chloro-ITtgr;

Hv represents sSip or Mai; HU represents Suz, Aby or Rep; X10 is 2-May, analog

Rpe, Tug or an analogue of Tug; X11 represents 1-May, 2-May, Pne(3,4-dimethoxy), 5-hydroxyTtgr,

Rpe(3,4-CI2), Tr or Tug((3-Vy); X12 is 3-Rai, Asrs, Asbs, Asms, Asps, Ar, Alib, a- diethyliu, o-MeiH uz, a-Mei uz(As), a-Mei ei, o-MeOgp, o-Mezeg, a-Memai, Sam, Sa, Sii, Sra, 0-

Avp, Niv, NI eyy, pAga, Huz, Gey, Osschiu, Ot, 4-amino-4-carboxypiperidine or TNR; X13 is Sii, Azr, bab, ar, Rie, Ni5, bar(Red2-Ac), bar(pyroglutaric acid), Sii, NAgo, Huz,

Huz(Ac), IGuz(benzoic acid), Iubz(glutaric acid), GU5(IMA), Huz(Red4-i5oStcy-Rait),

Hus (pyroglutaric acid), Hus (succinic acid), Azp, Ogp, SiIp, Ago, Tpg or Mai; X14 is rac(As), Oar(As), RNe, Niv, I uz(As), Mei, Azp, Sp, Aga or Tug; and X15 is Aa, 60 realia, Stpu, Avp, Sp or 5eg.

0014) In some embodiments, Xa: X1 is absent; X2 is absent; HZ is absent; X4 represents Suz, Aby or Rep; X5 is Rar, Rar(As), Spu, Huz, Sp, Aga, 5eg, TNg or Avp; Hb is TNg; X7 is Tgr or b-chloro-Tgr; X8 is Sp; XO is Suv,

Ari or Rap; X10 is 2-May, analog of Rie, Tug or analog of Tug; X11 represents May 1, 2-

May, Rpe(3,4-dimethoxy), Rpe(3,4-Si") or Tgr; X12 represents Asrs, Asbs, Asus, Asns, AIBb, a-diethyloiu, a-Mei uz, o-Mei! uz(As), a-Mei! yey, a-MeOt, a-Mezeg, a-Memai, Spa, Siy, No yey, Huz, Gey,

Agud or TNR; X1Z3 is Sii, Azr, Oar, OSar (Redag-Ac), bar (pyroglutaric acid), SIM, pAgo, Guz, Guv(Ac), I uz (benzoic acid), I uz (glutaric acid), GU5 (IMA ), Guv(Reda-ivosti-

Rait), Guz (pyroglutaric acid), I uz (succinic acid), Azp, Ot, Sip, Agu or Mai; X14 is Rac(As), Oar(As), Niv, Guv(As), Avp, Sip or Tug; and X15 represents Aa, actually,

Sspu, Up, Sp or 5eg. 0015) In some embodiments, Xa: X1 is absent; X2 is absent; HZ is absent; X4 is Suz, Ari or Rep; X5 represents ar, Oar(Ac), Sip, beg, TNg or Azp; Xb is a

TAig X7 is Tgr; X8 is Sip; XO is Suv, Aby or Rep; X10 is an analogue of PNe, Tug or an analogue of Tug; X11 is 2-May or Tr; X12 is Asrs,

Asbrs, Asus, Asns, AIb, a-dietilaitsu, a-Me! uz, a-Mei uv(As), a-Mei! yey, o-MeOt, a-Mezeg, a-Memai,

НГ ей, Гей or TNR; X13 is Sii, Avr, Sim, Guv, Guv(As), A5p or Sp; X14 is rac(Ac), Azp or Niv; and X15 is Aia, realia, Spu, Azp or Sp. 0016) In some embodiments, Xa:X4 is Suz, Rep, pSuz, O-Rep, Y-Suv, O-ySuz, Mei, Si, Avr, Huz, Ot, OYUOar, Oab, O-YUBar, O-Oar . azido-Aia-OH, propargylglycine, 2-(3'-butenyl)glycine, 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4-pentenyl)glycine, 2-(5'-hexenyl)glycine or Aby; X7 is Ttgr, Sim, Su,

Pe, Ap, Pho, Ag9, Tig or OsisSiu, or the corresponding α-methylamino acid form of any of the above; HU stands for Suz, Rep, pSuz, Yu-Rep, O-Suz, O-nSuz, Siy, Guz, Ot, Oar, slave,

O0-bar, O-Yurar, O-Avr, O-Cish, O-Huz5, A5r, em, Mai, Rpe, or Zeg, Zes, Ar, pB-azido-Aia-OH, propargylglycine, 2-2-allylglycine , 2-(3'-butenyl)glycine, 2-(4-pentenyl)glycine, Aa, pSuz5, Aby, Mei,

Mesuves, (0) Thug or 2-(5'-hexenyl)glycine; WHO is Tug, Rpe (4-OMe), 1-May, 2-May, Ais, a-

Co) MeRne, Vir, (0)Suz, Spa, OMT, (0) Hug, Sim, Niv, pRNe(3,4-dimethoxy), pTug, M-Me-Tug, Tgr, Rne(4-

СОМН», Rpe(4-phenoxy), Tpg, Tis, Tug((3-Vy), Rpe(4-1y), Rye(4-SM), RNe(4-Vg), RNe(4-MH» ),

Rie(4-E), Ripe(3,5-Eg), Rpe(4-CHgSO»H), Rpe(penta-E), Rnpe(3,4-SiI2), Rpe(4-SEz), Rpe( 4-OSN), Vir,

Sna, 4-pyridylalanine, VyATug, OcysIu, Ripe(4-Mz), PNe(4-B/), Rpe((4-(2-aminoethoxy)| or Re, an analogue of Rie, an analogue of Tug or the corresponding α-methylamino acid form any of the above;

X11 is 2-Mai, 1-Mai, 2,4-dimethylRie, Vir, Rpe(3,4-SiI2), Re (3,4-Eg2), Rpe(4-CO2H),

VyRPe(4-P), o-Me-Ttr, 4-phenylcyclohexyl, Rpe(4-SEz), o-MeRpe, VyMa!i, VyRpe, VyTug, VA Ttgr,

Mma(5-phenyl), Rpe, Nix5, pRpe, Tis, Tda, Tgtr, Tu, Rne(4-OMe), Rpe(4-Me), Ttri(2,5,7-tri-tert-butyl), Rpe(4-Oalyl), Thug(3-Vy), Rpe(4-4Vy), Rpe(4-guanidino, Rpe(4-OV82I), Osidio, SiIsh(B21i), 4-phenylbenzylalanine, Rpe(4-( 2-aminoethoxy))|, 5-hydroxy-Ttr, b-chloro-Ttr, M-MetTtr, 1,2,3,4- tetrahydronorharman, Rpe(4-SOMH»g), Rpe(3,4-dimethoxy) , Rpe(2,3-Si2), Rpe(2,3-Eg2g), Rpe(4-E), 4-phenylcyclohexylalanine, Vir or the corresponding sa-methylamino acid form of any of the above; Ago, M-Me-Niv, MaiY, Sam, Sra, I ey, Sii, NI ey, 3-Rai, butyl-AlYia, 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asms, Asrs, Aor, Alyib , a-diethyliu, a-

MegHuz, a-MeHuz(As), a-Me-IG em, a-MeOgp, o-Mezeg, o-Memai, AIyib, O-Aya, (0)Avp, (0)A5r, (0) ей, ( SR pe, (0) Hug, AIIB, a-MeH ei, a-MeOgp, r-Air, V-AIa, VpAia, VpAgo, Vy em, VyMai, r-spiro-pip, OM,

НАга, Пе, Гуз, М-Мей ей, М-МеАго, 09, От, Рго, Сп, Зег, ТНг, Тие, 1-butyl-Сиу or the corresponding α-methylamino acid form of any of the above; HIZ is TPg, Zags, Sim, Rpe,

Ago, H em, Huz, Agd, Ogpp, Mai, VpАЯa, ГИ уб(Ас), (С0)Ав5п, (0) ей, (0)Р Пе, (0)ТПг, Аа, а-МегГ ей, AB , D-

Aa, V-SiIm, Vp ei, VyMai, V-spiro-pip, Spa, Spo, Ar, bab, bar, s-dietilou, PI em, Azp, OO, Rgo,

SiIp, beg, B-spiro-pip, Tig, Tra, Thie or AIB, Sii, pAgu, Huz, Abp, Op, SiIp or the corresponding α-methylamino acid form of any of the above; X14 represents Re, Tug, Sim, SU, Niv,

Guz, em, Mei, Avp, Rgo, SiIp, Ago, 5eg, TAg, TisrpRPe, Ago, Guz(As), No; bar(Ac), Bar(Ac), Azr or the corresponding α-methylamino acid form of any of the above; X15 is su, Zeg,

Tng, Sp. And hey

Rgo, Ago, B-AIa, Zags or the corresponding α-methylamino acid form of any of the above;

X16 is Avzr, Sim, AIa, AEA, AER, VpAa, Sava, Su, Zeg, Rgo, Azp, Tpyg or absent, or is the corresponding c-methylamino acid form of any of the above; and X17 is IHea, Huz, Ago, Sim, bBeg, Siu, Sip, or absent, or is the corresponding α-methylamino acid form of any of the above. because ЙО017| In some embodiments of peptide inhibitors Xa, the bond is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefinic bond. 0018) In specific embodiments of Xa peptide inhibitors, X4 is Suvz, and X9 is Su, and the bond is a disulfide bond. In specific embodiments, X4 is Rep, and X9 is Rep, and the bond is a disulfide bond. In some embodiments: X7 is Tgr; X10 is Re, Tug, analog

Rpe or Tug analog; X11 represents Ttgr, May 1! or May 2; and X12 represents AIyib, a-Me- uv, a-

Me-Gays, Asps, Asms, Asrs, Asbs or TNR. In some embodiments: X7 is tr;

X10 is RpPe, Tug, analogue of Ppe or analogue of Tug; X11 represents Ttgr, May 1 or May 2; and

X12 is AIb, a-Me-G uh or a-Me-Hei. In specific embodiments, the peptide inhibitor contains any of the following amino acid sequences: Rep-O-T-M/-O-Rep-IRNe(4-

OMe)|-(2-MaC-(o-Me-I ug|I-E-M-2 (5EO 10 MO:254);. Rep-M-T-M/-0-(RepI-I(Pne (4-(2-aminoethoxy)|-(2-

MapP-(AivI-(uv(Ac3-M-M (5EBEO 10 MO: 255); Rep-O-T-M/-O-IRepiI-IRne(4-(2-aminoethoxy)|-(2-MaC- (and-

Me! esI-(Huz(Ac)|-M-M (ZEO IU MO:256); or Rep-O-T-M/-O-IRepiI-I(Rpe(4-SOMNHg)|-(2-MaC-( o- Me! uz|-

I uz(Ac)|-M-M (ZEO IU MO:257), and the peptide inhibitor contains a disulfide bond between two Rep amino acids.

І0019| In specific embodiments of peptide inhibitors Xa X4 is an amino acid, aliphatic acid, alicyclic acid or modified 2-methylaromatic acid with a carbon side chain capable of forming a thioether bond with Xu; XO is a sulfur-containing amino acid capable of forming a thioether bond with X4, and the bond between XA and

ХУ is a thioether bond. In some embodiments, X4 is Aby, 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid; and HU represents Ari, Sub, Rep, pSuz, O-Rep, Yu-Suz or O-nSuvz. In some embodiments, X4 is Aby; and X9 is Sub5. In some embodiments, X7 is Tgr; X10 is Re, Tug, an analogue of Rpe or an analogue of Tug; X11 represents Ttgr, May 1 or May 2; and X12 is a-Me-y uz, a-Me-Hei, a-Me-5eg, a-Me-Mai, Asps, Asms, Asrs, Asrs or |4-amino-4-carboxytetrahydropyran). In some embodiments, X7 is tr;

X10 is RpPe, Tug, analogue of Ppe or analogue of Tug; X11 is Tgr, May 1 or May 2; and 0 X12 is o-Me-I y5 or |4-amino-4-carboxytetrahydropyran|Y. In specific embodiments, the peptide inhibitor comprises any of the following amino acid sequences:

IAB11-O-T-M/-0-0-(Рпе(4-ОМе)|-(2-Ма|-(с-Мей ув|И-Е-М-2 (5EO 10 Мос258);. IAbBsh- O-T-M/-0-0-

IRpe(4-(2-aminoethoxy))|-UU-(c-Mei uzI-E-M-6 (ZEO IU MO:259); or IABshsh-O-T-M/-0-0-I(РНе |4-(2-aminoethoxy))|-(2-MaC-(4-amino-4-carboxytetrahydropyran|i-E-M-M (5EO 10 MO:260), and the peptide inhibitor contains a thioether bond between and S. 0020) In some embodiments of peptide inhibitors Xa: X4 is Rep, Su or

Su; X5 is any amino acid; Xb is any amino acid; X7 is Ttr, Vir, Syp, Ni, SiC(B2I), 4-phenylbenzylalanine, Thys, Rpe|4-(2-aminoethoxy)|, Rpe(3,4-Sig),

Rpe(4-OMe), 5-hydroxy-Ttr, b-chloro-Ttr, M-MetTgr, a-Me-Ttr, 1,2,3,4-tetrahydronorharman, Rpe(4-

SON), Rpe(4-SOMN"), Ripe(3,4-dimethoxy), Rpe(4-SEz), Rne(4-Vy), BB-aiRNelia, Spi, Spu, Pe, Avp,

Rho, Ag, TPg or Osidiu, or the corresponding "α-methylamino acid form of any of the above; X8 is any amino acid; ХУ is Rep, Suz or pSuv; X10 is 1-Mai, 2-Mai, Ais, Vir, (0)Suz, Spa, OMT, (0) THug, Spi, RNe, Niv, Tr, TNg, Tis, Tug, 4-pyridylAiia, Osidiu, analog Rpe or Tug analogue (optionally Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me),

Rie|(4-(2-aminoethoxy)), Rpe(4-(2-(acetylaminoethoxy))!, Rpe(4-Vu), Rpe(4-SOMH»g), RHe(4-C1),

Rpe(4-CM), Rpe(4-guanidino), Rpe(4-Me), Rpe(4-MH»g), Rpe(4-Mz), Rpe(4-OMe) or Rpe(4-OB1) ), or the corresponding α-methylamino acid form of any of the above; X11 is a 2-

May, 1-May, 2,4-dimethylRnNe, Vir, Rpe(3,4-Si2), Re (3,4-E2), Rne(4-СО2Н), VIR Ppe(4-E), o-Me - gr, 4-phenylcyclohexyl, Rpe(4-SEz), a-MeRpe, VyMai, VyRpe, VyTug, VATgr, Mma(5-phenyl), Re, Niv,

RNe, Thies, Tada, Ter, Tug, Rpe(4-OMe), RNe(4-Me), Ttri(2,5,7-tri-tert-butyl), Rpe(4-Oallyl), Tug(3-

IVy), Pne(4-IVy), Rpe(4-guanidino, Rpe(4-OB21I), Osidio, SiC(Ba2I), 4-phenylbenzylalanine, Rpe(4-(2-aminoethoxy)|, 5-hydroxy-Ttr , b-chloro-Ttr, M-MetTtr, 1,2,3,4-tetrahydronorharman, Rpe(4-SOMH 5),

Rpe(3,4-OMeg) RFe(2,3-Ci), RPE(2,3-E2), RPE(4-E), 4-phenylcyclohexylalanine or Vir, or the corresponding α-methylamino acid form of any of the above ; X12 is a-Mei! uv, o-MeOp, a-MegHes, «-Memai, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, Mee,

AB, (0)Aia, (0)Avp, (0)! ey, (0)Azr, (0)РНе, (0)TN"g, 3-Rai, AiB, V-AIa, VASIM, VpAPa, Vp em, VyMai, r- spiro-pip, Spa, Spo, Ar, bab, Var, a-Diethyloiu, Sim, Rpe, PI em, pAgo, pGei, Pe, Gu, Gei, Avp, M-

Mey, M-MeAgo, Osi, Ogp, Rgo, Sip, Agou, Zeg, Tig or Thie, or the corresponding α-methylamino acid form of any of the above; Х13 is I ub(As), (0)А5п, (0) ей, (0) Нг, (0)РНе, Ага, 60 АВ, а-МегГ ей, В-АІа, ВСИМ, Впаяя, ВыГей, ВыМай , B-spiro-pip, Spa, Spo, Ar, Guz, Agd9, Ot, ab,

Var, a-diethyloiu, Sim, Rpe, PI ei, Huz, Gay, Azp, Od, Rgo, SiIp, Azr, Ago, Zeg, spiro-pip, Tpg, Tba,

Tis, Ma! or Tug, or the corresponding c-methylamino acid form of any of the above; X14 is Avp, siy, Rpe, sSiu, Ni5, Gub5, Gay, Mei, Azp, Rgo, Sip, Ago, Zeg, TAg, Tis or Tug,

Huz(Ac), Ogp or the corresponding α-methylamino acid form of any of the above; X15 is Su, (C)Aia, (0)Av5p, (0)Azr, Avp, (0) ей, (0)РНе, (0)ТН"г, АИа, AEA, Avr, Спи, РНе, SU , Guz,

And em, Rgo, Sip, Agd or Zeg, B-AIa, Agd or the corresponding c-methylamino acid form of any of the above; X16 is absent, represents su, Aa, A5p, 5eg, Pgo, Azp or TpPg, or the corresponding α-methylamino acid form of any of the above; X17 is absent, is Sim, Beg, Su or SiP, or the corresponding α-methylamino acid form of any of the above; X18 is absent or is any amino acid; X19 is absent or is any amino acid; and X20 is absent or is any amino acid. In specific embodiments, the connection between XA and XU is a disulfide bond. In some embodiments, X1, X2, and X3 are absent. In some embodiments, X17, X19, and X20 are absent. In some embodiments, one or both of X4 or X9 are Rep. In some embodiments, both X4 and XU are Rep. In specific embodiments, X1I8 is (0)-Gu5. In some embodiments, the peptide inhibitors comprise one or more, two or more, three or more or four of the following: X5 is Ago, Avp, Sip, Yuar, Ogp; Xb is Tpg or Zeg; X7 is Ttgr, 2-Mai, 1-Mai, Rne(4-Oallyl), Tug(3-IVy), Rnpe(4-1Vy), Rne(4-guanidino),

Rpe(B2I) or Rpe(4-Me), 5-hydroxy-Ttr, b-chloro-Ttr, M-MeTtr, o-MeTtr or 1,2,3,4-tetrahydronorharman; and X8 represents Sip, Mai, Rpe, Sim, Gub5. In some 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: X10 is Tug, RPpe(4-

OB), Rne(4-OMe), Rpe(4-SOMN), Rie(3,4-C1I2), Rne(4-1Vy), Rpe(4-Mng), Rpe(4-VI), Rpe( 4-CM),

Rpe(4-CO»2H), Rpe(4-(2-aminoethoxy)) or Rpe(4-guanidino); X11 represents Tgr, May 2, May 1,

Rpe(4-Oallyl), Thug(3-IVy), Rpe(4-y1Vy), Rpe(4-guanidino), Rpe(B2iI) or Rpe(4-Me), 5-hydroxy-Ttgr, 6-chloro- Thtr, M-MetThr, o-MetThr or 1,2,3,4-tetrahydronorharman; X12 represents Ago, a-Mei in a-

Me! en, AIIB or a-MeOpt; X13 is Huz, Sim or I ub5(Ac); X14 is Re or Avp;

X15 is su, 5g or Aia; and X16 is absent or is AEA. In some embodiments, X4 and XO are Rep; X5 is Sip; Xb is TPg; X7 represents

Ko) is Tgr; X8 is sp; X10 is Tug, Rpe(4-OMe) or 2-May; X11 is a

Ter, May 2 or May 1; X12 is Ago, aMei uh or a-MeOgp; X13 represents I uz, Seven or

Huz (Ac); X14 is Re or Avp; X15 is a su; and X16 is absent. In some embodiments, one or more of X1, X2, and X3 are absent; and one or more, two or more, three or more or four of X17, X18, X19 and X20 are absent. 0021) In some embodiments of peptide inhibitors Xa: X4 is Aby, Rep or

Sub; X7 is Tr, Vir, Sp, Ni5, SiIshsh(B72), 4-phenylbenzylalanine, Tis, Rpe(4-(2-aminoethoxy)|, Rpe(3,4-CI2), Rpe(4-OMe), 5 -hydroxy-Ttr, b-chloro-Ttr, M-MetTtr, o-MetTr, 1,2,3,4- tetrahydronorharman, Rpe(4-СО2Н), Rpe(4-СОМН»), Rnpe(3, 4-dimethoxy), Rpe(4-SEz), BB-YaiRNelia,

Rpe(4-I0), Sim, SU, Pe, Azp, Rgo, Agd, Tig or Osidio, or the corresponding α-methylamino acid form of any of the above; ХУ represents Aby, Rep or Su; X10 represents May 1, 2-

May, Ais, Vir, (0)Suz, Spa, OMT, (0)THug, Spi, RNe, Ni, Tgr, TNg, Thys, Thug, 4-pyridylAia, Osidiu, Ripe analogue or Thug analogue, or the corresponding a- the methylamino acid form of any of the above; X11 is 2-Mai, 1-Mai, 2,4-dimethylRpe, Vir, 4-phenylcyclohexyl, sat(B2I), 4-phenylbenzylalanine, Tis, Rpe(4-(2-aminoethoxy)|, Pne(3,4 -Sig), Rne(3,4-E2), VyRPpe(4-E),

Rpe(4-OMe), 5-hydroxy-Ttr, b-chloro-Ttr, M-MetTtr, o-MetT"tr, 1,2,3,4-tetrahydronorharman, Rpe(4-

SON), Rpe(4-SOMH»g), Rpe(3,4-dimethoxy), Rpe(4-SEz), Rpe(2,3-CI2), Rpe(2,3-Eg), Rpe(4- E), 4-phenylcyclohexylalanine, s-MeRne, VyMai, vVyRpe, Vy Hug, VA Tgr, Vir, Mma(5-phenyl), Rpe, Ni, PRE,

Taa, Tgtr, Tug, Rpe(4-Me), Tgtr(2,5,7-tri-tert-butyl), Rpe(4-Oallyl), Tug(3-IVy), Rpe(4-IVy), Rpe (4-guanidino), Rpe(4-OB2I) or Osidio, or the corresponding α-methylamino acid form of any of the above; Х12 is a-MeiY uh, o-MeOgp, a-Mei y, Mei ey, Air, (0)Aia, (0)Avp, (B) yem, (0)Azr, (0)РНе, (0) TNg, 3-Rai, AB, V-AIa, VSIM, VpAPa, Vp ei, VyMai, V-spiro-pip, Spa, Spo,

Azr, Bab, Var, a-dietiloyu, Sim, Re, p ey, pAgo, NG ey, Pe, Guz, em, Azp, M-Mei! Hey, M-MeAgo, OdI,

Opt, Rgo, Sp, Agu, Zeg, Tig or Thie, or the corresponding α-methylamino acid form of any of the above; X13 is I uz(Ac), (0) Azp, (0) ей, (0) ТНг, (0) РПе, Ая, АЙБ, а-МегГ ем, Ваипа,

VASI, VrApa, VHei, ViMMai, V-spiro-pip, Spa, Spo, Azr, Ago, Ogp, ab, Var, a-diethyloiu, Sim, Rpe, pHei, Gu, Gei, Abp, Od, Rgo, Sp, Avr, Ago, Zeg, spiro-pip, Tpg, Tra, Tis, MaY or Tug, or the corresponding α-methylamino acid form of any of the above; X14 represents Avp, Sy,

Rpe, Spu, Niv, Guz, Hei, Mei, Ap, Rgo, Sip, Agd, Zeg, TAg, Tis or Tug, or the corresponding α-methylamino acid form of any of the above; ХИ5 is su, (0)Aia, (0)Av5p, 60 (B)Azr, Avp, (B) ей, (0)РНе, (0)ТНг, Аа, АЕА, Авр, Сим, РНе, Спу, GG uv, I ey, Rho, Sp, Aha or 5eg,

or the corresponding α-methylamino acid form of any of the above, or X15 is sipu, (Б)Аа, (0)Авп, (0)Авр, Авп, (0)ей, (0)РНе, (0)ТНг, Aa, Avp, 5eg, AEA, Avr, Spi, RNe, Spu,

Huz, Hem, Rgo, Sip, Agd or 5beg, or the corresponding c-methylamino acid form of any of the above; X16 is absent, represents su, Aa, A5p, 5eg, Pgo, Azp or TPg, or the corresponding α-methylamino acid form of any of the above; and X17 is absent, represents Seven, zeg,

Siu or Sip, or the corresponding α-methylamino acid form of any of the above. In specific embodiments, the peptide inhibitor is cyclized by an intramolecular bond between XA and XU. In some embodiments, one or more of

Х1, Х2 and ХЗ are absent. In some embodiments, one or more of X17, X19, and X20 are absent. In some embodiments, one of X4 or XU is an Aby, and the other of X4 or X9 is not an Aby. In some embodiments, the peptide inhibitors contain one or more, two or more, three or more, or four of the following: X5 is Ag, SiIp, YuSar, or Opt; Xb is Tpg or Zeg; X7 is Ttgr, 2-Mai, 1-Mai, Rne(4-Oalyl), Tuk(3-IVy), Rpe(4-IVy),

Rpe(4-guanidino), Rpe(4-O82I), Ripe(4-Me), 5-hydroxy-Ttr, b-chloro-Ttr, M-MeTgr or a-MetTtr, 1,2,3,4 -tetrahydronorharman; and Xv is Sip, Mai, Rpe, Siy, or Huz. In some 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: X10 is

Tug, Rpe(4-OV2I), Rpe(4-OMe), Rpe(4-SOMN"), Rpe(3,4-SI2), Rpe(4-48y), Rne (4-Mn»g), Rne (4-VIy),

Rpe(4-CM), Rpe(4-CO»H), Rpe(4-(2-aminoethoxy)) or Rpe(4-guanidino); X11 is Ttgr, 2-

May, 1-May, Pne(4-Oalyl), Thug(3-Vy), Pne(4-1Vy), Pne(4-guanidino), Rpe(B2I) or Rpe(4-Me), 5-hydroxy- Tgr, b-chloro-Ttr, M-MetTtr, a-MeTtgr or 1,2,3,4-tetrahydronorharman; X12 is a

Ago, PI em, (0) Avzp, AIyib, a-MeiG uh, o-MeiY ei or a-MeOgp; X13 represents I uz, Sim or I uv(As);

X14 is Re or Azp; X15 is Su, Beg or ApIa, or X15 is Avp, Su, zZeg, ValiIa or Aa; and X16 is absent or is AEA. 00221 In specific embodiments, any of the peptide inhibitors X4 and XO are Rep. In specific embodiments, XA and XU form a disulfide bond. 0023) In specific embodiments, X4 is Aby, and XO is Suv. In specific embodiments, XA and XU form a thioether bond.

In specific embodiments, the peptide inhibitor contains the amino acid sequence of any of ZEO IU MoMo: 365-370, 8857-1029. In specific embodiments, the peptide inhibitor is cyclized by binding between X4 and XU, and the peptide inhibitor inhibits the binding of interleukin-23 (II-23) to the 1-23 receptor. 00241 In some embodiments of peptide inhibitors Xa, the peptide inhibitor contains an amino acid sequence specified in any of the formulas (Ma), (MB), (ms), (Ma), (me), (MU, (MO) and (MI ).0025) In some embodiments of Xa peptide inhibitors, the peptide inhibitor contains any of the following amino acid sequences:

IRa!ti-(isos1y|-(RES4Y-(RepI-MTUU/O-|(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AIVI-( uz(AsD-MMMN)) I MO:1115);

As-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AIBI-(GuUv(PES4-ivoScyly-Rait)|-MM-MH)" (ZEO I MO:1116);

Ac-I(RepI-OTUMO-(Rep|-Pne(4-SOMN")-(2-Ma!|-(c-Mei uz(Ac)I-(Huz(Ac)-MM-MH)" (ZEO IO

MO:1117); (IoctanylI-(IsoxylschI-I(RESAI-(Rep|I-MTUUO-|RepiI-(Rpe(4-(2-aminoethoxy)|I-(2-MaP-(AiBI-(Huz(Ac)|-MM-

MN" (ZEO OO MO:1118);

I(IoctanylI-(RES41-(RepI-M TM O-(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaP|-(AivI-(uv(Ac)|-MM-MN)" (ZEO IU MO:1119);

IRa!tiI--RES41-(RepI-MPTUMO-(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)|-MM-MH: (5EO

IO MO:1120);

As-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Map|-(AIVI-(Suv(RESI4-octanyl)|-MM-MHg) (5EO

IO MO:1121);

As-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)|-(2-MaPC-(AiVI-( uUv(RES4-Rait)|-MM-MN: (ZEO Ir

MO:1122);

As-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)-(RESI4-Rait)|-(2-MaP-(AIVI-( uz(AsuMM-MH)" (5EO

IO MO:1123);

Ac-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)-(RESI4-Lauryl)|-(2-MaC-HAIVI-(Suv(Ac)|-MM-MH»g ( ZEO IOYU MO:1124);

As-I(RepI-OTUMO-(Rep|-Pne(4-SOMN")-(2-Ma!|-(c-Mei! uz(RES4-Rait)-(H uv(AsD-MM-MH: ( ZEO 10

MO:1125); 60 As-I(RepI-OTUMO-(Rep|-Pne(4-SOMN")-(2-Ma!|-(c-Mei! uz(RESYA4-lauryl)I-( uz(Ac)|-MM- MN: (5EO

IO MO: 1126);

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)-(RESaa4-Ivostpy-Rait)|-(2-MaP-(AivI-(Huz(Ac)|-MM -

MN" (ZEO 1Yu MO 1127);

Ac-I(RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)-(PES4-Ivocyyl i-lauryl)1I-(2-Ma!|-IaBi1-(Guv(Ac)|-

MM-MHg (ZEO and MO:1128);

Ac--(Rep|-OTUMMO-(Rep|-Rpe(4-SOMHn)-(2-MaC-(c-MeH uz(RES4-Isosp-Rai!t))|-(Suv(Ac))-MM- MN" (ZEO IU MO: 1129);

Ac-I(RepI-OTUMO-(Rep|-Pne(4-SOMN")-(2-Ma!|-(c-Mei! uz(RESI4-Isosti-lauryl)|-( uv(Ac)-MM- MN" (ZEO and MO:1130);

Ac-(Rep|-OTUMMO-(Rep|-Rpe(4-SOMHn)-(2-MaC-(a-MeH uUz(MA)I-(Suz(Ac)-MM-MH)" (ZEO IO

MO:1131);

Ac-(Rep|-OTUMMO-(Rep|-Rpe(4-COMNHg)-(2-MaC-(c-MegHuz(biotin)|I-(Guv(Ac)|)-MM-MNa (ZEBEO (10

MO: 1132);

Ac-(Rep|-OTUMMO-(Rep|-Rpe(4-SOMHn)-(2-MaC-(c-MegHus(octanyl)|-(Hus(Ac)-MM-MNa) (5EBEO (10 MO:1133) ;

Ac-IRepI-(GUB(IMA)X-TUMO-(RepiI-IRNe(4-(2-aminoethoxy)|-(2-MaC-(AIVI-(Suz(Ac)-MM-MHg) (5EO 10

MO:1134);

Ac-(Rep|I- MTM O-(RepiI-(Ppe(4-(2-aminoethoxy)I-(2-MapP-(AIVI-(Suv(Ac)I-(H U MA)X-M-MHg (5EO 10

MO:1135);

Ac-IRepI-IGuz(biotin)|- TMO-(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)|-MM-MH: (5EO

IO MO:1136);

As-I(RepI-M GU O-(Repi-(Pne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)I-(Huz(biotin)|-M-MH : (5EO

IO MO:1137);

Ac-IRepI-ISuz(octanyl)|- TUMO-GREpiI-(Rpe(4-(2-aminoethoxy)|-(2-MaP-(AiVI-(Huz(Ac)|-MM-MNe: (Z5EO

IO MO:1138);

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Map|-(AIBI1-(Suv(Ac)|-(Sus(octanyl)|-M- Mneg (5EO

IO MO:1139);

As-IRepI-(Huz(Rait)|- PM O-(RepI-I(Pne(4-(2-aminoethoxy)|-(2-Ma|--(AIVI-( uz(Ac))-MM-MNg (5EO

IO MO:1140);

Zo As-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(As)I-Huz(Rait)|-M- MN" (ZEO 10

MO:1141);

As-IRepI-(IG-uz(RES8)- ГМ/О-(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaP-(AIVI-( uz(Ac)-MM-MH: (5EO

IO MO: 1142);

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AIVI1-(Suv(Ac)I-(uUv(RESV8)|-M-MH : (ZE

IO MO:1143);

Ac-IRep|-K(Reda11-Rait) GPMMO-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-Ma-(AivI-(uz(Ac)-MM-MH)" (ZEO

IO MO: 1144);

As-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC--HAivI-(Huz(Ac)I-(Huz(Red11-ra!t)|- M-MN" (ZEO and MO:1145);

Ac-IRepI-(СЩ- ГМ-ИЩЧ-(RepiI-(Рпе|(4-(2-aminoethoxy)I-(2-Ma|--HAIVI-( uz(Ac)|-MM-MNa) (5EBEO 10

MO:1146);

As-IRepI-(Guv(As- GMU/-ISSCH-(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaC-(AivI-( uv(Ac)|-MM-MH: / (5EO

IO MO:1147);

Ac-IRep|-MT-(IRne(3,4-OSHz)21-0-IRepI-(Rpe(4-(2-aminoethoxy)|-(2-Ma!|-(AIVI-( uz (Ac)) -MM-MN" (MO FAILURE: 1148);

As-IRep|-MT-IRne(2,4-CHZ)21-O-(RepyI-(Rpe|(4-(2-aminoethoxy)I-(2-MaP-(AivI-(Suv(AsD-MM- MN" (ZEO IU MO:1149);

Ac-IRep|-MT-IRpe(3-CHZ)|-O-IRepI-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AiVI-(Sus(Ac)|-MM-MNeg) 5EO

IO MO:1150);

Ac-IRep|-MT-IRpe(4-SNZ)|-O-IRepI-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AiVI-(Huz(Ac)|-MM-MNeg) 5EO

IO MO:1151);

Ac((0)Aga|-(RepI-MTUMO-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MaP|-(AiBI-(Huz(Ac)|-M-IVATa|-MH (5EO

IO MO:1152);

As-KO)TUpP-(Repi-MTUO-H(Repi-IRpe(4-(2-aminoethoxy)|-(2-Ma|-(AIBI-(Guv(Ac)|-M-IVAia|-MNe)

IO MO:1153);

Ac-IRepI-MTM O-(RepyI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AiYVI-(uv(Ac)-OM-MH)g (ZEO IO

MO:1154);

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AIVI-(Suv(Ac)I-(Guv(Ac)-M-MNa) 5EBEO 10

MO:1155); because Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AIVI-(Suv(Ac)|-M-(Huz(Ac)-MNa (5EBEO 10

MO:1156);

As-I(RepI-M TU O-|Repi1-Irpe(4-(2-aminoethoxy)-(2-MaC-(AiVI-(Suz(Ac)|1-00O-MH)" (ZEO IO

MO:1157);

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AIVI-(Suv(Ac)|-O-IVAIa|i-MNa (5EBEO ( 1

MO: 1158);

As-I(RepI-M TU O-|Repi-Irpe(4-(2-aminoethoxy)I-(2-Ma|-(AiYVI-(Suz(Ac)|I-M-(SSHCHAMN)" (ZEO IO

MO:1159);

Ac-I(RepI-M TU O-|RepI1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AIBI-(Suv(Ac)I-(SSH-MMN)" (ZEO IO

MO:1160);

As-I(RepI-M TU O-|Repi-IRpe(4-(2-aminoethoxy) I-(2-MaP|-(AiYVI-(H uz (Ac)I-(SSH-O-MN)" (ZEO IO

MO:1161);

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AIVI-(Suv(Ac)I-(STSH-(Guv(Ac)|- MN" (ZEO 10

MO: 1162);

Ac-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)I-( uz(Ac)L-ISSH- MN" (ZEO 10

MO: 1163);

As-IRepI-M TU O-|RepI-IRpe(4-(2-aminoethoxy)I-(2-Ma|-(AiVBI-OM-|VATA|-MN)" (ZEO IO MO:1164);

As-I(RepI-MTM O-|(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AiYVI-E-ISISH-O-MH)" (ZEO IO MO:1165);

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MapP-(AiYVI-(SSH-M-(SSH-MN)" (ZEO 10 MO:1166 );

As-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AiVI-(SiSh-O-G(SSh-MN)g) (ZEO I MO 1167 );

As-IRepI-(SSH-TUO-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MaP-(AIVI-(-uv(AsD-MM-MN)" (ZEO IO

MO:1168);

As-I(RepI-M TU O-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AiVI-(Suz(Ac)|-MM-MN)" (ZEO IO

MO:1169);

As-I(RepI-MTUO-|RepI1-IRne(4-(2-aminoethoxy)I-(2-MaPC-(AiYVI-OMM-MH)" (5EO 10 MO 1170);

Ac-(Rep|I-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MaP-(AIVI-EMO-MH)" (ZEO 10 MO:1171);

As-I(Rep|-aRUMO-(RepiI-|(Rpe|(4-(2-aminoethoxy)|-(2-MaP-(AIVI-(Suv(AsD-MM-MH)" (ZEO IO

MO:1172);

As-I(RepI-REOUMMO-|RepiI-|(Rpe|(4-(2-aminoethoxy)|-(2-MaPP-(AIVI-(Suv(AsD-MM-MH)" (ZEO IO

MO:1173);

Ko) As-I(RepI-M Tu M-(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaC-H(Aiv1-(Suz(Ac)|A-MM-MH)" (5EO I MO 1174);

Ac-I(RepI-M5UMO-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MaP-(AiVI-(Suz(Ac)|1-MM-MH)" (ZEO IO

MO:1175);

Ac-(RepI-M-IAIVBI-UM O-H(RepiI-IRpe(|(4-(2-aminoethoxy)|-(2-Map|-(AlibI-(Suv(Ac)-MM-MNa (5BO ( Yu

MO:1176);

As-IRep|-M PM-IAIBI-(Repi-(RHe(4-(2-aminoethoxy)|-(2-MaP-(AivI-(Suv(Ac)M-IAIVBI-MN: (5EBEO 10

MO:1177);

Ac-IRepI-OTM/-(Guv(Ac)I-(Repi-IRpe(4-(2-aminoethoxy)|-(2-MaP-(AiBI-(Suz(Ac)-MM-MNa) (5EO 10

MO:1178);

Ac-IRepI-(Guv(Ac)|- GTM О-Г(RepI-IRpe(4-(2-aminoethoxy)|-(2-Ma--IAIVI-(Suv(Ac)uMMMH) (5EBEO 10

MO:1179);

Ac-(ReptI-OMMO-|RepiI-I(Rpe|4-(2-aminoethoxy)|-(2-MaP-(AIVI-(Suv(AcD-MM-MH)" (ZEO IO

MO:1180);

Ac-(RepI-MtT-(2-MaC-O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma!p|-(AibI)-(Suz(Ac)-MM-MNa). (5EBEO 10

MO:1181);

Ac-(RepI-MmT-(11-MaC-O-(RepI-(Rpe(4-(2-aminoethoxy)I-(2-Map|-(AlibI-(Sus(Ac)-MM-MNa. (5EBEO 10

MO: 1182);

Ac-(Rep|I- MTM O-(RepyI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(o-Mei!esI-(Suz(Ac)-MM-MNa) (5BO 10

MO:1183);

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-Mac-(o-Me! uzI-(Suv(Ac)|-MM-MNa) (5BO 10

MO:1184);

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

ISUz(As)|-MM-MN" (5EO 1O MO 1185);

Ac-I(RepI-M GU O-(Repi-I(RHne(4-(2-aminoethoxy)|-(2-Ma-(a-Mei ets|-( uv(Ac)I-M-(BAIa| -MN" (ZEO 10

MO:1186);

Ac-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)|-(2-MaC-(a-Me! uzI-(Huz(Ac)I-M-IVATa|- MN": (ZEO 10

MO:1187);

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

IS Uz(As)|-M-IVATa|-MN" (ZEO 1O MO 1188);

As-I(RepI-M TU O-|Repi1-Irpe(4-(2-aminoethoxy)I-(2-Ma|-(AiYVI-(Suz(Ac)|-IM-MN)" (ZEO OO MO:1189 ); because As-I(RepI-M TU O-|Repi1-IRNe(4-(2-aminoethoxy)I-(2-MaP-(AiVI-(Suz(Ac)-aM-MH)" (ZEO IO

MO:1190);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AlIV-(Guv(Ac)|-5M-MH)" (5EO 1O MO 1191);

As-I(RepI-M TU O-|RepI1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AIVI-(Suz(Ac)I-(AivBI-M-MN: / (5EO IO

MO:1192);

As-I(RepI-M TU O-|Repi1-Irpe(4-(2-aminoethoxy)I-(2-MaP|-(AiYVI-(Suz(Ac)|-EM-MN)" (ZEO IU MO:1193 );

As-I(RepI-M TUU-ISSH-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MaP-(AiVI-(Suv(Ac))-MM-MH" (ZEO IO

MO:1194);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AiIVI-(Suv(Ac)I-(ThisI-IVAia|i-MNa (5EBO o

MO:1195);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AiIVI-(Suv(Ac)I-(p ecI-IVA!a|-MNg) (5EO 10

MO:1196);

Ac-I(RepI-MTUO-|Repi1-Irne(4-(2-aminoethoxy)I-(2-MaP-(AlIIVI-(Suv(Ac)-c-IVAia|-MH): (5EO (10

MO:1197);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AiYVI-(Suv(Ac)|-B-IVAIa|-MNO) (5EBEO (1

MO:1198);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaC--IAIV-(Sus(Ac)|-UM-IVAIa|-MNa (5EBEO

MO:1199);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaC--IAIV-(Sus(Ac)|-5-IVAIa|-MNa (5EBEO (Yur

MO: 1200);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaC--IAIV-(Sus(Ac)I-I-(Baia|i-MNa (5EBEO (1

MO:1201);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaC--IAIV-(Sus(Ac)I-I(AIVI-IVATa|-MH: (5EO 10

MO:1202);

Ac-I(RepI-M TU O-|RepI-Irpe(4-(2-aminoethoxy) I-(2-Ma!|--IAIBI-(Suv(Ac)|-(M-MelA|a1-(VAia |-MN»g (5EBEOIYU MO: 1203);

Ac-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AiYVI-(Suv(Ac)I-(2-MariI-IVAchia|-MH)) (5EO 10

MO:1204);

Ac-I(RepI-MTUO-|Repi1-Irne(4-(2-aminoethoxy)I-(2-MaP-(AlIV-(Suv(Ac)-P-IVAIa|-MNa) (5EO (1

MO:1205);

Zo As-KO)Aga|-(RepI-MTUMO-(RepiI-(Rpe|(4-(2-aminoethoxy)I-(2-MaP-(4-amino-4- carboxytetrahydropyrani-(H uv(Ac)3MMMH » (ZEO 1Yu MO:1206); biotin-IRES41-cyclo(Aby|-OTUMOSI-(P pe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4- carboxytetrahydropyran|i- EMM-MN" (ZEO 1Yu MO 1269);

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

ISuv(As)|-MM-MN" (5EO IYU MO 270);

As-KO)Ago|-cyclo (Aby OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyrani-(H uz(Ac)|-MM- MN" (ZEO 1Yu MO1271);

As-KO)Ago|-cyclo (Aby OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyrani-(H uz(Ac)|-MM- MN" (ZEO 1Yu MO272);

As-E-KO)Aga|-cyclo(Avshsh-O HUMOSI-(P pe(4-(2-aminoethoxy)|-(2-Ma-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) ZEO IU MO 7273);

As-KO)Av5riI-KO)Aga|-cycloCABsh-OTUMOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) ZEO 1Yu MO 7274);

As-B-KO)Aga|-cyclo(ABsh-OTUMOSI-(PHe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyran|I-EMM-MH) (ZEO 1YU MO 1275); inoethoxy)I-(2-Ma1|-(4-amino-4-carboxytetrahydropyran|i-EMM-MH)" (ZEO IYU MO 1276);

As-E-KO)Ago|-cycloAry|-OTUMOSI-(Rpe(4-(2-aminoethoxy)|I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH) (ZEO IU MO 7277);

As-KOB)RPpeI-KO)Ago|-cyclo(ABshsh-O TU OSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4- carboxytetrahydropyran)) and EMM -MN" (ZEO 1Yu MO 7278);

As-I2-MacC-KO)Ago|-cyclo(ArshI-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyran)|i-EMM-MH) » (ZEO 1Yu MO 7279);

As-T-KO)Ago|-cycloHara|-OTUMOSI-(Rpe(4-(2-aminoethoxy)|I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1Yu MO 1280);

As-I -KO)Ago|-cyclo(ABsh-O TU OSI-(РНе(4-(2-aminoethoxy)|-(2-MaЦ-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) ZEO 1Yu MO 1281);

As-KO)a1p1-KO)Ago|-cyclo(AbBa-OTUOSI-(Rpe(4-(2-aminoethoxy) I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM- MN" (ZEO 1Yu MO 1282);

As-KO)Av5pI-(O)Aga|-cycloCABsh-OTUMOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4- 60 carboxytetrahydropyran)|i-EMM-MH) » (ZEO 1Yu MO 1283);

As-cyclo(Arsh-O HUMOSI-(Rpe(4-(2-aminoethoxy)-(RESI4-Alecha488)1-(2-Ma!|-(4-amino-4-carboxytetrahydropyran|i-EMM-MH)) ZEO 1Yu MO 1284);

IAIekha4881--RES41-cyclo (AbBiI-OTUMOSI-(Rpe(4-(2-aminoethoxy)|--(2-Ma!|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)" (ZEO 1U MO 1285);

IAIehab47|--RES41-cyclo(AbBaI-OTUMOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)" (ZEO 1U MO 1286);

IAiheka-647|-I(RES41-KO)Ago|-cycloGAVyI-OTUMOSI-(Rpe((4-(2-aminoethoxy)|-(2-Ma!/|-(4-amino-4- carboxytetrahydropyrani-(H) uz(Ac)|-MM-MN" (ZEO 1О MO:1287);

IAIehab47|-(RES121-KO)Ago|-cycloAVch-OTUMOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyrani)-(Guv(Ac)| -MM-MN" (ZEO IO MO 1288); and

IAIekha4881-(RES41-KO)Aga|-cyclo(AbBsch-OHUMOSI-(P pe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyrani-( uz(Ac )|-MM-MH" (ZEO 1О MO:1289), 0026) where the peptide inhibitor is cyclized using a disulfide bond between two

Rep residues or by means of a thioether bond between Aby and Su5 residue, and where the peptide inhibitor inhibits the binding of interleukin-23 (II-23) to the II-23 receptor.

I0027| In specific embodiments, any of the peptide inhibitors described herein contains one or more half-life extending fragments and/or one or more linker fragments conjugated to the peptide inhibitor. In specific embodiments, the half-life-extending fragment is conjugated to the peptide inhibitor through one or more linker fragments. 0028) In some embodiments, any of the peptide inhibitors described further herein contains a conjugated chemical substituent. In specific embodiments, the conjugated chemical substituent is a lipophilic substituent or a polymer fragment, for example, Ac, Rait, datasia-Rait, isosia-Rait, PES2-Ac, RESI4-ivosia-Rait, (PES)5-Rait, succinic acid , glutaric acid, pyroglutaric acid, benzoic acid, IMA, octanoic acid, 1,4 diaminobutane, isobutyl or biotin. In some embodiments, the conjugated chemical substituent is polyethylene glycol with a molecular weight of 400 Da to 40,000

Yes.

I0029| In another aspect, the present invention includes peptide inhibitors having the structure

From formula I:

B'-X-B: (I) or a pharmaceutically acceptable salt or solvate thereof, where

B' is a bond, hydrogen, C1-C6b alkyl, C6-C12 aryl, C6-C12 aryl, C1-C6 alkyl, C1-

C20 alkanoyl, and includes PEGylated variants alone or as spacers of any of the above;

Vg is a bond, OH or MH"; and

X represents any peptide sequence described herein, e.g.

Ha, I, Ta-Ib Ii, Pa-Pa, PI, Sha-She, IM, IMa-IMB, M or Ma-UN. 0030) In a related aspect, the present invention comprises a peptide dimeric inhibitor of the interleukin-23 receptor, wherein the peptide dimeric inhibitor comprises two peptide monomeric subunits connected by one or more linker fragments, wherein each peptide monomeric subunit has a sequence or structure, specified above in this document. In some embodiments, one or both peptide monomer subunits are cyclized by an intramolecular bond between X4 and XU. In some embodiments, one or both of the intramolecular bonds are a disulfide bond, a thioether bond, a lactam bond, a selenoether bond, a diselenide bond, or an olefinic bond. In some embodiments, the linker is any of those shown in Table 2 or described herein. In some embodiments, the linker fragment is a diethylene glycol linker, a linker based on iminodiacetic acid (ICA), a linker based on B-Aia-iminodiacetic acid (B-Aia-IIA), or a PEG linker. In specific embodiments, the M-end of each peptide monomer subunit is connected by a linker fragment. In specific embodiments, the C-terminus of each peptide monomer subunit is connected by a linker fragment. In some embodiments, the linker connects the internal amino acid residue of at least one of the peptide monomer subunits to the M-terminus, C-terminus, or internal amino acid residue of another peptide monomer subunit.

I0031) In an additional related aspect, the present invention comprises a polynucleotide containing a sequence that encodes a peptide inhibitor of the present invention or one or both of the peptide monomer subunits of a peptide dimeric inhibitor of the present invention. The present invention also includes a vector containing a polynucleotide.

0032) In another aspect, the present invention comprises a pharmaceutical composition comprising a peptide inhibitor or a peptide dimer inhibitor of the present invention and a pharmaceutically acceptable carrier, excipient, or solvent. In specific embodiments, the pharmaceutical composition contains an enteric coating. In some embodiments, the enteric coating protects and releases the pharmaceutical composition into the lower gastrointestinal system of the subject.

II0033| In another aspect, the present invention includes a method of treating or preventing a disease associated with II/-23 signaling, including, but not limited to, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, celiac disease, enteropathy, associated with seronegative arthropathies, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis, colitis associated with radio or chemotherapy, colitis associated with disorders of innate immunity, such as leukocyte adhesion disorder-1, chronic granulomatosis, glycogenosis type 16, Germansky-Pudlak syndrome, Chediak-Higashi syndrome and Wiskott-Aldrich syndrome, pouchitis after proctocolectomy and ileoanal anastomosis, cancer of the gastrointestinal tract, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, psoriasis, or a "graft-vs-host" reaction in a subject comprising administering to the subject an effective amount of a peptide inhibitor or pharmaceutical composition of this invention. In some embodiments, the inflammatory bowel disease is ulcerative colitis or Crohn's disease. In specific embodiments, the peptide inhibitor or peptide dimer inhibitor inhibits the binding of interleukin-23 (1-23) to the interleukin-23 receptor (I1/-23НА). In some embodiments, the pharmaceutical composition is administered to a subject by an oral, intravenous, peritoneal, intradermal, subcutaneous, intramuscular, intrathecal, inhalation, vaporization, nebulizer, sublingual, buccal, parenteral, rectal, intraocular, inhalation, vaginal, or topical route. introduction. In specific embodiments, the pharmaceutical composition is administered orally for the treatment of inflammatory bowel disease (IBD), ulcerative colitis, and Crohn's disease. In some embodiments, the pharmaceutical composition is administered to the subject topically, parenterally,

By intravenous, subcutaneous, peritoneal, or intravenous route for the treatment of psoriasis.

BRIEF DESCRIPTION DRAWING

(0034) Fig. 1 Figure 1 provides an example of a rat II-23 dose response curve as measured by levels of II--17A in a rat splenocyte assay. 00351 Fig. 2 is a graph showing the I--12-dependent production of IEM from the PBMC of a person treated with the indicated amounts of compound A or compound B.

I0OZ6) Fig. C shows the results of SAI values for day 7. Statistical analysis of significance was determined using the Student's test (SgarpRaai Rgizt). The differences were marked as significant "p-0.05, y"re0.01, "re0.001, 7p-0.0001.

I0037| Fig. 4 shows an alignment of human I23K, mouse 1-238, rat I/23K, chimpanzee I/-23K, dog I/-23K, and cow I/-23K amino acid sequences, with highly conserved amino acid sequences shaded. The II -23K region of the mouse, which is absent in the other shown varieties of II/-23K, is shown, and the region of P/23K, which can be bound by certain peptide inhibitors of this invention, is shown as a dashed line. 0038) Fig. 5 is a table showing the study design for TMB5-induced colitis in rats. 00391 Fig. BA-6Y0) are graphs that show the mass to the length of the colon (fig. bA), the thickness of the colon wall (table 6B, the macroscopic indicator of the colon (table 6C) or the concentration of myeloperoxidase (MPO) in extracts of the proximal part of the colon, which is calculated using EGISA, followed by sham treatment, treatment with medium or treatment with the indicated amounts of antibody to P./23p19 or compound C.

Values are shown as mean of 450. Statistical significance was assessed by one-tailed analysis

AMOMA: "0.055001; хр«0.001; ие"р«0.0001; p5, non-significant. 00401 Fig. 7 provides photomicrographs of colon lesions found in animals after sham treatment (upper left panel), medium treatment (upper right panel), indicating transmural inflammation, the presence of necrotic tissue and mucosa devoid of crypts, anti-II23p19 antibody (lower left panel) or 160 mg/kg/day Compound C (lower right panel), indicating limited mucosal lesions. 00411 Fig. BA-8E are graphs showing inflammation ( Fig. A), mucosal necrosis (Fig. 888), large weight loss (Fig. 8C), thickness of the colon wall (Fig. 80) and bo histological index (Fig. 8E) after treatment with medium, treatment with antibody against

And 23p19 or treatment with the indicated amount of compound S. 0042 Fig. 9 shows the plasma and proximal colon concentration of compound C determined one hour after PO dosing (left panel) and folds above the IC75 for its activity as determined by rat splenocyte assay (middle panel) and I/23K assay EGIS of rats (right panel). 00431 Fig. 10 provides a schematic diagram showing the structure of some peptide inhibitors and showing illustrative types of linkages between XA and XO. (0044 Figs. 11A-11E show pharmacokinetic data for the peptide inhibitor 1/-238 peptide 993 (5EO IUO MO: 993). Fig. 11A shows the serum concentration (NM) of peptide 993 measured at various time points up to 24 hours after of oral administration of peptide 993. Figures 11B-110 show the concentration of peptide 993 (in nM) in samples taken from Peyer's patches (Figure 118), small intestine (Figure 112) and colon (Figure 1103. The dashed line shows 350 mm.

Fig. 11mE shows the amount of peptide 993 detected in feces 24 hours after oral administration (95 doses). (0045) Fig. 12A-120 summarize experiments comparing systemic treatment with prednisolone or neutralizing antibody against I-23p19 to treatment with peptide 993 by oral administration in a TMB5 model of acute colitis. Fig. 12A shows the change in body weight (percentage) from day 0 to day 7 in rats treated with placebo, medium, and peptide 993.

Fig. 128 shows the ratio of colon mass to colon length in mg/cm of colon taken from rats on day 7. Fig. 12C shows a macroscopic view of the colon taken from rats on day 7. Fig. 120 shows the sum of histopathological scores for colons taken from rats treated with placebo, medium, and peptide 993. For all experiments, statistical comparisons between groups were made using 1-way

AMOMA with the following test: "p" 0.05; p" 0.01; ih p" 0.001; and p" 0.0001; p5, insignificant.

I0046| Fig. 13A-13C summarize experiments comparing systemic treatment with prednisone or a neutralizing anti-II/-23p19 antibody to treatment with peptide 1185 by oral administration in a TMB5 model of acute colitis. Fig. 13A shows the change in body weight (percent) from day 0 to day 7 in rats treated with placebo, medium, and peptide 1185. FIG. 138 shows the ratio of the mass of the large intestine to the length of the large intestine

From mg/cm of colon taken from rats on the 7th day. Fig. 13C shows a macroscopic view of the colon taken from rats on day 7. For all experiments, statistical comparisons between groups were performed using a 1-sided AMOMA with the following test: "p" 0.05; p" 0.01; and p" 0.001; and rea 0.0001; p5, insignificant.

I0047| Fig. 14A-140 summarizes experiments comparing systemic treatment with prednisolone or neutralizing antibody against II-23p19 with treatment with peptide 980 by oral administration in a TMB5 model of acute colitis. Fig. 14A shows the change in body weight (percent) from day 0 to day 7 in rats treated with placebo, medium, and peptide 980. FIG. 148 shows the ratio of colon mass to colon length in mg/cm of colon taken from rats on day 7. Fig. 13C shows a macroscopic view of the colon taken from rats on day 7. Fig. 140 shows the sum of histopathological scores for colons taken from rats treated with placebo, medium, and peptide 980. For all experiments, statistical comparisons between groups were performed using a 1-way

AMOMA with the following test: " p« 0.05; p« 0.01; ir ra 0.001; ir p« 0.0001; p5, insignificant. 00481) Fig. 15A-15E show the levels of biomarkers directed to diseases and 1- 23 measured in the colons of rats in the placebo experimental group (not exposed to TMV5) or experimental groups exposed to TMV5 and treated with medium and peptide 993. Data are shown for MPO (Fig. 15A), 1-6 ( Fig. 158), 1-1 beta (Fig. 150), 1-22 (Fig. 1503 and I/-17A (Fig. 15E). For all experiments, statistical comparisons between groups were performed using a 1-way AMOMA followed by a t-test : " p« 0.05; p« 0.01; and p« 0.001; and rea 0.0001; p5, non-significant. 00491 Figs. 16A-168 show the levels of biomarkers directed at diseases and 1-23 measured in colons of rats in the placebo experimental group (not exposed to TMV5) or the experimental groups exposed to TMV5 and treated with medium and peptide 980. Data are shown for MPO (Fig. 16A) and 1 -22 (fig. 168). For all experiments, statistical comparisons between groups were performed using 1-tailed

AMOMA with the following test: "p" 0.05; ra 0.01; ir ra 0.001; ir rea 0.0001; p5, not significant. 00501 Figs. 17A-170 show the Schild assay of inhibitor peptides. Fig. 17A shows a graph , which depicts 95 Emax responses as a function of increasing concentrations 1-23 in the presence of peptide 993 at concentrations of 0 nM (filled circles), 0.3 nM (filled squares), 1 nM bo (triangles), 3 nM (inverted triangles) , 10 nM (diamonds), 30 nM (light circles) or 100 nm

(light squares). The properties of the curves are shown in the graph below. Fig. 17B depicts the results of the same set of experiments and shows a graph that plots Iod (dose ratio-1) versus the concentration of peptide 993 (M) on a logarithmic scale. The properties of the resulting linear function are shown in the graph below. Fig. 17C shows a graph depicting 95 Emax. responses depending on the increase in the concentration of II-23 in the presence of the peptide ZEO IIU MO: 1169 in concentrations of 0 nM (filled circles), 0.3 nM (filled squares), 1 nM (triangles), C

NM (inverted triangles), 10 nM (diamonds), 30 nM (light circles) or 100 nM (light squares).

The properties of the curves are shown in the graph below. Fig. 170 shows a graph depicting 95 Emax. responses depending on increasing concentrations of II-23 in the presence of peptide ZEO IIU MO: 1211 in concentrations of 0 nM (filled circles), 0.3 nM (filled squares), 1 nM (triangles), C

NM (inverted triangles), 10 nM (diamonds), 30 nM (light circles) or 100 nM (light squares).

The properties of the curves are shown in the graph below.

I0O51| Fig. 18A-188 show pharmacokinetic data for the peptide inhibitor 1/-238 of peptide 1185. FIG. 18A shows the concentration of peptide 1185 in serum and in samples taken from the small intestine and colon. Fig. 188 shows the amount of peptide 1185 detected in urine and feces 24 hours after oral administration (95 doses). 00521 Fig. 19A and 198 show pharmacokinetic data for peptide inhibitor 1II/-238 of peptide 980. FIG. 19A shows the concentration of peptide 980 in serum and in samples taken from the small intestine and colon. Fig. 198 shows the amount of peptide 980 found in urine and feces 24 hours after oral administration (95 doses).

DETAILED DESCRIPTION OF THE INVENTION 0053) Unless otherwise specified herein, scientific and technical terms used in this application shall have the meanings generally accepted by those skilled in the art.

In general, the nomenclature used in relation to and technically related to the chemistry, molecular biology, cell and cancer biology, immunology, microbiology, pharmacology, and protein and nucleic acid chemistry described herein are well known and common in the art.

II0054| When used in this document, the following expressions have the meanings ascribed to them, unless otherwise indicated.

І0055| Throughout this description, the word "comprises" or variants such as "comprises" or "which

"contains" shall be understood as including the specified integer (or components) or group of integers (or components) and not excluding any other integer (or components) or group of integers (or components). 0056) Singular Forms include plural forms unless the context clearly indicates otherwise.

II0057| The expression "including" is used as such to mean "including, but not limited to". "Including" and "including but not limited to" are used interchangeably.

I0058| The terms "patient," "subject," and "person" are used interchangeably and refer to either a human or a non-human animal. These expressions include mammals such as humans, primates, domestic animals (eg, cows, pigs), companion animals (eg, dogs, cats), and rodents (eg, mice and rats).

I0059| 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 mean a specific length of the amino acid polymer, nor is it intended to include or distinguish whether the polypeptide is obtained by recombinant techniques, or by chemical or enzymatic synthesis, or is naturally occurring.

IOO60O| References to "sequence identity," "percent identity," "percent homology," or, for example, that include "a sequence 50 95 identical to," as used herein, refer to the degree to which the sequences are identical on a nucleotide-by-nucleotide basis or on an amino acid by amino acid basis in the comparison range. Thus, "percent sequence identity" can be calculated by comparing two optimally aligned sequences within the comparison range, determining the number of positions at which the nucleic acid bases are identical (e.g., A, T, C, b, I) or the amino acid residues are identical (e.g., Aa, Rgo, 5eg, Tig, Spu, Mai, I ey, Pe, Rnee, Tug, Ttr, Guz, Ak, Niv, Avr, SIM,

Aup, Sip, Suh, and Me) occur in both sequences, to obtain the number of matching positions, divide the number of matching positions by the total number of positions in the comparison range (ie, the size of the range), and multiply the result by 100 to obtain percent sequence identity.

ІОО61| Calculations of sequence similarity or sequence identity between percentage sequences (the terms are used interchangeably in this document) can be carried out as follows. To determine the percent identity of two amino acid 60 sequences or two nucleic acid sequences, the sequences may be aligned for optimal comparison purposes (eg, blanks may be introduced in one or both of the first and second amino acid or nucleic acid sequences for optimal alignment and non-homologous sequences may be disregarded for comparison purposes ). In some embodiments, the length of the control sequence aligned for comparison purposes is at least 30 95, preferably at least 40 95, more preferably at least 5095, 6095, and even more preferably at least 70 95, 8095, 90 95, 100 95 of the length of the control sequence. The amino acid residues or nucleotides in the 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 two sequences is a function of the number of identical positions that the sequences have, taking into account the number of gaps, and the length of each gap, that must be introduced to optimally align the two sequences.

II0063| Comparison of sequences and determination of percent identity between two sequences can be carried out using a mathematical algorithm. In some embodiments, the percentage identity between two sequences is determined using the algorithm of Meedietap and MUip5sp (1970, 9. Mo!. Vioi. 48: 444-453), which was included in the program

SAR in the CSO software package, using either the Viozzit 62 matrix or the RAM250O matrix, and a gap mass of 16, 14, 12, 10, 8, 6, or 4, and a length mass of 1, 2, 3, 4, 5, or 6. B in another preferred embodiment, the percent identity between two sequences is determined using the SAR program in the Co software package using the MUUZdarap.SMP matrix and a gap mass of 40, 50, 60, 70, or 80, and a length mass of 1, 2, 3, 4, 5 or 6. Another typical set of parameters includes a Vio55it 62 score matrix with a sequence gap penalty of 12, a continuation deletion 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 E. Meueeeegz and

MU. MiPeg (1989, Sabiov, 4: 11-17), which was included in the AGISM program (version 2.0), using the РАМ120 residue mass table, with a penalty for continuing the deletion of 12 and a penalty for a gap in the sequence of 4.

From I0064| Peptide sequences described in this document can be used as a "desired sequence" to perform a search in general databases, for example, to identify other family members or related sequences. Such searches can be performed with the help of programs MVI AB5T and KhVI A5T (version 2.0) by Aib5sPpii et al. (1990, 9.

My. Vioi, 215: 403-10). You can search for VHA5T nucleotides using the program

MVIGAZT, index - 100, word length - 12, to obtain nucleotide sequences homologous to nucleic acid molecules of this invention. The search for VHA5T proteins can be performed using the HVI A5T program, index - 50, word length - 3, to obtain amino acid sequences homologous to protein molecules of this invention. To obtain alignments with blanks for comparison purposes, VIAZT with blanks can be used as described in Aiii5zspia! and co-author (Myseis Asid5 Kev5. 25:3389-3402, 1997). When using VI AZ5T and VG A5T programs with spaces, the default parameters of the respective programs (for example, ХВИ АБ5Т and МВИ А5Т) can be used. 0065) The term "conservative substitution" as used herein means that one or more amino acids are replaced by another, biologically similar residue. Examples include substitution of amino acid residues with similar characteristics, such as small amino acids, acidic amino acids, polar amino acids, basic amino acids, hydrophobic amino acids, and aromatic amino acids.

See, for example, the table below. In some embodiments of the present invention, one or more Mye residues are replaced by norleucine (Mye), which is a bioisoster for Mey, but which, unlike Mey, is not easily oxidized. Another example of a conservative substitution for a residue that is not usually found in endogenous peptides and mammalian proteins is a conservative substitution of Ag or I uh, for example, with ornithine, canavanine, aminoethylcysteine, or another basic amino acid. In some embodiments, one or more cysteines of a peptide analog of the present invention can be replaced with another residue, such as serine. For additional information regarding phenotypically silent substitutions in peptides and proteins, see, e.g., Vol. zsiepse 247, 1306-1310, 1990. In the diagrams below, conservative substitutions of amino acids are grouped by physicochemical properties. I: neutral, hydrophilic, II: acids and amides, I: basic, IM: hydrophobic, U: aromatic, bulky amino acids.

1 Her "Her tm Uh 8 | o | v | Her Her xx t | E | Kk | m

R Her OI |mM a! 1 1 s 7 0066) In the diagram below, conservative substitutions of amino acids are grouped by physicochemical properties. MI: neutral or hydrophobic, MI: acidic, MP: basic, IH: polar, X: aromatic. - Her o | in |5 | xx 171 1 kt m

R YY HER | with her | m sew stitches on PO with Zo PO

І0067| The term "amino acid" or "any amino acid" as used herein refers to any and all amino acids, including naturally occurring amino acids (eg, α-amino acids), synthetic amino acids, modified amino acids, and non-natural amino acids. It includes both 0- and | - amino acids. Natural amino acids include those that are found in nature, such as, for example, the 23 amino acids that combine into peptide chains to form structural elements of many proteins. They are mainly |I- stereoisomers, although a few 10-amino acids are found in the envelopes of bacteria and some antibiotics. The 20 "standard", natural amino acids are listed in the tables above. "Non-standard", naturally occurring amino acids are opyrrolizine (found in methane-producing organisms and other eukaryotes), selenocysteine (found in many non-eukaryotes as well as most eukaryotes), and M-formylmethionine (encoded by the start codon

ACC in bacteria, mitochondria and chloroplasts). "Unnatural" or "unnatural" amino acids are non-proteinogenic amino acids (ie, those that do not encode or are not found naturally in the genetic code) that are either naturally occurring or chemically synthesized. More than 140 unnatural amino acids are known, and thousands or more combinations are possible. Examples of "unnatural" amino acids include B-amino acids (BZ and D2), homoamino acids, derivatives of proline and pyruvic acid, derivatives of C-substituted alanine, derivatives of glycine, derivatives of ring-substituted phenylalanine and tyrosine, linear nuclear amino acids, diamino acids, SO-amino acids, alpha-methylamino acids and M-methylamino acids. Unnatural or unnatural amino acids also include modified amino acids. "Modified" amino acids include amino acids (eg, naturally occurring amino acids) that have been chemically modified to include a group, groups, or chemical moiety not naturally occurring in an amino acid. In some embodiments, the peptide inhibitor contains an intramolecular bond between two amino acid residues in the peptide inhibitor. It is clear that the amino acid residues that form the bond will change slightly when they are bonded to each other compared to when they are not bonded to each other. Reference to a specific amino acid is meant to include that amino acid in both its unbound and bound states. For example, the amino acid residue homoserine (pZeg) or homoserine (SI) in its unbound form can take the form of 2-aminobutyric acid (Aby) when participating in an intramolecular bond according to the present invention. The present invention includes both peptide inhibitors containing crosslinks between XA and XO, and peptide inhibitors that do not contain crosslinks between X4 and XU, for example, before the formation of crosslinks. Thus, the names pbeg and Aby must indicate the same amino acid and are used interchangeably. 0068) In general, the names of the naturally occurring and non-naturally occurring aminoacyl residues used in the present invention conform to the naming convention proposed by the ISHSRAS Commission on Nomenclature in Organic Chemistry and the IORAS-ISV Commission on Biochemical Nomenclature as specified in "Motepsiait oi a-atipoacid5 (Kesottepaayop5, 1974)"

Viospetivzigu, 14(2), (1975). To the extent that the names and abbreviations of amino acids and aminoacyl residues used in this specification and the appended claims differ from these indications, they will be understood by the reader. Some abbreviations useful in describing the present invention are defined below in the following Table 1A.

I00O69

Table 1A

Abbreviation of unnatural amino acids and chemical fragments (for amino acid derivatives, all AND unless otherwise specified)

Layer, Isdiaminopropionovakislotad///://СС:(/4И1СССССССССsS bar Isdiaminobutyric acid.d//////СС:(/и//////////С/:/3//ЗКдДбС( and May 2. May 1.

Vr 77777771 1-44-biphenylalann.o/////////777777СсС1С

Table 1A

Abbreviations of unnatural amino acids and chemical fragments (for derived amino acids, all AND, unless otherwise indicated) ры я Мне (о)

Rpe|4-(2-aminoethoxy) sleep

Mne 4-(2-aminoethoxy)-I-phenylalanine

Table 1A

Abbreviation of unnatural amino acids and chemical fragments (for amino acid derivatives, all AND unless otherwise specified)

Nn

M

4-amino-4-carboxypiperidine sa

NM Son 4-amino-4-carboxypiperidine

PRPE(3,4-dimethoxy) 3,4-dimethoxy-1 -homophenylalanine

Rpe(2,4-Meg2 2,4-dimethyl-i!-phenylalanine

Rpe(3,5-ER2 C,5-difluoro-I-phenylalanine

Rpe(penta-E pentafluoro-y!-phenylalanine 2,5,7-tert-butyl-Ttr 2,5,7-tris-tert-butyl-I -tryptophan o

Yew

MN

I-1,2,3,4,-tetrahydroisoquinoline-3-carboxylic acid

Rpe(4-Oallyl)

Rpe (4-M

Asps Fr

NOM sleep 1-aminocyclohexanecarboxylic acid

Asus

Nam Song 1-aminocyclopentanecarboxylic acid

Asrs

NhM son 1-aminocyclobutanecarboxylic acid

Asrse; ' nom son 1-aminocyclopropylcarboxylic acid

Table 1A

Abbreviation of unnatural amino acids and chemical fragments (for amino acid derivatives, all AND unless otherwise specified) 6) 4-amino-4-carboxytetrahydropyran (also called TNR)

NM Son 4-amino-4-carboxytetrahydropyran

I0070| Throughout this specification, unless naturally occurring amino acids are referred to by their full names (eg, alanine, arginine, etc.), they are referred to by their common three-letter or one-letter abbreviations (eg, Aia or A for alanine, Agud or K for arginine, etc.). Unless otherwise indicated, three-letter or one-letter amino acid abbreviations refer to the GI isomeric form of the specified amino acid. The term "I-amino acid" as used herein refers to the "I" isomeric form of the peptide, and conversely the term "O-amino acid" refers to the "p" isomeric form of the peptide (eg, Oazr, (0)A5p or O-Azr; Orpe, (0)Rpe or p-Rpe). Amino acid residues in the JO isomeric form can be replaced by any |I- amino acid residue, since the desired function is preserved by the peptide. O-amino acids can be indicated as usual in lower case when using one-letter abbreviations. 0071) In the case of less common or non-naturally occurring amino acids, if they are not called by their full name (eg, sarcosine, ornithine, etc.), frequently used three- or four-digit codes are used for their residues, including zag or 5ags (sarcosine, i.e. M- methylglycine), AlYib (α-aminoisobutyric acid), Bab (2,4-diaminobutyric acid), Yuara (2,3-diaminopropanoic acid), y-SiIy (y-glutamic acid), Csaba (y-aminobutyric acid), B -Rho (pyrrolidine-3-carboxylic acid) and 8Ado (8-amino-3,b-dioxaoctanoic acid), Aby (2-aminobutyric acid), VpRho (B-homoproline), VyRpe (B-homophenylalanine) and Vir (B ,p-diphenylalanine), and Ida (iminodiacetic acid). 00721 One skilled in the art will appreciate that the peptide sequences disclosed herein are shown from left to right, with the left end of the sequence being the M-terminus of the peptide and the right end of the sequence being the C-terminus of the peptide. Among the sequences disclosed herein are sequences that include a "Nu-" fragment at the amino-terminus (M-terminus) of the sequence, and/or an "-OH" fragment, or a "-MHg" fragment at the carboxy-terminus (C -ends) of the sequence. In such cases and unless otherwise indicated, the "Nu-" fragment at the M-terminus of the desired sequence shows a hydrogen atom corresponding to the presence of a free primary or secondary amino group at the M-terminus, while the ""OH" or 3-MH:" fragment at the C-terminus of the sequence shows a hydroxy group or an amino group, corresponding to the presence of an amido (СОМН») group at the C-terminus, respectively. In each sequence of this invention, the "-OH" fragment of the C-terminus can be replaced by the "-МНе" fragment of the C-terminus, and vice versa.

From I0073| The term "OKR" as used herein refers to disulfide-rich peptides.

I0074| The term "dimer" as used herein refers broadly to a peptide containing two or more monomeric subunits. Some dimers contain two OCRs.

Dimers of the present invention include homodimers and heterodimers. Monomeric subunit

C5 of the dimer can be linked at its C- or M-terminus, or it can be linked through internal amino acid residues. Each monomer subunit of the dimer may be bound through the same site, or each may be bound through a different site (e.g.

C-end, M-end or internal site).

I0075| The term "MN" as used herein may refer to a free amino group located at the amino terminus of a polypeptide. The term "OH" as used herein may refer to a free carboxy group located at the carboxy terminus of a peptide.

In addition, the term "Ac" as used herein refers to acetyl protection by acylation of the C- or M-terminus of the polypeptide. In some of the peptides shown herein, MH'' located at the C-terminus of the peptide indicates an amino group. 0076) The term "carboxy" as used herein refers to -СО2Н.

I0077| The term "isostere replacement" as used herein refers to any amino acid or other similar fragment having chemical and/or structural properties similar to that of the 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 a polypeptide molecule to form a closed ring, for example by forming a disulfide bridge or other similar bond.

I0079| The term "subelement" as used herein refers to one of a pair of polypeptide monomers that are joined to form a dimeric peptide composition.

I0O80| The term "linker fragment" as used herein broadly refers to a chemical structure that is capable of linking or joining together two peptide monomer subunits to form a dimer.

I0081|) The term "pharmaceutically acceptable salt" as used herein indicates salts or zwitterionic forms of the peptides or compounds of the present invention which are soluble or dispersible in water or oil, suitable for the treatment of diseases without undesirable toxicity, irritation and allergic reaction ; which meet the appropriate effect/risk ratio and which are effective for their intended use. Salts can be obtained in the final separation and purification of compounds or separately by reaction of an amino group with a corresponding acid. Typical 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-hydroxyethanesulfonate (isothionate), lactate, maleate, mesitylene sulfonate, methanesulfonate, nicotinate, naphthalene sulfonate, 2-naphthalene sulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, para-toluenesulfonate and undecanoate. Also, amino groups in the compounds of this invention can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl and diamyl sulfates; decim-, lauryl-, myristyl- and steryl chlorides, bromides and iodides; and benzyl and phenethyl bromides. Examples of acids that can be used to prepare therapeutically useful addition salts include inorganic acids such as hydrochloric,

Of hydrogen bromide, sulfuric and phosphoric, and organic acids such as oxalic, maleic, succinic and citric. A pharmaceutically acceptable salt may accordingly be a salt selected, for example, from 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 from alkali metal cations such as sodium or potassium ions, alkaline earth metal cations such as calcium or magnesium ions, and substituted ammonium ions such as ions of the type M(К1ХК2Х(3)(К4 )k, where Q1, Q2, Q3, and Q4 will independently typically represent hydrogen, optionally substituted C1-6b-alkyl, or optionally substituted C2-6b-alkenyl. Examples of suitable C1-6-alkyl groups include methyl, ethyl, 1-propyl and 2-propyl groups. Examples of possible suitable C2-6-alkenyl groups include ethenyl, 1-propenyl, and 2-propenyl. Other examples of pharmaceutically acceptable salts are described in Ketipd(op'5 Rpagtasecisa!

Zsiepsev", 171st edition, AMopzo V. Seppago (Ed.), Mak Rybiizpipd Sotrapu, Eaviop, RA, О5А, 1985 (and more of his new editions), in "Epsusiorayedia oi Rpaptaseshisa! Thesppoiodu", For eaiiop,

Uatevs zuaggisk (Ea.), Ipiogta Neaipsage OA (Ips.), MU, OA, 2007, and in 9. Rpapt. from 66: 2 (1977). Also, for a review of suitable salts, see Naparook oi Rpagptasetschiysa! Extra: Rgorepgiev5, zeiiIesiop, apa Obe from eiapi apa UMegptii (UmMieu-MSN, 2002). Other suitable basic salts are formed from bases that form non-toxic salts. Typical examples include aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc salts. Half salts of acids and bases can also form, for example, hemisulfate and hemicalcium salts.

I0082| The term "M(alpha)methylation" as used herein describes methylation of the alpha-amine of an amino acid, also commonly referred to as M-methylation. 0083) The term "symmetric methylation" or "Agd-Me-zut" as used herein describes the symmetrical methylation of the two nitrogens of the guanidine group of arginine. In addition, the expression "asymmetric methylation" or "Agd-Me-nitrogen" describes the methylation of one nitrogen of the guanidine group of arginine. (0084) The term "acylating organic compounds" as used herein refers to various compounds with a carboxylic acid functional group that are used to acylate the M-terminus of an amino acid, or a monomer, or a dimer, e.g., a full-length subunit, before 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,

cyclopentanecarboxylic acid, 3,3,3-trifluoropropionic acid, 3-fluoromethylbutyric acid, tetrahydro-2H-pyran-4-carboxylic acid.

I0085| The term "alkyl" includes a straight or branched, acyclic or cyclic, saturated aliphatic hydrocarbon having 1-24 carbon atoms. Typical saturated straight alkyls include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, and the like, while saturated branched alkyls include, but are not limited to, isopropyl, sec-butyl, isobutyl , tert-butyl, isopentyl and the like. Typical saturated cyclic alkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like, while unsaturated cyclic alkyls include, but are not limited to, cyclopentenyl, cyclohexenyl, and the like. 0086) The term "mammal" refers to any kind of mammal, such as human, mouse, rat, dog, cat, hamster, guinea pig, rabbit, domestic cattle and the like.

I0087| As used herein, a "therapeutically effective amount" of a peptide inhibitor of the present invention is intended to describe a sufficient amount of the peptide inhibitor to treat an II-23/LI-23K induced disease, including, but not limited to, any of the diseases and disorders described herein. (eg, to reduce inflammation associated with IVI). In specific embodiments, a therapeutically effective amount will achieve the desired effect/risk ratio in the field of any medical treatment. (0088) "Analog" of an amino acid, for example, "analog Ppe" or "analog Tug" means an analog of the specified amino acid. Various amino acid analogs are known and available in the art, including analogs of PpNe and Tug. In some embodiments, an amino acid analog, for example, a Pe analog or a Tug analog, contains one, two, three, four, or five substitutions compared to Ppe or Tug, respectively. In some embodiments, substitutions are present on amino acid side chains. In some embodiments, the Ppe analog has the structure Ppe(K-), where K2 is Nu, OH, CHZ, SON, SOMN:, SOMNgOSnNSNeMH", I1-Vy, OCH2CHa2MH", phenoxy, OCHz,

Oalyl, Vg, SI, B, MH, MZ3 or guanadino. In some embodiments, K2 is

SOMnNgOoSnNgsSNaMNn»eg, OSNz, SOMNg, OSNz or SON. Examples of Ppe analogs include, but are not limited to: pPe, Ppe(4-OMe), a-Me-Pne, pPRNe(3,4-dimethoxy), PPE(4-COMH), PNe(4-phenoxy), Ppe( 4-guanadino), Rpe(4-IVy), Rpe(4-SM), Rpe(4-Vg), Rpe(4-OV821I), Rpe(4-MN»e), VIR Ppe(4-

E), Pne(4-E), Ripe(3,5-Oie), Pne(CH2CO»ZN), Rpe(penta-PE), Rpe(3,4-C1 2), Rne (3,4-Eg ), Rpe(4-CE),

Coo) BV-aRnelAia, Rie(4-Mz), Rpe((4-(2-aminoethoxy)|), 4-phenylbenzylalanine, RHE(4-SOMH»g), Rie(3,4-dimethoxy), Rpe( 4-SEz), Rnpe(2,3-SiI2) and RNE(2,3-Eg). Examples of Tug analogs include, but are not limited to: pTug, M-Me-Tug, Tuc(Z-IVy), Tup(4 -Mz) and VA Tug.

Peptide inhibitors I. -23A

I0089| Genome-wide association search (ZUMA5) showed a significant association of the receptor gene

I--23 (1-23K) with inflammatory bowel disease (IBD), showing that the signaling disorder

I/-23 may be related to the pathogenesis of the disease. The present invention provides compositions and methods for modulating the I/-23 pathway through selective antagonism of I/-23K by oral treatment with peptides that are stable and limited to gastrointestinal (GI) tissue. Novel inhibitory peptides that are uniquely limited by redox conditions and proteolytic cleavage in various assays that mimic different compartmental environments (Ci) have been identified. Functionally, these peptides potently neutralize 1-23-mediated signaling in a transformed human cell line and in primary cells binding of II-23E is selective, since the peptides do not block the interaction between II-6 and

I/-6K, or counteract the signaling pathway 1-12. In addition, these oral peptides are effective in ameliorating colitis in a 2,4,6-trinitrobenzenesulfonic acid (TMB5)-induced acute IVI model in the rat, as shown by significant reductions in colonic weight-to-length ratio, colonic macroscopic score, neutrophil infiltration, and histopathology in comparison with the control tAb against I-23p19. 0090) The present invention relates in general to peptides having antagonistic activity to II-- 23K, including both peptide monomers and peptide dimers. In some embodiments, the present invention provides a new type of treatment for IVI and other diseases and disorders by oral delivery of II/-23 antagonists. IVO represents local inflammation of intestinal tissue; thus, preferred therapeutic agents will act from the luminal side of the intestine, yielding high drug concentrations in the inflamed tissue, minimizing systemic availability, and providing superior efficacy and safety compared to systemic approaches. Oral administration of the compounds of the present invention is expected to maximize drug levels in inflamed intestinal tissue while limiting circulating drug concentrations, while providing effective, safe, and sustained delivery for the long-term treatment of IVI and other diseases and disorders. 60 ЙО091| In some embodiments, the present invention relates to various peptides or peptide dimers containing hetero- or homomonomeric subunits that form cyclized structures through disulfide or other bonds. In some embodiments, the disulfide or other bonds are intramolecular bonds. Cyclized structures of peptide monomeric inhibitors and monomeric subunits of peptide dimer inhibitors have been shown to increase the potency and selectivity of peptide inhibitors. In some embodiments, the peptide dimer inhibitor can include one or more intramolecular bonds connecting two monomeric peptide subunits in the peptide dimer inhibitor, for example, an intramolecular bridge between two cysteine residues, one in each peptide monomer subunit. 00921 The present invention provides peptide inhibitors that bind to II -23E, which can be monomers or dimers. In specific embodiments, peptide inhibitors inhibit the binding of 1I-23 to II-23K. In some embodiments, II-23K is a human 1I-23K, and

I/-23 is a person's II/-23. In some embodiments, the peptide inhibitor of the present invention reduces the binding of IL-23 to IL-23K by at least 20 95, at least 30 95, at least 40 95, at least 50 956, at least 60 956, at least 70 95, at least 80 95 or at least 90 95 compared to the negative control peptide.

Methods for determining binding are known in the art and include EGG I5A assays, as described in the accompanying examples. 0093) In some embodiments, the 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, " TO NM, " 5

NM, 2 NM, 1 nM or 5 mM, for example, to inhibit the binding of I/-23 to I/-238 (eg, human I/-23 and human I-23K). Methods for determining activity are known in the art and include any of those described in the accompanying examples. 0094) In some embodiments, the peptide inhibitor of the present invention has increased stability, increased stability in the gastrointestinal tract, or increased stability in simulated intestinal fluid (5IE) or simulated gastric fluid (5OBE), and/or under redox conditions (e.g., OTT) compared to the control peptide. In some embodiments, the control peptide is an unrelated peptide of the same or similar length. In specific embodiments, the control peptide is a peptide with an identical or very similar amino acid sequence (for example, » 90 95 sequence identity) as a peptide inhibitor. A control peptide is a peptide with an identical or very similar amino acid sequence (eg, » 90 95 sequence identity) to the peptide inhibitor, but which does not have a cyclized structure, for example by an intramolecular bond between two amino acid residues in the control peptide, or which does not dimerized, or which does not contain a conjugate for stabilization. In specific embodiments, one difference between a peptide inhibitor and a control peptide is that the peptide inhibitor contains one or more amino acid substitutions that introduce one or more amino acid residues into the peptide inhibitor, wherein the introduced amino residue(s) form an intersulfide, disulfide, or thioether bond. connection with another amino acid residue in the peptide inhibitor. One example of a control for a peptide dimer inhibitor is a monomer with the same sequence as one of the monomer subunits in the peptide dimer inhibitor. One example of a control for a peptide inhibitor containing a conjugate is a peptide with the same sequence but without the conjugate fragment. In some embodiments, the control peptide is a peptide (eg, a naturally occurring peptide) that corresponds to the II-23 region that binds to II-23B. 0095) Methods of determining peptide stability are known in this area. In some embodiments, the stability of the peptide inhibitor is determined using a BIR assay, e.g., as described in Example 3. In some embodiments, the stability of the peptide inhibitor is determined using a 5OE assay, e.g., as described in Example 3. In specific embodiments, the peptide inhibitor has a period half-deduction (for example, in 5IE, or

ZORE, or OTT) under specified conditions (for example, temperature) for more than 1 minute, more than 10 minutes, more than 20 minutes, more than 30 minutes, more than 60 minutes, more than 90 minutes, more than 120 minutes, more than 3 hours or more than four hours in action 5IE, or ZORE, or OTT. In some embodiments, the temperature is about 25°C, about 49°C, or about 372°C, and the pH is physiological pH, or a pH of about 7.4. 0096) In some embodiments, the half-life is measured by any suitable method, known in the field, for example, in some embodiments, the stability of the peptide of this invention is determined by incubating the peptide with preheated human blood serum (5IDTA) at 372 C. Samples are taken at various points in time, typically 60 to 24 hours, and the stability of the sample is analyzed by separation of the peptide or peptide dimer from serum proteins, and then analysis for the presence of the desired peptide or peptide dimer using I C-M5.

II0097| In some embodiments, a peptide inhibitor of the present invention exhibits improved solubility or improved agglomeration characteristics compared to a control peptide. Solubility can be determined by any suitable method known in the art. In some embodiments, suitable methods known in the art to determine solubility include incubating the peptides in various buffers (acetate pH 4.0, acetate pH 5.0, phosphate/citrate pH 5.0, phosphate/citrate pH 6.0, phosphate pH 6.0, 0, phosphoric pH 7.0, phosphoric pH?7.5, strong RVZ pH 7.5, tris pH 7.5, tris pH 8.0, glycine pH 9.0, water, acetic acid (pH 5.0 and others , known in the art) and testing for aggregation or solubility using standard techniques. These include, but are not limited to, visual deposition, dynamic light scattering, circular dichroism, and fluorescent dyes, to measure surface hydrophobicity and detect aggregation or fibrillation, for example. In in some embodiments, improved solubility means that the peptide is more soluble in a given fluid than a control peptide In some embodiments, improved aggregation means that a peptide has less aggregation in a given fluid under a given set of conditions than a control peptide.

I0098| In some embodiments preferred to obtain high concentrations of the compounds in intestinal tissues upon oral delivery, the peptide inhibitors of this invention are stable in the gastrointestinal (GI) environment. Proteolytic metabolism in this tract is provided by enzymes (including pepsins, trypsin, chymotrypsin, elastase, aminopeptidases and carboxypeptidases A/B), which are secreted from the pancreas into the lumen or 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 can be destroyed, which gives a linear peptide and rapid proteolysis. This oxidation-reduction environment of the lumen is largely determined by the oxidation-reduction cycle Suz/Suz5. In enterocytes, similar activities include a number of digestive enzymes, such as SUR450 and OOR-glucuronyltransferase. In the end, the bacteria present in the large intestine in a concentration ranging from 1010 to 1012 CFU/ml make up another

Co) metabolic barrier. In some embodiments, the peptide inhibitors are stable to different pHs ranging from highly acidic in the stomach (pH 1.5-1.9), through basic in the small intestine (pH 6-7.5), and then weakly acidic in the large intestine (pH 5-7). Such peptide inhibitors are stable as they move through various regions of the GI tract, a process estimated to take 3-4 hours in the intestine and 6-48 hours in the colon.

І0099| In some embodiments, the peptide inhibitors of the present invention degrade less, e.g., over a period of time (ie, are more stable to degradation, e.g., greater than or about 1095 less, greater than or about 20 95 less, greater than or about 30 95 less, greater or about 40 less or more or about 50 95 less than the degradation of the control peptide. In some embodiments, stability to degradation is determined by any suitable method known in the art. In some embodiments, the degradation is enzymatic degradation. For example, in in some embodiments, the peptide inhibitors have a reduced susceptibility to degradation by trypsin, chymotrypsin, or elastase. In some embodiments, suitable methods known in the art for determining stability to degradation include the method described in Nauge et al., in Rpagt 5si, MOG 101 , Mo. 3, 2012, pp. 895-913, which is fully included in this document. Such methods in some variants of implementation are used to select strong peptide sequences with increased shelf life. In specific embodiments, peptide stability is determined by BIR analysis or ZOE analysis as described herein. 00100) In some embodiments, peptide inhibitors of the present invention inhibit or reduce IL-23-mediated inflammation. In related embodiments, peptide inhibitors of the present invention inhibit or reduce 1-23-mediated secretion of one or more cytokines, for example, by binding to II-23K on the surface of cells, thus inhibiting the binding of II-23 to the cell. In specific embodiments, the peptide inhibitors of this invention inhibit or reduce 1-23-mediated activation of Chak2, Ttuk2, aj, az, ia or 5iaii5. Methods for determining inhibition of cytokine secretion and inhibition of signaling molecules are known in the art. For example, inhibition of IL-23/LI-23K signaling can be determined by measuring inhibition of phospho-5αi33 levels in cell lysates as described in the accompanying examples, including Example 2. In some embodiments, the peptide inhibitors of the present invention inhibit or reduce IL-mediated IL /-23 inflammation. In related embodiments, the peptide inhibitors of this invention inhibit or reduce 1-23-mediated secretion of one or more cytokines, for example, by binding to II-23K on the surface of cells, thus inhibiting I-23 binding to the cell. In specific embodiments, the peptide inhibitors of this invention inhibit or reduce 1-23-mediated activation of Chak2, Ttuk2, ai, zaz, ia, or 5(ai5). Methods of determining inhibition of cytokine secretion and inhibition of signaling molecules are known in the art. For example, inhibition of signaling I - 23/I -23K can be determined by measuring the inhibition of phospho-5αi33 levels in cell lysates, as described in the accompanying examples, including example 2. 00102) In some embodiments, peptide inhibitors have increased stability to redox conditions compared to a control peptide. Various assays that can be used to determine redox stability are known and available in the art. Any of them can be used to determine the stability to redox conditions of the peptide inhibitors of this invention. 00103) In some embodiments, the present invention provides various peptide inhibitors that bind or associate with II-23E, ip migo or ip mimo, to disrupt or block the connection between IC-23 and I/-231. In some embodiments, peptide inhibitors bind to and/or inhibit human I/-23K. In some embodiments, peptide inhibitors bind to and/or inhibit both human and rodent I/-23K. In some embodiments, peptide inhibitors bind to and/or inhibit both human and rat II-23K. In specific embodiments, the peptide inhibitors inhibit rat I/-23K by at least 5095, at least 6095, at least 7095, at least 8095, at least 9095, or at least 9595 as they bind or inhibit Human I--23K, for example, as determined by the assay described herein. In some embodiments, peptide inhibitors preferentially bind to and/or inhibit human and/or rat II-23K over II-23E. mouse In specific embodiments, peptide inhibitors preferentially bind to rat IL-23K compared to

I/-23K mouse. In specific embodiments, peptide inhibitors preferentially bind to human EI-23K compared to mouse EI-23K. In some embodiments, binding of the peptide inhibitor to mouse I/-23K is 75,956 less, 50,96 less, 40,95 less, 30,95 less,

Of 2095 less or 10 95 less than the binding of the same peptide inhibitor to human I/-23A and/or rat II-23K. In some embodiments, the peptide inhibitors that preferentially bind to and/or inhibit human I/-23E and/or rat I/-23K compared to mouse I/-23K, the peptide inhibitors bind to the II-23E region, which is destroyed due to the presence of additional amino acids present in I--23E. mouse, and not in human II-23K or rat I-23. In one embodiment, the additional amino acids present in mouse 1-23 are in a region corresponding from about amino acid residue 315 to about amino acid residue 340 of mouse protein I, 23K, e.g., the amino acid region MMORUZZREMNOTZOETOKK (5EO I

MO:1355) (see, for example, Fig. 4). In specific embodiments, the peptide inhibitors bind to the human II-23K region from about amino acid residue 230 to about amino acid residue 370. 00104) In some embodiments, the peptide inhibitors show limited localization after oral administration. In specific embodiments, more than 50 95, more than 60 95, more than 7095, more than 8095 or more than 9095 of the orally administered peptide inhibitor is localized in the organs and tissues of the gastrointestinal tract. In specific embodiments, the plasma levels of the orally administered peptide inhibitor are less than 2095, less than 10 95, less than 5 95, less than 2 95, less than 1 95, or less than 0.5 95 of the levels of the peptide inhibitor found in the mucosa of the small intestine, mucosa colon or proximal colon. 00105) The various peptide inhibitors of this invention can consist only of natural amino acids. Alternatively, peptide inhibitors may include unnatural amino acids, including, but not limited to, modified amino acids. In some embodiments, modified amino acids include naturally occurring amino acids that have been chemically modified to include a group, groups, or chemical moiety that is not naturally found in an amino acid.

Peptide inhibitors of this invention may additionally contain one or more O-amino acids.

Peptide inhibitors of this invention may also contain amino acid analogues. 00106) In some embodiments, the peptide inhibitors of this invention include one or more modified or unnatural amino acids. For example, in some embodiments, the peptide inhibitor contains one or more of Bab, Var, Rep, Zags, Siiii, Sam, PI ey, 2-

Mai, 0-1-Mai, O-2-Mai, Rpe(4-OMe), VyTgr, a-MeRve, a-Metug, o-MetTtr, B-NRnee, Rpe(4-SEz), 2-2- 60 indane, 1-1-indane, cyclobutyl, B-pRNe, Spa, Rne(4-MH»g), pRNeE, 1-Mai, Mie, homoamino acids, Yu-

amino acids, 4,4"-biphenylalanine (Vir), cyclobutyl-Al, pSpa, VyRPpe, Vcym, Rpe(4-guanidino),

Rpe|(4-(2-aminoethoxy))|, Rpe|4-(2-acetylaminoethoxy)), Rpe(4-SOMH»), Rpe(4-Me), Tu((B2I) or

Tuk(Me), Rpe(3,4-dig2), Rpe(3,4-Si"), Rpe(3-Me), Rpe|4-(2-aminoethoxy))|, Rpe|4-(2- Acetylaminoethoxy)|

Rpe(4-MNeg), Rpe(4-Mz), Tug, Tu((B2I) or Tug((Me), Rpe(3,4-dimethoxy), 5-hydroxyTgr, Rpe(3,4-Si") ,

Tuk(Z-IVy) and various M-methylated amino acids and alpha-methylated amino acids. In some embodiments of the present invention, the peptide inhibitor contains one or more of the unnatural amino acids shown in Table TA. One skilled in the art will appreciate that other modified or non-natural amino acids, and various other substitutions of natural amino acids with modified or non-natural amino acids, can be made to obtain similar desired results, and such substitutions are within the spirit and scope of this invention. In some embodiments, the peptide inhibitors of the present invention include any of those described herein, including, but not limited to, any of those containing the peptide inhibitor amino acid sequence or structure shown in any of the tables herein , accompanying sequence listings, or accompanying figures, wherein one or more residues are a substituted modified or non-natural amino acid.

I00107| The present invention also includes any of the peptide inhibitors described herein, either in free form or in salt form. Thus, embodiments of any of the peptide inhibitors described herein (and related methods of their use) 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 peptide inhibitor comprising a sequence shown in any of the tables herein, the accompanying sequence listings, or accompanying figures, and one or more I-amino acid residues are replaced by ХО with an isomeric form of an amino acid residue, for example, I-Aia is replaced by O-Aia.

IІ00109| In specific embodiments of the peptide inhibitors described herein, they contain one or more unnatural or non-naturally occurring

From amino acid residues. 00110) The present invention also includes any of the peptide monomeric inhibitors described herein linked to a linker fragment, including any of the specific linker fragments described herein. In specific embodiments, the linker is attached to an M-terminal or C-terminal amino acid, while in other embodiments, the linker is attached to an internal amino acid. In specific embodiments, the linker is attached to two internal amino acids, for example, an internal amino acid in each of the two monomer subunits that form a dimer. In some embodiments of the present invention, the peptide inhibitor is attached to one or more of the shown linker fragments. 00111) The present invention also includes peptides and peptide dimers containing a peptide with at least 90 95, at least 95 95, at least 98 95, or at least 99 95 sequence identity with the peptide sequence of the peptide inhibitor described herein.

In specific embodiments, the peptide inhibitors of the present invention contain a basic peptide sequence and one or more modifications at the M-terminus and/or C-terminus (for example, Ac and MHg) and/or one or more conjugated linker fragments and/or fragments , which prolong the half-life. When used in this document, the main peptide sequence is the amino acid sequence of the peptide, in which there are no such modifications and conjugates. For example, for a peptide inhibitor: (Rait|-(isos1ch|-(PES4A-(Rep|c-

MTM O-|Repi-I(Rpe(4-(2-aminoethoxy)|-(2-Ma!/|-(AiVBI-(uz(Ac))-MM-MNa (ZEO 10 MO:1115), main peptide the sequence is: (RepI-MTUMO-|RepiI-(Rpe(4-(2-aminoethoxy)1|-(2-Map|-I(AIBI|-

I uz(Ac)I-MM (ZEO 1О MO:С1115). 00112) In some embodiments, the peptide inhibitor or monomer subunit of the peptide inhibitor of the present invention contains, consists mainly of, or consists of 7-35 amino acid residues, 8-35 amino acid residues, 9-35 amino acid residues, 10-35 amino acid residues, 7- 25 amino acid residues, 8-25 amino acid residues, 9-25 amino acid residues, 10-25 amino acid residues, 7-20 amino acid residues, 8-20 amino acid residues, 9-20 amino acid residues, 10-20 amino acid residues, 7-18 amino acid residues residues, 8-18 amino acid residues, 9-18 amino acid residues, or 10-18 amino acid residues, and optionally one or more additional non-amino acid bo fragments, such as a conjugated chemical fragment, for example, PEG or a linker fragment. In specific embodiments, the peptide inhibitor of this invention (or its monomer subunit), including, but not limited to, any of the embodiments of formula X, formula I, formula II, formula II, formula IM, or formula MU, contains more than 10, more 12, more than 15, more than 20, more than 25, more than 30 or more than 35 amino acids, for example, 35-50 amino acids. In some embodiments, the peptide inhibitor (or its monomer subunit) contains 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 specific embodiments, the monomer subunit of the peptide inhibitor (or peptide monomeric inhibitor) contains 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 amino acid residues. In specific embodiments, the monomer subunit of the peptide inhibitor of this invention contains or consists of 10-18 amino acid residues and, optionally, one or more additional non-amino acid fragments, such as a conjugated chemical fragment, for example, PEG or a linker fragment. In various embodiments, the monomer subunit contains or consists of 7-35 amino acid residues, 7-amino acid residues, 8-20 amino acid residues, 9-20 amino acid residues, 10-20 amino acid residues, 8-18 amino acid residues, 8-19 amino acid residues , 8-18 amino acid residues, 9-18 amino acid residues or 10-18 amino acid residues. In specific embodiments of any of the various formulas described herein, X contains or consists of 7-35 amino acid residues, 8-35 amino acid residues, 9-35 20 amino acid residues, 10-35 amino acid residues, 7-25 amino acid residues residues, 8-25 amino acid residues, 9-25 amino acid residues, 10-25 amino acid residues, 7-18 amino acid residues, 8-18 amino acid residues, 9-18 amino acid residues or 10-18 amino acid residues. 00113) Some typical peptide inhibitors described herein contain 12 or more amino acid residues. However, the present invention also includes peptide inhibitors containing a fragment of any of the peptide sequences described herein, including peptide inhibitors with 7, 8, 9, 10 or 11 amino acid residues. For example, peptide inhibitors of this invention include peptides containing or consisting of X4-X9, xX4-X10, XA-X11, XA-X12, X4A-X13, XA-X14, XA-X15 or X4-X16. In specific embodiments, the present invention includes peptide inhibitors with any of the sequences described herein, including, but not limited to, those shown in any of the formulas described herein, the sequence listings, or any of the tables provided in this document, where one or more of X10, X11, X12, X13, X14, X15 or X16 are absent. In specific embodiments, one or more of X13, X14, X15, or X16 are absent. 00114) In specific embodiments of the present invention, peptide inhibitors or their X regions are not found in the antibody. In specific embodiments, the peptide inhibitors or their X regions are not in the UN or MI. antibody region.

І00115| In specific embodiments, the peptide inhibitors described herein contain one or more unnatural or non-naturally occurring amino acid residues. 00116) In specific embodiments, the peptide inhibitors of this invention are cyclized through a cyclic amide bond, a disulfide bond, or a thioether bond. In specific embodiments, the bond is an intramolecular bond between two amino acid residues in the peptide inhibitor or its monomer subunit.

Peptide inhibitors

II00117| Peptide inhibitors of the present invention include peptides with any of the amino acid sequences described herein, compounds with any of the structures described herein, including compounds containing any of the peptide sequences described herein, and dimers of any such peptides and compounds.

Peptide inhibitors of this invention include both peptides that do not have, and those that have a connection between X4 and X9, for example, before and after the introduction of crosslinks between X4 and XU. Exemplary peptides of the present invention that contain an amino acid sequence or structure are described in any of the accompanying tables, examples, figures, and sequence listings. 00118) In some embodiments, the present invention includes a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, where the peptide inhibitor contains the amino acid sequence of the formula (xa): xX1-X2-X3-X4-X5-X6-X7-X8- X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Xa) (5EO I

MO:1354), where 60 X1 represents any amino acid or is absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

XA is any amino acid or chemical fragment capable of forming a bond with

HO;

X5 is any amino acid;

Xb is any amino acid;

X7 is any amino acid;

XV is any amino acid;

ХУ is any amino acid or chemical fragment capable of forming a bond with

HA;

X10 is any amino acid;

X11 is any amino acid;

X12 is any amino acid;

X13 is any amino acid;

X14 is any amino acid;

X15 is any amino acid,

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

ИЙО0О119| where X4 and XU are able to form a connection with each other. In specific embodiments, the bond is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefinic bond. In specific embodiments, the bond is a disulfide bond or a thioether bond. In some embodiments, the peptide inhibitor is cyclized via a linkage between XA and XU. In some embodiments, the peptide inhibitor inhibits the binding of interleukin-23 (1-23) to the II/-23 receptor. In specific embodiments, when X4 is not an amino acid, then X1, X2, and X3 are absent. In some embodiments, X1 is Y-

Amino acid or absent. In some embodiments, X2 is a 10-amino acid or is absent. In some embodiments, XZ3 is a Y-amino acid or is absent. In some embodiments, X1b6 is a Y-amino acid or absent. In some embodiments, X17 is an O-amino acid or absent. In some embodiments, X18 is a Y-amino acid or absent. In some embodiments, X19 is a Y-amino acid or absent. In some embodiments, X20 is an O-amino acid or absent. 00120) In one embodiment of the peptide inhibitor of formula Xa,

X1 is absent;

X2 is absent;

XZ is Sim, O-C1y, Ago, (0)Aga, Rpe, (0)P Ne, 2-Mai, TNg, Gey, (0)SiIp or absent;

XA represents Suh, Aby or Rep;

X5 is Aa, a-MeOgp, a-Meseg, Sii, bar, ar, Rar(As), Snu, Huz, Azp, M-Mesip, M-

MeAgo, Op, Sip, Agou, Zeg or TNg;

Xb is Ar or TnHg;

X7 is Tgr or b-chloro-Tgr;

XV represents Sim, SiIp or Mai;

ХУ represents Suh, Aby or Rep;

X10 is 2-Mai, an analogue of Rie, Tug or an analogue of Tug, and in specific embodiments, X10 is 2-MaY, РНе(3,4-dybg2), РНе(3,4-СИ2), РНе(3-Me ), Pne(4-(2-aminoethoxy)|, Ppe(4-(2-acetylaminoethoxy)|, Ppe(Vg), Ppe(4-SOMN"), Pne(SI), Ppe(4-CM), Pne (4-guanadino), Rpe(4-Me), Rpe(4-Mn»e), Rpe(4-M3z), Tug, Tuc(B2I) or Tug(Me);

X11 is 1-Mai, 2-Mai, Pne(3,4-dimethoxy), 5-hydroxyTgr, Ppe(3,4-Sig), Ttr or Tug(3-

And you);

X12 is 3-Rai, Asrs, Asbs, Asms, Asps, Adr, AlYib, a-diethyliu, a-MeH uz, a-Me! uz(As), o-Mei eyy, a- a-MeOpt, a-Mezeg, a-Memai, Sam, Spa, Siy, Sra, O-Azp, Spi, Niv, PI ey, pNAgo, GI uv, I eyy ,

Osidiu, Ot, piperidine, Ago, Zeg, Tig or TNR;

X13 is Sii, Azr, bab, bar, Re, Nix5, bar(Red2-Ac), bar(pyroglutaric acid),

Sim, pAgo, GG uv, Huz(Ac), I uz(benzoic acid), I uz(glutaric acid), GU5(IMA), GG uz(Redi -ivoSsti-

Rait), Guz (pyroglutaric acid), and uz-succinic acid, Avp, Op, Sp, Ago, TAg or mMai; because X14 is Azr, Bac(Ac), bar(Ac), Re, Ni, Iz(Ac), Mei, Azp(isobutyl), Sip, Ag, Tug or A5p(1,4-diaminobutane);

X15 is Aa, regalia, Sim, Su, Azp, Sip, Agu or 5eg,

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00121) In some variants of implementation, the HZ is absent. In specific embodiments of X16,

X17, X18, X19 and X20 are absent. In specific embodiments, XA and XU are Sub, and X4 and XU are linked by a disulfide bond. In specific embodiments, X4 is

Ar, and XU represents Rep, and X4 and XU are connected by a thioether bond. In specific embodiments, X4 is Aby, and XO is Sub, and X4 and X9 are linked by a thioether bond. (00122) In another embodiment of the peptide inhibitor of formula Xa,

X1 is absent;

X2 is absent;

XZ is Sim, O-C1y, Ago, (0)Aga, Rpe, (0)P Ne, 2-Mai, TNg, Gey, (0)SiIp or absent;

XA represents Suh, Aby or Rep;

X5 is Aa, a-MeOgp, a-Meseg, Sii, YuSar, rab, Oar(As), Spu, Guz, Avp, Opt, Sp, Ag, beg or TNpg;

Xb is Ar or TnHg;

X7 is Tgr or b-chloro-Tgr;

XV represents cSip or Mai;

ХУ represents Suh, Aby or Rep;

X10 is 2-Ma!Y, an analogue of Ppe, Tug or an analogue of Tug, where in specific embodiments X10 is 2-Ma, Rpe(3,4-diE»g), Rpe(3-Me), Rpe(( 4-(2-aminoethoxy)|, Rpe|4-(2-acetylaminoethoxy)| -guanadino), Rpe(4-Me),

Rpe(4-MNaeg), Ripe(4-Mz), Tug, Tu((B2I) or Tug((Me);

X11 is 1-Mai, 2-Mai, Pne(3,4-dimethoxy), 5-hydroxyTgr, Ppe(3,4-Sig), Ttr or Tug(3-

From IVY);

X12 is 3-Rai, Asrs, Asbs, Asms, Asps, Adr, AlYib, a-diethyliu, a-MeH uz, a-Me! uz(As), o-Mei ei, o-MeOgp, o-Mezeg, a-Memai, Sam, Spa, Sii, Sra, O-Avp, Niv, Pi ei, Aga, Guz, I ei, Osiu,

So, 4-amino-4-carboxypiperidine or TNR;

X13 is Sii, Azr, bab, bar, Re, Nix5, bar(Red2-Ac), bar(pyroglutaric acid),

Sim, pAgo, GG uv, Huz(Ac), I uz(benzoic acid), I uz(glutaric acid), GU5(IMA), GG uz(Redi -ivoSsti-

Rait), Guz (pyroglutaric acid), And uz-succinic acid, Azp, Op, Sp, Agou, Tig or Mai;

X14 is rab(As), bar(As), Re, Niv, I ub(As), Mei, Azp, Sp, Agod or Tug;

X15 is Aa, pAia, su, Azp, SiP or Zeg,

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00123) In some variants of implementation, the HZ is absent. In specific embodiments of X16,

X17, X18, X19 and X20 are absent. In specific embodiments, XA and XU are Sub, and X4 and XU are linked by a disulfide bond. In specific embodiments, X4 is

Ar, and XU represents Rep, and X4 and XU are connected by a thioether bond. In specific embodiments, X4 is Aby, and XO is Sub, and X4 and X9 are linked by a thioether bond. (00124) In another embodiment of the peptide inhibitor of formula Xa,

X1 is absent;

X2 is absent;

XZ is Sim, O-C1y, Ago, (0)Aga, Rpe, (0)P Ne, 2-Mai, TNg, Gey, (0)SiIp or absent;

XA represents Suh, Aby or Rep;

X5 is Ar, Rar(As), Su, Guz, Sp, Ago, Zeg, Tig or Avp;

Xb is TPg;

X7 is Tgr or b-chloro-Tgr;

XV is IP;

ХУ represents Suh, Aby or Rep; 60 X10 is 2-Ma!Y, an analogue of Ppe, Tug or an analogue of Tug, where in specific embodiments X10 is 2-Ma), Rie(3-Me), Rpe(|4-(2-aminoethoxy))! ), Rpe(4-(2-acetylaminoethoxy)|, Rpe(4-SOMH), Rpe(4-Me), Rpe(4-MHg), Tug, Tu((B2I) or Tug(Me);

X11 is 1-Ma, 2-Ma, Rpe(3,4-dimethoxy), Rpe(3,4-Sig) or Tgr;

X12 is Asrs, Asbs, Asms, Asps, AIB, a-diethyliu, a-MeH uv, a-MeH uz(As), a-MeH ei, a-

MeOp, a-Mezeg, a-Memai, Sa, Sii, NI ey, GG uv, I em, Agud or TNR;

X13 is sia, Azr, bar, Yuar (Red2-Ac), bar (pyroglutaric acid), Sim, pAgao, Guv,

Huz(Ac), IGuz(benzoic acid), Iubz(glutaric acid), GU5(IMA), Huz(Red4-i5oStcy-Rait),

Huz (pyroglutaric acid), Huz (succinic acid), Azp, Ogp, SiIp, Agud or Mai;

X14 is rab(As), Bar(As), Ni, I uz(As), Azp, Sp or Tug;

X15 is Aa, regalia, Su, Azp, SiIp or 5eg,

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00125) In some variants of the implementation of the HZ is absent. In specific embodiments of X16,

X17, X18, X19 and X20 are absent. In specific embodiments, XA and XU are Sub, and X4 and XU are linked by a disulfide bond. In specific embodiments, X4 is

Ar, and XU represents Rep, and X4 and XU are connected by a thioether bond. In specific embodiments, X4 is Aby, and XO is Sub, and X4 and X9 are linked by a thioether bond. (00126) In another embodiment of the peptide inhibitor of formula Xa,

X1 is absent;

X2 is absent;

XZ is Sim, O-C1y, Ago, (0)Aga, RHe, (0)P He, 2-Mai, TNg, Hei, (0)SiIp or absent;

XA represents Suh, Aby or Rep;

X5 is Ar, Rar(As), Sp, Zeg, Tig or Avp;

Xb is TPg;

X7 is Tr;

Ko) ХВ is a cSip;

ХУ represents Suh, Aby or Rep;

X10 is an analog of Phe, Tug, or an analog of Tug, where in specific embodiments, X10 is Rpe(|4-(2-aminoethoxy)|, Rpe(4-(2-acetylaminoethoxy))|, Rpe(4-COMNH»g ), Rne(4-Me),

Tug, Tuk((B2I) or Tu((Me);

X11 is 2-May or Ttgr;

X12 is Asrs, Asbs, Asms, Asps, AB, a-Diethyliu, a-MeH uv, a-MeH uz(As), a-MeH ei, a-

MeOp, a-Mezeg, a-Memai, p eits, Yi ei or TNR;

X13 represents Sii, Ar, Sim, Iuv, Iu(As), Azp or ip;

X14 is rac(Ac), Azp or Niv;

X15 is Aa, Realia, Siu, Azp or Sip;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent.

I00127| In some variants of the implementation of the HZ is absent. In specific embodiments of X16,

X17, X18, X19 and X20 are absent. In specific embodiments, XA and XU are Sub, and X4 and XU are linked by a disulfide bond. In specific embodiments, X4 is

Ar, and XU represents Rep, and X4 and XU are connected by a thioether bond. In specific embodiments, X4 is Aby, and XO is Sub, and X4 and X9 are linked by a thioether bond.

I00128| In specific embodiments, the peptide inhibitor comprises an amino acid sequence specified in any of the various formulas described herein, for example, Ia-

And, Pa-Pa, Sha-She or IM. 00129) In some embodiments, the present invention includes a peptide inhibitor of the interleukin-23 receptor, wherein the peptide inhibitor has the structure of formula I:

B'-X-B:2 (I) 001301 or its pharmaceutically acceptable salt or solvate, 00131) where K' is a bond, hydrogen, C1-C6 alkyl, C6-Styryl, C6-C12 aryl C1-C6 bo alkyl, C1-C20 alkanoyl and contains PEGylated variants alone or as spacers of any of the above; 00132) In? is a bond, OH or MH"; and 00133) X represents an amino acid sequence, for example, an amino acid containing 7-35 amino acid residues. In some variants of implementation of HB? is OH or MH". 00134) In some embodiments, X comprises a sequence of formula x. (00135) In specific embodiments of formula (I), X contains the sequence of formula Ia:

X1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Ia) (ZEO I

MO:1356), where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X4 stands for Suvz, Rep, pSuz, O-Rep, Y-Suz, O-nSuz, Mei, Spi, Avr, Huz, Ot, Oar, rab, p-

Bar, O0-OSar, O-A5zr, O-Sish, O-uz, Zes, 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid , Aby, p-azido-Aia-OH, propargylglycine, 2-(3-butenyl)glycine, 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4-pentenyl)glycine, 2-(5' -hexenyl)glycine or absent;

X5 is Aa, Ago, Sim, Re, I em, Tng, Zeg, AIV, Zags, O-AIa, O-Ag9, O-StIy, O-Rne, O-iI ey, p-Tng, O0-zeg , a-MeOt, a-Mezeg, Sibar, bar, bar (As), Stpu, Guv, Avp, M-Me-Sip, M-Me-Ag9, Ot or Sp,

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

ХУ stands for Suv, Rep, pSuz, O-Rep, O-Suz, O-pSuz, SIM, Huz, Ot, Var, Sab, O-Oar, 0- rab, 0-Avr, 0-S1y, O-IG uv, Avr, I ey, Mai, Rie, 5eg, Zes, Aby, B-azido-Aia-OH, propargylglycine, 2-2- allylglycine, 2-(3'-butenyl)glycine, 2-(4"-pentenyl )glycine or 2-(5'-hexenyl)glycine;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 (acetylaminoethoxy)|

Rpe(4-Me), Rpe(4-MH"), Rne(4-Mz), Rne(4-OMe), Rne(4-OB21Y) or Tug;

Zo X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Niv, RNe, Ag9, M-Me-Niv, or Mai, Sam, Sra, Ie, Sii, NIe, 3-Rai, II-butyl-Aya,

1-butyl-Siu 4-amino-4-carboxytetrahydropyran, Asis Asrs, Asvs, Asms, Aar, Air, o-diethyliu, a-

MeGuvs, a-MeGuv(As), a-Me-Gay, o-MeOt, a-Mezetg, a-Memai, Spa, Sii, Sra, (0)Avp, Sim, pAgo, or

G uv;

X13 represents TNg, Zags, Sim, Re, Ago, I ey, G uv, Mai, VAAia, AIB, Guv(As), Sii, A5r, bab, Var,

Sim, pAgo, Guz, Azp, Ogp or Sip;

X14 represents Riye, Tug VYRPe, Azp, Ago, Op, I y(As), Ni5; bar(As), bab(As) or Azr;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent.

In specific embodiments of Ia: X5 is Aa, Ago, SiIy, Rpe, GI em, Tpg, 5eg, AIb,

Zags, O-Aia, O-Ag9, Yu-Siy, O-RNe, O-I ey, O-TNg, O-5eg, O-Ayr or O-bZags" X10 is Tug or РПе; X11 is Tgr , 1-Ma!Y or 2-Mai; X12 represents Ni, Rie, Ago, M-Me-Niv, or

May, Sam, Sra, I ei, Sii, NI ei, 3-Rai, II-butyl-AIa or i-butyl-Siu; Х1ИЗ3 is ТНг, Загс, СИМ,

RNe, Aga, H em, Guz, Mai, VpAia or Air; X14 represents Riye, Tug or VyRPe; X15 is a

Siu, Zeg, TPg, SiIp, Aia or Zags; X16b6 is Azr, Sim, Aia, AEA, AER, DVPAia, Saba or

BO is absent; and X17 represents and ей, ГГ ув, Агд or absent. (00136) In specific embodiments, XA is present.

I00137| In some embodiments, the peptide inhibitor is cyclized. 00138) In some embodiments, the peptide inhibitor is linear or non-cyclized.

II00139| In some embodiments, the peptide inhibitor is cyclized or contains an intramolecular bond between XA and X9. (00140) In some embodiments of the implementation of the formula I X contains the sequence of the formula II:

X1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (IV) (ZEO Ir

MO:1357), 001411 where: 60 X1 is any amino acid or absent;

Zo

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

HA stands for Suz, Rep, pSukh, Yu-Rep, O-Suv, Yu-nSuv, Spi, Avr, I uv, Ot, ar, rab, O-Rar, r-bab, 0-Avzr, 0-Sim, 0-II uv, bes, 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid, Aby, B-azido-Aia-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 Aa, Ago, Sim, Re, I em, Tng, Zeg, AIV, Zags, O-AIa, O-Ag9, O-StIy, O-Rne, O-iI ey, p-Tng, O-5eg , a-MeOt, a-Mezeg, Sibar, bar, bar (As), Stpu, Guz, Avp, M-Me-Sip, M-Me-Ag9, Ot or Sp;

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

HU represents Su, Rep, pSuz, O-Rep, O-Suv, O-nSuvz, SIM, uv, Ot, Var, bab, O-Obar, 0- rab, 0-Azr, 0-SIy, O-Guv5 , Ar, Zes, Aby, B-azido-Aia-OH, propargylglycine, 2-allylglycine, 2-(3-butenyl)glycine, 2-(4-pentenyl)glycine or 2-(5'-hexenyl)glycine;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 (acetylaminoethoxy)|

Rpe(4-Me), Rpe(4-MH"), Rne(4-Mz), Rne(4-OMe), Rne(4-OB21Y) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-C12), Tuk(3-I-Vy);

X12 is Ni, Rie, Ago, M-Me-Niv, Mai, Sam, Sra, Gei, Sii, pei, 3-Rai, 1-butyl-Aiia, 1-butyl-Siu4-amino-4-carboxytetrahydropyran, Asps Asrs, Asbs, Asms, Aodr, AB, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-G hey, s-MeOgp, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgou or

G uv;

X13 represents TPNg, Zags, sim, Re, Ago, G em, Guz, Mai, VPApalib, I ub(As), Sii, A5zr, Bab, Var,

Sim, pAgo, Guz, Azp, Ogp or Sip;

X14 represents Re, Tug, or VyRPe, Azp, Ago, Op, I uz(As), Ni; bar(As), bab(As), or Azr;

X15 is su, Zeg, TNpg, Sp, Aa, or Zags, V-Aya, Sim, Agu or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

Zo X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00142) In specific variants of implementation of IB: X5 is Aa, Agd, Si, Rie, H em, TNg, zZeg, AB, Zag, O-AIa, Yu-Aga, Yu-Sim, O-Rpe, O-H ey , O-TNg, O-Zeg, O-AIIB or O-Zags; X10 is Tug or Re; X11 represents Ttgr, May 1 or May 2; X12 represents Ni, Rpe, Agu, M-Me-

Ni, Mai, Sam, Sra, Iy, Siy, NIy, 3-Rai, Ii-butyl-AIa or Ibutyl-Siu; X1I3 is TpHg, registry office,

Sim, Re, Ago, Gay, Guz, Mai, VpAЯa or AЙb; X14 is Re, Tug or ViYRPe; X15 is su, Zeg, TAg, Sp, Aa or Zags; X16 is Ar, Sim, AIa, AEA, AER, VpAPa, Sara or absent; and Х17 represents I ей, ГИ ув, Agu or absent. 001431) In specific embodiments, XA is present. 00144) In some embodiments, the peptide inhibitor is cyclized. 00145) In some embodiments, the peptide inhibitor is linear or non-cyclized.

IІ00146| In some embodiments, the peptide inhibitor is cyclized or contains an intramolecular bond between XA and X9.

IІ00147| In some embodiments of the formula I, X contains the sequence of the formula Is: xX1-X2-X3-X4-X5-X6-M/-X8-X9-7-X11-X12-X13-X14-X15-X16-X17-X18-X19 -X20 (Is) (ZEO IYU MO:1358), 001481 where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

HA stands for Suzh, Rep, pSuz, O-Rep, O-Suvz, O-pSuvz, Mei, Spi, Avr, I uv, Ot, Oar, rab, 0-

Bar, О0-OSar, 0-А5зр, 0-Сиш, О-уз, Зес, 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid , Aby, B-azido-Aia-OH, propargylglycine, 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4"-pentenyl)glycine, 2-(5'-hexenyl)glycine or absent;

X5 is Aa, Ago, Sim, Re, I em, Tng, Zeg, AIV, Zags, O-AIa, O-Ag9, O-StIy, O-Rne, O-iI ey, p-Tng, O-5eg , a-MeOt, a-Mezeg, Sibar, bar, bar (As), Stpu, Guv, Avp, M-Me-Sip, M-Me-Ag9, Ot or Sp; 60 Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

HU represents Su, Rep, pSuz, O-Rep, O-Suv, O-nSuvz, SIM, uv, Ot, Var, bab, O-Obar, 0- rab, 0-Azr, 0-SIy, O-Gu5 .

X11 represents Tgr, May 1, May 2! Pne(3,4-OMeg) 5-Hydroxy-Tgr, Ripe(3,4-SiI2) or Tug(3--B8y);

X12 is Ni, Rie, Ag, M-Me-Niv, Mai, Sam, Sra, Iem, Sii, pei, 3-Rai, i-butyl-Aia 1-butyl-Siu; 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asrs, Asmus, Aor, Alib, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-G hey, s-MeOgp, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgou or

G uv;

X13 is TpNg, Zags, Sim, Rpe, Aga, I ey, I uz, Mai, VpApa, or AB, G ub(As), Sii, A5r, Rab,

Bar, Sim, pAgo, Guz, Azp, Opt, or Sp;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I uz(As), Ni; Sar(As), Bbac(As) or Azr;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00149) In specific embodiments, Is X5 is Aa, Agod, Sim, Rpe, Genes, TNg, zZeg, AB, Zag, O-AIa, Y-Aga, Y-SIM, O-Rpe, O-H ey, O -TNg, O-Zeg, 0-AIIB or O-Zags; X11 represents Tgr, 1-Ma!Y or 2-Mai; X12 represents Ni, Rpe, Agd, M-Me-Niv, Mai, Sam, Sra, I ey, Sii,

NO, 3-Ra, I-butyl-Al, or I-butyl-Si; X13 is TpNg, Zags, Sim, Rpe, Aha, Genes, Guz, mAi,

VpAia or AIIBb; X14 is Re, Tug or ViRpe; X15 is su, 5eg, TPg, SiIp, Aa or

Registry office; X16 is Avzr, Sim, Aa, AEA, AER, VpAIa, Saba or absent; and X17 represents

And em, Guv, Ag or missing. 00150) In specific embodiments, XA is present. 00151) In some embodiments, the peptide inhibitor is cyclized. 00152) In some embodiments, the peptide inhibitor is linear or non-cyclized.

І00153| In some embodiments, the peptide inhibitor is cyclized or comprises

Z is an intramolecular bond between XA and X9. 00154) In some embodiments of formula I X contains the sequence of formula a:

X1-X2-X3-0-X5-X6-M/-X8-0-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (4) (ZEO IU MO:1359) , 001551 where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X5 is Aa, Ago, Sim, Re, I ey, TNg, 5eg, AB, Zags, O-AIa, O-Ag9, 0-StIy, О-РНе, 0-ІІ ей, р-Тнг, О-5eg , a-MeOt, a-Mezeg, Sibar, bar, bar (As), Stpu, Guv, Avp, M-Me-Sip, M-Me-Ag9, Ot or Sp;

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

ХВ represents Mai, Sip, Sim or I uv;

X10 is Thug Ripe, Rpe(3,4-Eg), Rpe(3,4-SiI2), E(3-Me), Rpe(|4-(2-aminoethoxy)), Rpe|4-(2- (acetylaminoethoxy)), Rpe(4-Vg), Rpe(4-SOMH), Rpe(4-SI), Rpe(4-CM), Rpe(4-guanidino), Rpe(4-

Me), Rpe(4-Mn"), Ripe(4-Mz), Rpe(4-OMe), Rpe(4-OVYAI) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-C12), Tuk(3-I-Vy);

X12 is Ni, Rie, Ago, M-Me-Niv, Mai, Sam, Sra, Gei, Sii, pei, 3-Rai, 1-butyl-AIa, 1-butyl-Siu, 4-amino-4- carboxytetrahydropyran, Asps Asrs, Asrs, Asus, Adr, AlibB, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-G hey, s-MeOgp, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgou or

G uv;

X13 represents TNg, Zags, Sim, Re, Ago, I ey, G uv, Mai, VAAia, AIB, Guv(As), Sii, A5r, bab, Var,

Sim, pAgo, Guv, Azp, Ogp or Sip;

X14 is Re, Tug, VYPe, Azp, Ago, Op, Iuz(As), Ni5, Oar(As), Bbac(As) or Azr;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent, because 001561 where XA and X9 are not necessarily connected by an intramolecular disulfide bridge.

I00157| In some embodiments, Id: X5 is Aa, Ago, Sim, Re, Hei, Tpg, 5eg,

Ar, Zags, O-AIa, O-Ago, O-C1y, O-RNe, O-Hei, O-TNng, O-5eg, O-AIr or O-Zags; X10 is Tug or Rpe; X11 represents Ttgr, May 1 or May 2; X12 represents Ni, Rieh, Ago, M-Me-Niv, Mai,

Sam, Sra, I ey, Sii, NI ey, 3-Rai, 1-butyl-AiYa or 1-butyl-Siu; X13 is TnHg, Zags, Sim, Re,

Ago, I ey, Guz, Mai, VpAiia or AIIBb; X14 is Re, Tug or ViRPe; X15 is Su, 5eg,

Tig, Sp, AIa or Zags; X16 is Azr, Sim, AIa, AEA, AER, rVpAa, Sava or absent; and X17 represents Iii ei, GG uv, Agd or absent. 00158) In some variants of implementation of formula I X contains the sequence of formula Ie: xX1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18 -X19-X20 (Ie) (ZEO I MO:1360), 001591 where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

XA is Rep, pSuz, O-Rep, Yu-Su5 or O-pSuz;

X5 is Aa, Ago, Sim, Re, I ey, TNg, 5eg, AIV, Zags, O-Aia, O-Aga, О-С1y, О-РНе, О-ии ей, р-Тнг, О-5eg , a-MeOt, a-Mezeg, Sibar, bar, bar (As), Stpu, Guv, Avp, M-Me-Sip, M-Me-Ag9, Ot or Sp;

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

ХУ represents Rep, pSuz, O-Rep, Yu-Suv, O-NSuv;

X10 is Tug, Rpe Rpe(3,4-Eg), Rpe(3,4-SiI2), E(3-Me), Rpe(|4-(2-aminoethoxy)), Rpe|4-(2- (acetylaminoethoxy)), Rpe(4-Vg), Rpe(4-SOMH), Rpe(4-SI), Rpe(4-CM), Rpe(4-guanidino), Rpe(4-

Me), Rpe(4-Mn"), Ripe(4-Mz), Rpe(4-OMe), Rpe(4-OVYAI) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Ni, Rie, Ago, M-Me-Niv, Mai, Sam, Sra, Gei, Sii, pei, 3-Rai, 1-butyl-AIa, 1-butyl-Siu, 4-amino-4- carboxytetrahydropyran, Asps Asrs, Asrs, Asmus, Aor, Alib, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-G hey, s-MeOgp, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgou or

G uv;

X13 is TNg, Zags, Sim, Re, Ago, I ey, Guz, Mai, VpAPa, AIIB, Guz(As), Sii, A5r, Bar, Var,

Sim, pAgo, Guz, Azp, Ogp or Sip;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I uz(As), Ni; Sar(As), Bbac(As) or Azr;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

I00O1601 where XA and XU are optionally connected by an intramolecular disulfide bridge. 00161) In some embodiments of Iee: X5 is Aa, Ago, Sim, Re, Gey, Tpg, 5eg,

Ar, Zags, O-AIa, O-Ago, O-C1y, O-RNe, O-Hei, O-TNng, O-5eg, O-AIr or O-Zags; X10 is Tug or Rpe; X11 represents Ttgr, May 1 or May 2; X12 represents Ni, Rieh, Ago, M-Me-Niv, Mai,

Sam, Sra, I ey, Sii, NI ey, 3-Rai, 1-butyl-AiYa or 1-butyl-Siu; X13 is TnHg, Zags, Sim, Re,

Ago, I ey, Guz, Mai, VpAiPa or AIIBb; X14 is Re, Tug or ViRPe; X15 represents Su, Zeg,

Tig, Sp, AIa or Zags; X16 is Avhr, Sim, Aa, AEA, AER, VpAPa, Sava or absent; and X17 represents Iii ei, GG uv, Agd or absent. (00162) In specific embodiments, XA is present. 00163) In some embodiments, the peptide inhibitor is cyclized. 00164) In some embodiments, the peptide inhibitor is linear or non-cyclized.

IІ00165| In some embodiments, the peptide inhibitor is cyclized or contains an intramolecular bond between XA and XO. 00166) In specific embodiments, both XA and XO are Rep.

I00167| In some embodiments of formula I, X contains the sequence of formula II xX1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19- X20 (I) (ZEO IYU MO:1361), 001681) where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent; 60 HA represents Sim, Guz, Ogp, Juar, bar, O-Yubar, O-Obab, O-Avr, 0-S1im, O-I y or Azr;

X5 is Aa, Ago, Sim, Re, I em, Tng, Zeg, AIV, Zags, O-AIa, O-Ag9, O-StIy, O-RHne, O-iI ey,

O-Tng, O-Zeg, o-MeOgp, a-Mezeg, Sii, bar, rab, bar (As), Spu, Guz, Azp, M-Me-S1p, M-Me-Ag9, Ot or Sp;

Xb is Ar, Tpg, Azp, Rie, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

ХУ represents Siy, Guz, Ogp, Yuar, bar, O-Yubar, O-Obab, O-Avr, O-S1im, O-I u5 or Azr;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 (acetylaminoethoxy)|

Rpe(4-Me), Rpe(4-MH"), Rne(4-Mz), Rne(4-OMe), Rne(4-OB21Y) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Ni, Rie, Ago, M-Me-Niv, Mai, Sam, Sra, I ey, Siyi, PI ey, 3-Rai, I-butyl-Aya, or

1-butyl-Siu, 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asbs, Asms, Aor, Alib, a-diethyliu, a-

Me" uz, a-Mei! uz(As), a-Me-I em, a-MeOt, a-Mezeg, a-Memai, SNa, Sii, Sra, (0)Azp, Sim, pAgu or

G uv;

X13 represents TNg, Zags, Sim, Re, Ago, I ey, G uv, Mai, VAAia, AIB, Guv(As), Sii, A5r, bab, Var,

Sim, pAgo, Guz, Azp, Ogp or Sip;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I uz(As), Ni; Sar(As), Bbac(As) or Azr;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

ИЙО0169| where X4 and XO are optionally cyclized using an intramolecular bond. 00170) In some embodiments, X5 is Aa, Ago, Sim, Re, Iei, TNg, Zeg,

Ar, Zags, O-AIa, O-Ago, O-ST1y, O-RNe, O-I ey, O-TNg, O-5eg, O-AIr or O-Zags; Hb represents Azr,

Tit, Avp, Rie, O-Avr, O-TNg, O-Azp or O-RPpe; X8 represents Mai, SiIp, sim or I y5; HO is seven, Guz, Ogp, Yuar, bab, O-Oar, O-bar, O-Avr, O-C1Yy, O-G uz or Ar; X10 is Tug

Ko) or Rpe; X11 represents Ttgr, May 1 or May 2; X12 represents Ni, Rieh, Ago, M-Me-Niv, Mai,

Sam, Sra, I ey, Sii, NI ey, 3-Rai, 1-butyl-AiYa or 1-butyl-Siu; X13 is TnHg, Zags, Sim, Re,

Ago, I ey, Guz, Mai, VpAiPa or AIIBb; X14 is Re, Tug or ViRPe; X15 represents Su, Zeg,

Tig, Sp, AIa or Zags; X16 is Avzr, Sim, Aa, AEA, AER, DVpAya, Sava or absent; and

Х17 represents И ей, И у, Агу or absent.

IІ00171| In some embodiments, the intramolecular bond is a lactam bond. 00172) In some variants of implementation of formula I X contains the sequence of formula 1e: xX1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18 -X19-X20 (14) (ZEO IU MO:1362), 001731 where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

XA is BvB-azido-Aia-OH or propargylglycine;

X5 is Aa, Ago, Sim, Re, I em, Tng, Zeg, AIV, Zags, O-AIa, O-Ag9, O-StIy, O-RHne, O-iI ey,

Or-Tng, O-Zeg, o-MeOgp, a-Mezeg, Sii, bar, Oab, Oar(As), Sipu, Guz, Azp, M-Mesip, M-MeAgo, Ogp or

Sip;

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

XU is BvB-azido-Aia-OH or propargylglycine;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 (acetylaminoethoxy)|

Rpe(4-Me), Rpe(4-MH"), Rne(4-Mz), Rne(4-OMe), Rne(4-OB21Y) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Ni, Rie, Agu, M-Me-Niv, Mai, Sam, Sra, I ey, Siyi, PI ey, 3-Rai, I-butyl-Aya, or

1-butyl-Siu, 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asrs, Asus, Adr, AIbB, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-I em, a-MeOpt, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgo, or

G uv;

X13 is TNg, Zags, Sim, Re, Ago, I ey, G uv, Mai, VAAia, AIB, Guv(As), Sii, A5r, bab, Var, 60 Sim, pAgo, Guv, Azp, Ogp or Sip ;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I uz(As), Ni; Sar(As), Bbac(As) or Azr;

X15 is su, Zeg, TNpg, Sp, Aa, or Zags, V-Aya, Sim, Agu or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

IІ00174| where X4 and XU are optionally cyclized using an intramolecular triazole ring. 00175) In specific variants of the implementation of Id: X5 is Aa, Ago, Si, Rie, H em, Tng, zZeg, Aib, zags, O-AIa, O-Ago, O-C1y, O-Rne, O-H ey , О-ТНг, О-зЗег, О0-АЙБ or О-Загс; Xb is a

Ar, TNt, Avp, Ripe, 0-Avr, O-TNg, 0-Azp or Yu-Rpe; X8 represents Mai, Sip, Sim or I uh; X9 is B-azido-AlIa-OH or propargylglycine; XIO is Tug or Rpe; X11 represents Tgr, 1-Ma!Y or 2-Mai; X12 represents Ni, Rpe, Agd, M-Me-Niv, Mai, Sam, Sra, I ey, Sii,

NO, 3-Ra, I-butyl-Al, or I-butyl-Si; X13 is TpNg, Zags, Sim, Rpe, Aha, Genes, Guz, mAi,

VpAia or AIIBb; X14 is Re, Tug or ViRpe; X15 is su, 5eg, TPg, SiIp, Aa or

Registry office; X16 is Avzr, Sim, Aia, AEA, AER, VpAIa, Sava or absent; and X17 represents

And em, Guv, Ag or absent. 00176) In some variants of implementation of formula I X contains the sequence of formula IJ: xX1-X2-X3-0-X5-X6-M/-X8-0-x-X11-H-X13-E-X15-X16-X17-X18 -X19-X20 (I) (ZEO IU MO:1363),

I00177| where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ 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 Aa, Agu, zags, a-MeOgp, a-Mezeg, Sii, bar, bab, Oar(As), Spu, Guz, Avp, M-

Mesip, M-MeAgo, OGPP or sSip;

Ko) Xb is Azr, Tpg or Avp;

XV represents Mai, SiIp or Si;

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

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X13 is TNg, Zags, Sim, Re, Ago, I ey, Gu, VpAPa, Mmai, AIB, Guv(As), Sii, A5r, bab, Var,

Sim, pAgo, Guz, Azp, Ogp or Sip;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

ИО0О178| where X4 and XU are optionally cyclized using an intramolecular ring closing reaction to obtain the corresponding olefins. 00179) In specific variants of implementation of Iy: X5 is Aa, Agud or Zags; Xb is Azr, Tpg or Azvp; X11 represents Ttgr, 1-MaiY or 2-Mai; X13 is TpNg, Zags, SIM,

Rpe, Ago, Hey, Guz, VPAia, Ma! or AIyib; X15 is Su, Beg, Tig, Sip, Aia or Zags; X16 is Abhr, Sim, AIa, AEA, AER, DVpAa, Saba or absent; and X17 represents Ii ei, I uv, Aga or absent. 001801) In some variants of the implementation of the formula I X contains the sequence of the formula I:

X1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Ii) (5EO Ir

MO:1364), 001811 where:

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X4 is Su5, Rep, pSuz, Y-Rep, Y-Suz, Y-npSuz, 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid or 3-chloroisobutyric acid acid;

Ge) X5 is Aa, Ago, Sim, Re, I em, Tng, Zeg, AIV, Zags, O-AIa, O-Ag9, O-StIy, O-РНе, О-иІІеy,

r-tng, O-5eg, 0-AIIB, or O-Zags, a-MeOgp, a-Mevzeg, Sii, OSar, bab, bar(As), Spu, Guv, Avp, M-

Mesip, M-MeAgo, OGPP or sSip;

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

ХУ stands for Suz, Rep, pSuz, O-Rep, O-Suv, O-pSuz or Aby;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 (acetylaminoethoxy)|

Rpe(4-Me), Rpe(4-MH"), Rne(4-Mz), Rne(4-OMe), Rne(4-OB21Y) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Ni, Rie, Ago, M-Me-Niv, Mai, Sam, Sra, Ie!y, Sii, pei, 3-Rai, I-butyl-Aya, 1-butyl-Siu, 4-amino -4-carboxytetrahydropyran, Asps Asrs, Asbs, Asms, Adr, AB, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-G hey, s-MeOgp, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgou or

G uv;

X13 represents TNg, Zags, Sim, Re, Ago, I ey, G uv, Mai, VAAia, AIB, Guv(As), Sii, A5r, bab, Var,

Sin, pAgo, Guz, Azp, Ogp or sSip;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I uz(As), Ni; Sar(As), Bbac(As) or Azr;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

I00182| where X4 and XU are optionally cyclized using an intramolecular thioether bond. 00183) In specific variants of its implementation: X5 is Aa, Ago, Sim, Rpe, Genes, TNg, zZeg, AIb, zags, O-AIa, O-Ago, O-C1y, O-RNe, O-H ey, О-ТНг, О-зЗег, О0-АЙБ or О-Загс; Xb is a

Ar, TNt, Azp, Rpe, O-Avr, O-TNg, O-Azp or O-Rpe; X10 is Thug or Ripe; X11 represents Tgr, 1-Ma!Y or 2-Mai; X12 represents Ni, Rpe, Agd, M-Me-Niv, Mai, Sam, Sra, I ey, Sii,

NO, 3-Ra, I-butyl-Al, or I-butyl-Si; X13 is TpNg, Zags, Sim, Rpe, Aha, Genes, Guz, Mai,

Co) VpAia or AIIBb; X14 is Re, Tug or ViRpe; X15 is su, 5eg, TPg, SiIp, Aa or

Registry office; X16 is Abzr, Sim, Aa, AEA, AER, DVPAIa, Saba or absent; and X17 represents

And em, Guv, Ag or missing. 00184) In some embodiments of formula I X contains the sequence of formula 1):

X1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (I) (ZEO Ir

MO:1365), 001851 where:

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X4 is Zes, 2-chloromethylbenzoic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid or Aby;

X5 is Aa, Ago, Sim, Re, I em, Tng, Zeg, AIV, Zags, O-AIa, O-Ag9, O-StIy, O-RHne, O-iI ey,

Or-Tng, O-Zeg, o-MeOgp, a-Mezeg, Sii, bar, Oab, Oar(As), Sipu, Guz, Azp, M-Mesip, M-MeAgo, Ogp or

Sip;

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

XV represents Mai, SiIp, Sim or GG uv;

ХУ represents 5es or Aby;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 -aminoethoxy), Ppe|4-(2-(acetyl-aminoethoxy)|, Ppe(4-VI), Pne(4-СОМН»), РНе(4-СИ), Pne(4-СМ),

Rpe(4-guanidino), Rpe(4-Me), Rpe(4-MH), Rpe(4-Mz), Rpe(4-OMe), Rpe(4-OVY) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Ni, Rie, Ago, M-Me-Niv, Mai, Sam, Sra, Gei, Sii, pei, 3-Rai, 1-butyl-AIa, 1-butyl-Siu, 4-amino-4- carboxytetrahydropyran, Asps, Asrs, Asbs, Adr, AiYib, a-diethyliu, o-Mei! uz, o-MegG uz(As), a-Me-I ep, a-MeOt, a-Mezeg, o-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgo or I uv;

X13 is TNg, Zags, Sim, Re, Ago, I ey, G uv, Mai, VAAia, AIB, Guv(As), Sii, A5r, bab, Var, spin, NAgo, I uh, Azp, Ogp or Sip ;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I uz(As), Ni; Sar(As), Bbac(As) or Azr;

X15 is su, Zeg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agud or Avp;

X16 is any amino acid or absent; 60 X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

ИЙО0186|Й where X4 and XU are optionally cyclized with the help of an intramolecular thioseleno- or diselenide bond. 00187) In specific variants of the implementation of I): X5 is Aa, Ago, Sim, Rpe, Genes, TNg, zZeg, AB, Zag, O-AIa, Y-Aga, Y-SIM, O-Rpe, O-H ey , O-TNg, O-Zeg, O-AIIB or O-Zags; X10 is Tug or Re; X11 represents Ttgr, May 1 or May 2; X12 represents Ni, Rpe, Agu, M-Me-

Ni, Mai, Sam, Sra, Iy, Siy, NIy, 3-Rai, Ii-butyl-AIa or Ibutyl-Siu; X1I3 is TpHg, registry office,

Sim, Re, Ago, Gay, Guz, Mai, VpAЯa or AЙb; X14 is Re, Tug or ViRPe; X15 is su, Zeg, TAg, Sp, Aa or Zags; X16 is Ar, Sim, AIa, AEA, AER, VpAPa, Sara or absent; and X17 represents and ей, ГГ ув, Агд or absent. 00188) In some variants of implementation of formula I X contains the sequence of formula IC:

X1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (IR) (ZEO Ir

MO:1366), 001891 de

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X4 stands for Suvz, Rep, pSuz, O-Rep, Y-Suz, O-nSuz, Mei, Spi, Avr, Huz, Ot, Oar, rab, p-

Bar, O-Oab, r-Azr, 0-S1ym, O-I uz or absent;

X5 represents Aa, Ag, Spy, RNe, I ey, Tng, 5eg, AIB, Zags, O-Aia, O-Aga, O-C1y, O-RHe, O-iI ey,

O-Tng, O-5eg, o-MeOt, o-Mezeg, Sii, bar, Sab, Sar(As), Spiu, G uv, Avp, M-Mesip, M-MeAg9, Ot or

Sip;

Xb is Avr, TNg, Avp, Ripe, O-Avr, O-TNg, O-Azp or O-RNe;

X8 represents Mai, Sp, Sim or I uv;

HU stands for Suv, Rep, pSuz, O-Rep, O-Suz, O-pSuz, SIM, Guz, Ot, Var, Sab, O-Oar, 0- rab, O-Azr, 0-Sly, O-I uv, Avr, I ey, Mai, Rne or ze";

X10 is Tug, Rpe, Rie(3,4-P2), Rpe(3,4-C1I2), E(3-Me), Rpe(|4-(2-aminoethoxy)), Rpe|4-

Coo) (2-(acetyl-aminoethoxy))Y, РПе(4-Ві), РПе(4-СОМН»г), РПе(4-СІ), РПе(4-СМ), РПе(4-guanidino),

Rpe(4-Me), Rpe(4-MH"), Rpe(4-Mz), Rpe(4-OMe), Rpe(4-OB21) or Tug;

X11 is Ttgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Tgr, Ripe(3,4-SiI2) or Tuc(3--Vy);

X12 is Niv, Rie, Agu, M-Me-Niv, Mai, O-Niv, Sam, Sra, I ey, Sii, PI ey, 3-Rai, II-butyl-

Aa, I-butyl-Siu, 4-amino-4-carboxytetrahydropyran, Asns Asrs, Asrs, Asms, Adr, Air, a-diethyliu, o-Mei! aww, oh-Mei! uv(As), o-Me-iI eyy, a-MeOt, a-Mezeg, a-Memai, SNa, Sii, Sra, (0)Avp, Spi, NAga or

G uv;

X13 is TNg, Zags, Sim, Riye, Ago, I ey, I uv, Mai, VRAPa, AIB, GG uz(As), Sii, A5r, bab, Rar, spim, pAko, Guv, Avp, Ot or ap ;

X14 represents Riye, Tug, VyRPe, Azp, Ago, Op, I uv(As), Niv; bar(Ac), OSac(Ac) or Avr, or absent;

X15 is Su, 5eg, TNg, Sp, Aa, Zags, B-Aia, Sim, Agu or Avzp, or absent;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00190) In specific variants of IR implementation: X5 is AIa, Ago, Sim, Rie, Hei, TNg, zZeg, AB, Zag, O-AIa, Y-Aga, Y-SIM, 0-Rpe, O-H ey, O-TNg, O-Zeg, O-AIIB or O-Zags; X10 is Tug or Re; X11 represents Ttgr, May 1 or May 2; X12 represents Ni, Rpe, Agu, M-Me-

BO Ni, Mai, O-Niv, Sam, Sra, I ey, Sii, NI ey, 3-Rai, 1-butyl-AIa or 1-butyl-C1u; Х1ИЗ3 is ТНг,

Zags, Sim, Riye, Ago, Iei, Guz, Mai, VaaPa, AiB or absent; X14 is Re, Tug, VAIRpe or absent; X15 is Su, 5eg, TPg, Sp, Aa, Zags or absent; X16 represents Avr, Sim,

Aa, AEA, AER, VpAa, saBva, I ei or absent; and X17 represents and ей, Гуз, Агд or absent.

In some embodiments of formula I, X contains or consists of the sequence of formula II:

X1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (I) (5EO Ir

MO:1367), 001911 de

X1 is any amino acid or absent; 60 X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

HA stands for Suzh, Rep, pSuz, O-Rep, O-Suvz, O-pSuvz, Mei, Spi, Avr, I uv, Ot, Oar, rab, 0-

Bar, O-Oab, O-Azr, 0-S1im, O-I uh or absent;

X5 is Aa, Ago, Sim, Rpe, I em, Tng, Zeg, AIV, Zags, a-MeOgp, a-Mezetg, Sii, bar, Rab,

Bar(As), Siu, Guv, Avp, M-Mesip, M-MeAgo, Ogp or ip;

Xb is Azr, Tpg, Azp or Re;

XV represents Mai, SiIp, Sim or GG uv;

ХУ represents Su, Rep, pSuz, O-Rep, O-Suv, O-nSuvz, SIM, uv, Ot, Var, bab, O-Obar, 0- rab, 0-Avr, O-S1y, 0-I uz, Azr, I ey, Mai, Riye or 5eg;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 (acetylaminoethoxy)|

Rpe(4-Me), Rpe(4-MH), Rpe(4-Mz), Rpe(4-OMe), Rpe(4-OVI) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Ni, Rpe, Agd, M-Me-Niv, Mai, O-Niv, Sam, Sra, Ie, Sii, NIe, 3-Rai, i-butyl-

Aa, 1-butyl-SiIu, 4-amino-4-carboxytetrahydropyran, Asyps Asrs, Asbs, Asus, Adr, AIB, a-diethyliu, o-MeH uz, a-MeH uz(As), a-Me-I em , o-MeOt, a-Mezeg, o-Memai, Spa, Sii, Sra, (0)Avp, Sim, pAgd or

G uv;

X13 represents TNg, Zags, Sim, Re, Ago, I ey, G uv, Mai, VAAia, AIB, Guv(As), Sii, A5r, bab, Var,

Sp, pNAgo, GG uv, Azp, Ot or cSip, or absent;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I ub(As), Ni; bar(As), Bbac(As) or Azr, or absent;

X15 is su, Zeg, TNpg, Sp, Aa, Zags, V-Aia, Sim, Agud or Avp, or absent;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00192) In specific variants of the implementation of II: X5 represents AIa, Agd, Sim, Rpe, Gey, TNg, zeg, AIb, or Zags; X10 is Tug or РПе; X11 represents Ttgr, May 1, or May 2!; X12

Co) is Ni, Rie, Ago, M-Me-Nizv, Mai, O-Niv, Sam, Sra, I ey, Sii, NI ey, 3-Rai, I-butyl-Aya, or y-butyl-Siu ; X1Z3 is TpPg, Zags, Siy, Riye, Ago, GI em, Guz, Mai, VpAPa, AIIBb or absent; X14 is Re, Tug, VpyRPe or absent; X1I5 is su, Zeg, TPg, Sp, Aa, Zago or absent; X16 is Avzr, Sim, AIa, AEA, AER, VpLia, SaBba, I ei or absent; and X17 represents I ey, Gu, Agu or absent. 00193) In some embodiments, X13 is TPg, Zags, Sim, Rie, Ago, Hem, Huz,

VpAia, AIyib, Gub(As), Siy, Ar, bab, Bar, Sim, pAgo, Gu, A5p, Ogp or Sip. In some embodiments, X13 is TPg, Zags, Sim, Rpe, Aga, Iey, Guz, VpAia, or AB. 00194) In some embodiments, X14 is Re, Tug, VpyRPe, Ap, Ago, Op,

Guz(Ac), Ni5; bar(As), rbats(As) or Ar. In some embodiments, X14 is Re, Tug, or VIR Pe. 00195) In some embodiments, X15 is su, Zeg, Tpg, Sp, Aa, Zags, B-Aya,

Sim, Agd or Azhp. In some embodiments, X15 is Su, Zeg, TPg, Sip, Aia, or Zags. 00196) In some embodiments, X12 is an alpha-amino acid, for example, 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asps, AIV, a-Mesiu(diethyl), a-MeiH uz, a-Me! uz(As), a-Me-Gei, a-MeOgp, a-Mezeg, a-MemaiY. (00197) In some embodiments, X13 is present. (00198) In some embodiments, X13 and X14 are present. (00199) In some embodiments, X13, X14, and X15 are present. (002001 In specific embodiments, XA is present. 002011 In some embodiments, the peptide inhibitor is cyclized. (00202) In some embodiments, the peptide inhibitor is linear or non-cyclized.

I00203| In some embodiments, the peptide inhibitor is cyclized or contains an intramolecular bond between XA and X9.

I00204| In some embodiments, the implementation of the peptide inhibitor of the formula | X contains or consists of the sequence of the formula It: xX1-X2-X3-X4-X5-X6-M/-X8-X9-y-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 ( It) (5EO I

MO:1368), 002051 where 60 X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

HA stands for Suzh, Rep, pSuz, O-Rep, O-Suvz, O-pSuvz, Mei, Spi, Avr, I uv, Ot, Oar, rab, 0-

Bar, O-Oab, O-Azr, 0-S1im, O-I uh or absent;

X5 is Aa, Ago, Sim, Rpe, I em, Tng, Zeg, AIV, Zags, a-MeOgp, a-Mezetg, Sii, bar, Rab,

Bar(As), Siu, Guv, Avp, M-Mesip, M-MeAgo, Ogp or ip;

Xb is Azr, Tpg, Azp or Re;

XV represents Mai, SiIp, Sim or GG uv;

HU represents Su, Rep, pSuz, O-Rep, O-Suv, O-nSuvz, SIM, uv, Ot, Var, bab, O-Obar, 0- rab, 0-Avr, O-S1im, O-G uz, Azr, I em, Mai, Rpe or Zeg;

X11 is Tgr, 1-Mai, 2-Mai, Pne (3,4-OMeg); 5-hydroxy-Tgr, Rpe(3,4-Si2) or Tug(3-I-Vy);

X12 is Ni, Rie, Agu, M-Me-Niv, Mai, Sam, Sra, I ey, Siyi, PI ey, 3-Rai, I-butyl-Aya, or

1-butyl-Siu, 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asbs, Asms, Aor, Alib, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-G hey, s-MeOgp, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgou or

G uv;

X13 is TpNg, Zags, Sim, Re, Ago, I ei, I uh, VPAPa, Mai, AIB, Guz(As), Sii, A5r, Bar, Var,

Sim, pAgo, Guz, Azp, Opt or cSip, or absent;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I ub(As), Ni; bar(As), Bbac(As) or Azr, or absent;

X15 is su, Zeg, TNpg, Sp, Aa, Zags, V-Aia, Sim, Agud or Avp, or absent;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. (00206) In some embodiments, It: X5 is Aa, Ago, Sim, Rpe, Iei, Tpg, Zeg,

AIIB or bZags; X11 represents Ttgr, 1-MaiY or 2-Mai!; X12 represents Ni, Rpe, Agod, M-Me-N iv,

Mai, Sam, Sra, I ei, Sii, NI ei, 3-Rai, Ii-butyl-AIa or i-butyl-Siu; ХИЗ3 is ТНг, Загс, СИМ,

Re, Ago, Gay, Guz, VPAPa, Mai, AIib or absent; X14 is Re, Tug, VAIRPe or absent;

Ko) X15 is su, 5eg, TPg, Sip, Aa, Zags or absent; X16 is Avhr, Sim, Aa, AEA,

AER, VpAia, Saba or absent; and X17 represents I ei, I uv, Agu or absent. (00207) In some embodiments, X13 is TPg, Zags, Sim, Rie, Ago, Hem, Huz,

VpAia or AIB. In some embodiments, X13 is TPg, Zags, Sim, RNe, Ago, I ey, GG uv,

VpAa, AB, I uz(As), Sii, Azr, bab, Rar, Sim, pAgo, Guz, Azp, Ot or sip. (00208) In some embodiments, X14 is Re, Tug, VpyRPe, Ap, Ago, Op,

Guz(As), No; YuSar(As), rac(As) or Ar. In some embodiments, X14 is Re, Tug, or VIR Pe. 00209) In some embodiments, X15 is Su, Zeg, Tpg, SiIp, Aa or Zags, p-

Aa, Sim, Agud or Azp. In some embodiments, X15 is Su, 5eg, TPg, Sp, Aa, or Zags. 00210) In some embodiments, X12 is an alpha-amino acid, for example, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbrs, AiB, a-Mesiu(diethyl), a-Mei uh, a-Me! uz(As), a-Me-Gei, a-MeOgp, a-Mezeg, a-MemaiY. (00211) In some embodiments, X13 is present. (00212) In some embodiments, X13 and X14 are present. 00213) In some embodiments, X13, X14, and X15 are present. (00214) In specific embodiments, XA is present. 00215) In some embodiments, the peptide inhibitor is cyclized. 00216) In some embodiments, the peptide inhibitor is linear or non-cyclized.

I00217| In some embodiments, the peptide inhibitor is cyclized or contains an intramolecular bond between XA and X9.

I00218| In some embodiments, the implementation of the peptide inhibitor of the formula | X contains or consists of the sequence of formula Ip:

X1-X2-X3-0-X5-X6-M/-X8-0-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (ip) (5EO Ir

MO:1369), 002191 de

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent; 60 X5 represents Aa, Ago, Sim, Rpe, I em, Tng, Zeg, AIV, Zags, a-MeOgp, a-Mezetg, Sii, bar, Rab,

Bar(As), Siu, Guv, Avp, M-Mesip, M-MeAgo, Ogp or ip;

Xb is Azr, Tpg, Azp or Re;

XV represents Mai, SiIp, Sim or GG uv;

X10 is Thug Ripe, Rpe(3,4-Eg), Rpe(3,4-Si2), E(3-Me), Rpe(4-(2-aminoethoxy)), Rpe(4-(2- acetylaminoethoxy)), Rpe(4-Bi), Rpe(4-SOMH), Rpe(4-CI), Rpe(4-CM), Rpe(4-guanidino), Rpe(4-

Me), Rpe(4-Mn"), Ripe(4-Mz), Rpe(4-OMe), Rpe(4-OVYAI) or Tug;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X12 is Ni, Ripe, Ago, M-Me-Niv, Mai, Sam, Sra, Ie, Sii, NIe, 3-Rai, II-butyl-AiYa or

1-butyl-Siu, 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asbs, Asms, Aor, Alib, a-diethyliu, a-

Me! uz, a-MeH uv(As), a-Me-G hey, s-MeOgp, a-Mezeg, a-Memai, Spa, Siii, Sra, (0)Avp, Sim, pAgou or

G uv;

X13 is TNg, Zags, Sim, Re, Ago, I ey, Gu, VpAPa, Mmai, AIB, Guv(As), Sii, A5r, bab, Var,

Sim, pAgo, Guz, Azp, Ot or sSip, or absent;

X14 represents Re, Tug, VYRPe, Azp, Ago, Op, I ub(As), Ni; bar(As), Bbac(As) or Azr, or absent;

X15 is su, Zeg, TNpg, Sp, Aa, Zags, V-Aia, Sim, Agud or Avp, or absent;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent, 00220) where Su in position X4 and Sub in position XU are optionally connected by a disulfide bridge. (00221) In some embodiments, Ip: X5 is Aa, Ago, Sim, Re, Heiy, Tpg, 5eg, Dir, Zags, a-MeOt, o-Meseg, Sii, Oar, Ar, Rar(As), Spu , Guz, Azp, M-Mesip, M-MeAgo, Ogp or

SiIP; X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe(4-(2-aminoethoxy)|, Rpe(4- (2- (acetyl-aminoethoxy)), Rpe(4-B/), Rpe(4-SOMH»g), RFe(4-SI), RPE(4-CM), RFe(4-guanidino),

Rpe(4-Me), Rpe(4-Mn»g), Rpe(4-Mz), Rpe(4-OMe), Rpe(4-OVAI) or Tug; X11 is Ttgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-Hydroxy-Ttr, Ppe(3,4-Ci2") or Tuk(3-i-Vy); X12 represents No, Re, Aha,

Co) M-Me-Niz, MaY, Sam, Sra, Iec, Si, Niyei, 3-RaY, i-butyl-AIa, or i-butyl-SiU, 4-amino-4- carboxytetrahydropyran, Asps Asrs, Asbs, Asums, Adr, AIIBb, a-Dietilou, o-Mei uv, a-MeiG uz(As), a-

Me-G hey, o-MeOt, a-Mezeg, «-Memai, Spa, Sii, Sra, (0)Avzp, Sim, pAgo, or Guz; X13 is a

Tpg, zags, Sim, Rpe, Ago, I em, Guz, VpAPa, mai, Air, Guv(As), Sii, Azr, bab, bar, Sim, pAgo, Guz, Avp,

Op, or Sp, or absent; X14 represents Rie, Tug, VyRpe, Avp, Ag9, Op, Guv(As), Niv; rar(As), babf(As) or Ar, or absent; X15 is Su, Zeg, TAg, Sip, Aa, Zags, V-AIa, Spi,

Agud or Avp, or absent; X16 is Avhr, Sim, AIa, AEA, AER, VpLia, Saba or absent; and

Х17 represents И ей, И у, Агу or absent. (00222) In some embodiments, X13 is TPg, Zags, Sim, Rie, Ago, Hem, Huz,

VpAia, AIyib, Gub(As), Siy, Ar, bab, Bar, Sim, pAgo, Gu, A5p, Ogp or Sip. In some embodiments, X13 is TPg, Zags, Sim, Rpe, Aga, Hei, Huz, VPAia, or AIb. (00223) In some embodiments, X14 is Re, Tug, VpyRPe, Ap, Ago, Op,

Guz(As), No; YuSar(As), rac(As) or Ar. In some embodiments, X14 is Re, Tug, or VIR Pe. (00224) In some embodiments, X15 is Su, Zeg, TAg, Sp, Aa, Zags, B-Aia,

Sim, Agd or Azhp. In some embodiments, X15 is Su, Zeg, TPg, Sip, Aia, or Zags. (00225) In some embodiments, X12 is an alpha-amino acid, for example, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, AlIb, a-Diethyliu, a-MeH uz, a-Mei uz(Ac) , a-Me-Gay, a-MeOgp, a-Mezeg, a-MemaiY. (00226) In some embodiments, X13 is present.

I00227| In some embodiments, X13 and X14 are present. (00228) In some embodiments, X13, X14, and X15 are present.

I00229| In some embodiments, the implementation of the peptide inhibitor of the formula | X contains or consists of the sequence of the formula Io:

X1-X2-X3-0-X5-X6-M/-X8-0--X11-H-X13-X14-X15-X16-X17-X18-X19-X20 (0) (5BEO Ir

MO:1370), 002301 de

X1 is any amino acid or absent;

X2 is any amino acid or absent; 60 HZ is any amino acid or absent;

X5 is Aa, Ago, Sim, Rpe, Gei, Tng, Zeg, AIV, Zags, a-MeOgp, a-Mezetg, Sii, bar, Rab,

Bar(As), Siu, Guv, Avp, M-Mesip, M-MeAgo, Ogp or ip;

Xb is Azr, Tpg, Azp or Re;

XV represents Mai, SiIp, Sim or GG uv;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X13 is TNg, Zags, Sim, Re, Ago, I ey, Gu, VpAPa, Mmai, AIB, Guv(As), Sii, A5r, bab, Var,

Sim, pAgo, Guz, Azp, Opt or cSip, or absent;

X14 represents Re, Tug, Ap, Ago, Op, I uz(As), Nih; YBar(Ac), bar(Ac) or Ar, or absent;

X15 is su, Zeg, TNpg, Sp, Aa, Zags, V-Aia, Sim, Agud or Avp, or absent;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

I00231| where Su in the X4 position and Sub in the XU position are not necessarily connected by a disulfide bridge. (00232) In some embodiments, Io: X5 is Aa, Ago, Sim, PNe, Ie, TNg, 5eg, dir, Zags, a-MeOt, o-Mezeg, Sii, Oar, ar, Rar(As), Spu, Guz, Azp, M-Mesip, M-MeAgo, Ogp or

SiIP; X11 is Ttgr, 1-Mai, 2-Mai, Rnpe(3,4-OMeg), 5-hydroxy-Ttr, Rie(3,4-SiIg) or Tug(3-1-

You); Х1ИЗ3 is TpPg, Zags, Sim, Rpe, Ago, Gay, Gu, VPAIa, Mai, AB, Guz(As), Sii, Ar, bab,

Bar, Sim, pAgo, Gu, Azp, Op, Sp or absent; X14 is Re, Tug, Azp, Aga, Op, I uz(As),

No; bar(As), bab(As) Ar or absent; X15 is su, 5eg, TAg, Sp, Aa, Zags, V-Aia, Spy,

Agd or Ap or absent; XIB is Ar, Sim, Sim, AIa, AEA, AER, VpAia, Sara or absent; and X17 represents and ей, ГГ ув, Агд or absent. 00233) In some embodiments, X12 is an alpha-amino acid, for example, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbs, Asus, Air, a-diethylol, a-MeH uz, a-Mei uz(As), a-Me-Gay, a-MeOgp, a-Mezeg, a-MemaiY. (00234) In some embodiments, X13 is TPg, Zags, Sim, Rie, Ago, Hem, Huz,

VpAia, AIyib, Gub(As), Siy, A5zr, bab, Bar, Sim, pAgo, Gu, Ap, Ogp or Sip. In some embodiments, X13 is TPg, Zags, Sim, Rpe, Aga, Iey, Guz, VpAia, or AB. 00235) In some embodiments, X14 is PpNe, Tug, Azp, Ago, Op, GG uz(As), Niv; rar(As), bac(As) or Ar. In some embodiments, X14 is Re or Tug. (00236) In some embodiments, X15 is su, Zeg, Tpg, Sp, Aa, Zags, B-Aya,

Sim, Agd or Azhp. In some embodiments, X15 is Su, Zeg, TPg, Sip, Aia, or Zags.

I00237| In some embodiments, X13 is present. 00238) In some embodiments, X13 and X14 are present. (002391 In some embodiments, X13, X14, and X15 are present.

I00240| In some embodiments, the implementation of the peptide inhibitor of the formula | X contains or consists of the sequence of formula II: xX1-X2-X3-0-X5-X6-M/-X8-0-x-X11-H-X13-E-X15-X16-X17-X18-X19-X20 ( Ir) (ZEO IU MO:1371), (002411 de

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X5 is Aa, Agu, zags, a-MeOgp, a-Mezeg, Sii, bar, bab, Oar(As), Spu, Guz, Avp, M-

Mesip, M-MeAgo, OGPP or sSip;

Xb is Azr, Tpg or Avp;

BECAUSE X8 represents Mai, SiIp or Si;

X11 is Tgr, 1-Mai, 2-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Rpe(3,4-Si") or Tug(3--Vy);

X13 is TNg, Zags, Sim, Re, Ago, I ey, Gu, VpAPa, Mmai, AIB, Guv(As), Sii, A5r, bab, Var,

Sim, pAgo, Guv, Azp, Opt, Sip or absent;

X15 is su, 5eg, Tpg, Sp, Aa, Zags, B-Aia, Sim, Ago, Azp or absent;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent, because I00242| where Su in the X4 position and Suz in the XO position are not necessarily connected by a disulfide bridge. 00243) In some embodiments of Ir: X5 is Aa, Agd or Zags; X11 represents Ttgr, May 1 or May 2; X13 is TpNg, Zags, Sim, Rpe, Ago, Genes, I uz, VAAPa, Mai, AIib or absent; X15 is Su, Zeg, Tyg, Sp, Aa, Zags or absent; X16 represents Avzr, Sim,

Aa, AEA, AER, VpAa, Sava or absent; and X17 represents and ей, и ух, Агу or absent. (00244) In some embodiments, X13 is TPg, Zags, Sim, Re, Aga, Hei, Guv,

VpAia, AIyib, Gub(As), Siy, Ar, bab, Bar, Sim, pAgo, Gu, A5p, Ogp or Sip. In some embodiments, X13 is TPg, Zags, Sim, Rpe, Aga, Iey, Guz, VpAia, or AB. (00245) In some embodiments, X15 is su, beg, TPg, Sp, Aia or Zags, p-

Aa, Sim, Agu, or Azp. In some embodiments, X15 is su, 5eg, TPg, Sp, AIa or zags. (00246) In some embodiments, X13 is present.

I00247| In some embodiments, X13 and X14 are present. (00248) In some embodiments, X13, X14, and X15 are present.

I00249| In some embodiments, the implementation of the peptide inhibitor of the formula | X contains or consists of the sequence of the formula Id:

X1-X2-X3-0-X5-X6-M/-X8-0-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Id) (5EO Ir

MO:1372), where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X5 is Aa, Ago, Sim, Re, I em, Tng, Zeg, AIB, Zags, O-AIa, O-Ag9, 0-StIy, O-RHne, 0-iI eyy, p-Tng, O-5eg .

MeAgo, OGP or Sip;

Xb is Ar, Tpg, Azp, Re, O-Avr, O-TNg, O-Azp or O-RNe;

ХВ represents Mai, Sip, Sim or I uv;

X10 is Tug, Rpe, Rpe(3,4-Eg2), Rpe(3,4-C12), E(3-Me), Rpe|(4-(2-aminoethoxy)|, Rpe|4- (2 (acetylaminoethoxy)|

Coo) Rpe(4-Me), Rpe(4-MH), Rpe(4-Mz), Rpe(4-OMe), Rpe(4-OVY) or Tug;

X11 is Ttgr, 1-Mai, 2-Mai,, Ppe(3,4-OMEeg) 5-hydroxy-Ttr, Pne(3,4-SiIg) or Tug(3-1-

You);

X12 is Ni, Rpe, Ago, M-Me-Niv, Mai, or O-Niv5, Sam, Sra, Iy, Sii, Niy, 3-Rai, y-butyl-APa, II-butyl-Siu, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbs, Asms, Adr, AIBBb, a-Diethyliu, a-MeH y, a-MeH uz(As), a-Me-I esh, a-MeOgp, a- Mezeg, a-Memai, SNna, Sii, Sra, (0)Avp,

Sim, pAgo or I uz;

X13 is TNg, Zags, Sim, Re, Ago, I ey, Gu, VpAPa, Mmai, AIB, Guv(As), Sii, A5r, bab, Var, spin, NAgo, Guz, Azp, Opt, ip or absent ;

X14 represents Re, Tug, VyRPe, Azp, Ago, Op, I ub(As), Ni5; Bar(As), Bac(As), Ar or absent;

X15 is su, 5eg, Tpg, Sp, Aa, Zags, B-Aia, sim, Ago, Azp or absent;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or is absent, 002501 where Sux at position XA and Su at position XO9 are optionally linked. 00251) In some embodiments, Id: X5 is Aa, Ago, Sim, Re, Hei, Tpg, 5eg,

Ar, Zags, O-AIa, O-Ago, O-C1y, O-RNe, O-Hei, O-TNng, O-5eg, O-AIr or O-Zags; X10 is Tug

BO or Rpe; X11 represents Ttgr, May 1 or May 2; X12 is Niv, Rie, Ago, M-Me-Niv, MaiYi or p-Niv, Sam, Sra, Iy, Siy, Niyy, 3-Ray, I-butyl-AlYia, or y-butyl-Siy; X1I3 is TnHg, registry office,

SiIi, Riie, Ago, Gei, Huz, VPAia, Mai, AIIB or absent; X14 is Re, Tug, ViRpe or absent; X15 is Su, Zeg, Tyg, Sp, Aa, Zags or absent; X16 represents Avzr, Sim,

Aa, AEA, AER, VpAa, saBva, I ei or absent; and X17 represents and ей, Гуз, Агд or absent. 00252) In some embodiments, X12 is an alpha-amino acid, for example, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, AlIb, a-Diethyliu, a-MeH uz, a-Mei uz(Ac), a-Me-Gay, a-MeOgp, a-Mezeg, a-MemaiY. 00253) In some embodiments, X13 is TPg, Zags, Sim, Rpee, Ag, Genes, GG uv,

VpAia, AIyib, Gub(As), Siy, Ar, bab, Bar, Sim, pAgo, Gu, A5p, Ogp or Sip. In some embodiments 60, implementation of X13 is TPg, Zags, Sim, Rpe, Aha, Iay, Guz, VpAia, or AB.

(00254) In some embodiments, X14 is Re, Tug, VpyRPe, Avp, Ago, Op,

Guz(As), No; YuSar(As), rac(As) or Ar. In some embodiments, X14 is Re, Tug, or VIR Pe. 00255) In some embodiments, X15 is su, Zeg, Tpg, Sp, Aa, Zags, B-Aya,

Sim, Agd or Azhp. In some embodiments, X15 is su, Zeg, TAg, SiIp, AiIa, or zags. (00256) In some embodiments, X13 is present.

I00257| In some embodiments, X13 and X14 are present. (00258) In some embodiments, X13, X14, and X15 are present. 00259) In some embodiments, Id comprises or consists of a sequence of formula

Id"

X1-X2-X3-0-X5-X6-M/-X8-0-X10-X11-X12-X13-X14-X15 (197) (ZEO IU MO:1373), where X1-X14 have the definition presented for Id, and de Suz in position XA and Su in position X9 are not necessarily connected. 00260) In some embodiments, Id": X5 is Aa, Ago, Sim, Rpe, Iei, Tpg, 5eg,

Ar, Zags, O-AIa, O-Ago, O-C1y, O-RNe, O-Hei, O-TNng, O-5eg, O-AIr or O-Zags; X10 is Tug or Rpe; X11 represents Ttgr, May 1! or May 2!; X12 is Ni, Rie, Aga, M-Me-Niv, Mai, or O-Nih, Sam, Sra, Iei, Sii, pei, 3-Rai, I-butyl-AIa, or Yibutyl-Siu; ХИЗ3 is TnHg,

Zags, Sim, Riye, Ago, I em, Guz, VPAЯa, Mai, AiB or absent; X14 is Re, Tug, VPIRpe or absent; X15 is Su, Zeg, Tyg, Sp, Aa, Zags or absent; X1b represents Avr, seven,

Aa, AEA, AER, VpAa, saBva, I ei or absent; and X17 represents and ей, Гуз, Агд or absent. 00261) In some embodiments, X13 is TPg, Zags, Sim, Rie, Ago, Hem, Huz,

VpAia, AIyib, Gub(As), Siy, Azr, bab, Bar, Sim, pAgo, Guz, Azp, Ogp or Sip. In some embodiments, X13 is TPg, Zags, Sim, Rpe, Aga, Iey, Guz, VpAia, or AB. (00262) In some embodiments, X14 is Re, Tug, VpyRPe, Ap, Ago, Op,

IGuz(As), Niv; OSar(As), rac(As) or Ar. In some embodiments, X14 is Re, Tug, or VIR Pe. 00263) In some embodiments, X15 is su, 5eg, TPg, SiIp, Aa or Zag, p-

Aa, Sim, Ago, or Azp. In some embodiments, X14 is Re, Tug, or ViRPpe.

Zo (00264) In some embodiments, X13 is present. (00265) In some embodiments, X13 and X14 are present. (00266) In some embodiments, X13, X14, and X15 are present.

I00267| In some embodiments, the peptide inhibitor of formula I X contains or consists of the sequence of formula Ig: xX1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17 -X18-X19-X20 (I) (5EO I

MO:1374), where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

HA stands for Suzh, Rep, pSuz, O-Rep, O-Suvz, O-pSuvz, Mei, Spi, Avr, I uv, Ot, Oar, rab, 0-

Bar, О0-OSar, 0-А5зр, 0-Сиш, О-уз, Зес, 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid , Aby, B-azido-Aia-OH, propargylglycine, 2-(3'-butenyl)glycine, 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4-pentenyl)glycine, 2-(5 '-hexenyl)glycine, Ab or absent;

X5 is any amino acid;

Xb is any amino acid;

X7 represents Tgr, Sim, Su, Me, Avp, Pgo, Agu, Tyg or OsiciIu, or the corresponding α-methylamino acid form of any of the above;

XV is any amino acid;

ХУ represents Su, Rep, pSuz, O-Rep, O-Suv, O-nSuvz, SIM, uv, Ot, Var, bab, O-Obar, 0- rab, 0-Avr, 0-S1y, 0-I uv, Azr, GI ei, Mai, Rpe, or Zeg, 5es, Aby, B-azido-AIa-OH, propargylglycine, 2-2-allylglycine, 2-(3'-butenyl)glycine, 2-(4-pentenyl) )glycine, Aa, pSuz, Aby, Mei, MesSuvh, (0)Tug or 2-(5'-hexenyl)glycine;

X10 is Tug, Rpe(4-OMEe), 1-Mai, 2-Mai, Ais, «-MeRne, Vir, (0)Suz, Spa, OMT, (0) THug,

Sim, Niz, pRNe(3,4-dimethoxy), pTug, M-Me-Tug, Tr, Rpe(4-SOMH»g), RNe(4-phenoxy), TNg, Tis,

Tup(3-iVy), Rne(4-18Vy), Rnpe(4-SM), Ripe(4-VI), Rpe(4-MN"), Rne(4-E), Rne(3.5-Eg ), Rpe(4-CH»CO»H),

Rpe(penta-P), Rpe(3,4-SiIg), Rne(4-SEz), Vir, Spa, 4-pyridylalanine, VyTug, OsisIu, Rpe(4-Mz), 60 Rpe(4-Vi), РНе(4-(2-aminoethoxy)) or Ре, an analogue of Рпе, an analogue of Tug or the corresponding a-

the methylamino acid form of any of the above;

X11 is 2-Mai, 1-Mai!, 2,4-dimethylRpNe, Vir, Rpe(3,4-C12), Rne (3,4-Eg), Rne(4-СО2Н),

ViRPe(4-E), o-Me-Ttr, 4-phenylcyclohexyl, Rpe(4-SEz),, Rpe(3,4-OMeg), a-MeRpe, ViMai, VAR Pe,

You Tug, VATgr, Mma(5-phenyl), Re, Nix5, pRPe, Tis, Tda, Tgr, Tug, Rpe(4-OMe), Rne(4-Me), Ttr(2,5,7-tri- tert-butyl), Rpe(4-Oallyl), Thug(3-IVy), RHe(4-480), RHe(4-guanidino, Rpe(4-OV21I), Osidiu, Snitz(B2I), 4-phenylbenzylalanine, Rpe(4-(2-aminoethoxy))|, 5-hydroxy-Tgr, b-chloro-Tgr, M-MetT"r, 1,2,3,4-tetrahydronorharman, Rpe(4-SOMH»), RNe (3,4-dimethoxy), РПе(2,3-SiI2), РНе(2,3-Е»g),

Rie(4-E), 4-phenylcyclohexylalanine or Vir, or the corresponding α-methylamino acid form of any of the above;

X12 is Ni, Rie, Agu, M-Me-Niv, or Mai, Sam, Sra, Iy, Siy, NIy, 3-Rai, i-Butyl-Apa, a-MeHuz, O-AYa, (0 )Azp, (0)Azr, (0) ei, (0)RPpe, (C0)TGug, AiYib, a-MeHey, a-MeOgp, B-AIiB, B-APa,

VpAia, VpAgo, Vp ei, VimMai, B-spiro-pip, sim, pAgo, Pe, Huz, M-Mei vy, M-MeAgo, Od, Ot, Rgo, Sp, zZeg, TNg, Thie or I-butyl- Siu, 4-amino-4-carboxytetrahydropyran, Asps Asrs, Asbs, Asms, Adr, AB, a-diethyl, a-Mei uh, o-Mei uz(As), a-Me-I em, o-MeOgp, a -Mezeg, a-MemMai, Sa, Sii, Sra, (B)Avp,

Sim, pAgo, or Huz or the corresponding α-methylamino acid form of any of the above;

X13 is Tpg, Zags, Sim, Rpe, Ago, Gay, Azp, Sii, Guz, Agd, Opt, Mai, VpAia, GG uz(As), (F)Azp, (СО) ей, (С)РПе, (C)TNg, Aa, o-MegH em, AiYIB, B-AIa, D-Sim, Vy em, VyMai, V-spiro-pip, Spa,

Spo, Ar, Bab, Var, a-Diethyliu, PI em, Azp, Oddi, Rho, Sip, Zeg, VD-spiro-pip, TAPg, Tra, Thie or AIB, or the corresponding a-methylamino acid form of any of the above ;

X14 represents Re, Tug, Sim, Su, Niv, Iuv, em, Mei, Avp, Gub(As), Bar(As), Ar, Rgo, Sip,

Agud, Zeg, TPg, Tis or DViRPe, or the corresponding α-methylamino acid form of any of the above;

X15 is su, b5eg, TPg, SiIp, Aa, (Aa, (0)Avp, (0)А5р, (0) ей, (СОР Pe, (С)ТНг, Aеа,

Avr, Azp, Syp, Rije, Su, Guv, Gei, Rgo, Ago, B-AIa, or Zags, or the corresponding α-methylamino acid form of any of the above;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

Zo X20 is any amino acid or absent. (00268) In specific embodiments, the peptide is cyclized with XA and X9.

I00269| In specific embodiments, ХЗ3 is Sim, O-C1y, Ag9y, (0)Ag9, РНе, (0)РНе, 2-Май, Тнг, Гем, (0)С1н. 00270) In some embodiments of Ig: X11 is 2-Mai, 1-Mai, 2,4-dimethylRNe, Vir,

Rpe(3,4-Sig), Rpe (3,4-Eg2), Rpe(4-СО»2Н), BP Pe(4-P), a-Me-Ttr, 4-phenylcyclohexyl, Rpe(4-SEz ), a-

MeRpe, rViMai, VyRpe, V Tug, V Ttgr, Mma(5-phenyl), Rpe, Nix5, pRpe, Tis, Tda, Tgr, Tut, Rpe(4-OMEe),

Rpe(4-Me), Teri(2,5,7-tri-tert-butyl), Rpe(4-Oallyl), Thug(3-IVy), RHe(4-1Vy), RHe(4-guanidino,

Rpe(4-OV821), Osidio, sat(B2I), 4-phenylbenzylalanine, Rpe(|4-(2-aminoethoxy)), 5-hydroxy-Ttr, 6-chloro-Ttr, M-MetT"tr, 1, 2,3,4-tetrahydronorharman, Rpe(4-SOMH), RHe(3,4-dimethoxy), Rpe(2,3-

Sig), Ppe(2,3-E2), PNe(4-E), 4-phenylcyclohexylalanine or Vir, or the corresponding α-methylamino acid form of any of the above; X12 represents Ni, Rpe, Ago, M-Me-

Ni5, or Mai, Sam, Sra, I em, Sii, PI ei, 3-Rai, II-butyl-AiYa, a-Mei uv, O-AiIa, (0)Avp, (0)Avr, (0) ei , (P Pe, (0) THug, AB, a-MegH ey, o-MeOgp, V-AiB, V-AIa, VpAiIa, VpAgo, Vp em, VyMai, B-spiro-pip, SIM,

Naga, Pe, Guv, M-Mei! εy, M-MeAgo, Oadi, Ogpp, Pgo, SiIp, Zeg, TNg, Thie or i-butyl-Siu, or the corresponding α-methylamino acid form of any of the above; X13 is TPg, Zags, Sim, Re,

Ago, G em, Huz, Agd, Ogpp, Mai, VpAia, GG uz(As), (0)А5п, (0) ей, (OR Pe, (С)ТПг, Аа, а-МегГ ей, AB, D -

Aa, B-SiIy, Vp ei, VimMai, B-spiro-pip, Spa, Spo, Azr, bab, Var, a-diethylOiyu, NI ei, Avp, Oai, Rgo,

Sip, Beg, B-spiro-pip, Tig, Tra, Thie, or Aib, or the corresponding α-methylamino acid form of any of the above; X14 is Re, Tug, Sim, Su, Ni, Iuv, Iei, Mei, Avp, Rgo, Sp, Ago, zZeg, TTG, Tis or DVyRPe, or the corresponding α-methylamino acid form of any of the above; X15 is su, Zeg, TPg, Sp, Aa, ()Aia, (0)Avzp, (0)A5r, (0)ei, (0)P Pe, (C)Tpg, Aea, Avr, Ap, Sim , RIPe, su, Gu5, Hei, Rgo, Agd or Zags, or the corresponding α-methylamino acid form of any of the above; XIB represents Avzr, Sim, Aa, AEA,

AER, VPAia, Sara, Siu, Zeg, Rgo, Azp, TPg is either absent or is the corresponding α-methylamino acid form of any of the above; and X17 is I en, Huz, Ago, SIM, zZeg, Su, SiP or absent, or is the corresponding α-methylamino acid form of any of the above. 00271) In some embodiments, both X4 and XO are Rep. In specific embodiments, XA and XU are cyclized using a disulfide bond. 60 (00272) In some embodiments, X4 is Aby and X9 is Sub5. In some embodiments, XA and XU are cyclized using a thioether bond. (00273) In specific embodiments, X5 is Aa, Ago, Sim, Rpe, Iei, Tpg, Zeg,

Ar, Zags, O-Aia, O-Aga, O-S1Iy, O-RNe, O-I ey, O-Tng, O-5eg, O-AYir, Suv, Sii, Avr, Rab, Oar, SU, Niv ,

NSuz, I uv, Mei, Azp, M-Me-AiIa, M-Me-Azp, M-Me-I uz, M-Me-SiIp, Ot, Rgo, Rep, Sip, Mai, a«Me-! uv, aMe-Ot, or O-Zags, a-MeOt, a-Mezeg, Sii, Sar, rab, bar(As), Spu, Guv, Azp, M-Mesip, M-MeAga or SiIp. In some embodiments, X5 is Sip or Ap. In specific embodiments, X5 is Aa, Ago, Sim, Rpe, Ie, Tng, Zeg, AIB, Zags, O-AIa, O-Ago, O-C1y, O-Rne,

O-Gey, O-Tng, O-5eg, O-АЙЙ, Suv, Siy, Azr, Rab, ar, Stu, Ni, pSuv, Guz, Mei, Avp, M-Me-Aia, M-Me-

Avp, M-Me-G uz, M-Me-Sip, M-Me-Agu, Op, Rgo, Rep, SiIp, Mai, "Me-Guz, oMe-Ogp or O-5Zags. In some embodiments, X5 represents himself cSip. (00274) In specific embodiments, Xb is Ar, TNg, Azp, Rie, O-Avr, O-TNg, p-Avp, Sim, Ago, Zeg, or O-Rpe. In specific embodiments, Xb is TpHg. 002751) In specific embodiments, X7 is Ttgr. (00276) In specific embodiments, X8 represents Mai, SiIp, Siy, Re, Avzp, Rgo, Ag,

TNg, Tgr or Guz. In specific embodiments, X8 is a cSip.

I00277| In specific embodiments, X1, X2, and XZ are absent. (00278) In some embodiments, X11 is an analog of Tgr.

I00279| In specific embodiments, HTO is an analogue of RPE. In specific embodiments, the HTO is Rpe(4-OMe), Rpe(4-SOMH), or Rpe(|4-(2-aminoethoxy)) (also referred to herein as Rpe|4-2ae))). In specific embodiments, X10 is Ppe(4-OMe) or Ppe|4-(2-aminoethoxy)) (also referred to herein as Ppe|4-g2ae)|).

I00280| In specific embodiments, X11 is a 2-Ma! or 1-May. In some embodiments, X11 is 2-May.

I00281| In some embodiments, X12 is α-MeH, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbrs, Asums, Adr, AB, α-diethylthio, α-MeH, α-MeH (As), and -

Me-Gay, a-MeOgt, a-MezZeg or a-MemMaY. In some embodiments, X12 is a-

Me" uv. (00282) In some embodiments, X13 is sim or I uz(Ac). In some embodiments, X13 is sy.

Зо 00283) In some embodiments, X14 is an Aup. (00284) In some embodiments, X15 is Siu or Azp. In some embodiments, X15 is a su. 00285) In some embodiments, one or more, two or more, three or more, or four or more of X16, X17, X18, X19, and X20 are absent. In specific embodiments of X16,

X17, X18, X19 and X20 are absent. (00286) In specific embodiments, Ig X4 and XO are Su, X7 is

Tgr, and X1I8 is MO) uv). In specific embodiments, Ig X4 and XO are

Suz, X7 represents Tgr, X10 represents Tug, and X18 represents MO) Uub|. In specific embodiments of Ig XA and XU are Suvx, X7 is Ttgr, X1, X2 and XZ are absent, X17 is absent, X18 is KO) in, and X19 and X20 are absent. In specific embodiments of Ig XA and XO are Suvx, X7 and X11 are Ttgr, X10 is Tug, and X18 is

MKO)GU5. In some embodiments, X1, X2, and XZ are absent; and in some embodiments, X17 is absent.

I00287| In specific embodiments, Ig X4 and XO represent Rep, and X12 represents o-Me! uh In specific variants of the implementation of Ig XA and XO are Rep, X12 is a-

Me" is a bond, and X16, X17, X18, X19, and X20 are absent. In specific embodiments, X4 and XO are Rep, X12 is α-Mei, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbs,

Asus, Adr, AB, a-diethyliu, c-MeGuv(As), a-Me-I ey, o-MeOpt, o-Meseg, a-Memai, X16, X17, X18,

X19 and X20 are absent, and X7 is Ttgr. In specific embodiments, Ig X4 and XO are represented

BO is Rep, X12 is a-Me!/ uh, X16, X17, X18, X19 and X20 are missing, and X7 is Tr. In specific embodiments, Ig X4 and XU are Rep, X7 is Ttgr, and X12 is α-MeiYyh. In some embodiments, X1, X2, and XZ are absent. In specific embodiments, there is a disulfide bond between XA and X9. (00288) In specific variants of implementation, IgXi4 represents Ar, XO represents Su", and

X12 is 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbs, Asms, Aor, AIBb, a-diethyliu, a-Mei uz, or o-Me! ub(As), a-Me-I ey, a-MeOgp, a-Mezeg, or s-Memai. In specific embodiments, X4 is Aby, XU is Sub, and X12 is a-Me! uv. In specific embodiments, Ig X4 represents Aby, XU represents Suvz, X12 represents o-Me! uv, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbs, Asms, Aodr, AB, a-diethyliu, a- 60 Me" uz, or a-Me! uz(As), a-Me-I ey, a-MeOt, a-Mezeg, or a-Memai, and X16, X17, X18, X19, and X20 are absent. In specific embodiments, X14 is Aby, XU is Su, X12 is a-Meg/uv, and Х16, Х17, Х18, Х19 and Х20 are absent.

X4 is Ar, XU is Su5z, X12 is α-Mei, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, Adr, Alb, α-Diethyliu, o-MeiU, or a-

Me! uz(As), a-Me-Hei, a-MeOgp, a-Mezeg, or a-Memai!, X16, X17, X18, X19 and X20 are absent, and X7 is Tgr. In specific embodiments, Ig X4 represents Ar, XO represents

Su, X1I2 is a-Mei uh, X16, X17, X18, X19 and X20 are absent, and X7 is Tgr. In specific variants of the implementation of Ig, X4 is Aby, XO is Su, and X7 is

Tgtr, and X12 is oh-Me! uz. In some embodiments, X1, X2, and XZ are absent. In specific embodiments, there is a thioether bond between XA and X9.

I00289| In some embodiments, the implementation of the peptide inhibitor of the formula | X contains or consists of the sequence of formula 15:

X1-X2-X3-0-X5-X6-M/-X8-0-X10-X11-X12-X13-X14-c2-X16-X17-X18-X19-X20 (Ii) (5BO I

MO:1375), where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X5 is any amino acid;

Xb is any amino acid;

XV is any amino acid;

X10 represents Tug, 1-Ma! 2-May, Rpe(3,4-Eg2g), Rpe(3,4-CI2), E(3-Me), Rpe|4-(2-aminoethoxy)|,

Rpe(4-(2-(acetylaminoethoxy)|, Rpe(4-Vg), Rpe(4-SOMH), Rpe(4-SI), Rpe(4-CM), RHne(4-guanidino),

Rpe(4-Me), Rpe(4-MH"), Rne(4-Mz), Rne(4-OMe), Rne(4-OB21Y) or Tug;

X11 is Tgr, 1-Mai, Pne(3,4-OMeg) 5-hydroxy-Ttr, Pne(3,4-SiIg) or Tuk(3--81);

X12 represents Ago, GI uv, Ni, NAgu, Sii, Ot, 1-Mai, O-Aia, 0-I ei, O-Rpe, O-Azp, O-Azvr, Adr,

I em, VyHey, Aib, VpAia, VpMmai, vprAgo, p em, Var, 4-amino-4-carboxytetrahydropyran, Asps, Asrs,

Asrs, Asms, Aodr, Aib, a-diethylOiu, a-MeGuv, o-MegHuz(As), a-Me-Hei, o-MeOt, o-Mezeg, a-Memai,

Spa, Sii, Sra, ()Az5p, Sim, pAgo or I uz;

X13 represents Spa, Oda, AB, I ey, Mai, Oab, Sim, Guz, VpGaey, VpAia, VimMa! To all, Guv(As), Siya,

Azr, rab, Bar, Sim, pAgo, Guz, Azp, Opt, GG uv(As) or Sp;

X14 is Re, Tis, Azp Tug, Azp, Ago, Op, Guz(As), Ni; bar(As), bab(As) or Azr;

X16 is any amino acid;

X17 is absent;

Х18 is 0-ІІ uv;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00290) In specific embodiments of Ie: XIO is Tug, 1-MaI or 2-Mai!; X11 is Tgr or May 1; X12 represents Ago, GG uv, Nib, pAgo, SIii, Ogp, 1-Mai, O-Aya, 0-I eyi, O-

Rpye, 0-Avp, O-Avr, Aodr, Gay, VPI em, Aib, VpAia, VyMai, VpAgo, PI ei or Var; X13 is a

Sna, Osi, АЙБб, I ey, Mai, bab, Sim, Guz, YOU ey, VpApia, YouMa! or VO and; X14 is RnHe, Tis,

Azp or Tug; and X16 is AEA, Aia, or pAia. 002911 In specific embodiments, X5 is Sim, Ago, Aa, M-Me-Ag9, M-Me-AIa,

M-Me-Sip, Ogp, M-Me-Avp, M-Me-I uh, Beg, Sip, Ogp, Azp or Mar. In specific embodiments, X5 is Sim, Ago, Aa, M-Me-Aga, M-Me-Aia, M-Me-Sip, Ot, M-Me-Avp, M-Me-

Guz, Zeg, Azp or Var. (002921 In specific embodiments, Xb is Azr or TNg. 00293) In specific embodiments, X8 is cSip or Mai.

I00294| In specific embodiments, the peptide is cyclized using a disulfide bond between XA and X9.

I00295| In some embodiments, the implementation of the peptide inhibitor of the formula | X contains or consists of a sequence of formula IC

X1-X2-X3-0-X5-X6-M/-X8-0-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (I (5EO Ir

MO:1376), where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any amino acid or absent;

X5 is any amino acid; 60 Xb is any amino acid;

XV is any amino acid;

X10 is Tug, 1-Mai, 2-Mai, Pne(4-(2-aminoethoxy)|, Ppe(4-SOMN"), Pne(4-OMEEe);

X11 is Tgr, 1-Mai, 2-Mai, Vir, Pne(3,4-OMeg) 5-hydroxy-Tr;

X12 represents Ago, Ni, 3-Rai, em, TAg, Sp, Azp, Sim, Pe, Rie, 5eg, Guv, pe ey, a-Mei ey, 0-

Yey, 0O-Avp, -And you, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, Aaor, Aiib, a- dietiloiu, a-Mei y, o-Me! uz(As), a-Me-I em, a-MeOgp, a-Mezeg or o-Memai;

X13 represents TPg, Sim, Tug, Gu, Sp, Avp, GG uv, I uz (As), Ar, Ago, La, 5eg, I ei;

X14 is Re, Tug, Azp, Su, Zeg, Mei, Ago, Niv, Gu, Yi ey or Sp;

X15 is su, Zeg, Ago, I em, Ar, Aa, B-AIa, Sim, Agud or Avp;

X16 is absent or is any amino acid;

X17 is absent or is any amino acid;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. (00296) In some embodiments, IC X10 is Tug, 1-Mai, or 2-Mai; X11 represents Tgr, 1-Mai, 2-Mai or Vir; X12 represents Ago, Ni, 3-Rai, I ei, TNAg, Sp, Avp, Spi, Pe, RNe, zeg, Huz, p ei, a-MeiG ei, 0-I vy, 0-Azp or p-IGei ; X13 is Tpg, Sim, Tug, G uv, Sp, Avp,

Guz, A5r, Ago, Aa, Zeg, I ey; X15 is su, Zeg, Ago, Gei, Ar or AiPa; X16 is missing or

Azp, Sim, Re, Aa, SpPu, Rgo, Avr, Sp, Zeg, TNg, O-Sim or Guz; ii X17 is absent or is present

Rgo, Ago, Sim, A5r, Zeg, Su or Sp.

I00297| In specific embodiments, X5 is 5Zeg, А5р, Авп, ип, Аа, Мей, Ага,

No or Su. In specific embodiments, X5 is 5Zeg, Azr, Sp, Aa, Mei, Ago, Nib, or Su. (00298) In specific embodiments, Xb is any Azr, Zeg or TNg. 002991) In specific embodiments, X8 is Sip, Sim or TnHg.

ИЙОО30О0| In specific embodiments, the peptide is cyclized via a disulfide bond between XA and X9.

ИОО30О1| In an additional embodiment, the present invention includes a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, where the peptide

The inhibitor contains the amino acid sequence of the formula (Ma): Ma) (5EO I

MO:1377), where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

ХЗ is any Y-amino acid or absent;

X4 is Su, pSu5, Rep, pRep, Ar, beg, pbeg or a chemical fragment capable of forming a bond with XO;

X5 is Aa, a-MeOt, a-Mezeg, Sii, OSar, bab, bar(As), Spu, Guz, Azp, M-Meadip, M-

MeAgo, Ot, Sp, Agu, beg or TNg;

Xb is TNg, 5eg, A5p, Pe or any amino acid;

X7 is tr, 6b-chloro-Ttr, 1-Mar or 2-Mar;

X8 is Sim, Sp, Avp, IG uz(Ac), Sii, Sam, I ub(M-e-(M-a-palmitoyl-Y-y-glutamyl)) or

Guz (M-e-palmitoyl);

XU is Sub, pSu5, Rep, pRep Aby, or any amino acid or chemical fragment capable of forming a bond with X4;

X10 is 2-May, an analogue of PNe, Tug or an analogue of Tug;

X11 is 1-Mai, 2-Mai, Ppe(3,4-dimethoxy), 5-hydroxy-Tgtr, Pne(3,4-Si2g), Ttr or Tuc(3-

And you);

X12 is /AIB, 4-amino-4-carboxytetrahydropyran, any alpha-methylamino acid, alpha-ethylamino acid, Asps, Asms, AsBs, Asrs, 4-amino-4-carboxypiperidine, 3-Rai, Adr, a-diethyliu . , GG uz, I ey, Osidiu, Ot, piperidine, Ago, zeg,

Tpgabo TNR;

X13 is I uz(Ac), SiIp, SI, Sim or any amino acid;

X14 is Azp, Sp, I ub(Ac), Sii, Sam, I ub(M-e-(M-a-palmitoyl-y-y-glutamyl)), GG uv (M-e-palmitoyl), or any amino acid;

X15 is p-Aia, Avp, Spu, Sp, Aa, Zeg, AiYIB or sii;

X16 is any amino acid or absent; 60 X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent, where X4 and XU are able to form a bond with each other. In specific embodiments, the bond is an ether bond, a disulfide bond, or a thioether bond. In some embodiments, the peptide inhibitor is cyclized via a bond between XA and XO.

I00302| In some embodiments, the implementation of XI! is a YU-amino acid or is absent. In some embodiments, X2 is an O-amino acid or absent. 00303) In some embodiments, X1Ib is a 10-amino acid or absent. In some embodiments, X17 is an O-amino acid or absent. In some embodiments, X18 is an O-amino acid or absent. In some embodiments, X19 is a Y-amino acid or absent. In some embodiments, X20 is a Y-amino acid or absent. 00304) In specific variants of the implementation of formula (Ia), HTO is 2-Mai, PNe(3,4-dig2), Ppe(3,4-SiIg), Ppe(3-Me), Pne((4-(2- aminoethoxy)|), Rpe|(4-(2-acetylaminoethoxy)|, Rpe(Bg),

Rpe(4-SOMN»g), Rpe(SI), Rpe(4-SM), Rpe(4-guanadino), Rpe(4-Me), Rpe(4-MH»g), Rpe(4-M» c), Longing,

Tug(B2I), or Tu((Me). In some variants of implementation of formula (Ia), X1O is Rpe(4-28),

Rpe(3-2B8), Rpe(2-2K), where K-СНИ(СНО)пу, and р-1-25, 2-МН, О, СО, СОМН or СН2, and M-МН»

SON, ON or SNZ.

I00305| In additional related embodiments, the present invention includes a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises the amino acid sequence of formula (MB): xX1-X2-X3-X4-X5-X6-X7-X8 -X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (MB) (5EO I

MO:1378), where

X1 is any amino acid or absent;

X2 is any amino acid or absent;

XZ is 0-Ago, О-РНе, any О amino acid or absent;

X4 is Sub, pSu5, Rep, pRep, Aby or a chemical fragment capable of forming a bond with XO;

X5 represents Sp, Avp, I uv(Ac), Sii, Sam, I uv(M-e-(M-a-palmitoyl-y-y-glutamyl)), or Guv(M-e-palmitoyl);

Xb is TNg, 5eg, A5p, Pe or any amino acid;

X7 is Ttgr, 1-Mar or 2-Mar;

ХВ is Sip, Avp, G uz(Ac), Sii, Sam, I uz(M-e-(M-a-palmitoyl-Y-y-glutamyl)) or I uz(M-e-palmitoyl);

XU represents Suzh, pSuv, Rep, pRep, Aby, any amino acid or chemical fragment capable of forming a bond with X4;

X10 is РНе(4-(2-aminoethoxy)), РНе(4-(2-acetylaminoethoxy))І, РАе(4-СОМН»5),

Rpe(4-guanidino), Rpe(4-MHg), Tu/(Me) or Rpe(4-2H), where B-CHNa(CHg)pu; n-1-25; 2-0, SO, MN,

SOMN or SN"; and mA-MH»g, SON, OH or CH;

X11 is 2-May or Tr;

X12 is Air, 4-amino-4-carboxytetrahydropyran, a-diethyliu, a-Mei uh, a-Mei! uz(Ac), a-MeHei, o-MeOgt, sa-Mezeg, a-Memai, asia, Asps, Asmus, Asbs Asrs or 4-amino-4-carboxypiperidine;

X13 is I uz(Ac), Sip, Sii, Sim or any amino acid;

X14 is Azp, Sp, Iub(Ac), Sii, Sam, Iub(M-e-(M-a-palmitoyl-y-y-glutamyl)), GG uv (M-e-palmitoyl) or any - which amino acid;

X15 is VD-Aya, Azp, Sp, Aa, beg or AB;

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent, where X4 and XU are able to form a bond with each other. In specific embodiments, the bond is a disulfide bond or a thioether bond. In some embodiments, the peptide inhibitor is cyclized via a linkage between XA and X9.

I00306| In some embodiments, the implementation of XI! is a YU-amino acid or is absent. In some embodiments, X2 is an O-amino acid or absent. because I00307| In some embodiments, X1b6 is a 10-amino acid or is absent. In some embodiments, X17 is an O-amino acid or absent. In some embodiments, X18 is an O-amino acid or absent. In some embodiments, X19 is a Y-amino acid or absent. In some embodiments, X20 is a Y-amino acid or absent. 00308) In another related embodiment, the present invention includes a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, where the peptide inhibitor contains the amino acid sequence of the formula (Ms): xX1-X2-X3-X4-X5-X6-X7 -X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Ms) (ZEO I

MO:1379), where

X1 is absent;

X2 is absent;

XZ is 0-Agu or absent;

XA is Suh, Rep, Ar, or a chemical fragment capable of forming a bond with XO;

X5 is Sp, Avp, I uv(As), Sii or Sam;

Xb is TPpg or 5eg;

X7 is Ttgr, 1-Mar or 2-Mar;

ХВ is sp, Avp, I uz(As), Sii or Sam;

ХУ is Su, pSu5, Rep, pRep, Aby, or any amino acid or chemical fragment capable of forming a bond with ХА;

Х10 is РНе(|4-(2-aminoethoxy)|), Рне(4-СОМН»:) or Ripe(4-ОВ), where Б-СНа(СнНв) pu; n-1-25; and MAMN", SON, OH or SN;

X11 is Tgr or 2-May;

X12 is AIB, 4-amino-4-carboxytetrahydropyran, a-Mei uh, a-MeH uz(As), a-Mei! hey

Asps, Asus, Asbs or Asrs;

X13 represents I uz(Ac) or sy;

X14 is Avp, Sp, I ub(Ac), I uz(M-e-(M-a-palmitoyl-I -y-glutamyl)) or I1uz(M-e-palmitoyl);

X15 is Su, B-Aia, Azp, Sip, Aa, beg or AIBb;

X16 is absent;

X17 is absent;

X18 is absent;

X19 is absent; and

X20 is absent, where X4 and XU are able to form a connection with each other. In specific embodiments, the bond is a disulfide bond or a thioether bond. In some embodiments, the peptide inhibitor is cyclized via a linkage between XA and X9.

I00309| In some embodiments, the implementation of XI! is a YU-amino acid or is absent. In some embodiments, X2 is an O-amino acid or absent. 00310) In some embodiments, X1b6 is a Y-amino acid or absent. In some embodiments, X17 is an O-amino acid or absent. In some embodiments, X18 is an O-amino acid or absent. In some embodiments, X19 is a Y-amino acid or absent. In some embodiments, X20 is a Y-amino acid or absent. 00311) In another related embodiment, the present invention includes a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, where the peptide inhibitor contains the amino acid sequence of the formula (Ma): xX1-X2-X3-X4-X5-X6-X7 -X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Ma) (5EO I

MO:1380), where

X1 is absent;

X2 is absent;

HZ is absent;

XA represents Rep or Aby;

X5 is ap or Avp;

Xb is TPpg or 5eg;

X7 is Tr;

XV represents cSip or Avp;

ХУ represents Rep or Subh; because X10 is PHe(|4-(2-aminoethoxy)| or Ppe(4-COMH");

X11 is Tgr or 2-May;

X12 is AIB, 4-amino-4-carboxytetrahydropyran, c-Me!H uh, a-MeH ey or Asps;

X13 represents I uz(Ac) or sy;

X14 is Avp, Sip or I uv(As);

X15 is Su, Aa, 5eg, B-AIa, Azp or Sp;

X16 is absent;

X17 is absent;

X18 is absent;

X19 is absent; and

X20 is absent, where X4 and XU are able to form a connection with each other. In specific embodiments, the bond is a disulfide bond or a thioether bond. In some embodiments, the peptide inhibitor is cyclized via a linkage between XA and X9. 00312) Any of the peptide inhibitors of this invention (for example, any of the formulas

And (for example, Their, Ia-I)) can be further defined, for example, as described below. It is clear that each of the additional features described herein can be applied to any of the peptide inhibitors where the amino acids specified in the specific provisions provide the presence of the additional property.

ИЙО0313| In some embodiments, any of the Ppe(|4-(2-aminoethoxy)| residues present in the peptide inhibitor can be substituted with Ppe|4-(2-acetylaminoethoxy)|.

I00314| In some embodiments, X1-X20 are any of the amino acids shown in the corresponding position relative to the cyclized Rep-Rep or cyclized Aby-Suv residues of the typical peptide inhibitors listed in Tables 2-5. 00315) In some embodiments, any of the peptide inhibitors described herein, including, but not limited to, those of formulas (X), (Ma), (MB), Mc), (Ma), (me), (MO), (M9) or (Mi), additionally contain a linker fragment or a spacer fragment between any two amino acid residues of the peptide. In specific embodiments, the linker fragment or spacer fragment is a PEG fragment.

IІ00316| In some embodiments, the peptide inhibitor is cyclized with a disulfide bridge.

I00317| In some embodiments, X10 is Tug, Ppe(4-(2-aminoethoxy)), Ppe(4-

SOMN") or Rpe(4-OMEe). In some embodiments, X10 is Tug. 00318) In some embodiments, X11 is 2-Ma, Tgr or 5-hydroxy-Tgr. In some embodiments, X11 is Tgr. 00319) In some embodiments, X1O0 is Tug or Rpe|4-(2-aminoethoxy)i, and

X11 is Tgr or 2-MaY. In some embodiments, X10 is Tug, and X11 is Ttgr. 003201 In specific embodiments, both XA and XO are Sub. 003211 In specific embodiments, XA is Subh, Rep, pSuz, or absent. 003221 In specific embodiments, both X7 and X11 are not MU. 00323) In specific embodiments, both X7 and X11 are MU. (00324) In specific embodiments, both X7 and X11 are MU, X10 is Y, and both X4 and XO are Suv. 00325) In specific embodiments, X1I5 is Su, Azp, B-aia or 5eg. In specific embodiments, X15 is Su or 5eg. (00326) In specific embodiments, X16 is AEA or AER.

I00327| In specific embodiments, X10 is Tug, Ppe or Ppe|4-(2-aminoethoxy). In specific embodiments, X10 is Tug or Rpe. 00328) In specific embodiments, X11 is Tgr or 2-MaI. In specific embodiments, X11 is a tr. (003291) In specific implementation options, X1, X2 and X3Z are absent. (00330) In specific embodiments, X18, X19 and X20 are absent. (00331) In specific embodiments, X1, X2, X3Z, X18, X19 and X20 are absent. 003321) In specific embodiments, one or more of X1, X2, or X3Z are present. 00333) In specific embodiments of any of They, Ia-Ig, one of X1, X2, and XZ is present, and the other two are absent. In one embodiment, X1, X2, or X3 present is Aa. 00334) In some embodiments, HZ is present. In specific variants of implementation of ХЗ is sim, (0)Sim, Ago, (0)Ago, Rpe, (0)P Pe, 2-Mai, Tig, em, (0)SiIp. In some embodiments, XZ3 is (O)Agd or (O)Rpe. In specific implementation options, X1 and XX2 are absent, and XZ is present.

00335) In specific embodiments, two of X1, X2, and XZ are present, and the other one is absent.

In some embodiments, the two present consist of 50, MK, BA, RE, OM, or OH.

I00336| In specific embodiments, HIT, X2, and XZ are present. In some embodiments, X1, X2, and XZ consist of OR, KEM, MOE, CEE, OSE, MAO, EEM, KMO, KAM, or

HOOOO.

I00337| In some embodiments, the peptide comprises an AER residue. In specific embodiments, any of X15, X16, X17, X18, X19 or X20 is an AER.

I00338| In some embodiments, the implementation of any of the peptide inhibitors or peptide monomer subunits X13 is TPg, Zags, Sim, Rpe, Ago, Iei, Huz, Iuv(Ac), BpAia or

AB. In some embodiments, the implementation of any of the peptide inhibitors or peptide monomeric subunits of the KIZ is Tpg, Zag, Sis, Rpe, Ago, Ge, uh, BpAia, or Air. In some embodiments, X14 is Re, Azp, Tug, or VyRPe. In some embodiments

X14 is Re, Tug or ViRPe. In some embodiments, X15 is Su, Avp, Zeg, Tig, SiIp, Aa, or Zags. In some embodiments, X15 is Su, 5eg, TAg, Sip, Aa, or Zags. In some embodiments, X12 is an alpha-amino acid, for example, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, AlIb, α-diethylyl, α-MeH uz, α-Mei uz(As), a- Me-Gei, a-MeOt, a«-Mezeg or a-Memai. 00339) In some embodiments, X13 is present. (00340) In some embodiments, X13 and X14 are present.

I00341| In some embodiments, X13, X14, and X15 are present. 00342 In specific embodiments of any one of Ia-y, one or more of X16-

X20 are present. In specific embodiments, two or more or three or more of X16-X20 are present. In specific embodiments, X18 is (KO) uv). In specific embodiments, X17 is absent, and X18 is (0) uv). In some embodiments, where XA and X9 are optionally Sub, XA and XU are Suz, X7 is Ttgr, and X18 is MO)Lub5|. In specific embodiments, where X4 and XU are not necessarily

Sub, X4 and XU are Su5, X7 is Tgr, X10 is Tug or РPE|4-(2-aminoethoxy)) and X18 is MO) ub5|. In specific embodiments, where X4 and xX9 are optionally Sub, X4 and XO are Su, X7 is Tgr, X10 is

Tug is with him, and X18 is MO) y5|. In specific embodiments, where X4 and XX9 are optionally Sub, XA and XU are SuVx, X7 is Ttgr, X1, X2 and XxZ3 are absent, X17 is absent, X18 is KO), and X19 and X20 are absent . In specific embodiments of Ig, X4 and XO are Sub, X7 and X11 are Tgr, X10 is Tug, and

X18 represents |(С)Й uh. In some implementations, XII, X2 and XZ are absent; and in some embodiments, X17 is absent. 00343) In some embodiments, any of the peptide inhibitors (or monomer subunits) described herein is cyclized. In specific embodiments, the peptide inhibitor is cyclized using a bond between two or more internal amino acids of the peptide inhibitor. In specific embodiments, the cyclized peptide inhibitors are not cyclized via a bond between the M-terminal and C-terminal amino acids of the peptide inhibitor. In some embodiments, one of the amino acid residues involved in the intramolecular bond cyclizes the peptide at the amino acid residue with an amino at the end. In some embodiments, any of the peptide inhibitors is cyclized via a peptide bond between its M-terminal amino acid and its C-terminal amino acid. (00344) In some embodiments of any of the peptide inhibitors or one or both of its monomeric subunits, the peptide inhibitor (or one or both of its monomeric subunits) is cyclized via an intramolecular bond between X4 and XU or via a triazole ring. In specific embodiments, the intramolecular bond is any of a disulfide bond, a thioether bond, a lactam bond, a triazole, a selenoether bond, a diselenide bond, or an olefinic bond. 00345) In one embodiment, XA and XU of the peptide inhibitor (or one or both of its monomeric subunits) are Su, Rep, pSuz, O-Rep, O-Sub5 or p-pSuv, and the intramolecular bond is a disulfide bond connection In some embodiments, both X4 and XO are Sub, both X4 and XO are Rep, and the intramolecular bond is a disulfide bond. (00346) In one embodiment, XA and XU of the peptide inhibitor (or one or both of its monomer subunits) are Sim, A5p, Huz, Ogp, bar, bab, O-bar, O-rabr, 0-

Ar, O-SiIshm or O-I bond, and the intramolecular bond is a lactam bond. because I00347| In one embodiment, X4 is Aby, 2-chloromethylbenzoic acid,

mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid or 3-chloroisobutyric acid; ХУ stands for Aby, Suv, Rep, pSuz, O-Rep, Yu-Suz or Yu-pSuz; and the intramolecular bond is a thioether bond. In some embodiments, X4 is Aby, and XO is Rep, and the intramolecular bond is a thioether bond. In specific embodiments, X4 is a 2-methylbenzoyl fragment capable of forming a thioether bond with XO, and XU is selected from Su, M-Me-Suz, Yu-Suv, pSuv, Rep and O-Rep. In specific embodiments, X4 is Ar, and XO is Su, and the intramolecular bond is a thioether bond. In specific instances of 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 Zeg, modified p5eg (e.g., Noto-5e1g-CI), an appropriate isother, and appropriate O - amino acids. In other cases, X4 is an aliphatic acid having one to four carbons and forming a thioether bond with X9. In some cases, X4 is a five- or six-membered alicyclic acid having a modified 2-methyl group that forms a thioether bond with XU. In some embodiments, X4 is a 2-methylbenzoyl fragment. In some embodiments, X4 is selected from Su, pSuvx, Rep, and a 2-methylbenzoyl moiety. In some embodiments, X4 is selected from the group consisting of modified 5eg, modified p5eg, the corresponding isothere, and the corresponding O-amino acids. In one embodiment, X4 is p5exy (before forming a thioether bond with XO, whereby SI is removed) or a pZeg precursor (e.g., pPotoZe(O-TVOM5). In other cases, X4 is an aliphatic acid having one to four carbon and forms a thioether bond with XO. In some cases, X4 is a five- or six-membered alicyclic acid having a modified 2-methyl group that forms a thioether bond with XO. In some cases, X4 is 2-methylbenzoyl moiety In some embodiments where X4 is not an amino acid but is a chemical moiety that binds to XO, X1, X2, and X3 are absent and X4 is conjugated to or linked to X5. in some embodiments, the amino acid directly carboxyl of XU is an aromatic amino acid.In some embodiments, X4 is an amino acid, while in other embodiments, X4 is another chemical moiety capable of binding to XU, such as to form

From the thioether bond. In specific embodiments, X4 is another chemical moiety selected from any of the non-amino acid moieties described herein for X4. In specific embodiments, where X4 is another chemical fragment, X1, X2 and X3Z are absent, and the other chemical fragment is linked to or conjugated to X5. In some embodiments, X4 is defined as a chemical moiety that includes a group such as chloride, for example, in 2-chloromethylbenzoic acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid. However, one skilled in the art will understand that once the peptide has undergone ring-closing cyclization to form a thioether bond between X4 and XO, the chloride group is no longer present. The description of chemical fragments on XA that include a reactive group such as chloride thus means both a group with chloride and a group without chloride, that is, after the formation of a bond with XO. The present invention also includes peptides having the same 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 present invention, it can generally be considered that the amino acid residues or other chemical fragments shown on X4 are instead present on X9, and the amino acid residues shown on XU are instead present on X4, i.e., the sulfur-containing amino acid residue of the resulting thioether compound a bond that is on XA instead of XU, and an amino acid residue or other fragment with a carbon side chain capable of forming a thioether bond with X4 is on X9. In this reverse orientation, however, the amino acid or chemical moiety at position XU is one containing a free amine. For example, in specific embodiments, the amino acid on the XO is a protected homoserine, such as, for example, homoserine (OTVOM5). Thus, in specific embodiments of reverse orientation peptide inhibitors of any of the formulas described herein, XO is an amino acid residue having a one or two carbon side chain and forming a thioether bond with X4, and X4 is selected from groups including Su5, M-Me-Suvz, O-Suv,

NSSuvh, Rep and O-Rep. Specific examples of amino acid residues and other chemical fragments present at the corresponding positions of other formulas and tables are described in this document. 00348) One skilled in the art will understand that some amino acids and other chemical moieties are modified when bound to another molecule. For example, the side chain of an amino acid can be modified when it forms an intramolecular bridge with another 60 side chain of an amino acid, for example, one or more hydrogens can be removed or replaced by a bond. In addition, when pZeg-SiI binds to an amino acid, such as Su5 or Rep, through a thioether bond, the CI fragment is released. Accordingly, when used herein, a reference to an amino acid or modified amino acid, such as ypbeg-CI, present in a peptide dimer of the present invention (e.g., at the X4 position or the XO position) means one that includes a form of such amino acid or modified amino acid, that is present in the peptide, both before and after the formation of an intramolecular bond. 00349) In some embodiments of the peptide inhibitor, the peptide inhibitor (or one or both of its monomeric subunits) is cyclized via a triazole ring. In some embodiments of the peptide inhibitor, the peptide inhibitor (or one or both of its monomeric subunits) is linear or non-cyclized. In some embodiments of any of the peptide inhibitors described herein, including both monomeric peptide inhibitors and dimeric peptide inhibitors, one (or both) of the peptide monomeric subunits comprises or consists of a cyclized peptide having the structure or sequence indicated in any of Ih, Ia, IB, Is, 1d, Ie, I, Id, IJ, Ii, I), IK, PI, It, Ip, Io, Ir, Id, Id", Ig or represents Her , Na-Pa,

Sha-She, Ima or MB. 00350) In some embodiments of any of the peptide inhibitors or monomer subunits, both X7 and X11 are MU.

И0ООЗ351| In some embodiments, the implementation of any of the peptide inhibitors or monomer subunits, both X7 and X11 are not MU. In specific embodiments, X7 is a MU, and X11 is not a MU. 00352) In some embodiments of the implementation of any of the peptide inhibitors or monomer subunits X4 and XU are amino acid residues capable of forming an intramolecular bond with each other, which is a thioether bond, lactam bond, triazole, selenoether, a diselenide bond or an olefinic bond. 00353) In some embodiments, both X7 and X11 are MU, X10 is

U, Ppe4-(2-aminoethoxy) or Ppe(CoOMN"), and X4 and XU are amino acid residues capable of forming an intramolecular bond with each other, which is a thioether bond, a lactam bond, a triazole, selenoether, diselenide bond or olefinic bond. In some embodiments, both X7 and X11 are MU, X10 is Y, and

Zo X4 and XU are amino acid residues capable of forming an intramolecular bond with each other, which is a thioether bond, a lactam bond, a triazole, a selenoether bond, a diselenide bond, or an olefin bond. 00354) In some embodiments, both X7 and X11 are M, X10 is

U, and both X4 and XO are C. 00355) In some embodiments, each of XA and XU is Subh, Rep, pSuz, O-Rep,

O-Suv or O-pSuv, and the intramolecular bond is a disulfide bond. 00356) In some embodiments, each of XA and XU is Sim, Ar, Iy5, Ot, Var, Rab, O-Oar, O-rar, O0-Azr, O-SiIy or O-I bond, and the intramolecular bond the bond is a lactam bond.

I00357| In some embodiments, each of X4 and XO is B-azido-Aia-OH or propargylglycine, and the peptide inhibitor (or monomer subunit) is cyclized via a triazole ring. 00358) In some embodiments, each of X4 and XO is 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4-pentenyl)glycine or 2-(5'-hexenyl)glycine, and the peptide inhibitor ( or monomeric subunit) cyclized via ring closure to give the corresponding olefin / "cross-linked peptide".

Y00359| In some embodiments, X4 is 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid, or pZeCl); HU represents

BO pzZekSiI), Suz, Rep, nSuz, O-Rep, O-Suz or Yu-pSuvz; and the intramolecular bond is a thioether bond. In some embodiments, X4 is 2-chloromethylbenzoic acid or pZeg(SiI); XO is Su or Rep, and the intramolecular bond is a thioether bond. In some embodiments, X4 is Abra and XU is

Suz or Rep. 00360) In some embodiments, X4 is 2-chloromethylbenzoic acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid, Aby or Zes; XO represents Aby or 5es; and the intramolecular bond is a selenoether bond. 00361) In some embodiments, the intramolecular bond between XA and XU is a diselenide bond.

(00362) In some embodiments of any of the peptide inhibitors described herein that contain two amino acid residues, e.g., cysteine residues, connected by an intramolecular bond, e.g., a disulfide bond, two amino acid residues that participate in the intramolecular connection, both are located neither at the M-terminus nor at the C-terminus of the peptide inhibitor. In some embodiments, none of the two amino acid residues, for example, cysteines involved in the intramolecular bond, are located either at the M-terminus or at the C-terminus of the peptide inhibitor. In other words, in some embodiments, at least one or both of the two amino acid residues, for example, cysteines, participating in the intramolecular bond, are internal amino acid residues of the peptide inhibitor. In some embodiments, none of the two amino acid residues, for example, cysteines involved in the intramolecular bond, are located at the C-terminus of the peptide inhibitor. In some embodiments, the two amino acid residues participating in the intramolecular bond are Suz, Rep, pSuz, O-Rep, O-Suv or O-pSuz residues. In some embodiments, the two amino acid residues participating in the intramolecular bond are located on X4 and XU. In one embodiment, there is a disulfide bond between amino acid residues, for example, cysteines or Rep residues, on XA and X9. In specific embodiments, both X4 and XU are Rep. In some embodiments, one or both of the peptide monomer subunits in the peptide inhibitor are cyclized via a disulfide bond between two Rep residues, for example, at positions XA and X9. 00363) In specific embodiments of any of the peptide inhibitors described herein, one or both of the peptide monomer subunits present in the peptide inhibitor, whether it is a monomer or a dimer, is cyclic or cyclized, for example, by intramolecular linkage a bond, such as a disulfide bond, between two cysteine residues present in a peptide monomer or peptide monomer subunit. In some embodiments, the peptide inhibitor contains two or more cysteine residues. In some embodiments, the peptide inhibitor is cyclized via an intramolecular disulfide bond between two cysteine

With leftovers. In specific embodiments of the peptide inhibitors having any of the formulas described herein, the two cysteines are in the XA and XU positions. In other embodiments, one or both peptide monomeric subunits in the peptide inhibitor are cyclized via a disulfide bond between two Rep residues, for example, at positions XA and X9. 00364) In some embodiments, the peptide inhibitor has the structure of any of the formulas described herein (eg, formula 1) and contains a disulfide bond, for example, an intramolecular disulfide bond or a thioether bond. Typical examples of such peptide inhibitors are shown in Tables 3A-3 and 4A, 48, 9, 11 or 15. Such disulfide-linked peptides may have the particular advantage that disulfide bonds increase structural stability and may improve the biological activity of many bioactive compounds. peptides However, in some situations, these connections are labile to restorative agents. One skilled in the art will appreciate that the disulfide is responsible for simple isosteric replacement.

Typical examples of such substitutions include, but are not limited to, thioethers, dithioethers, selenoethers, diselenides, triazoles, lactams, alkane and alkene groups. Accordingly, in some embodiments of any of the peptide inhibitors described herein, one, two, or more cysteine residues are substituted with, for example, a thioether, dithioether, selenoether, diselenide, triazole, lactam, alkane, or alkene group, including but not limited to without limitation, any of those shown below or described herein. In specific embodiments, two of these substituted groups form a bond (eg, an intramolecular bond), thereby cyclizing the peptide inhibitor or one or both of its monomer subunits.

I00365| In some embodiments, the peptide inhibitor of the present invention comprises or consists of an amino acid sequence shown herein, for example, in any one of Tables 3A-3, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10 , 11, 12, 13, 14 or 15. In some embodiments, the peptide inhibitor of the present invention has a structure shown herein, for example, in any one of Tables 3A-3H, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

I00366| In some embodiments, the present invention includes a peptide inhibitor that contains a basic consensus sequence selected from one of the following (shown from the M-terminus to the C-terminus): 60XIX2X2MIX»Xx2MM (ZEO IU MO:1381);

ХХХ2 MI XXX" (May 1) (ZEO IU MO:1382);

ХХХ2Х2МХХХХ" (May 2) (ZEO IYUO MO:1383);

ХХХ2х2МХ2Х MM (ZEO 10 MO 1384);

ХИХах2 MI Х2Х 1 (May 1) (ZEO I MO:1385);

ХХХ2МХХ»Х Х(2-May) (ZEO IYU MO:1386);

ХиХХХХ"Х ХХ" (FAILURE MO:1387);

ХХХ2ХМХХХ ХХХ Х2Х2-ЦОМ uz| (ZEBEO 10 МО:1388); ХиХ2Х2МуХ»аХиХХ2 (З5БО 10 МО:1389);

ХХХ2Х2 МХХ" Khz (May 1) (ZEO IU MO:1390) and

ХХХ2ХМИХ»ХХз (May 2) (ZEO IU MO:1391).

I00367| where UM is tryptophan, M is tyrosine, every two X1 residues are amino acids or other chemical fragments capable of forming an intramolecular bond with each other; each X2 is independently selected from all amino acids, which include, for example, natural amino acids, I1-amino acids, Y-amino acids, synthetic amino acids, and non-natural amino acids; and ХЗ3 is any amino acid. In specific variants of the implementation of ХЗ is a Рие, an analogue of Рпе (for example,

Ppe|(4-(2-aminoethoxy)) or Ppe(4-COMNHg)), Tug, or a Tug analog (eg, Tugp(Me)). In specific embodiments, each X1 is selected from Suh, Rep, and Avra. In specific embodiments, each X1 is a Suv. In some embodiments, each X1 is a

Rep. In some embodiments, one X1 is a Sub and the other X1 is an Abra. In specific embodiments, X1 of the M-end is Aby, and X1 of the C-end is Sub. In specific embodiments, X1 of the M-terminus is Sub, and X1 of the C-terminus is Aby. In specific embodiments, the residues between two X1 residues are cSip, Tpg, Tgr and SiP. In specific embodiments, each X1 is selected from Su, Rep, and Aba; and XZ3 is Re, an analog of Ppe (for example, Ppe(4-(2-aminoethoxy)| or Ppe(4-carbomide)), Tug or an analog

Tug (eg Tug(Me)). In specific variants of the implementation of ХЗ is an analogue of Ре. 00368) In some embodiments, the peptide inhibitors of the present invention comprise any of the following consensus sequences, where X1, X2, X3, X4, X5, Xb, X7, X8, XU, X10, X11, X12,

X13, X14, and X15 are defined as shown in any of the various formulas or peptide inhibitors described herein:

Zo X1-X2-X3-Rep-X5-X6-Mu/-X8-Rep-X10-X11-X12-X13-X14-X15 (ZEO and MO:1392);

Rep-X5-X6-M/-O-Rep (ZEO IU MO: 1393);

Rep-X5-X6-Mu-X8-Rep (ZEO IU MO:1394);

Rep-X5-X6-Mu-X8-Rep-IRpe(4-SOMNag)) (ZEO IO MO:1395);

Rep-X5-X6-zhM/-X8-Rep-|Rpe|(4-(2-aminoethoxy)|) (ZEO IU MO:1396);

X1-X2-X3-Ary-Xx5-X6-Mu-X8-0-X9-X10-X11-X12-X13-X14-X15 (5EO IU MO:1397);

Ary-X5-X6-M-0-0 (5EO I MO:1398);

Ary-X5-X6-M/-X8-S (5EO I MO:1399);

Ary-xX5-X6-Mu-X8-0-IRne(4-SOMNH))Y (ZEO IU MO: 1400); or

Ary-X5-X6-Mu-X8-0-|РНе|4-(2-aminoethoxy)|| (ZEO 1О MO:1401). 00369) In some embodiments of any of the peptide inhibitors or monomer subunits, both X7 and X1 are MU. In some embodiments of any of the peptide inhibitors, both X7 and X1I1 are UM and X10 is U. In some embodiments, both X7 and X1I1 are UM and X10 is РПе|4-(2 - aminoethoxy)| or Rpe(4-OMe).

Y00Z370)| In some embodiments, the implementation of any of the peptide inhibitors or monomer subunits, both X7 and X11 are not MU. 00371) In some embodiments of the peptide inhibitors of formula I, each of X4 and X9 is a Rep, and the intramolecular bond is a disulfide bond.

I00372| In some embodiments, the peptide inhibitor of this invention contains or consists of an amino acid sequence shown in any one of the tables, sequence listings, or accompanying figures herein. 00373) In some embodiments of any of the peptide inhibitors described herein that contain two amino acid residues, e.g., Rep residues, linked by an intramolecular bond, e.g., a disulfide bond, one or both of the two amino acid the residues involved in the intramolecular bond are not located either at the M-end or at the C-end of the peptide inhibitor. In some embodiments, none of the two amino acid residues, for example, Rep, participating in the intramolecular bond, are located either at the M-terminus or at the C-terminus of the peptide inhibitor. In other words, in some embodiments, at least one or both of the two amino acid residues, for example, Rep, participating in the intramolecular bond, are internal amino acid residues of the peptide inhibitor. In some embodiments, none of the two amino acid residues, for example, Rep, participating in the intramolecular bond, are located at the C-terminus of the peptide inhibitor. 00374) In some embodiments, where a peptide of the present invention is conjugated to an acidic compound, such as, for example, isovaleric acid, isobutyric acid, valeric acid, and the like, such conjugation is in an acidic form. Thus, for example, without limitation in any way, instead of indicating the conjugation of isovaleric acid to the peptide by reference to isovaleroyl (eg, isovaleroyl-IRep|-OTPMUO(Repi-(Rpe(4-OMe)|I-(2-

MyP-(a-Me!uziI-(Guv(Ac)|-MOa-MNg (ZEO IU MO:262) in some embodiments, this application refers to such a conjugation as isovaleric acid-IRepI-OTM/O( GrepiI-IRNe(4-

OMe)I-(2-Ma!c|-(a-Me!ugI-(Guv(As)-Ma-MH)" (ZEO 10 MO:262).

I00375| The present invention also includes peptide inhibitors that selectively bind to the epitope or binding domain present in amino acid residues 230-349 of human I/23 protein. In specific embodiments, the peptide inhibitor binds to human IL-23K rather than mouse IL-23A. In some embodiments, the peptide inhibitor also binds to rat II-238. 00376) In some embodiments of peptide inhibitors of formula I, X4 is Aby;

ХУ represents Su, Rep, POTASS", and the intramolecular bond is a thioether bond.

I00377| In some embodiments, peptide inhibitors do not include compounds disclosed in

PCT application M"PCT/O52014/030352 or PCT application MyARPST/O52015/038370.

Typical Peptide Inhibitors Containing Rep-Rep Disulfide Bonds 00378) In some embodiments, the present invention includes a peptide inhibitor of the interleukin-23 receptor, wherein the peptide inhibitor has the structure of formula II:

B'-X-B:2 (I) 003791 or its pharmaceutically acceptable salt or solvate, where KK! is a bond, hydrogen, C1-Salkyl, C6-C12aryl, C6-C12aryl, C1-Salkyl, C1-

C2alkanoyl, alkylsulfonate, acid, y-Sys or Roxy attached to the M-terminus, and including

PEGylated variants (e.g. 200 Da to 60000 Da), alone or as a separator

From any of the above; 003801 B: represents a bond, OH or MH"; and

ЙО0381| X is an amino acid sequence of 8-20 amino acids or 8-35 amino acids. (00382) In specific variants of implementation of the peptide inhibitor of formula II X contains or consists of the sequence of formula Ia: xX1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15- X16-X17-X18-X19-X20 (Pa) (ZEO I

MO:1402), where

X1 is absent or is any amino acid;

X2 is absent or is any amino acid;

ХЗ is absent or is any amino acid;

XA is Rep, Su5 or post-Suv;

X5 is any amino acid;

Xb is any amino acid;

X7 represents Tgr, Vir, SiIp, Ni5, SiSh(B2I), 4-phenylbenzylalanine, Tis, Rpe|(4-(2-aminoethoxy)|,

Rpe(3,4-Си2), Rpe(4-OMe), B-hydroxy-Ttr, b-chloro-Ttr, M-MeTgr, o-Me-Ttr, 1,2,3,4- tetrahydronorharman, Rpe( 4-СО2Н), Ripe(4-СОМН»), Rpe(3,4-dimethoxy), Rpe(4-SEz), Rpe(4-IVy),

BB-diRPelia, Sim, su, Pe, Azp, Rgo, Agod, Tig or Osidiu, or the corresponding α-methylamino acid form of any of the above;

XV is any amino acid;

ХУ is Rep, Suz or pSuzh;

X10 represents May 1, May 2, Ais, Vir, (0) Suz, Sna, OMT, (0) TGug, Spy, RNe, Niv, Tr, TNg, Tis,

Thug, 4-pyridylAia, Osidium, analogue of Ppe or analogue of Thug (optionally Ppe(3,4-Eg2), Ppe(3,4-Sig),

E(3-Me), Rpe(4-(2-aminoethoxy)), Rpe|(4-(2-(acetylaminoethoxy)), Rpe(4-Bi), Rpe(4-SOMH), Rpe(4-

SI), Rpe(4-CM), Rpe(4-guanidino), Rpe(4-Me), Rpe(4-Mn), Rpe(4-Mz), Rpe(4-OMe) or Rpe(4-

OVAYI)), or the corresponding α-methylamino acid form of any of the above;

X11 is 2-Mai, 1-Mai!, 2,4-dimethylRpNe, Vir, Rpe(3,4-C12), Rne (3,4-Eg), Rne(4-СО2Н),

VyRPe(4-P), o-Me-Ttr, 4-phenylcyclohexyl, Rpe(4-SEz), o-MeRpe, VyMa!i, VyRpe, VyTug, VA Ttgr,

Mma(5-phenyl), Rpe, Nix5, pRe, Tis, Tda, Tgr, Tug, Rne(4-OMe), Rpe(4-Me), Ttr(2,5,7-tri-tert-60 butyl) .

phenylbenzylalanine, Рпе(4-(2-aminoethoxy))|, 5-hydroxy-Ttr, b-chloro-Ttr, M-MetTtr, 1,2,3,4- tetrahydronorharman, Rpe(4-СОМН»), РНе (3,-OMeg) РНе(2,3-СИ2), РНе(2,3-Ег), Рпе(4-Е), 4-phenylcyclohexylalanine or Vir, or the corresponding α-methylamino acid form of any of the above;

X12 is α-Mei, α-MeOgp, α-MegH, α-Memai, 4-amino-4-carboxytetrahydropyran,

Asps, Asrs, Asbs, Asms, Me! ей, АЙБ, (0)Ая, (0)Авп, (0) ей, (0)AZR, (0)РНе, (0) нг, 3-Рай, AB, р-

AIa, VASIm, VpAPa, Vi ei, VimMai, V-spiro-pip, Spa, Spo, Azr, bab, Var, a-diethyloiu, Sim, Rie, pHei,

NAga, Ni, Pe, Guz, Gei, Avp, M-Mei, M-MeAgo, Osi, Opt, Rgo, Sip, Agud, Zeg, Tig or Thie, or the corresponding α-methylamino acid form of any of the above;

Х13 is ГГ уз(Ас), (Ф)А5п, (0) ей, (С3ТНг, (0)Р Пе, Аа, АіЙб, а-Мейі em, В-АІа, ВІІі,

VpAa, VP ei, VyMai, B-spiro-pip, Spa, Spo, Azr, Huz, Ago, Opt, Bar, bar, a-diethyliu, Sim, Rpe, pHei, Hu, Hei, Abp, Od, Rgo, Sp , Avr, Ago, Zeg, spiro-pip, Tpg, Tra, Tis, MaY or Tug, or the corresponding α-methylamino acid form of any of the above;

X14 is Avzp, SiImts, Rpe, su, Niv, I y, I em, Mei, Azp, Rgo, Sip, Ago, Zeg, TNg, Tis or

Tug, Huz(As), Ot, or the corresponding α-methylamino acid form of any of the above;

X15 is su, (0)Aia, (0)Av5p, (0)A5p, Azp, (0) ey, (SORPe, (0)TNg, Aa, AEA, Azr, SIM,

Re, Su, Huz, I em, Rgo, Sip, Agd or 5eg, p-AIa, Agu or the corresponding α-methylamino acid form of any of the above;

X16 is absent, Su, Aa, Ar, Zeg, Pgo, Azp or Tpg, or the corresponding α-methylamino acid form of any of the above;

X17 absent, Sim, Zeg, SiIu or SiP, or the corresponding α-methylamino acid form of any of the above;

X18 is absent or is any amino acid;

X19 is absent or is any amino acid; and

X20 is absent or is any amino acid. 00383) In some embodiments, Pa: X10 is 1-May, 2-May, Ais, Vir, (0)Suv,

Sna, OMT, (0)THug, Sim, RNe, Niv, Tgr, TNg, Tis, Tug, 4-pyridylAlya, Osidiu, analogue of Rpe or analogue

Tug, or the corresponding α-methylamino acid form of any of the above; X11 is 2-Mai, 1-Mai, 2,4-dimethylRNe, Vir, Ripe(3,4-SiI), Rpe (3,4-Eg), Rpe(4-CO2H), ViRPe(4-E ), a-Me-Ttr,

Zo 4-phenylcyclohexyl, Rpe(4-SEz), a-MeRpe, VyMai, VyRpe, VyTug, VyTgr, Mma(5-phenyl), Rpe, Niv,

RNe, Thies, Tada, Ter, Tug, Rpe(4-OMe), RNe(4-Me), Ttri(2,5,7-tri-tert-butyl), Rpe(4-Oallyl), Tu(3-

IVy), Rpe(4-IVy), Rpe(4-guanidino), Rpe(4-OB21I), Osidio, Cs(Ba2I), 4-phenylbenzylalanine, Rpe(|4-(2- aminoethoxy)|, 5-hydroxy - Ttr, b-chloro-Ttr, M-MetTtr, 1,2,3,4-tetrahydronorharman, Rpe(4-SOMH 5),

Ppe(3,4-dimethoxy), Ppe(2,3-SiI2), Pne(2,3-Eg), Ripe(4-E), 4-phenylcyclohexylalanine or Vir, or the corresponding α-methylamino acid form of any of of the above; X12 is a-Mei! ув, о-МеОгп, а-Мей ей, Мей ей, АЙБ, (0)Ая, (Б)Азп, (0) ей, (0)А5р, (0)РНе, (0)ТН"г, 3- Rai, Aib, r-Aya,

VasSiy, VpApa, Vp em, rpyMai, V-spiro-pip, Spa, Spo, Azr, rab, bar, a-diethyloiu, Sim, Rpe, pei,

NAga, Ni, Pe, Huz, Gei, Avp, M-Mei, M-MeAgo, Oadi, Ot, Rgo, SiIp, Agud, Zeg, Tig or Thie, or the corresponding c-methylamino acid form of any of the above; X13 is I uz(As), (F)Azp, (0) em, (C) Hg, (C)Rpe, AiPa, AiYib, a-MegG ei, B-AIa, VysSim, VpAia, Vp em, VyMai , B-spiro-pip,

Spa, Spo, Ar, Guz, Agud, Op, Bar, bar, a-Dietilou, Sim, Re, Pi en, Guz, em, Azp, Oddi, Rgo, Sp,

Azr, Ago, Zeg, spiro-pip, TAg, Tra, Tis, MaiY or Tug, or the corresponding α-methylamino acid form of any of the above; X14 represents Avzp, Sim, Riye, SU, Niv, I uv, I ei, Mei, Avp, Rgo, Sp,

Agd, Zeg, Tpg, Tis or Tug, or the corresponding α-methylamino acid form of any of the above; and X15 is Su, (0)Aya, (0)Avp, (0)Avr, Azp, (0) ei, (0)RNe, (0), Aga,

AEA, Ar, Simy, RPe, Su, Gu, Iem, Rgo, SiIp, Agd or 5eg, or the corresponding α-methylamino acid form of any of the above. 00384) In some embodiments, HZ is present. In specific variants of implementation of ХЗ is sim, (0)Sim, Ago, (0)Ago, Rpe, (0)P Pe, 2-Mai, Tig, em, (0)SiIp. In some embodiments, XZ3 is (0)Agd or (0)RPpe. In specific embodiments, X1 and XX2 are absent, and XZ is present. 00385) In some embodiments, X5 is cSip, Aa, Sii, A5r, bab, Rar, Sii Sim,

RNe, Su, No, pSuv, And uv, And ey, Mei, Azp, M-Me-Aia, M-Me-Azp, M-Me-G uv, ah! Me-G uz, ah! Me-Ogp, M-

Me-SiIp, M-Me-Ago, a-Mebeg, Ot, Rgo, Agud, Zeg, Tig or Mai. In some embodiments, X5 is Sip, Aa, Sii, A5r, bab, Oar, Spi, Rne, Spu, Niv, NSuz, GG uv, Iei, Mei, Azp, M-Me-Aia, M-

Me-Avp, M-Me-Guv5, aMe-G uz, aMe-Ogt, M-Me-Sip, M-Me-Agud, Ogp, Rgo, Ago, Zeg, Tig or Mai. In some embodiments, the implementation of X5 is a sip or Avp. 00386) In some embodiments, Xb is TPg, Ar, Simy, Rpe, Avzp, Rgo, Agd or zeg. because I00387| In some embodiments, X7 is Tgr.

00388) In some embodiments, X8 is Sp, Sim, Rpe, Guz, Azp, Rgo, Ago, Mmai,

Tig or Ttr.

I00389| In some embodiments, X1O is an analog of Tug or an analog of Ppe. In specific embodiments, X10 is an analogue of Rie. 00390) In some embodiments, where X1O0 is an analog of Ppe, X10 is selected from pPe, PHe(4-OMe), a-Me-Ppe, HPe(3,4-dimethoxy), Ppe(4-COMH»g), Rpe(4-phenoxy), Rpe(4-guanadino), Rpe(4-IVy), Rype(4-SM), Rpe(4-Vi), Rpe(4-OV8721I), Rpe(4-MH»g) , Riet (4-E), Riet (3,5-PIR),

Ppe(CH2CO»H), Ppe(penta-P), PNe(3,4-SiIg), PNe(4-SEz), BB-diPpeAIa, Ppe(4-Mz) and Ppe|c4-(2-aminoethoxy) ) In specific embodiments, X1O0 is Rpe(4-OMe) or Rpe|4-(2-aminoethoxy))|. In specific embodiments, X10 is Rpe(4-OMe), Rpe(4-COMH 5) or Rpe|4-(2-aminoethoxy)). In some embodiments, where X10 is an analogue of Ppe, X10 is selected from pPe, Ppe(4-OMe), o-Me-RNe, pPe(3,4-dimethoxy), Ppe(4-COMH»g), Ppe( 4-phenoxy),

Rpe(4-guanadino), Rpe(4-IVy), Rpe(4-SM), Rpe(4-Vg), Rpe(4-OV21I), Rpe(4-MH"), Rphne(4-E), Ries (3.5-

Rie), Rpe(CH2SO»H), Rpe(penta-P), Rpe(3,4-SiI2), Rpe(4-SEz), BB-diRpelia, Rpe(4-Mz) and Rpe|4-(2 - aminoethoxy)). In specific embodiments, X10 is Rpe(4-OMe). 00391) In some embodiments, where X10 is an analog of Tug, X10 is selected from PpTuUg, a-MetTug, M-Me-Tug, Tuc(3-IVy), Pne(4-SOMN), Rpe|4-(2 -aminoethoxy)) and By Tug. In some embodiments, where X10 is a Tug analog, X10 is selected from pTug, α-MeTug, M-Me-Tug, Tuc(3-IVy), and ritu"g.

II00392| In some embodiments, X10 is Tug, Rpe(4-OMe), RHe(|4-(2-aminoethoxy)|, Rpe(4-COMH"), or 2-Ma. In some embodiments, X10 is Rpe(4 -

OMe) or Rpe|4-(2-aminoethoxy)). In some embodiments, X10 is not Tug.

In some embodiments, X11 is an analog of Tgtr. In specific embodiments, X11 is May 2 or May 1. In some embodiments, X11 is 2-may. 00393) In some embodiments, X12 is AB, a-Mei! uz or "ah! Me! yes (00394) In specific embodiments of the peptide inhibitor of formula II, one or both of X4 or X9 are Rep. In specific embodiments, both XA and XO are Rep.

From II00395| In some embodiments, the peptide inhibitor of formula II is cyclized. In specific embodiments, the peptide inhibitor of formula II is cyclized using an intramolecular bond between X4 and XU. In specific embodiments, the intramolecular bond is a disulfide bond. In specific embodiments, both XA and XO are Rep.

IІ00396| In some embodiments, the peptide inhibitor of formula I is linear or noncyclized. In specific embodiments of the linear peptide inhibitor of formula I, X4 and/or XU are any amino acid.

I00397| In specific embodiments of the peptide inhibitor of formula I, one or more, two or more, or all three of X1, X2, and X3 are absent. In some embodiments, X1 is absent. In some embodiments, X1 and X2 are absent. In some embodiments, the implementation of X1, X2 and

HZ are absent.

I00398| In specific embodiments of the peptide inhibitor of formula II, one or more, two or more, three or more, four or more, or all of X16, X17, X18, X19, and X20 are absent. In specific embodiments of the peptide inhibitor of formula I, one or more, two or more, three or more, or all of X17, X18, X19, and X20 are absent. In some embodiments, one or more, two or more, or all three of X17, X19, and X20 are absent. In some embodiments, one or more of X1, X2, and X3 are absent; and one or more, two or more, three or more or four of X17, X18, X19 and X20 are absent.

I00399| In specific variants of the implementation of the peptide inhibitor of the formula II X18 is an (0)-II bond. In some embodiments, X18 is (0)-I uv, and X17 is absent.

I00400| In specific embodiments of the peptide inhibitor of formula II, the peptide inhibitor contains one or more, two or more, three or more, or four of the following features:

X5 is Avp, Agud or Sip; Hb is Tig; X7 is Ttgr; and Hv represents

Sep. In specific embodiments of the peptide inhibitor of formula I X4 is Rep; X5 is Sp, Azp or Agu; Xb is Tpg; X7 is Ttgr, 5-hydroxy-Tgr, b-chloro-

Ter, M-MetTr, alpha-Me-Tgr or 1,2,3,4-tetrahydronorharman; X8 is Sp; and XO is Rep. In specific embodiments, X5 is a Sip. In some embodiments, X1, X2, and XZ are absent. In specific embodiments, both XA and XO are

Rep. because IІ00401| In specific embodiments of the peptide inhibitor of the formula II, the peptide inhibitor contains 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 Tug, an analog of Rie, analog

Tug or May 2; X11 is Ttgr, 5-hydroxy-Ttr, b-chloro-Ttr, M-MetTtr, alpha-Me-Ttr, 1,2,3,4-tetrahydronorharman, 2-Mai or 1-Mai; X12 is AIBb, a-MeH uh, a-MeOgpp and a-Mei eyy; X1Z3

B represents I uz, Sim or I ub(As); X14 is Re or Avzp; X15 is su, zeg or

Ah; and X16 is absent or is AEA. In some embodiments, X10 is Tug,

Rpe(4-OMe), RHne(4-(2-aminoethoxy)), Rpe(SOMN") or 2-May. In some embodiments, X11 is 2-Mai or 1-Mai. In some embodiments, X10 is not Tug. In some embodiments, X1, X2, and XZ are absent. In specific embodiments, both X4 and X9 are Rep.

I00402| In specific embodiments of the peptide inhibitor of formula II, the peptide inhibitor is 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 signs: X5 represents Agud or Sip; Xb is Tpg; X7 is Tgr; X8 is Sp; X10 is an analogue of Re; X11 is Ttgr, 2-Mai or 1-

Mai; X12 is Air, a-Me uh or a-MeOgp; Х1И3 is I uv, Sim or ГГ uz(Ac); Х14 is Azvp; X15 is su, bZeg or Aia; and X16 is absent or is AEA. In some embodiments, X10 is Rpe(4-OMe) or Rpe(|4-(2-aminoethoxy)). In some embodiments, X11 is 2-Mai or 1-Mai. In some embodiments, the implementation of X1, X2 and

X3Z are absent. In specific embodiments, both X4 and XO are Rep.

I00403| In specific embodiments of the peptide inhibitor of formula I, the peptide is cyclized using XA and XO; X4 and XU represent Rep; X5 is cSip; Xb is Tpg; X7 is Tgr; X8 is Sp; X10 is Tug, an analogue of Rpe or 2-

Mai; X11 is Tgr, 2-MaI or 1-Mai; X1I2 is Agod, ag MeHovs, a-MeOgp or a-

Me! hey X13 is I uz, Sim or Guz (As); X14 is Re or Avp; X15 is a

Su, Zeg or Aia; and X16 is missing. In some embodiments, X10 is Tug, Rpe(4-

OMe), Pne|4-(2-aminoethoxy)), Rpe(4-OMe) or 2-Mai. In some embodiments, X10 is Rpe(4-OMe). In some embodiments, X10 is not Tug. In some embodiments, X11 is 2-Mai or 1-Mai. In some embodiments, X1, X2, and XZ are absent.

From I00404| In specific embodiments of the peptide inhibitor of formula I, the peptide is cyclized using XA and XO; X4 and XU represent Rep; X5 is cSip; Hb is Tig; X7 is Tgr; X8 is Sp; X10 is Tug, Rpe(4-OMe) or 2-

Mai; X11 represents Ttgr, 2-Ma!Y or 1-Mai; X12 is Agod, a-MeH uh or «-MeOpt; X13 is I uh, Sim or I ub(As); X14 is Re or Azp; X15 is a su; and X16 is missing. In some embodiments, X1O is RPE(4-OMe). In some embodiments, X11 is 2-Mai or 1-Mai. In some embodiments, X1, X2, and XZ are absent.

IІ00405| In specific embodiments of the peptide inhibitor of formula I! the peptide is cyclized using XA and XO; X4 and XU represent Rep; X5 is Sp; Hb is TNg; X7 is Tgr; X8 is IP; X10 is Rpe(4-OMe) or Rpe|4-(2-aminoethoxy)|; X11 is Ttgr, May 2 or May 1; X12 is a Me uz, a-MeOgt or a-

Me! hey X13 represents I uh, Seven or I uz(Ac); X14 is Aup; X15 is Su, Zeg or Aia; and X16 is missing. In some embodiments, X10 is Rpe(4-OMe). In some embodiments, X11 is 2-Mai or 1-Mai. In some embodiments, the implementation of X1, X2 and

HZ are absent. 00406) In specific embodiments of the peptide inhibitor of formula II X10 is not Tug.

I00407| In some embodiments, the present invention includes a peptide, optionally 8-35, 8-20, 8-16, or 8-12 amino acids long, optionally cyclized, comprising or consisting of the main sequence of formula II:

Rep-Haab5-Haab-Ttr-Haav-Rep-Haa10-(2-Ma!) (Pb) (ZEO IU MO:1403), (00408) where Khaa5, Khaab and Khaav represent any amino acid residue; and Khaa10 is an analogue of Rpeschie, and the peptide inhibits the binding of 1/-23 to I1/-23K. In specific embodiments, X10 is an analogue of Phe selected from among IMe-Phne, Phe(4-OMe), PHe(4-

OB), Rne(4-OMe), Rpe(4-SOMN), Rie(3,4-C1I2), Rne(4-1Vy), Rpe(4-Mng), Rpe(4-VI), Rpe( 4-CM),

Rpe(4-СО2Н), Rpe(4-(2-aminoethoxy)| or Rpe(4-guanadino). In specific variants of implementation

Xa10 is Rpe(4-OMe) or Rpe|4-(2-aminoethoxy)). In one embodiment, Xa10 is Rpe(4-OMe). In some embodiments, the peptide is cyclized using an intramolecular bond between Rep on Xa4 and Rep on Xa9. In specific embodiments, the peptide is a peptide inhibitor of formula II, and in some embodiments, X1, X2, and X3 are absent. In specific embodiments, the peptide inhibits the binding of HER -

23 from 1-23. In some embodiments, the peptide of formula IB additionally contains an amino acid linked to the Rep residue at the M-terminus. In specific embodiments, the bound amino acid is Sim, (O)Sim, Ago, (O)Ago, Re, (C0)RPe, 2-Mai, Tpg, Hei, or (O)Sip. In some embodiments, it is (F)Ago or (O)RPe.

IІ00409| In some embodiments, the present invention includes a peptide, optionally 8-35, 8-20, 8-16, or 8-12 amino acids long, optionally cyclized, comprising or consisting of the main sequence of formula Ic:

Rep-Haab5-Haab-Ttr-Haav-Rep-Haa10-(2-Ma!)) (Ps) (ZEO IYUO MO:1404), 00410) where Haa5, Haab and Haav represent any amino acid residue; and Khaa10 is Tug, an analogue of Ppe, a-Me-Tugp o-Me-Tgr or 2-Mai, and the peptide inhibits binding

I/-23 with P/-23K. In some embodiments, X1O0 is Thug, Ppe(4-OMe), PHe|4-(2-aminoethoxy)|, α-Me-Thug α-Me-Ppe, α-Me-Ttr or 2-MaI). In some embodiments, Xa10 is Tug, Rpe(4-OMe), Rpe(SOMH), Rpe(|4-(2-aminoethoxy))| or May 2. In some embodiments, Xa10 is Tug, Ppe(4-OMe), Pne|4-(2-aminoethoxy)| or May 2!. In specific embodiments, Xa1!0 is Rpe(4-OMe) or Rpe|4-(2-aminoethoxy))Y. In one embodiment, Xa10 is Rpe|4-(2-aminoethoxy)| or Rpe(SOMN»g). In specific embodiments, Xa1!0 is Rpe(4-OMe) or Rpe|4-(2-aminoethoxy))Y. In one embodiment, Xa1!0 is RPE(4-(2-aminoethoxy)|. In some embodiments, the implementation

Haa10 is not Thug. In some embodiments, the peptide is cyclized using an intramolecular bond between Rep on Xaa4 and Rep on Xaa9U. In specific embodiments, the peptide is a peptide inhibitor of formula II, and in some embodiments, X1, X2, and X3 are absent. In specific embodiments, the peptide inhibits the binding of HER-23 to 1-23K. In some embodiments, the peptide of formula Ic additionally contains an amino acid linked to a Rep residue at the M-terminus. In specific embodiments, the bound amino acid is Sim, (O)Cim, Ago, (O)Ago, Rpe, (O)Rpe, 2-Mai, Tng, Hei, or (O)SiIp. In some embodiments, it is (F)Ago or (O)RPe.

І00411| In some embodiments, the present invention includes a peptide, optionally 8-35, 8-20, 8-16, or 8-12 amino acids long, optionally cyclized, comprising or consisting of the main sequence of formula Pa:

Koo) Rep-Xaa5-Xaab-Ttr-Xaav-Rep-Rpe|4-(2-aminoethoxy)|-(2-May| (Pa) (ZEO OO MO:1405), 00412) where Xa5, Xaab and Xa8 are is any amino acid residue. In some embodiments, the peptide contains a disulfide bond between Xaa and Xaa9. In some embodiments, the peptide is a peptide inhibitor of formula I, and in some embodiments, X1, X2, and X3 are absent. In specific embodiments, the peptide inhibits the binding of I-23 to I-23K. In some embodiments, the peptide of formula and additional contains an amino acid linked to a Rep residue at the M-terminus. In specific embodiments, the bound amino acid is Sim, (O)Sim, Ago, (O)Ago, Re, (C0)RPe, 2-Mai, Tpg, Hei, or (O)Sip. In some embodiments, it is (F)Ago or (O)RPe.

IІ00413| In specific embodiments of the peptide inhibitor of formula II, the peptide inhibitor has the structure shown in any of Tables 2, 3, 4A, 4B, 8, 11 or 15, or contains the amino acid sequence shown in Tables 2, 3, 4A, 48, 8, 11 or 15.

Table 2

Typical Ri-Rep inhibitors

IRai!ti-(isos1i1-(PEG41-(RepI-M GPU O-(Repi-(PHe(4-(2-aminoethoxy)|-(2-MaC-(AlivI-( uv (Ac)-MM-MH))

ZEO IU MO:1115

As-IRepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MapP-(AIBI1-(SUz(PEGa4-isosti-Rait)|-MM-MH)" (BEO

IO MO:1116

IOctanyl-(IsoslIchI-IPEG41-(RepI-MTUMO-(RepI-IRNe(4-(2-aminoethoxy)|-(2-Ma|-(AiBI1-(Suv(Ac)|-MM-MH))

ZEO IYUO MO:1118

IOctanilI-IPEGA1-(RepI-MPGUMUO-(RepiI-I(Pne(4-(2-aminoethoxy)|-(2-MaPC-(AIVI-(uz(Ac3-MM-MH)" (ZEO 10

MO:1119

IRa!tI-(PEGA-(RepIi-MTM/O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-Ma!|-(AiVI-(Huz(Ac)-MM-MH)) ZEO IU

MO: 1120

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MapP-(AliiVI-(Guv(PEG4A-Octanyl)D-MM-MN)" (ZEO 10

MO: 1121 bo

Table 2

Typical Ri-Rep inhibitors

ZE IU MO: 1127

MN" (5EO1O MO 1128

ZE IU MO:1145

Table 2

Typical Ri-Rep inhibitors

MO: 1150

Ac-IRepI-MT-IRpe(4-CH3)I-O-IRepI-(Rpe(4-(2-aminoethoxy)|-(2-Ma!p|-(AIVI-(Suv(Ac)|-MM- MN" (5EO 1O

MO:1151

Ac((0)Aga|-(RepiI-MTMO-|Repi-I(Rpe(4-(2-aminoethoxy) I-(2-MaP|--IAIVI-(uv(Ac)I-Mm-(BATa| -MN" (5EO 10

MO:1152

As-KO)Tup-(Repi-MTUMO-|Repi-IRpe(4-(2-aminoethoxy)|-(2-MaP-(AIBI-(Guv(Ac)|-M-IVAia|-MH)" (ZEO 10

MO:1153

As-GTRepi-M TM O-GREpi-IRNe/(4-(2-aminoethoxy)-(2-MaPP-HTAIVI-P y(Ac)3-OM-MN" (5EO IU MO:1154

Ac-I(RepI-MTM O-(RepiI-(Ppe(4-(2-aminoethoxy)|-(2-MapP-(AIVI1-(Suv(Ac)I-(Guv(Ac)|-M-MH» (ZEO 10

MO:1155

Ac-I(RepI-M TM O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MapP-(AIVI-(Suv(Ac)I-M-(H uz(Ac)I- MN" (5EO 10

MO:1156

As-IRepi-MTM O-GREpi-TRpeH4-(2-aminoethoxy)1-(2-MaP-TAYVI-P uv(As3YAT-00-MN" (5EO I MO:1157

As-I(RepI- MTM O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MapC-(AIVI-(Guv(Ac)I-O-IVAia|-MH)" (5EO 10

MO:1158

As-Trepi-M TM O-Grepi-IRNe/4-(2-aminoethoxy)-(2-MaPppP-TAYBI-P uz(Ac)-M-GSSH-AMN" (ZEO IU MO:1159

As-Trepi-M TM O-Grepi-IRNe/4-(2-aminoethoxy)-H2-MaPp-TAYBI-P uv(Asl-TSSH-MMN" (ZEO IU MO:1160

As-GREpi- TM O-GREpi-GIRNe/4-(2-aminoethoxy)-12-MaPP-HTAIYBI-P uz(Ac)l-TSSH-O-MN" (ZEO IU MO:1161

As-IRepI-MTM O-(Repy-(Rpe(4-(2-aminoethoxy)|-(2-Map-(AiYVI-(SuUv(Ac)-(СТСХ-(H uv(Ac)|-МН») BEO 10

MO:1162

As-IRepI-MTM O-|(RepyI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AIBI-(Suv(Ac)I-(GUuv(Ac)I-ISISH-MH)) ZEO 10

MO:1163

As-(RepI-M GU O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AivI-OM-(VATa|-MN)" (ZEO IU MO:1164

As-Grepi-M TM O-Grepi-IRNe/4-(2-aminoethoxy)I-(2-MaiPp-TAiIVBI-E-GSISHCHN-O-MN" (ZEO IU MO:1165

As-Grepi-M TM O-Grep!i-IRNe/(4-(2-aminoethoxy)-(2-Mypyp-TAiVBI-SYMSYMN" (ZEO IU MO:1166

As-Trepi-M TM O-Grep!i-IRNe/(4-(2-aminoethoxy)|-(2-MaP-TAiVBI-TYA-O-GSSH-MN" (ZEO OO MO:1167

As-Trepi-"SSH- GMO-GREpiI-GRpe/4-(2-aminoethoxy)|-T2-MaP-HAIVI-P in (Ac3-MM-MN" (ZEO IU MO:1168

As-Grepi-M TM O-Grepi-IRNe/4-(2-aminoethoxy)-(2-MaiPp-TAiYBI-P y(Ac)3-AMM-MH" (5EO IU MO:1169

As-Grepi-M TM O-Grepi-IRNe/(4-(2-aminoethoxy)-(2-Mapyp-TAiBBI-OMM-MN" (ZEO 10 MO:1170

As-GREpi-M TM O-GREpi-IRNe/(4-(2-aminoethoxy)-I2-Myp-TAIVBI-EMO-MN" (ZEO 1 MO:1171

As-TRepi-YARMO-GREpi-("RpegH4-(2-aminoethoxy)-(2-MaPP-TAYVI-P y(Ac3-MM-MH)" (5EO IO MO:1172

As-TRepi-RaUMO-GREpi-("RpegH4-(2-aminoethoxy)-(2-MaPP-TAIVI-P y(Ac3-MM-MH)" (5EO IO MO:1173

As-Trepi-M TM M-Trepi-IRne/4-(2-aminoethoxy)1-(2-MaiP-HAIBI-Y y(Ac)-MM-MN" (ZEO IU MO:1174

As-Trepi-M5UMO-Grepi-IRNe(4-(2-aminoethoxy)|-(2-MaipP-HAIVI-P uz(As3-MM-MN)" (ZEO OO MO:1175

As-IRepI-M-IAIVBI MO-(Repy-(Rpe(|(4-(2-aminoethoxy)|-(2-MapP-(AiYVI-(Suv(Ac)|-MM-MH)" (5EO 1Y

MO:1176

As-IRepI-M TP Mu-IAIVI-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MapP-IAIVI-(uz(Ac)|M-(AiVI-MN)" (5EO 1О

MO:1177

Ac-IRepI-OTMU/-(Huz(Ac)I-(Rep1-IRpe(4-(2-aminoethoxy)|-(2-MaP-(AiBI-(Huz(Ac)|-MM-MH)" (5EO 10

MO:1178

Ac-IRepI-(Guv(Ac)|- GMO-(RepiI-IRNe(4-(2-aminoethoxy)|-(2-Ma|--IAIVI-(Guv(Ac)|YMMMN" (ZEO 10

MO:1179

As-HTRepi-OSYUMMO-GREpi-("RpegH4-(2-aminoethoxy)-(2-MaPP-TAIVI-P y(Ac3-MM-MH)" (5EO I MO:1180

As-IRepI-MT-(2-MaC-O-(Rep1-Irpe(4-(2-aminoethoxy)|-(2-MapP-IAIV-( uv(Ac)-MM-MH)" (ZEO 10

MO:1181

As-IRepI-MT-11-MaC-O-(Rep1-IRpe(4-(2-aminoethoxy)|-(2-MapP-IAIV-( uv(Ac)-MM-MH)" (ZEO 10

MO:1182

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(o-Mei echI-(Huz(Ac)-MM-MH)" (ZEO 10

MO:1183

Ac-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(o-Me! uz1I-(Suv(Ac)|-MM-MH)" (ZEO 10

MO:1184

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|-

GG uv(As) I-MM-MN" (5EO 1Yu MO 1185

Ac-I(RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(o-Me! echI-(Suv(Ac)-M-(VAHa|-MH) (5EO 10

MO:1186

Table 2

Typical Ri-Rep inhibitors

Ac-I(RepI- MTM O-|(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(o-Me! uz1-(Guv(Ac)|-M-IVAia|-MH » (ZEO 10

MO:1187

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-M-IVAia|-MN" (ZEO 1O MO 1188

As-(RepI-M GU O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AivI)-(Suv(AsD-SM-MN)" (ZEO IU MO:1189

Ac-(RepI-M GU O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AivI-(Suv(Ac)-amM-MH)" (ZEO IU MO:1190

Ac-(RepI-M GU O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AivI-(Suv(Ac)-5M-MH)" (ZEO 1O MO:1191

Ac-(RepI-M GU O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AivI-(Suv(Ac)I-(AivI-M-MN)" (ZEO I MO :1192

As-(RepI-M GU O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(AiYVI)-(Suv(AcCD-AEM-MN)" (ZEO IU MO:1193

Ac-(Rep|-M GUU-ISSH-(Repi-(Rnpe(4-(2-aminoethoxy)|-(2-Ma!|-(AIVI-( uz (Ac)-MM-MH)" (ZEO I MO :1194

Ac-(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AIBI-(Suv(Ac)I-PisI-(BAia|-MH)" (ZEO 10

MO:1195

Ac-I(RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AlBi-(Guv(Ac)I-(pi esc|-IVAia|-MH)) ZEO 10

MO:1196

Ac-I(RepI-MTM O-|(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AIBI-(Suv(Ac)|1-a-IVAia|-MH)" (ZEO 10

MO:1197

Ac-I(RepI-MTM O-|(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AliiBI1-(Suv(Ac)I-B-IVATa|-MH)" (ZEO 10

MO:1198

Ac-IRep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-Mas--IAIV-(uz(Ac)-UM-IVAia|-MN)" (ZEO 10

MO:1199

Ac-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC--IAIV-(Hus(Ac)I-5-IVYa|-MH" (5EO 10

MO 200

As-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC--IAIVI-(Huz(Ac)I-I-(BAIa|-MH)" (5EO 10

MO 1201

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MaP|--IAIBI-(Huz(Ac)I-(AIVI-IVATa|-MN)) ZEO 10

MmOop202

As-IRep|I- MTM O-(RepyI-(Rpe(4-(2-aminoethoxy)|-(2-Mas--IAIBI-(Hus(Ac)I-(M-MelApa1-(BaiTa|-MH) (5EO 10

MO 203

Ac-I(RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MapP-(AIBI1-(Suv(Ac)I-(2-MariI-IVAia|-MH)) ZEO 10

MO 1204

Ac-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AIBI-(Suv(Ac)-P-IVAia|-MH)" (ZEO 10

MO 11205

As-KO)Aga|-(RepI-MTUMO-(RepiI-(Rpe|(4-(2-aminoethoxy)|-(2-Ma!|- (4-amino-4- carboxytetrahydropyrani-(uv(Ac)- MM-MN" (ZEO 1Ю0 MO:1206

Table C

Typical peptides containing the motif As-IRep|-ХХУХ-IRep|-ХХХХ (ZEO IO MO 1406) and their analogues

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MM-MN" (ZEO 10 MO:1207

As-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-MME-MN" (ZEO 1 MO:1208

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Гув(Ас)|-ММЕ-МН" (ZEO 10 MO:1209

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMK-MN" (ZEO 1О MO:1210

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMM-MN" (ZEO OO MO7L211

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMUU-MN (ZEO 10 МО212

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Гув(Ас)|-ММа-МН» (ZEO 10 MO:1213

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMT-MN" (ZEO 10 MO:1214

Table C

Typical peptides containing the motif As-IRep|-ХХУХ-IRep|-ХХХХ (ZEO IO MO 1406) and their analogues

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMRK-MN" (ZEO 1 MO 7215

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMRY-MN" (ZEO 10 MO:1216

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Гув(Ас)|-ММЕР-МН" (ZEO 1 MO 7217

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMak-MN" (ZEeEO 10 MO:1218

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMRT-MN" (ZEO 1О MO7L1219

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMKavg-MN" (ZEO 1 MO:1220

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMamu-MN" (ZEO 10 MO:1221

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMeas-MN" (5EO 1Ю МО7Л222

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMasia-MN" (ZEO 1 MO:1223

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMKKKK-MN" (5EO 1Ю MO: 1224

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMEEEE-MN" (ZEO 10 MO 1225

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MMEEEE-MN" (ZEO 1 MO 1226

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MMTTTT-MN" (ZEO 1 MO1227

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Гув(Ас)-ММасие В-МН" (ZEO 1О MO:1228

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As) D-MMasia B-MN" (ZEO 1 MO:1229

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)-MMasy E-MH" (ZEO 10 MO:1230

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)-MMasas-MN" (ZE 1 MO:1231

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)-MMasy T-MN" (ZEO 1 MO:1232

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv (Asu-MMasiasiA-MN" (ZEO 1О MO:1233

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv (Asu-M Masy se-MN" (ZEO 1 MO 234

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv (Asu-M Masa se-MN" (ZEO 10 MO:1235

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)-MMasyaaso-MN" (ZEO 10 MO1236

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(Asu-M Mas at-MN»g (ZEO 1 MO 7237

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)-MMAAAAVV-MN" (ZEO 10 MO:1238

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)-MMEREEE-MN" (ZEO 1 MO:1239

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|D-MMEEEEEEEEEE-MN" (ZEO 10 MO:1240

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)-MMOOOOOO-MN" (ZEO 1 MO 7241

Table C

Typical peptides containing the motif As-IRep|-ХХУХ-IRep|-ХХХХ (ZEO IO MO 1406) and their analogues

Ac-aaac-(RepiI-MTUMO-(RepiI-IRNe(4-(2-aminoethoxy)|-(2-Ma!|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MM-MN" (5EO 10 MO: 1243

As-AAV-IRepIi-MTUMO-|RepiI-(РНе(4-(2-aminoethoxy)|-(2-Mas|-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-MM-MN" (5EO 10 MO:1244

As-REB-(IRep|I-MTUUO-H(RepI-IRpe(4-(2-aminoethoxy)|-(2-Mas|-(4-amino-4-carboxytetrahydropyrani-

Guv(As)|-MM-MN" (5EO 10 MO:1245

As-EEB-(IRepI-MPMO-|RepiI-I(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-MM-MN" (5EO 10 MO :1246

As-000-(IRepI-MTUMO-(RepiI-IRNe(4-(2-aminoethoxy)|-(2-Ma!|-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-MM-MN" (5EO 10 MO:1247

As-TTT-(IRepI-MTUUO-H(RepI-IRpe(4-(2-aminoethoxy)|-(2-Mas|-(4-amino-4-carboxytetrahydropyrani-

Guv(As) |-MM-MN" (5EO 10 MO:1248

As-na-IRep-M TP UMO-|(RepyI-(Rpe(|(4-(2-aminoethoxy)I-(2-Ma!|-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-MM-MN" (5EO 10 MO:1249

As-BS-IRepI|I-MTUMO-(RepiI-IRNe(4-(2-aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-MM-MN" (5EO 10 MO 1250

As-ES-IRepI-MTUMO-(RepiI-I(РНе(4-(2-aminoethoxy)I-(2-Ma!|-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|I-MM-MN" (5EO 1OYU MO 1251

As-dDda-(RepI-MTUMO-(RepI-I(Rpe(4-(2-aminoethoxy)|-(2-Mas|-(4-amino-4-carboxytetrahydropyrani-

Guv(As)|-MM-MN" (5EO 10 MO 1252

As-TO-IRepI-MTUUO-(RepiI-IRNe(4-(2-aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyran|-

Guv(As)|-MM-MN" (5EO 10 MO 1253

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(Ra!t)|-MM-MN" (ZEO 1О MO:1254

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(ivosti-Rait)|-MM-MN" (ZEO 1О MO:11255

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

ISUB "PEG11-Rait)|-MM-MN" (ZEO 1 MO:1256

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(Ankh-Rai!t)|-MM-MN" (ZEO 10 MO:1157

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(ivosti-AiNh-Rai!t)-MM-MN" (ZEO 10 MO 1258

IRa!tI-(RepI-MTUO-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma|-(4-amino-4-carboxytetrahydropyran|-

Guv(As) |-MM-MN" (5EO 10 MO :1259

IRai!t-isosIsh|-(Rep|-MTU/SU(RepiI-(Rpe|4-(2-aminoethoxy)I-(2-MaP-(4-amino-4-carboxytetrahydropyrani-(Suv(Ac)-MM -MN" (ZEO IU0 MO:1260

IRa!t-PEG111-(RepI-M TM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyrani)-(Guv(Ac) |-MM-MN" (ZEO OO MO:1261

IRait-AnxI-I(RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy) I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyrani-(Suv(Ac)-MM -MN" (ZEO OO MO:1262

IRa!t-Anx-isosic|-(Rep|-MTUUO-(Repi-(Rpe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyrani-(Suv) As)-MM-MN" (ZEO OO MO:1263

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MM-Guv(Rait|-MN" (ZEO IU MO:1264

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MM-Guv(isosti-Rai!t|-MNg (ZEO 10 MO:1265

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)I-MM-Suz(PEGI11-Ra!t|-MNg (ZEO 10 MO:1266

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

Guv(As)|-MM-Guv(Aikh-Ra!t|-MN»g (ZEO 10 MO:1267

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

G uv(As)|-MM-I uv(isosti-Aikh-Ra!t|-MN»e (ZEO 10 MO:1268

Typical peptide inhibitors containing thioether linkages

00414) In some embodiments, the present invention includes a peptide inhibitor of the interleukin-23 receptor, where the peptide inhibitor has the structure of the formula:

B'-AX-B:2 (PP), 00415) or a pharmaceutically acceptable salt or solvate thereof, 00416) where EE" is a bond, hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl, C1-C6 alkyl, C1-C20 alkanoyl, alkylsulfonate, acid, y-Sys or rhom attached to the M-terminus, and including PEGylated variants (eg, from 200 Da to 60,000 Da), alone or as a spacer of any of the above ; 00417) В? is a bond, ОН or МН"; and

І00418| X is an amino acid sequence of 8-20 amino acids or 8-35 amino acids. 00419) In specific variants of implementation of peptide inhibitors of formula I X contains or consists of the sequence of formula Sha: xX1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16 -X17-X18-X19-X20 (Sha) (ZEO I

MO:1407), where

X1 is absent or is any amino acid;

X2 is absent or is any amino acid;

ХЗ is absent or is any amino acid;

XA represents Aby, Rep or Sub;

X5 is any amino acid;

Xb is any amino acid;

X7 represents Tgr, Vir, SiIp, Ni5, SiSh(B2I), 4-phenylbenzylalanine, Tis, Rpe|(4-(2-aminoethoxy)|,

Rpe(3,4-Си2), RNi(4-OMe), B-hydroxy-Ttr, b-chloro-Ttr, M-MeTgr, a-MeTtr, 1.234 zNYAMmE- tetrahydronorharman, Rpe(4-СО2Н), Rpe( 4-SOMN»g), RNe(3,4-"OSH3)g), Rpe(4-SEz), BrV-aDiRNelia,

Rpe(4-I0), Sim, SU, Pe, Azp, Rgo, Agd, Tig or Osidio, or the corresponding α-methylamino acid form of any of the above;

XV is any amino acid;

ХУ represents Aby, Rep or Subv;

Co) X10 represents May 1, May 2, Ais, Vir, (0) Suz, Sna, OMT, (0) TGug, Spy, RNe, Niv, Tr, TNg, Tis,

Thug, 4-pyridylAia, Osidium, analogue of Ppe or analogue of Thug (optionally Ppe(3,4-Eg2), Ppe(3,4-Sig),

E(3-Me), Rpe(4-(2-aminoethoxy)), Rpe|(4-(2-(acetylaminoethoxy)), Rpe(4-Bi), Rpe(4-SOMH), Rpe(4-

SI), Rpe(4-SM), Rpe(4-guanidino), Rpe(4-Me), Rpe(4-MH), Rpe(4-Mz), Rpe(4-OMe), Rpe(4- ОВ21)), or the corresponding α-methylamino acid form of any of the above;

X11 is 2-Mai, 1-Mai, 2,4-dimethylRie, Vir, 4-phenylcyclohexyl, (SiIshS(Ba2i), 4-phenylbenzylalanine, Tis, Rpe(|4-(2-aminoethoxy))|, Rpe( 3,4-С12), РНе(3,4-Е2), ВыРПе(4-Р), РНе(4-

OMe), 5-hydroxy-Tgr, b-chloro-Ttr, M-MetTtr, a-MetTr, 1,2,3,4-tetrahydronorharman, Pne(4-СО2Н),

Rpe(4-SOMN"), RHne(3,4-dimethoxy), Rpe(4-SEz), Rpe(2,3-C1I2), Ripe(3,4-SiI"), Ripe(2,3-E2 ),Rpe(4-E), 4-phenylcyclohexylalanine, «-MeRpe, VyMai, VyRPe, VyTug, VyTgr, Vir, Mma(5-phenyl), Re, Ni, pRNe, Tada, Tr, Tug, Rpe(4 -Me), Tgr(2,5,7-tri-tert-butyl), Rpe(4-Oallyl), Tug(3-1Vy), Rpe(4-I1Vy),

Rpe(4-guanidino), Rpe(4-OVY) or Osidio, or the corresponding α-methylamino acid form of any of the above;

X12 is a-Mey uz, o-MeOgp, a-Mey ey, Mey ey, AIB, (0)Aia, (0)Avp, (Bey, (0)Azr, (FR Ne, (0)TNg, 3-Rai, Aib, V-AIa, VASI, VpAPa, Vp em, VyMai, V-spiro-pip, Spa, Spo, Azr, bab, Var, a-dietilou, SIM, Re, p em, pAgo, p ei , Pe, G uv, Gey, Azp, M-Mei you, M-MeAgo, 91, Opt, Rgo, Sp,

Agou, Zeg, Tig or Thie, amino-4-carboxytetrahydropyran (TNR), Asys, Asrs, Asbs, Asus, Alyb, or the corresponding α-methylamino acid form of any of the above;

Х13 is an I bond ГГ ув(Ас), (0)Ав5п, (0) ей, (С)ТПг, (С)Рпе, Аа, АЙБб, а-МегГ ем, ВАіІіа, ВАСИІ,

VpAa, VyHei, VimMai, V-spiro-pip, Spa, Spo, Azr, Ago, Ot, bab, Var, a-diethyloiu, Sim, Rie, pHei,

Huz, Hei, Azp, Od, Rgo, SiIp, Azr, Ago, Zeg, spiro-pip, TAg, Tra, Tis, MaiYi or Tug, or the corresponding α-methylamino acid form of any of the above;

X14 is Azp, Sim, Rpe, Su, Niv, GG uv, I uz (As), Gei, Mei, Azp, Rgo, SiIp, Ag9, zeg, TNg,

Tis, A5p or Tug, or the corresponding α-methylamino acid form of any of the above;

X15 is su, (0)Aia, (0)Av5p, (0)A5p, Azp, (0) ey, (SORPe, (0)TNg, Aa, AEA, Azr, SIM,

RPpe, Su, Huz, em, Rgo, Sip, Ago, B-Aia or 5eg, or the corresponding c-methylamino acid form of any of the above;

X16 is absent, Su, Aa, Ar, Zeg, Pgo, Azp or Tpg, or the corresponding α-methylamino acid form of any of the above;

X17 absent, Sim, Zeg, SiIu or SiP, or the corresponding α-methylamino acid form of any of

Gs10) of the above;

X18 is absent or is any amino acid;

X19 is absent or is any amino acid; and

X20 is absent or is any amino acid. 00420) In some embodiments, X14 is Avzp, Sim, Rpeye, Su, Niv, I uv, I uz (Ac),

Y em, Mei, Avp, Rgo, Sip, Ago, Zeg, TNAg, Tis or Tug, or the corresponding "-methylamino acid form of any of the above. 00421) In some embodiments, Xa: X7 is Ttgr, Vir, Sip, Ni, Cis(B2i), 4-phenylbenzylalanine, Tis, Rpe|(4-(2-aminoethoxy)), Rpe(3,4-Cl2) , Rpe(4-OMe), 5-hydroxy-Ttr, b-chloro-

Ter, M-MetTgr, o-MetTtr, 1,2,3,4-tetrahydronorharman, Rpe(4-СО2Н), РНе(4-СОМН»), RНе(3,4-dimethoxy), Rpe(4-СЕз) . X10 represents May 1, 2-

May, Ais, Vir, (0)Suz, Spa, OMT, (0)THug, Spi, RNe, Ni, Tgr, TNg, Thys, Thug, 4-pyridylAia, Osidiu, Ripe analogue or Thug analogue, or the corresponding a- the methylamino acid form of any of the above; X11 is 2-Mai, 1-Mai, 2,4-dimethylRpe, Vir, 4-phenylcyclohexyl, sat(B2I), 4-phenylbenzylalanine, Tis, Rpe(4-(2-aminoethoxy)|, Rpe(3,4 -Sig), Rne(3,4-E2), VyIRPPe(4-E),

Rpe(4-OMe), 5-hydroxy-Ttr, b-chloro-Ttr, M-MetTtr, o-MetT"tr, 1,2,3,4-tetrahydronorharman, Rpe(4-

SON), Rpe(4-SOMH»g), Rpe(3,4-dimethoxy), Rpe(4-SEz), Rpe(2,3-CI2), Rpe(2,3-Eg), Rpe(4- E), 4-phenylcyclohexylalanine, c-MePe, VAMai, VyRNe, Vp Tug, VA Tgr, Vir, Mma(5-phenyl), Rpe, Ni, pRPe,

Taa, Tr, Tug, Rne(4-Me), Tgr(2,5,7-tri-tert-butyl), Rpe(4-Oalyl), Tug(3-IVy), Rpe(4-IVy), Rpe (4-guanidino), Rpe(4-0B7I) or Osidio, or the corresponding α-methylamino acid form of any of the above; X12 is a-Mei uh, o-MeOgp, a-Mei y, Mei ey, Air, (0)Aia, (0)Avp, (B) yem, (0)Azr, (0)РНе, (0) TNg, 3-Rai, AB, V-AIa, VSIM, VpAPa, Vp ei, VyMai, V-spiro-pip, Spa, Spo,

Azr, Bab, Var, a-diethyloiu, Sim, Re, pe ey, pAgo, NG ey, Pe, Huz, em, Azp, M-Mei ei, M-MeAgo, OdI,

Opt, Rgo, Sp, Agu, Zeg, Tig or Thie, or the corresponding α-methylamino acid form of any of the above; X13 represents I uz(As), (0)Avp, (0) ei, (0) Pg, ()P pe, Aa, AIB, a-Me! hey wow

Vasi, VrApa, VyGei, VimMai, V-spiro-pip, Spa, Spo, Azr, Ago, Ogp, ab, Var, a-diethyloiu, Sim, Rpe, pe, Guz, Gei, Azp, Od, Rgo, SiIp, Azr, Ago, Zeg, spiro-pip, Tig, Tba, Tis, Ma! or Tug, or the corresponding α-methylamino acid form of any of the above; X14 represents Avp, Sy,

RPpe, Su, Nib, Guz, Gei, Mei, Ap, Rgo, Sip, Ago, Zeg, TPg, Tis or Tug, or the corresponding a-

The methylamino acid form of any of the above; and X15 is Su, (0)Aia, (0)Av5p, (0)A5p, Avzp, (0) ei, (C)P Pe, (0) Pg, Aa, AEA, Ar, Sim, Re, Su , Huz, I em, Rho, SiIp, Agu or 5eg, or the corresponding α-methylamino acid form of any of the above. (00422) In some embodiments, an XZ is present. In specific embodiments, XZ3 is Sim, (0)Sim, Ago, (0)Ago, Re, (C0)RPe, 2-Mai, Tpg, Hei, or (0)SiP. In some embodiments, it is (0)Agu or (0)Rpe. (00423) In specific embodiments, X5 is Sp, Aa, Su, Sii, A5p, Bar, Var,

Spim, Rpe, Su, Ni, pSuv, Guz, I ey, Mei, Azp, M-Me-AiIa, M-M-Avzp, M-Me-G uz, M-Me-Sip, M-Me-Ago,

Op, Rgo, Rep, Sip, Ago, Zeg, TPg or Mai. (00424) In specific embodiments, Xb is TPg, Ar, Sim, Rpe, Avp, Rgo, Ago, zeg or TNg. 00425) In specific embodiments, X8 is Sp, Sim, Re, Gu, Avp, Rgo, Aga, Mai, Tig, or Tr.

I00426| In some embodiments, X1O is an analog of Tug or an analog of Ppe. In specific embodiments, X1O is RPE(4-OMe), RPE(SOMH:) or RPE|4-(2-aminoethoxy)). In some embodiments, X10 is an analog of Tug or an analog of Ppe. In specific embodiments, X10 is Rpe(4-OMe) or Rpe|4-(2-aminoethoxy)|. 00427) In some embodiments, where X1O0 is an analogue of Ppe, X10 is selected from

RPE, RPE(4-OMe), α-MeRNE, RPE(3,4-dimethoxy), RPE(4-SOMH), RPE(4-0-82I)), RPE(4-guanadino), RPE(4- IVy), Pne(4-SM), Ripe(4-Vy), Rpe(4-MH»g), Rpe(4-E), Rpe(3,5-OIE), Rine(CH2SO»H),

Rpe(penta-P), Rpe(3,4-Si2), Ripe(4-SEz), BB-diRpeAia, Rpe(4-Mz) and Rpe(|4-(2-aminoethoxy)).. In specific variants implementation of X10 is Rpe|4-(2-aminoethoxy)| or Rpe(cSoOMN"). In specific embodiments, X10 is RIP (4-(2-aminoethoxy)). (00428) In some embodiments, where X10 is a Tug analog, X10 is selected from PpTuUg,

M-Me-Tug, Tug((3-IVy), Rpe(4-OMEe) and BpTug. In specific embodiments, X10 is

Rpe(4-OMe). (00429) In specific embodiments, X10 is Tug, Rpe(4-OMe), Rpe(4-OB21),

Rpe(4-OMe), Rpe(4-SOMN"), Rne(3,4-SiIg), Rne(4-1Vy), Rpe(4-Mn»g), Rpe(4-Vi), Rpe(4 -CM), РНе(4-carboxy), Рпе|4-(2aminoethoxy)| or Rpe(4-guanadino). In specific embodiments, X10 is not Tug. bo 00430) In some embodiments, X11 is Tgr or an analog of Tgr. In specific embodiments, X11 is May 2 or May 1. 00431) In specific embodiments, the peptide inhibitor of formula I is cyclized. In some embodiments, the peptide inhibitor is cyclized using an intramolecular bond between X4 and XU. In some embodiments, the intramolecular bond is a thioether bond.

I00432| In some embodiments, the peptide inhibitor of formula ISH is linear or non-cyclized. In specific variants of the implementation of a linear peptide inhibitor of the formula PI

XA and/or XU are any amino acid.

I00433| In specific embodiments of the peptide inhibitor of formula I, one or more, two or more, or all three of X1, X2, and X3 are absent. In some embodiments, X1 is absent. In some embodiments, X1 and X2 are absent. In some embodiments, the implementation of X1, X2 and

HZ are absent.

I00434| In specific embodiments of the peptide inhibitor of formula I, one or more, two or more, three or more, four or more, or all of X16, X17, X18, X19, and X20 are absent. In specific embodiments of the peptide inhibitor of formula I, one or more, two or more, three or more, or all of X17, X18, X19, and X20 are absent. In some embodiments, one or more, two or more, or all three of X17, X19, and X20 are absent. In some embodiments, one or more of X1, X2, and X3 are missing; and one or more, two or more, three or more or four of X17, X18, X19 and X20 are absent. 00435) In specific embodiments of the peptide inhibitor of formula I, one of X4 or

XU represents Aby, and the other of X4 or X9 does not represent Aby. In some embodiments, X4 is Ab and X9 is Sub. (00436) In specific embodiments, the peptide inhibitor of formula I contains one or more, two or more, three or more or four of the following features: X5 is Agd or

SiIP; Xb is TPg; X7 is Tgr; and X8 is Sip. In specific embodiments, X5 is sp, Xb is TPg, X7 is Ttgr, and X8 is ip.

In some embodiments, X5 is Sp. In some embodiments, X1, X2, and Xx3 are absent. In some embodiments, X4 is Aby and XU is Sub.

I00437| In specific embodiments, the peptide inhibitor of formula PI contains one or

Ko) more, two or more, three or more, four or more, five or more, six or more or seven of the following signs: X10 is Tug or an analogue of Rie; X11 represents Tgr, 2-May, 1-

MaYi, Rpe(4-O-allyl), Tug(3-Vy), Rpe(4-48Vy), Rpe(4-guanidino), Rpe(4-OOV7I) or Rpe(4-Me); X12 is Ago, pey, (0)A5p or any alpha-methylamino acid, including AIB, a-

Me! uz, a-MeH ei or a-MeOgp; X13 is I uz, Sim or Guz (As); X14 is Rpe or

Archbishop; X15 is B-AIa, Sip, SiIu, beg, AIa; and X16 is absent or is AEA. In specific embodiments, the peptide inhibitor of formula I contains 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 Tug or an analogue of Ppe; X11 is Tgr, 2-May, 1-May, Rne(4-

O-allyl), Tug(3-IVy), Rpe(4-IVy), Rpe(4-guanidino), Rpe(4-OVII) or Rpe(4-Me); X12 is a

Aha, NO e, (0)Azp or any alpha-methylamino acid, including Al, c-Mey, a-Mey, or a-MeOt; X13 is Huz, Sim or I ub(As); X14 is Riye or Avp; X15 is Su, Zeg, Aa; and X16 is absent or is AEA. In some embodiments, the analog

Rpe is Rpe(4-OV821I), Rpe(4-OMe), Rpe(4-SOMH»g), Rpe(3,4-SiIg), Rpe(4-1Vy), Rpe(4-MHg),

Rpe(4-Bi), Rpe(4-CM), Rpe(4-carboxy), Rpe|4-(2aminoethoxy)| or Rpe(4-guanadino). In some embodiments, X11 is 2-Mai or 1-Mai. In some embodiments, the implementation of X1, X2 and

HZ are absent. In some embodiments, X4 is Aby and X9 is Subv. (00438) In specific embodiments, the peptide inhibitor of formula PI contains 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 Tug or an analogue of Rie ; X11 represents Tgr, 2-May, 1-

MaYi, Rpe(4-O-allyl), Tug(3-Vy), Rpe(4-48Vy), Rpe(4-guanidino), Rpe(4-OOV7I) or Rpe(4-Me); X12 is Ago, Pec, (0)Avp, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, Adr,

AI, a-Diethyliu, a-Mei uz, a-MeH uz(As), a-Me-IG em, a-MeOpt, a-Mezeg, a-Memai; X13 is a

Guz, Sim or I uz (As); X14 is Rpe or Avp; X15 is a su; and X16 is absent or is AEA. In some embodiments, the Ppe analog is Ppe(4-OV71I), Ppe(4-

OMe), Rpe(4-SOMN»g), RNe(3,4-Sig), Rpe(4-48y), RNe(4-MHg), RNe(4-B), RNe(4-SM), RNe (4-carboxy), Rpe(4-(2-aminoethoxy)) or Rpe(4-guanadino). In some embodiments, X11 is 2-MaY or 1-MaY. In some embodiments, X1, X2, and XZ are absent. In some embodiments, X4 is Ab and X9 is Sub. 00439) In specific embodiments, the peptide inhibitor of formula PI contains one or 60 more, two or more, three or more, four or more, five or more, six or more,

or seven or more, eight or more, nine or more, ten or more or eleven of the following signs: X5 represents Agud or Sip; Xb is Tpg; X7 is Tgr; X8 is Sp; ХИО is an analogue of Рпе; X11 is Ttgr, 2-May, 1-May, Pne(4-O-allyl), Tug(3-IVy), Rpe(4-1Vy), Rpe(4-guanidino), Rpe(B2I) or Rpe( 4-Me); X12 is AIB, a-

Me uz, a-Mei em, 4-amino-4-carboxytetrahydropyran, AspPs, Asrs, Asrs, Asms, Adr, AIB, a-diethyliu, a-MeH uz, a-MeH ub(As), a-Me-Ie , o-Mebeg, a-Memai, a-MeOgp; X13 represents I uh,

SiIsh or Gub(As); X14 is Rpe or Ahp; X15 is B-aia, su, Zeg, Aa; and X16 is absent or is AEA. In specific embodiments, the peptide inhibitor of the formula

It contains contains one or more, two or more, three or more, four or more, five or more, six or more, or seven or more, eight or more, nine or more, ten or more, or eleven of of the following signs: X5 represents Ago or Sip; Hb is TNg;

X7 is Tgr; X8 is Sip; X10 is an analogue of Rieu; X11 is Ttr, 2-

May, 1-May, Rpe(4-O-allyl), Tug(3-II), Rpe(4-I8y), Rpe(4-guanidino), Rpe(B2I) or Rpe(4-Me); X12 is Air, a-Meyi uz, a-MeY ei or o-MeOgp; X13 is Huz, Sim or I uz(As); X14 is Re or Avzp; X15 is c1u, Zeg, Aa; and X16 is absent or is AEA.

In some embodiments, the Rpe analog is Rpe(4-O872I), Rpe(4-OMe), Rpe|A-(2aminoethoxy)), Rpe(4-SOMH), Rpe(3,4-CI2), Rpe( 4-4В0), РНе(4-MNeg), РНе(4-В/), РНе(4-СМ),

Rpe(4-СО2Н) or Rpe(4-guanadino). In some embodiments, X11 is 2-May or 1-

May In some embodiments, X1, X2, and XZ are absent. In some embodiments, X4 is Aby and XU is Sub. (00440) In specific embodiments, the peptide inhibitor of formula PI contains one or more, two or more, three or more, four or more, five or more, six or more, or seven or more, eight or more, nine or more, ten or more or eleven of the following signs: X5 represents Agud or Sip; Xb is Tpg; X7 is Ttgr; X8 is Sip; XIO is Tug or an analogue of Rpe; X11 represents Tgr, May 2, May 1,

Rpe(4-O-allyl), Thug(3-IVy), Rpe(4-IVy), Rpe(4-guanidino), Rpe(B2i) or Rpe(4-Me); X12 is a

Ага, пей, (0)Авп, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbrs, Asus, AIb, a-diethyliu, a-

Me uz, o-MeiG uz(As), o-Me-I em, o-Mezeg, a-MemMayi!; Х1І3 is I uz, Sim or I uz(Ac); X14 is Re or Avp; X15 is p-Aya, Azp or Su; and X16 is absent or is present

From AEA. In specific embodiments, the peptide inhibitor of formula I comprises one or more, two or more, three or more, four or more, five or more, six or more, or seven or more, eight or more, nine or more, ten or more or eleven of the following signs: X5 represents Agud or Sip; Xb is Tpg; X7 is Ttgr; X8 is Sip; XIO is Tug or an analogue of Rpe; X11 represents Ttgr, May 2, May 1,

Rpe(4-O-allyl), Thug(3-IVy), Rpe(4-IVy), Rpe(4-guanidino), Rpe(B2i) or Rpe(4-Me); X12 is a

Ag9, p em, (0)Azp, a-MeiH uz, o-Mei ei or a«-MeOpt, Air; X13 is I uz, Sim or Iuz (As);

X14 is РПе or Ап; X15 is a su; and X16 is absent or is AEA. In some embodiments, the analogue of Ppe is Ppe(4-OV2I), Ppe(4OMe), Ppe(4-SOMN 5),

Ripe(3,4-СИ2), Rpe(4-І8y), Rpe(4-МН»г), Rpe(4-ВІ), Rpe(4-СМ), Rpe(4-СО2Н), RPE(4- (2-aminoethoxy)) or Rpe(4-guanidino). In some embodiments, X11 is 2-Mai or 1-Mai. In some embodiments, X1, X2, and XZ are absent. In some embodiments, XA is Aby, and

ХУ is a Subv. (00441) In some embodiments, the present invention includes a peptide of 8-20, 8-16, or 8-12 amino acids, optionally cyclized, containing or consisting of the main sequence of the formula:

Haa4-Haab5-Haab-Ttr-Haav-Haa9-Haa10-Haa11 (FIRST) (ZEO AND MO:1408), (00442 where each of Haai4 and Haa9 is independently selected from Aba and Su, and each of Haai and

Haa9 are not the same; Haa5, Haab and Haav represent any amino acid residue;

Khaa10 is Tug, an analogue of Rpe or 2-Mai, and Khaa11 is 2-Mai or Tgr, and the peptide inhibits the binding of 1-23 with II-23K. In specific embodiments, Xa10 is a

Rpe(4-OMe), 2-Ma! or Rpe|4-(2-aminoethoxy)). In one embodiment, Xa10 is

Rpe(4-OMEe). In one embodiment, Xa7 is Rpe|4-(2-aminoethoxy)|. In one embodiment, Haa1!!1! is 2-MaI). In some embodiments, the peptide is cyclized with Xaa4 and Xaa9. In specific embodiments, the analogue of Ppe is Rie|4-(2aminoethoxy)| or Rpe(4-OMe). In some embodiments, Xa4 is

Ar, and Xa9 is Su", and the peptide is cyclized with Xa4 and Xa9. In specific embodiments, the peptide is a peptide inhibitor of formula I, and in some embodiments, X1, X2, and X3 are absent. In specific embodiments, the peptide inhibits the binding of I/-23 to I/-23K. In some embodiments, the peptide of the formula PPB contains SI, 60 (f)Cly, Aga, (0)Aga, PNe, (O)PNe, 2-Mai, TNg, Hei, or (O)SiIp bound to Xa4. In some embodiments, it is (O)Agu or (C)RPe. (00443) In some embodiments, the present invention includes a peptide of 8-20, 8-16, or 8-12 amino acids, optionally cyclized, comprising or consisting of the main sequence of formula Ps:

Ary-Haa5-Haab- Ttr-Haa8-Suz-IRpe(4-OMe)|-(2-Mai) (Ps) (ZEO IO MO:1409), (00444) where Haa5, Haab and Haav are any amino acid residue; and the peptide inhibits binding of 1-23 with I-23E. In some embodiments, the peptide is cyclized with Aba on Xa4 and Suh on Xa9. In some embodiments, the peptide is a peptide inhibitor of formula I, and in some embodiments, X1, X2, and X3 are absent. In specific embodiments, the peptide inhibits the binding of II-23 to II-23E. In some embodiments, the peptide of formula Ps contains Sim, (O)Cim, Ago, (O)Ago, Rie, (O)Rpe, 2-Mai, TNg, Hei, or (O)Sip linked to Ar. In some embodiments, it is (O)Agd or (C)Rpe. (00445) In some embodiments, the present invention includes a peptide of 8-20, 8-16, or 8-12 amino acids, optionally cyclized, comprising or consisting of the main sequence of formula Xa:

Ary-Haa5-Haab-Ttr-Haa8-Suz-Haa10-Ttr (Sha) (ZEO IU MO:1410), (00446) where Haa5, Haab and Haav represent any amino acid residue; Khaa10 is a modified Re; and the peptide inhibits the binding of II/-23 to I-23. In specific embodiments, modified Rpe is Rpe(4-IVy), Rpe(4-guanidino),

Rpe|(4-(2-aminoethoxy))|, Rpe(4-СО2Н), Rpe(4-CM), Rpe(4-Hg), Rpe(4-MHg), Rpe(СОМН») or Rpe(4 -

Me). In specific embodiments, the modified Rpe is Rpe(4-1Vy), Rpe(4-guanidino), Rpe(|4-(2-aminoethoxy))Y, Rpe(4-CO»H), Rpe(4-CM) , Rpe(4-Vg), Rpe(4-MNeg) or RNe(4-

Me). In one embodiment, Xa10 is Rpe(|4-(2-aminoethoxy)| or Rpe(4-OMEe). In one embodiment, Xa!O0 is Rpe(|4-(2-aminoethoxy))R. In some in some embodiments, the peptide is cyclized with Aba on Xaa4 and Su on Xaa9. In some embodiments, the peptide is a peptide inhibitor of formula I, and in some embodiments, X1, X2, and X3 are absent. In specific embodiments, the peptide inhibits the binding of HER - 23 with I/-23 K. In some embodiments, the peptide of formula Pa contains Sim, (0)c1m, Agu, (0)Aga,

Re, (0)RHe, 2-Mai, Tng, Gei or (0)SiIp related to Ar. In some embodiments, it represents

With him (0)Agu or (0)P Pe.

I00447| In some embodiments, the present invention includes a peptide of 8-20, 8-16, or 8-12 amino acids, optionally cyclized, comprising or consisting of the main sequence of formula She:

Ary-Xa5-Xaab-Ttr-Xaav8-Suvz-Rpe(4-(2-aminoethoxy) |I-(2-Mai| (She) (ZEO 10 MO:1411), (00448) where Xa5, Xaab and Xa8 are is any amino acid residue. In some embodiments, the peptide is cyclized with Abra on Xaa4 and Su on Xaa9. In some embodiments, the peptide is a peptide inhibitor of formula I, and in some embodiments, X1, X2, and X3 are absent. In specific in some embodiments, the peptide inhibits the binding of I/-23 to I/-23 K. In some embodiments, the peptide of the formula PPB contains SI, (F)Csly, Ago, (0)Aga, Rie, (0)PHe, 2-Mai, TNg, Y ei, or (B)SiP linked to Ar. In some embodiments, it is (O)Ago or (C)Rpe. (00449) In one embodiment, Xaa5 and Xaab are SiP. In one embodiment, an embodiment of Haab is a TPg In some embodiments, the peptide is cyclized with Aba to Haa1 and Sus to Haa9.

I00450| In specific embodiments of the peptide inhibitor of formula I, the peptide inhibitor has the structure shown in any of Tables 5A-5C, or contains the amino acid sequence shown in Tables 5A-56.

IІ00451| In some aspects, the present invention provides a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of the formula (MO):

X1-X2-X3-Ary-x5-X6-X7-X8-Suv-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (M) (5EO

IO MO:1412), where:

X1 is absent;

X2 is absent, or X2 is O-Avr, E, B, O-Ago, E, O-RNe, 2-Mai, T, I, O0-SiIp or O-Avp;

ХЗ is O-Aga;

HB is M, OO, Si, Huz or a conjugate of I u5 (for example, I UB5(IMA), Huz(biotin),

Huz(octanyl), Huz(Rait), Huz(PEG), Huz(PEG8), Huz("PEGI11-Rait), Guv(As));

Xb is T, 5 or Y; 60 X7 represents MU, May 1 or May 2;

ХВ is ОС), СИиЙ, M, АЙБ or I uz(Ас);

X10 is Рие|4-(2-aminoethoxy)), Рпе|4-(2-acetylaminoethoxy)| or Rpe(4-SOMN");

X11 represents May 2;

X12 is a 4-amino-4-carboxytetrahydropyran, Aib, "Me ei, oMei uz or an oMe!H uz conjugate (eg, oMegHus(As), omMmeghUs(PEG4-Rait), omeH uz(PEG4lauryl), oMei! uz(PEG4I5osyllauryl), aMeH u5(PEG4I5osyllauryl), omey uz(IMA), omey uz(biotin) or omeguz(octanyl));

X13 is OO, E, Si or a conjugate of Huz (for example, GI uz(As), I U5(PEG4-ivos1y-Rait),

Huz(PEG4-Octanyl), Gu5(PEG4-Rait), Huz(Biotin), Huz(Octanyl), Guv(Rait), Rooz(PEG8) or

GuUz (PEG11-Rait));

X14 is M, SY, 0.1, 0.5, AB, E, 2-Mar, M-Me-Aia, EK, MU, pi em, Tis, or a conjugate of I ub (for example, GG uz(Ac ));

X15 is M, Sii, O, Vapa, I uz(As) or AIBb; and

X16, X17, X18, X19 and X20 are absent.

In specific embodiments, X2 is O-Avr, E, B, O-Aga, E, O-RNe, 2-Mai, T, i, O-SiIp or O-Avp.

I00452| In some aspects, the present invention provides a peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises the amino acid sequence of formula (MP):

X1-X2-X3-Ary-x5-X6-X7-X8-Suv-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (MY) (ZEO

IO MO:1413), where:

X1 is any amino acid or absent;

X2 is any amino acid or absent;

XZ is any O-amino acid or absent;

X4 is Su, pSu5, Rep, pRep, Aby, beg, pZeg or a chemical fragment capable of forming a bond with XO;

X5 is Aa, a-MeOgp, a-Meseg, Sii, bar, ar, Rar(As), Snu, Huz, Azp, M-Mesip, M-

MeAgo, Op, Sip, Agou, Zeg, Sim or TNg;

Ko) Xb is ТНг, 5ег, А5р, Пе or any amino acid;

X7 is Ttgr, b-chloro-Ttr, 1-Mar or 2-Mar;

X8 is Sim, Sp, Avp, I uv(Ac), Sii, Sam, I uv(M-e-(M-a-palmitoyl-Y-y-glutamyl)) or

Guz (M-e-palmitoyl);

XU is Su, pSub5, Rep, pRep Ar or any amino acid or chemical fragment capable of forming a bond with XA;

X10 is 2-May, an analogue of Rpe, Tug or an analogue of Tug;

X11 is 1-Mai, 2-Mai, Pne(3,4-dimethoxy), 5-hydroxyTgr, Ppe(3,4-Sig), Ttr or Tug(3-

And you);

X12 is /AIB, 4-amino-4-carboxytetrahydropyran, any alpha-methylamino acid, alpha-ethylamino acid, Asps, Asms, AsBs, Asrs, 4-amino-4-carboxypiperidine, 3-Rai, Adr, a-diethyliu . , Guz, I em, Osidiu, Ot, piperidine, Ago, z5eg,

Tpgabo TNR;

X13 is I ubz(Ac), Sp, Sii, Oi or any amino acid;

X14 is Azp, Sp, I ub(As), Sii, Sam, I ub(M-e-(M-a-palmitoyl-y-y-glutamyl)), GG uv (M-e-palmitoyl), A5p or any amino acid;

X15 is VD-APa, Avp, Su, Sip, Aa, Zeg, AIB, Az5r or Sis

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent. 00453) In some embodiments of any of the peptide inhibitors described herein, including, but not limited to, the following formulas (I) and (II), the peptide inhibitor is cyclized via a linkage, e.g., a thioether linkage, between X4 and XU. In some embodiments, the peptide inhibitor inhibits the binding of interleukin-23 (PI/-23) to the I-23 receptor. 00454) In some embodiments, X1, X2 and XZ are absent. In some embodiments, X1 and X2 are absent. In some embodiments, the implementation of X1! is a YU-amino acid or is absent. In some embodiments, X2 is an O-amino acid or absent.

00455) In some embodiments, X5 is Aa, a-MeOgp, a-Meseg, Sii, Oar, Rab,

Rar(As), Siu, Guv, Avp, M-Mesip, M-MeAgo, Ot, Sp, Agu, Zeg or TNg. 00456) In some embodiments, X5 is M, Xb is T, X7 is

M, or X8 is OS). In some embodiments, X5 is M, Xb is T,

X7 represents MU, and X8 represents 0.

I00457| In some embodiments, X5 is CO), Xb is T, X7 is

M, or X8 is CO). In some embodiments, X5 is CO, Xb is T,

X7 is MU and X8 is 0. (00458) In some embodiments, X5 is M, Xb is T, X7 is

MI, and X8 is SIiY. 00459) In some embodiments, X10 is Rpe|4-(2-aminoethoxy)|. 00460) In some embodiments, X12 is 4-amino-4-carboxytetrahydropyran,

AIIB, oMeiei or oMei uh. In some embodiments, X12 is 4-amino-4-carboxytetrahydropyran. 00461) In some embodiments, X13 is E or I uz(Ac). In some embodiments, X13 is I uz(Ac). (00462) In some embodiments, X14 is Avzp, Sp, I uv(Ac), Sii, Sam, GG uv(M-e-(M-a-palmitoyl-Y! -y-glutamyl)), I ub( M-is-palmitoyl) or any amino acid. 00463) In some embodiments, X15 is B-Aya, Azp, Su, Sip, Aa, Zeg, Air, or

SI. (00464) In some embodiments, X14 is M. 00465) In some embodiments, X15 is M. (00466) In some embodiments, X1b6 is a 10-amino acid or absent. In some embodiments, X17 is an O-amino acid or absent. In some embodiments, X18 is a 10-amino acid or is absent. In some embodiments, X19 is a Y-amino acid or absent. In some embodiments, X20 is a Y-amino acid or absent. (00467) In some embodiments, X2 is absent; ХЗ3 is absent; X5 represents 0, Xb represents T, X7 represents UM, and X8 represents 0; X10 is РПе(|4-(2-

From aminoethoxy))Y; X12 is 4-amino-4-carboxytetrahydropyran, Aib, "MeiYi ei or aMei! bonds;

X13 is E or GG uz(Ac); X14 is M; and X15 is M. In some embodiments, X12 is 4-amino-4-carboxytetrahydropyran, and X13 is I uv(Ac). (00468) In some embodiments, any of the amino acids of the peptide inhibitor is connected by a linker fragment, for example, PEG. 00469) In some embodiments, the M-terminus of the peptide inhibitor contains an Ac group. (00470) In some embodiments, the C-terminus of the peptide inhibitor contains an MHe group.

I00471| In some embodiments, the present invention includes a peptide comprising or consisting of an amino acid sequence shown in any of Table 45 or Table 55, or a peptide inhibitor comprising or consisting of a structure shown in any of Table 45 or Table 55 (or its pharmaceutically acceptable salt). In specific embodiments, the peptide does not contain conjugated fragments, but contains an Aby residue. In specific embodiments, the peptide or inhibitor contains a thioether bond between two Ar and Su residues or between the two extreme amino acids in parentheses after the term "cyclo", indicating the presence of a cyclic structure. In specific embodiments, the inhibitor is an acetate salt. The peptide sequence of typical inhibitors is shown in Tables 4 and 5 beginning with

M-terminus to C-terminus, with conjugated fragments, and indicated by an As group at the M-terminus and/or an MHe group at the C-terminus. The cyclic structure is shown by "cyclo" as indicated in Table 5, indicating the presence of a thioether bond between Avry at XA and Suz at X9 in parentheses.

Table 4

Typical thioether peptide inhibitors

Biotin-IPEG4|Y-cycloABsh-OTUOSI-(PHe|(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-EMM-MH)" (ZEO 10 MO:1269

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

Guv(As)|-MM-MN" (ZEO 1Yu MO1270

As-KO)Ago|-cyclo (Aby OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyrani)-(Guv(Ac)|-MM-MH) » (ZEO 1O MO:1271

Table 4

Typical thioether peptide inhibitors

As-KO)Ago|-cyclo (Aby OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyrani)-(Suv(Ac)-MM-MH» (ZEO OO MO:1272

As-E-KO)Aga|-cyclo(Avshsh-O HUMOSI-(P pe(4-(2-aminoethoxy)|-(2-Ma-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1273

As-KO)A5riI-KO)Aga|-cycloCAbsch-OTUMOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyran)|i-EMM-MH»g (ZEO 1O MO:1274

As-B-KO)Aga|-cyclo(ABsh-OTUMOSI-(PHe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyran|i-EMM-MH) g (ZEO 1O MO:1275

As-KO)Aga|-KO)Ago|-cyclo((Avsh-O TU OSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyrani- EMM-MN" (ZEO 10 MO:1276

As-E-KO)Ago|-cycloAry|-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1277

As-KOB)RPpeI-KO)Ago|-cyclo(ABsh-O TU OSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4- carboxytetrahydropyran)|i-EMM - МН»г (ZEO 1О MO:1278

As-I2-MazC-KO)Ago|-cycloCaria-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1279

As-T-KO)Ago|-cycloHara|-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1280

As-I-KO)Ago|-cyclo(AbBa-OT OXY-(Rpe(4-(2-aminoethoxy)|-(2-Ma!/|-(4-amino-4-carboxytetrahydropyranIi-EMM-MH)) (ZEO 1O MO:1281

As-KO)a1p1-KO)Ago|-cyclo(AbBa-OTHUOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyran|i-EMM- MN»g (ZEO 1O MO:1282

As-KO)Av5pI-(O)Aga|-cycloCAbsh-OTUMOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) g (ZEO 1O MO:1283

As-cyclo(Arsh-O HUMOSI-(Rpe(4-(2-aminoethoxy)-(PEG4-Alecha488)|-(2-Ma||-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1284

IAIekha4881-(PEG4|-cycloAbsh-OTUMOSI-(P pe(4-(2-aminoethoxy)|--(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1285

IAIehab47|-(PEG4|-cyclo(ABsh-OTUMOSI-(P pe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|i-EMM-MH)) ZEO 1O MO:1286

IAIekha-6471-IPEG41-KO)Ago|-cyclo(ABsh-OTUMOSI-(P pe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyrani-P uz( As)-MM-MN»g (ZEO 10 MO:1287

IAIehab47|-(PEG121-KO)Ago|-cyclo(ABAI-OTUMOSI-(P pe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani)-(Suv(Ac )-MM-MN" (ZEO and MO:1288

IAIekha4881-(PEG41-KO)Ago|-cyclo(AraI-OTUMOSI-(Rpe(4-(2-aminoethoxy) |-(2-MaC-(4-amino-4- carboxytetrahydropyrani-(Suv(Ac)-MM- MN" (ZEO IU0 MO:1289

Table 5A

Typical thioether peptide inhibitors of the pekovyutyutnia angle

Ascyclo-TsAVNHYUZHX SI Rene OO Me o-Mmats-XXX KHAMN" (BEO 0 MOL414)

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMM-MN" (ZEO 10 MO:1290

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMME-MN" (ZEO IO MO: 11291

As-cyclo(AbBi|-O PM OSI-(RPe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

Table 5A

Typical thioether peptide inhibitors of eutuchnns. mercury contamination.

Ascyclo-TsAVN ХХ ХСН ОМен-а- map xxx ХАМН. (BEO 10 MOCH414)

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMK-MN" (ZEO 10 MO: 1293

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMM-MN" (ZEO 1O MO: 1294

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMMUU-MN" (ZEO IU MO: 1295

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMT-MN" (ZEO and MO:1296

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMO-MN" (ZEO 10 MO:1297

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMRK-MN" (ZEO 1О MO:1298

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMRO-MN" (ZEO 10 MO:1299

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMER-MN" (5EO IYU MO:1300

Ac-cyclo(Aby-O HMOSI-(PNe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani|-

EMMOK-MN" (ZEO 10 MO:1301

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMRT-MN" (ZEO IU MO:1302

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMO BE-MN" (ZEO 10 MO:1303

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSYMU-MN" (ZEO 10 MO:1304

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMOSO-MN" (ZEO IO MO:1305

Ac-cyclo|(AvschI-O HMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSYasOa-MN" (ZEO 10 MO:1306

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMKKK-MN" (ZEO 10 MO:1307

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMEEE-MN" (ZEO Ir MO:1308

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMEEE-MN" (ZEO IO MO:1309

As-cyclo(Arsh-O GTHUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma!|-I(4-amino-4-carboxytetrahydropyrani-

EMMTTT-MN" (ZEO and MO:1310

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSaSsOV-MN" (ZEO OO MO:1311

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSASSIAVR-MN" (ZEO 10 MO:1312

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMOASSYAEB-MN" (ZEO 1 MO:1313

Ac-cyclo(Aby-O HMOSI-(PNe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani|-

EMMOASSIVO-MN" (ZEO 1 MO:1314

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMOaSsOT-MN" (ZEO 10 MO:1315

Table 5A

Typical thioether peptide inhibitors of eutuchnns. mercury contamination.

Ascyclo-TsAVN ХХ ХСН ОМен-а- map xxx ХАМН. (BEO 10 MOCH414)

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSYasshasiA-MN" (ZEO 10 MO:1316

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSYSSSTE-MN" (ZEO 10 MO:1317

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSOaSsisSESSIE-MN" (ZEO 1 MO:1318

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMOASSYASIO-MN" (ZEO I MO:1319

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSOSsyASIT-MN" (ZEO IU MO:1320

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMANAVV-MN" (ZEO and MO:1321

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMSORRREB-MN" (ZEO 10 MO:1322

As-cycloGABSHSH-O HMOSI-(РНе(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMEEEEB-MN" (ZEO 1 MO:1323

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMOSOOS-MN" (ZEO 1O MO:1324

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMMTTTTT-MN" (ZEO IU MO:1325

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMM-MN" (ZEO 10 MO 1326

As-aasi-cyclo(Avsh-OgUmOCI-(Rpe(|(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1327

As-AAB-cyclo(Abia|-OTUMOSI-(Rpe(|(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1328

As-ERE-cyclo|(АБЯ-О TU ОСИ1-(РНе(4-(2-aminoethoxy)|-(2-Ма/!|-(4-amino-4-carboxytetrahydropyran|-

EMM-MN" (ZEO 10 MO: 1329

As-EEE-cycloD(АВХ-ОТХОСІ-(Рпе(|4-(2-aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyrani-

EMM-MN" (ZEO 10 MO:1330

As-000-cyclo(AbBsch-OTUMOSI-(Rpe(|(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyrani-EMM-MH)" (ZEO IO MO: 1331

As-TTT-cyclo|(ABYA-O TU OXY-(РНе(4-(2-aminoethoxy)|-(2-Ма/!|-(4-amino-4-carboxytetrahydropyran|-

EMM-MN" (ZEO 10 MO: 1332

As-na-cycloCAbBsh-OTUOSI-(Rpe|4-(2-aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyrani|-

EMM-MN" (ZEO 10 MO: 1333

As-Ba-cyclo||(ABSHI-O HMOSI-(P pe(4-(2-aminoethoxy) |-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani-

EMM-MN" (ZEO 10 MO: 1334

As-Es-cyclo(AbBa|-O TU OSI-(Rpe|(4-(2-aminoethoxy)|-(2-Ma-(4-amino-4-carboxytetrahydropyrani-

EMM-MN" (ZEO 10 MO:1335

As-da-cycloC(АВрч-О ГУУОСИ-(Р pe(4-(2-aminoethoxy)|-(2-Ma1|-(4-amino-4-carboxytetrahydropyran|-

EMM-MN" (ZEO 10 MO:1336

As-Ta-cyclo|(АБшШ-О ГМОСИ-(Р pe(4-(2-aminoethoxy)|-(2-Ма/|-(4-amino-4-carboxytetrahydropyrani-

EMM-MN" (ZEO 10 MO 1337

As-cyclo(GABSHSH-O HMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

Guv(Rait)|-MM-MN" (ZEO 10 MO:1338

As-cyclo(AbBi|-O PM OSI-(RPe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

Table 5A

Typical thioether peptide inhibitors of eutuchnns. mercury contamination.

Ascyclo-TsAVN ХХ ХСН ОМен-а- map xxx ХАМН. (BEO 10 MOCH414)

As-cyclo|(AB1I-O HMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

I uv(ivosti-Rait)|-MM-MN" (ZEO IO MO:1340

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

Guv(Aph-Rai!t)|Y-MM-MN" (ZEO 10 MO:1341

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

Guv(isosti-Aich-Rai!t)|-MM-MN" (ZEO 10 MO:1342

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

Guv(ivosti-AiNh-Rait)|-MM-MN" (ZEO 10 MO: 1343

IRa!t|-cycloAbBsch-OTUOSI-(Rpe|4-(2-aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyran|-

EMM-MN" (ZEO 10 MO: 1344

IRai!t-isosiic|-cyclo(Aby|-OTUMOSI-(P pe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4-carboxytetrahydropyran)|i-EMM-MH)) (ZEO 10 MO:1345

IRait-PEG11|-cycloHAbshsh-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO:1346

IRait-Anh|-cycloHyro-OTUMOSI-(P pe(4-(2-aminoethoxy)|-(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)) (ZEO 1O MO :1347

IRait-Anx-isosic|-cyclo(Ary|-OHUMOSI-(P pe(4-(2-aminoethoxy)|I-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH) g (ZEO 1O MO:1348

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMM-GuvG(Ra!t|-MN" (ZEO 10 MO:1349

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMM-Gu5z(PEG11-Ra!t|-MN»g (ZEO IU MO:1350

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMM-Guv(isoSty-Ra!t|-MN»g (ZEO 10 MO:1351

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMM-Guv (Ankh-Ra!t|-MN" (ZEO 1O MO:1352

As-cyclo(Aby-O GMOSI-(PHe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani-

EMM-I uv(isoSsti-Aich-Rait|-MN" (ZEO 10 MO:1353

Table 5B

Typical thioether peptides

As-I0-Agao|-cyclo-(Abi-ETHUMOSI-(Rpe(4-2ae)I-(2-MaC-I(Tetrahydropyran-AI-EMO-MH)" (ZEO 10

MO:1422

As-I0-Agao|-cyclo-(Abi-ETHUMOSI-(Rpe(4-2ae)I-(2-MaC-I(Tetrahydropyran-AI-EOM-MH)" (ZEO 10

MO:1424

Table 5B

Typical thioether peptides

Ac-10-Ago|-cyclo-(Abi-OTUMOSI-(Rpe(4-gae)|-(2-MaC-(Tetrahydropyran-AI-EUOM-MN)" (ZEO 10

MO:1426

As-IO-Ago|-cyclo-(Abi-ETHUMOSI-(Rpe(4-2ae)I-(2-MaC-(Tetrahydropyran-AI-EMM-OH) (ZEO 10

MO:1427

Typical Peptide Inhibitors Containing Cyclic Amides (00472) In some embodiments, the present invention includes a peptide inhibitor of the interleukin-23 receptor, wherein the peptide inhibitor has the structure of formula IM:

B'-X-B:2 (IM), (00473) or its pharmaceutically acceptable salt or solvate,

I00474| where EC" is a bond, hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl C1-C6 alkyl, C1-C20 alkanoyl, and including PEGylated variants alone or as spacers of any of the following; 00475 ) В? represents a bond, ОН or МН"; i

I00476| X is an amino acid sequence of 8-20 amino acids, containing or consisting of the sequence of the formula Ma:

X1-X2-X3-X4-X5-X6-M/-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (IMa) (ZEO Ir

MO; 1428),

I00477| where

X1 is absent or is any amino acid;

X2 is absent or is any amino acid;

ХЗ is absent or is any amino acid;

HA represents Var, bab, Sim, Avr, (0)-Azr or (0)-Oabr;

X5 is sSip, Aa, Su, Sii, A5r, bab, bar, Sim, Rpe, Su, Ni, pSuv, GI uv, I ei, Mei, Avp,

M-Me-AiIa, M-M-Avzp, M-Me-I uv, M-Me-Sip, M-Me-Ag9, Ot, Rgo, Rep, Sp, Agou, Zeg, Tig or Mai;

Xb is TNg, Ar, Sim, Rie, Avp, Rgo, Ago, beg or TNg;

X7 is Tgr, Sim, Su, Pe, Azp, Rgo, Ago, Tpg or Osisiu;

ХВ is sp, sim, Rpe, H uv, Azp, , Rgo, Agod, Tyg or Tgr;

ХУ represents Var, bab, spy, Avr, (0)-Azr or (0)-Oabr;

X10 is Tu(OMe)RPpe(4-OMe), 1-Mai, 2-Mai, Aiis, a-MeRne, Vir, (0)Suz, Sna, OMT, (B)Thuyu, Sim, Re, Niv, pPe(3,4-dimethoxy), pTug, M-Me-Tug, Ttr, Pne(4-SOMN"), Pne(4-phenoxy),

Tit, Tis, Tug, Tuk(Z3-Vy), Rpe(4-4Vy), Rpe(4-SM), Rpe(4-Vg), Ripe(4-MN»eg), RNe(4-E), РНе(3,5-Е"),

Rpe(penta-P), Rpe(3,4-SiIg), Rne(4-SEz), Vir, Spa, 4-pyridylalanine, VyTug, OsisIu, Rpe(4-Mz),

From Rpe(4-Hg) or Rpe|4-(2-aminoethoxy))|;

X11 is 2-Mai, 1-Mai, 2,4-dimethylRpNe, Vir, Rpe(3,4-Sig), Rpe(3,5-Eg), Rpe(4-SOMH),

Rpe(4-P), 4-phenylcyclohexylalanine, Rpe(4-SEz), a-MeRpe, VyRpe, VyTug, VyTgr, VIR, Mma(5-phenyl), Rye, Nich, pRpe, Tis, Tda, Tgr, Tug , Rpe(4-OMe), RNe(4-Me), Ttri(2,5,7-tri-tert-butyl),

Rpe(4-Oalyl), Tug(3-IVy), Rpe(4-Vy), Rpe(4-guanidino), Tu(B2y) or Osisiu;

X12 is a-MeHuz, a-MeOt, a-Meg! Yey, Air, (0)Aia, (0)Avzp, (0) em, (0)Avr, (C)RNe, (0)Tpg, 3-Rai, Aib, B-AIa, D-SIM, VpAia, Vp ei, rpMai, V-spiro-pip, Spa, Spo, Azr, ab, Var, a- dietiloiu, SIM, Re, p ei, pAgo, p ei, Pe, G uv, Hey, Azp, M-Mei vy , M-MeAg9, Od, Opt, Rgo, Sp,

Aha, 5eg, Tig Te, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, a-diethylOiu, a-

MegG uz, o-MegHuz(As), a-Me-G em, o-Mezeg, a-Memai;

X13 is I ub(As), (0) Azp, (0) ei, (0) Pg, (SOR Pe, Aipa, Aib, o-Me! ei, AiYIBb, B-AIa, VD-STY,

VpAia, Vp ei, ryMai, p-spiro-pip, Spa, Spo, Ar, bar, Bar, a-diethyliu, sii, Rpe, Pec, Huz,

Guz(As), I em, Azp, Od, Rgo, Sip, Ago, 5eg, V-spiro-pip, Tpg, Tra, Tis, Ma! or Tug;

X14 is Avzp, SiImts, Rpe, su, Niv, I ub, em, Mei, Azp, Rgo, Sp, Ago, Zeg, TAg, Tis or

TU;

X15 is p-aia, Avp, Spu, (0)Aia, (0)Avp, (0)Azr, (0) ей, (0)РНе, (0) ТНг, Ага, AEA, Авр,

Sim, Riye, Su, Guz, I em, Rgo, Sp, Agud or 5eg;

X16 is absent, Su, AIa, A5r, 5eg, Rgo, Azp or TNg;

X17 absent, Sim, beg, SiIu or Sp;

X18 is absent or is any amino acid;

X19 is absent or is any amino acid; and

X20 is absent or is any amino acid. (00478) In some embodiments of IM: X12 is a-MeH uz, o-MeOgt, a-Mei! hey

AB, (0)Aya, (0)Azp, (B ei, (0)Avr, (0)РНе, (0)ТНг, 3-Рай, АиЙБ, В-Ая, В-СИм, ВпАпа, Вп ей, VyMai, p- spiro-pip, Spa, Spo, Azr, rab, Var, a-dietyloOiu, Sim, Rie, p em, pAgo, Pi ey, Pe, Guz, Gay, Avp, M-

Mei Yei, M-MeAg9, Oai, Opt, Rgo, Sip, Agu, Zeg, Tig or Ti; ХИЗ3 is ГГ уз(Ас), (0)А5п, (0) ей, (С)ТНг, (0)Ре, Аа, АЙБб, а-Ме! ей, АЙБ, В-Аиия, D-Сим, Впаия, Вп ей, ВыМай, В-spiro-pip, Spa,

Spo, Azr, bab, bar, a-diethyloiu, Sim, Rie, p ecG uv, I em, Azp, Oddi, Rgo, Sp, Ago, zeg, B-spiro-pip,

Tig, Tra, Tis, MaiYi or Tug; X14 represents Avzp, Sim, Re, Su, Niv, I uv, I ei, Mei, Avp, Rgo, Sp,

Agod, Zeg, TNg, Tis or Tug; and X15 represents su, (F)Aia, (0)Avp, (0)A5p, (0) ei, ()P Pe, (C)TNg,

Aa, AEA, Avr, Spi, Rpe, Spu, I uv, I ey, Rgo, Sp, Aga or 5eg. 00479) In specific embodiments of the peptide inhibitor of the formula (IM): X5 is Suh, Sii, A5p, Oab, bar, Su, Ni5, pSuv, Huz, Mei, Azp, M-Me-Aia, M-Me-Avp, M-Me-G University, M-

Me-aip, M-Me-Ago, Opt, Rgo, Rep, Sip, Mai; Hb represents hay, Ago, Zeg; X7 is Ttgr, Sim,

Su, Pe, Azp, Rgo, Agud, Tig or OsisSiu; Hv represents Re, Avzp, Rgo, Ago, TPg, Tgr; X10 is Rpe(4-OMe), 1-Mai, 2-Mai, Ais, o-MeRne, Vir, (0)Suz, Sna, OMT, (0)Tug, Sim, Niv, pRNe(3,4- dimethoxy), pThug, M-Me-Thug, Ttr, Rpe(4-SOMH»g), Ripe-(4-phenoxy), TNg, Tis, Thug(3-4Vy), Rpe(4-IVy),

Rpe(4-SM), Ripe(4-VI), Rpe(4-MN»g), Rpe(4-E), Ripe(3,5-E2), RnesSnSoO»nH, Ripe(penta-E), Rne(3,4-Si"),

Rpe(4-SEz), Vir, Spa, 4-pyridylalanine, VyTug, OxidsiIu, Tugp(4-Mz), Pne(4-B), Pne(4-(2-aminoethoxy))Y; X11 is 2-Mai, 1-MaiI, 2,4-dimethylRie, Vir, Rpe(3,4-SiIg), RHne(3,5-Eg),

Rpe(4-SOMN"), Rie(4-E), 4-phenylcyclohexyl, Rpe(4-SEz), o-MeRpe, Mai, VyRpe, VpyTug, VAyTgr,

HIV, Mma(5-phenyl), Rpe, Nix5, pRpe, Thys, Tda, Tug, Rpe(4-OMe), Rpe(4-Me), Tup2,5,7-tri-tert-butyl), Rpe( 4-Oalyl), Rpe(3-y1Vy), Rpe(4-yIVy), Rnpe(4-guanidino), Tug(B2yI), Osisu; X12 is a-Me-Huz, O-Aya, (0) Azp, (0) Azr, (0) ei, (0) P Pe, (0) Hug, Air, a-MeH em, o-MeOgpp, Aib, V-Aia, VpAa,

VpAgo, VP em, VyMai, V-spiro-pip, Sim, pAgo, Pe, Guz, M-Mei ey, M-MeAg9, Od, Ot, Rgo, Sip, Be",

TNg, TiIe, 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asbs, Asms, a-diethyliu, a-MeiH uz(As), a-

Mezegh, a-Memai; Х13 represents I uv, I ub(As), (0)Azp, (С) ей, (0)РПе, (С)ТНг, Aia, а-Me! hey air

V-Aia, V-SiIy, Vp ei, VyMai, V-spiro-pip, Spa, Spo, Azr, bab, Var, s-dietilou, pPG em, Azp, Od, Rgo,

Sp, Zeg, TAg, Tra, Tiye; X14 represents sim, SU, Niv, I uv, em, Mei, Azp, Rgo, Sp, Ago, Zeg, TNg,

Yew; X15 is (B) Aia, (0) Azp, (0) A5p, (0) ei, ()P pe, (0) TNg, Aea, Avr, Sim, Rne, Su, Huz,

And em, Rgo, Azp, Agd or rV-AIa; X16 represents su, 5eg, Rgo, Azp, TYg; or Х17 is sSiIy, zeg, SPu, Sp. 00480) In specific embodiments of the peptide inhibitor of the formula (IM): X5 is Suh, Sii, Az5r, bab, ar, Stpu, Ni5, pSuv, Guv, Mei, Azp, M-Me-Aia, M-Me-Avzp, M-Me-Guv, M-

Me-a1p, M-Me-Ago, Ot, Rgo, Rep, Sip, Mai; Hb represents hay, Agou, Zeg; X7 is Tgr, SIM,

Su, Pe, Azp, Rgo, Agud, Tig or OsisSiu; Hv represents Re, Avzp, Rgo, Ago, TPg, Tgr; X10 is Rpe(4-OMe), 1-Mai, 2-Mai, Ais, o-MeRne, Vir, (0)Suz, Sna, OMT, (0)Tug, Sim, Niv, pRNe(3,4- dimethoxy), pTug, M-Me-Tug, Ttr, Rpe(4-SOMH»g), Ripe-(4-phenoxy), TNg, Tis, Thug(3-4Vy), Rpe(4-IVy),

Rpe(4-SM), Ripe(4-VI), Rpe(4-MN»g), Rpe(4-E), Ripe(3,5-E2), RnesSnSoO»nH, Ripe(penta-E), Rne(3,4-Si"),

Rpe(4-SEz), Vir, Spa, 4-pyridylalanine, VyTug, OxidsiIu, Tugp(4-Mz), Pne(4-B), Pne(4-(2-aminoethoxy))Y; X11 is 2-Mai, 1-MaiI, 2,4-dimethylRie, Vir, Rpe(3,4-SiIg), RHne(3,5-Eg),

Rpe(4-SOMN"), Rie(4-E), 4-phenylcyclohexyl, Rpe(4-SEz), o-MeRpe, Mai, VyRpe, VpyTug, VAyTgr,

HIV, Mma(5-phenyl), Rpe, Nix5, pRpe, Thys, Tda, Tug, Rpe(4-OMe), Rpe(4-Me), Tup2,5,7-tri-tert-butyl), Rpe( 4-Oalyl), Rpe(3-y1Vy), Rpe(4-yIVy), Rnpe(4-guanidino), Tug(B2yI), Osisu; X12 is a-Me-Huz, O-Aya, (0) Azp, (0) Azr, (0) ei, (0) P Pe, (0) Hug, Air, a-MeH em, o-MeOgpp, Aib, V-Aia, VpAa,

VpAgo, VP em, VyMai, V-spiro-pip, Sim, pAgo, Pe, Guz, M-Mei ey, M-MeAg9, Od, Ot, Rgo, Sip, Be",

ТНг, Te; X1I3 is I uz(As), ()A5p, (0) ei, (SOR Pe, (C)TNg, Aa, a-Meg! ei, AIB, B-AiIa, B-C1y,

VAGei, VyMai, p-spiro-pip, Spa, Spo, Azr, bab, Var, a-diethyloisu, PI ey, Azp, OO, Rgo, Sp, zeg, TNg,

Tva, TiIe; X14 represents Sim, Su, Ni, G uv, I em, Mei, Azp, Rgo, Sp, Agu, Zeg, TAg, Tis; X15 represents

BO itself (0)APa, (0)Azp, (0)Azr, (B) ей, (0)РНе, (0)ТНг, Avea, Avr, Sim, Rpeye, spu, Гув, I ей, Ро, Ahu;

X16 represents su, Zeg, Rgo, Azp, TAg; or X17 is sim, beg, su, Sp.

I00481| In some embodiments, the peptide inhibitor is cyclized. In specific embodiments, the peptide is cyclized using an intramolecular bond between

X4 and XU. In specific embodiments, the intramolecular bond is an amide bond. (00482) In some embodiments, the peptide inhibitor is linear or non-cyclized.

I00483| In specific embodiments of the peptide inhibitor of formula IM, one or more, two or more, or all three of X1, X2, and X3 are absent. (00484). itself (F)Agu or (0)RPe.

I00485| In specific embodiments of the peptide inhibitor of formula IM, one or more, two or more, or all three of X17, X19, and X20 are absent. (00486) In specific variants of the implementation of the peptide inhibitor of the formula IM X4 is

Bar, slave, or (S)raBb, and X9 represents Sim, (0)A5r, or Azr. In specific embodiments of the peptide inhibitor of formula I, X4 represents Sim, (0)A5p or Ar, and XU represents ab,

Bar or (0)rar.

I00487| In specific variants of the implementation of the peptide inhibitor of the formula IM X18 is an (0)-Ig bond. In some embodiments, X17 is absent, and X18 is (0)-I uv.

I00488| In specific embodiments of the peptide inhibitor of the formula IM, the peptide inhibitor contains one or more, two or more, three or more, or all four of the following features: X5 is Sip; Xb is TPg; X7 is Tr; and X8 is a sip.

I00489| In specific embodiments of the peptide inhibitor of the formula IM, the peptide inhibitor contains 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 Tug, Рппец|4 -(2-aminoethoxy)|, Rpe(4-SOMH») or Rpe(4-OMEe); X11 is 2-May or Tgr; X12 is 4-amino-4-carboxytetrahydropyran, Asps, Asrs, Asrs, Asms, Alib, a-diethylOiu, o-MeGuv, a-

Me" uz(As), a-Me-I em, o-MeOt, o-Mezeg, a-Memai or Agu; X13 represents Siy or I ub(As); X14 represents Avp; X15 represents Su, Ap or pD-Aia; and X16 is AEA. In specific embodiments of the peptide inhibitor of formula IM, the peptide inhibitor contains one or more, two or more, three or more, four or more, five or more, six or more, or seven of of the following signs: X10 is Tug, X11 is Tgr, X12 is Ago;

X13 is Sy; X14 is Aup; X15 is a su; and X16 is an AEA.

IІ00490| In specific embodiments of the peptide inhibitor of formula IM, the peptide inhibitor contains 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 signs: X5 is a Sip; Xb is TPg; X7 is Tr;

X8 is Sp; X10 is Tug; X11 is Tgr; X12 is Ago; X13 is seven or HH ubz(Ac); X14 is Aup; X15 is a su; and X1b6 represents itself

AEA. In specific embodiments, the peptide inhibitor of formula IM is a peptide inhibitor

Co) contains 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 signs: X5 is a Sip; Xb is Tpg; X7 is Tgr; X8 is Sip; X10 is Tug; X11 is Ttgr; X12 is Ago; X13 is a

Seven; X14 is Avzp; X15 is Su; and X16b6 is AEA.

IІ00491| In some embodiments of the peptide inhibitor of formula IM, the peptide is cyclized with XA and X9; X5, Xb, X7 and Xv represent cSip, TPg, Tgr and SiIp, respectively; and Х10, Х11, Х12, Х13, Х14, Х15 and Х1І6b are Tug, Tgtr, Ago, Sim, Abp, Siu and ABEA, respectively. 00492) In some embodiments, the present invention includes a peptide of 8-20 amino acids, optionally cyclized, comprising or consisting of the main sequence:

Khaad4-Khaa5-Khaab-Ttr-Khaav8-Khaa9-IRpe(4-OMe)|- (2-Mai| (IMB formula) (ZEO IYU MO 1429), 00493) where each of Khaa4 and Khaa9 is independently selected from Var, slave , Sim, Ar, (0)-Avzr apa(0)-

Bar, and Khaa4 and Khaa9 are able to form an intramolecular bond, for example, a cyclic amide; and Khaab5, Khaab and Khaav represent any amino acid residue, and the peptide inhibits the binding of 1-23 to II-23K. In specific variants, the peptide inhibitor is a peptide inhibitor of formula IM. In specific embodiments, the peptide inhibits the binding of II-23 to I-23NA. (00494) In some embodiments of the peptide inhibitor of formula IM, the peptide inhibitor has the structure shown in Table 7 or contains the amino acid sequence shown in Table 7. 00495) Some typical peptide inhibitors of the present invention are also shown in any of the formulas (ma) , (MB), (ms), (Ma), (me), (MO, (M9) and (MI) and in Tables 2-5 providing the amino acid sequence of selected peptide inhibitors. These peptide inhibitors are acetate salts.

Optional features of peptide inhibitors

I00496| Any of the peptide inhibitors of this invention can be further defined, for example, as described below. It is clear that each of the additional defined features described herein can be applied to any of the peptide inhibitors where the amino acids designated in specific positions ensure the presence of the additional defined feature. because I00497| In some embodiments of any of the peptide inhibitors described herein, the peptide inhibitor is cyclized. (00498) In some embodiments of any of the peptide inhibitors described herein, the peptide inhibitor or its monomer subunit is linear or noncyclized. In some embodiments, where the peptide is linear or non-cyclized, XA and XU can be any amino acid.

I00499| In some embodiments, the peptide inhibitor is cyclized, for example, with XA and X9. 00500) In various embodiments, B' is a bond, hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl, C1-C6 alkyl, or C1-C20 alkanoyl, and including PEGylated variants alone or as spacers of any --th of the above, for example, acetyl. It is clear that K' can replace or be present in addition to the typical amino group located at the amino-terminus of the peptide. It is also clear that K' may be absent. In some embodiments, the peptide inhibitor comprises an M-terminus selected from hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl, C1-C6 alkyl, or C1-C20 alkanoyl, including PEGylated variants alone or as spacers of any which of the above, for example, acetyl. In specific embodiments of any of the peptide inhibitors described herein, the B' or M-terminal moiety is hydrogen. In some embodiments, B' is a bond, e.g., a covalent bond. 00501) In some in embodiments of any of the peptide inhibitors having any of the various formulas specified herein, the B' or M-terminal moiety is selected from methyl, acetyl, formyl, benzoyl, trifluoroacetyl, isovaleryl, isobutyryl, octanyl, and con' of conjugated amides of lauric acid, hexadecanoic acid, and y-Si-hexadecanoic acid. In one embodiment, K!' or the M-terminal moiety is rum. In some embodiments, K" is hydrogen. In specific embodiments, K' is acetyl and the peptide inhibitor is acylated at its M-terminus, e.g., to cap or protect an amino acid residue at the M-terminus, e.g., a Rep or Aby residue at

M-ends. 00502) In some embodiments of any of the peptide inhibitors described herein, the B' or M-terminal fragment is an acid. In some embodiments, the EC or M-terminal moiety is an acid selected from acetic acid, formic acid,

From benzoic acid, trifluoroacetic acid, isovaleric acid, isobutyric acid, octanoic acid, lauric acid, hexadecanoic acid, 4-biphenylacetic acid, 4-fluorophenylacetic 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, A-methylbicyclo( 2.2.2)-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, laurylsulphuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid acid, alkylsulfonic acid and arylsulfonic acid.

Y00503| In specific embodiments, the B' or M-terminal fragment is an alkylsulfonic acid selected from methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, and 2-hydroxyethanesulfonic acid.

Y00504| In specific embodiments, the K' or M-terminal fragment is an arylsulfonic acid selected from benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid and camphorsulfonic acid. 00505) In some embodiments, where a peptide of the present invention contains a conjugation with an acidic compound, such as, for example, isovaleric acid, isobutyric acid, valeric acid, and the like, the presence of such conjugation is indicated in the acidic form. Thus, for example, but without limitation in any way, instead of indicating the conjugation of isovaleric acid to a peptide by reference to isovaleroyl (eg, isovaleroyl-

IRepI-OTMO((RepiI-I(Rpe(4-OMe)1I-(2-MaPC-(a-Me!uziI-(Huz(As)|-MaE-MNa (ZEBEO IU MO:262)), in some versions) the implementation of this application refers to such a conjugation as isovaleric acid-IRep|I-OTMOGRep1-IRpe(4-OMe)|-(2-MaC-(o-MeHGusiI-(Suv(Ac)|-MOa-MNa) 5EBEO 10 MO:262).

Reference to the conjugation in its acid form is intended to include the form present in the peptide inhibitor. 00506) In some embodiments, the peptide inhibitor comprises a C-terminus (eg, B?60 or a C-terminal fragment) selected from a bond, OH, or MH. In some embodiments, implementation 2 is a bond. In various embodiments of any of the peptide inhibitors having any of the various formulas specified herein, B? or the C-terminal fragment is OH or MH". It is clear that V? or the C-terminal fragment may replace or be present in addition to the carboxyl group typically located at the carboxy-terminus of the peptide. It is also clear that V? may be absent.

IІ00507| In specific embodiments of any of the peptide inhibitors having any of the various formulas specified herein, X contains or consists of 7-35 amino acid residues, 8-35 amino acid residues, 9-35 amino acid residues, 10- 35 amino acid residues, 7-25 amino acid residues, 8-25 amino acid residues, 9-25 amino acid residues, 10-25 amino acid residues, 7-20 amino acid residues, 8-20 amino acid residues, 9-20 amino acid residues, 7-18 amino acid residues residues, 8-18 amino acid residues, 9-18 amino acid residues or 10-18 amino acid residues. 00508) In some embodiments of any of the formulas specified herein, any or both Xs do not contain or do not consist of the amino acid sequence specified in US patent application publication Me0052013/0029907. In some embodiments of any of the formulas specified herein, any or both of the X's do not contain or do not consist of the amino acid sequence specified in patent application publication MegO52013/0172272. 00509) In some embodiments of any of the peptide inhibitors described herein, the peptide inhibitor or each monomer subunit thereof contains or consists of at least 3, at least 4, at least 5, at least b, or at least 7 amino acid residues from the carboxy-end of the XO amino acid residue. In specific embodiments of any of the peptide inhibitors described herein, the peptide inhibitor comprises 3-11, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4 , 3, 4,5,6, 7,8, 9, 10 or 11 amino acid residues from the carboxy-terminus of the X9 amino acid residue. 00510) In some embodiments of any of the peptide inhibitors described herein, the peptide inhibitor or each monomer subunit thereof contains or consists of 4 amino acid residues between XA and XO. In one embodiment, both XA and

CH are cysteines. 00511) In some embodiments, a peptide inhibitor of any of the formulas described herein comprises amino acid residues or fragments designated as X4-X15. In specific embodiments, the peptide inhibitor does not contain X1I-X3 or X16-X20. In some embodiments, the peptide inhibitors contain an M-terminal extension of one to three amino acid residues corresponding to any of X1-X3. In specific embodiments, any one or more of X1, X2, and X3, if present, is a 10-amino acid. In some embodiments, the peptide inhibitors contain a C-terminal extension of one to five amino acid residues corresponding to any of X16-X20. In specific embodiments, any one or more of X16, X17, X18, X19, and X20, if present, is a Y-amino acid. Typical amino acid residues that may be present in the M-terminal and/or C-terminal extensions are shown in Tables 3 and 5. Each of these tables shows first the peptide inhibitor, with its derivatives containing the M-terminal extension, the C-terminal extension end and/or conjugated fragments. The present invention includes derivatives of any of the peptide inhibitors described herein containing one or more of the following M-terminal extensions, C-terminal extensions and/or conjugated fragment. In some embodiments, any of the amino acid residues shown in the extended position in Tables 3 and 5 may be present in any combination in the peptide inhibitor of the present invention. In specific embodiments, the lengthening of the M-terminus or the lengthening of the C-terminus is associated with an increased half-life, for example, upon administration to a subject. 00512) In some embodiments of any of the peptide inhibitors described herein, the peptide the inhibitor or each of its monomeric subunits contains a motif

BO of the amino acid sequence, M/-X-X-U-M/ (ZEO IU MO:1430), for example, in positions X7-X11.

In some embodiments, the peptide inhibitor or each of its monomeric subunits contains the motif of the amino acid sequence C-X-X-M/-X-C-y-MM (5EO IU MO:1431), for example, in positions X4-X11. In some embodiments, the peptide inhibitor or each of its monomeric subunits contains the motif of the amino acid sequence Rep-xX-X-M/-X-Rep-U-M/ (ZEO I MO:1432), for example, in positions X4-X11. In some embodiments of any of the peptide inhibitors described herein, the peptide inhibitor or both of its monomeric subunits do not contain the amino acid sequence motif, MU-X-X-U-MU (5EO Ir

MO:1430), for example, in positions X7-X11, where X is any amino acid.

Y00513| In some embodiments of any of the formulas or peptide inhibitors described herein, the peptide inhibitor comprises one or more amino acid residues at the M-terminus to X4. In specific embodiments, the HZ is present. In some embodiments, the XZ is Sim, (O)C1y, Ago, (0)Ago, RHe, (0)RHe, 2-May, Tng, Hei, or (C)SiP. In some embodiments, the XZ is (O)Agd or (C)Rpe. 00514) In specific embodiments of any of the formulas or peptide inhibitors described herein, the peptide inhibitor comprises an amino acid at X2. In specific embodiments, X2 is Sim, (O)A5p, Ago, (0)Ago, Rpe, (O)Ppe, 2-Ma, TNg, Ie, (0)SiP, or (O)Ax5p. In some embodiments, X2 and X3 are present. In specific embodiments, X2 is Sim, (0)A5p, Aga, (0)Ago, Rpe, (0)Ppe, 2-Mai, TNg, Iem, (0)SiIp or (0)A5, and XZ is (0)Aha. 00515) In some embodiments, the peptide inhibitor of the present invention or one or both of its monomeric subunits optionally contains at its C-terminus one of the following amino acid sequences:

EMO;

EMM;

I4-amino-4-carboxytetrahydropyran|-EMM (ZEO 10 MO:1433); (Uz(As)|-MM; (o-Me!H uz|I-EMOa (ZEO 1O MO:1434); (o-Me! uzi- (uv(As)-MM (ZEO IYU MO 1435); ( o-Me! 5EO IYUO MO:1438);

AIIB-(Guz(As)|-Ma (5EO 10 MO:1440);

AIB-(Huz(As)|-MM (ZEO IU MO:1441);

Ma-(IAEAY-KO)-H in (ZEO IU MO:1442);

ISara|-Ma-IAEAII-KO)-I uz) (ZEO IYU MO:1443);

IYut!|-Ma-(AEAYI-KO)-G uz) (ZEO I1YU MO: 1444); (o-Mei! uz|-EMM (ZEO I MO 1445);

I4-amino-4-carboxytetrahydropyrani- (uz(Ac)|-MM (ZEO I MO:1446);

Koo) IAspsiI-(Huz(As)|-MM (5EO 1O MO:1447) or

IAsrei-(Guz(As)|-MM (5EO 1O MO:1448).

IІ00516| In specific embodiments, one of these amino acid sequences constitutes the C-terminal amino acids of the peptide. In a specific embodiment, these amino acid sequences correspond to X13-X15, or X12-X15, or X14-X16, or X13-X17. 00517) In some embodiments, the peptide inhibitor of the present invention or one or both of its monomeric subunits optionally contains at its C-terminus one of the following amino acid sequences:

MOSU-(2-MaC-(o-Me!uzi) (ZEO IU MO:1449);

МОС-ИРНне(4-ОМе)|-(2-МаЦС-(о-МегГ уз| (ZEO 10 МО:1450) М ОС-|Рпе(4-ОМе)|-(2-МаЦС-(АииВИ) (ZEO)

IO MO:1451);

MO-(RepiI--(Pne(4-OMe)|I-(2-MapC-(c-Me/ uz)| (ZEO IU MO:1452);

M/-Xa8-C-RHne(|(4-(2-aminoethoxy))| -(2-MaiC (ZEO IU MO:1453);

M/-Xa8-C-RHne(|(4-(2-aminoethoxy))-1-MaiC (ZEO IU MO:1454);

M/-Xa8-C-RNpe(|4-(2-aminoethoxy)| (ZEO IU MO:1455) or 00518) M/-Xa8-C-IRne(4-OSN")Y (ZEO IU MO:1456) . In specific embodiments, one of these amino acid sequences constitutes the C-terminal amino acids of the peptide. In a specific embodiment, these amino acid sequences correspond to X7-X12, or X7-X11, or X7-

Xx10. 00519) In some embodiments of any of the peptide inhibitors described herein, including both peptide monomeric inhibitors and monomeric subunits of peptide dimer inhibitors, the peptide monomeric inhibitor or monomeric subunit is cyclized via a peptide bond between its M-terminal amino acid residue and its C-terminal amino acid residue. In specific embodiments, the peptide inhibitor (or its monomer subunit) contains as an intramolecular bond between XA and

ХУ, and the peptide bond between its M-terminal amino acid residue and its C-terminal amino acid residue. In some embodiments, the intramolecular bond is any of those described herein, for example, a disulfide bond or a thioether bond.

IІ00520| In some embodiments, the present invention includes a peptide inhibitor that contains a core consensus sequence selected from one of the following (shown from the M-terminus to the C-terminus):

X1-X2-X3-Rep-X5-X6-Mu/-X8-Rep-X10-X11-X12-X13-X14-X15 (ZEO and MO:1457);

Rep-X5-X6-Mu-O-Rep (ZEO IU MO 1458);

Rep-X5-X6-Mu-X8-Rep (ZEO IU MO:1459);

Rep-X5-X6-Mu-X8-Rep-IRpe(4-SOMNag)) (ZEO I MO:1460) and

Rep-X5-X6-Mu-X8-Rep-|Rpe(|(4-(2-aminoethoxy))) (ZEO IU MO:1461), where Rep residues connected by an intramolecular bond, for example, disulfide bond. X1, X2, X3, X5, Xb, X8, X10, X11, X12, X13, X14 and X15 can be any amino acid. In some embodiments, X5 is Ago, Azp, SiIp, Yuar, Op; Xb is TPg or beg; and X8 represents sp, MaiY, Rpe, Sim, Sub. In specific embodiments, X1, X2, X3, X5, Xb, X8, X10, X11, X12, X13, X14, and X15 are defined as described in any of the various formulas and peptide inhibitors described herein.

IІ00521| In some embodiments, the present invention includes a peptide inhibitor that comprises a core consensus sequence selected from one of the following (shown from the M-terminus to the C-terminus):

X1-X2-X3-Ary-Xx5-X6-Mu-X8-0-X9-X10-X11-X12-X13-X14-X15 (5EO IU MO:1462);

Ary-X5-X6-Mu/-0-6 (5EO IU MO:1463);

Ary-X5-X6-Mu-X8-0 (5EO IU MO:1464);

Ary-X5-X6-Mu-X8-0-IRpe(4-SOMNH)Y (ZEO IU MO 1465) and

Ary-X5-X6-Mu-X8-0-|РНе|4-(2-aminoethoxy)|| (ZEO IO MO:1466), where Aby and C are connected by an intramolecular thioether bond. X1, X2, X3Z,

X5, Xb, X8, X10, X11, X12, X13, X14 and X15 can be any amino acid. In a specific embodiment, X5 is Ago, Avp, Sip, Yuar, Ogp; Xb is Tpg or 5eg; and X8 represents sp, Mai, Rpe, Sim, Huz. In specific implementation variants of X1, X2, X3, X5, Xb, X8,

X10, X11, X12, X13, X14 and X15 are defined as described in any of the various formulas and peptide inhibitors described herein. (00522) In some embodiments, any of the peptide inhibitors described herein may be further cyclized via a peptide bond between its M-terminal amino acid residue and its C-terminal amino acid residue. In specific embodiments, the peptide inhibitor comprises a peptide bond between X3 or XA and any one of XO, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19 or X20. In specific embodiments, the peptide inhibitors of this invention contain a peptide bond between their M-terminal and C-terminal amino acid residues, and they also contain an intramolecular bond between X4 and XU. In some embodiments, the intramolecular bond is a disulfide bond, a thioether bond, a lactam bond, or any of the other bonds described herein.

Peptide dimers

I00523| In some embodiments, the present invention includes dimers of monomeric peptide inhibitors described herein, including dimers of any of the monomeric peptide inhibitors described herein or in the accompanying tables, figures, or sequence listing. These dimers are within the scope of the general term "peptide inhibitors" as used herein. Typical dimers of the present invention are also shown in the accompanying tables, which show the dimerized monomer subunits in parentheses after the linker. Unless otherwise indicated, sub-elements are linked by their C-termini. The term "dimer" as in peptide dimer refers to compounds in which two peptide monomer subunits are linked. The peptide dimeric inhibitor of this invention may contain two identical monomeric subunits, giving a homodimer, or two non-identical monomeric subunits, giving a heterodimer. A cysteine dimer contains two peptide monomer subunits linked by a disulfide bond between a cysteine residue in one monomer subunit and a cysteine residue in another monomer subunit. 00524) In some embodiments, the peptide inhibitors of this invention may be active in a chimeric conformation, particularly when free cysteine residues are present in the peptide. In some embodiments, it occurs either as a synthesized dimer or, in particular, when a free cysteine monomeric peptide is present, and under oxic conditions it dimerizes. In some embodiments, the dimer is a homodimer. In other embodiments, the dimer is a heterodimer. 00525) In some embodiments, the peptide dimer inhibitor of the present invention is a peptide dimer comprising two peptide inhibitors of the present invention, including, but not limited to, a homodimer or heterodimer comprising any of the peptide

Ge) sequences shown in this document, for example, in tables ZA-ZN, 4A, 4B, BA-5C, 6,

7,8,9,10, 11, 12, 13, 14 or 15. 00526) Some amino acid sequences shown in tables ZA-ZN, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11 , 12, 13, 14, or 15 are indicated by single-letter amino acid codes. Where only the sequences of monomeric peptide inhibitors are shown; however, it is understood that in some embodiments, these monomeric peptide inhibitors, i.e., monomeric subunits, are dimerized to form peptide dimeric inhibitors in accordance with the concepts of the present invention and as shown generally, for example, in Tables 3A-3, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

I00527| In some embodiments, the monomeric subunits of the present invention can be dimerized with a suitable linker moiety, for example, a disulfide bridge between two cysteine residues, one in each peptide monomeric subunit, or with another suitable linker moiety, including but not limited to defined in this document. Some of the monomer subunits are shown as having C- and M-termini, both of which contain a free amine. Thus, to obtain a peptide dimeric inhibitor, the monomeric subunit can be modified to exclude the free amine of either the C- or M-terminus, while allowing dimerization on the remaining free amine. In addition, in some cases, the end of one or more monomer subunits is adylated with an acylating organic compound selected from the group consisting of: trifluoropentyl, acetyl, octonyl, butyl, pentyl, hexyl, palmityl, trifluoromethylbutyrate, cyclopentanecarbonate, cyclopropylacetate, 4-fluorobenzoic, /4-fluorophenylacetic, 3-phenylpropionic, tetrahydro-2H-pyran-4-carboxylic acid, succinic acid and glutaric acid. In some cases, the monomer subunits contain both a free carboxy terminus and a free amino terminus, whereby the user can selectively modify the subunit to obtain dimerization at the desired terminus. One of ordinary skill in the art will thus appreciate that the monomer subunits of the present invention can be selectively modified to produce a single, specific amine for the desired dimerization.

I00528| It is also understood that the residues at the C-terminus of the monomer subunits disclosed herein are not necessarily amides. In addition, it is understood that in some embodiments, dimerization at the C-terminus is facilitated by an appropriate

From an amino acid with a side chain having an amine functional group, as is commonly understood in the art. With respect to M-terminal residues, it is generally understood that dimerization can be achieved with the free amine of the terminal residue, or can be achieved with the corresponding amino acid side chain having a free amine, as is generally understood in the art.

I00529| The linker fragments that connect the monomer subunits can have any structure, length and/or size compatible with the ideas of this document. In at least one embodiment, the linker fragment is selected from the non-limiting group containing linkers based on cysteine, lysine, BIS, PEG4, PEG4-biotin, PEG1IZ3, PEG25, PEGIK, PEG2K, PEGZ.AK,

PEGA4K, PEG5OK, ISA, ABA, Bos-IBA, glutaric acid, isophthalic acid, 1,3-phenylenediacetic acid, 1,4-phenylenediacetic acid, 1,2-phenylenediacetic acid, triazine, Bos-triazine, ISA-biotin, PEG4 -biotin, AABA, corresponding aliphatic, aromatic, heteroaromatic compounds and polyethylene glycol with a molecular weight of about 400 Da to about 40,000 Da. Non-limiting examples of suitable linker fragments are shown in Table 2A.

Table 2A

Typical linker fragments about

EF iv) o o polyethylene glycol elements o o Evil o

I Y I o c) polyethylene glycol elements and pe zvo o

Table 2A

Typical linker fragments

The structure of

Bifunctional PEG-linker with 25 pEG25 polyethylene glycol elements А vich ions in

Bifunctional PEG linker with

PEGIK polyethylene glycol with a molecular weight of 1000 Da

Bifunctional PEG linker with

PEG2K polyethylene glycol with a molecular weight of 2000 Da

Bifunctional PEG linker with

PEGZ.4K with polyethylene glycol with a molecular weight of 3400 Da

Bifunctional PEG linker with

PEGOK with polyethylene glycol with a molecular weight of 5000 Da

B-Aia-ISA /|D-Aia-iminodiacetic acid MOL o- o s a y- s:

Vos-V-Aia-Isa| Bos-rB-AIa-iminodiacetic acid o Z k o i o

With o o o

As-V-Aga-IVA | As-D-Aia-iminodiacetic acid Momshi o , o

IOA-B'-Aa:- Palmityl-Br-AIa-iminodiacetic acid WHAT

Wright and

This is a o o atA Glutaric acid rorchu in o o

Table 2A

Typical linker fragments

The structure of O

РМА Pemiltic acid ХА АХ o 0 o o o

AHA Azelaic acid rpulray o o (9)

IRA Isophthalic acid: o o 1,3-POA /|1,3-phenylenediacetic acid 0, o so) o OO 14A-POA 1,4-phenylenediacetic acid (lo o o 12-POA /|1,2-phenylenediacetic acid acid z, o o o /

M M where n-

Triazine Aminopropyl triazine diacid m-X /Y n-th

M us o o o o

Le and

M-

Vos-triazine | Vos-triazindic acid k- schi

Kk

M u c)

Aminodiacetic acid o o (which can also be called iminodiacetic acid

ArA acid) i

Table 2A

Typical linker fragments

Abbreviation Description Structure n-Acetylaminoacetic acid o

AAOA (which can also be called M- o 5 o acetyliminodiacetic acid) is present. PEGA-biotin (product number 10199 iy ?

PEGA-biotin tin (E r of the product ' NOT a

OmapiavioOezidp) still AH ; ' muy and Vo about NN Z ; i Ki V z on vu Z

IOA-biotin | M-biotin-B-AIa-iminodiacetic acid With y, about 5-0 on

YUM

. he

Guz Lysin vit (5)

IІ00530| In some embodiments, the peptide dimeric inhibitor is dimerized with a linker fragment. In some embodiments, the peptide dimeric inhibitor is dimerized by an intramolecular disulfide bond formed between two cysteine residues, one in each monomer subunit. In some embodiments, the peptide dimeric inhibitor is dimerized using both a fragment linker and an intramolecular disulfide bond formed between two cysteine residues. In some embodiments, the intramolecular bond is a thioether, lactam, triazole, selenoether, diselenide, or olefin bond instead of a disulfide bond. 00531) A typical diagram of one embodiment of the dimer is shown below:

Compound Y 0)

Oh Me MN" e)

Gee) but. o MH" o -- (o) Ge) C (e) MH" eye MH 8 (o)

Mn

NM

8-- -8sh-Z 5-26 62 stitches. l -.l yshm,' with (0; m e) c) and o chn

Ge) Mne MN" (o, o) no. Mne o n o n o n o n o n o n o

NM M M M M M M

(c) (9) o fo (c) (9) Mne on; Mn 8 (o) nm in-- - - - 6 - - 3 - 6Ж-Z -2 --in8 in (in)

(00532) One skilled in the art will understand that linker fragments (eg, a linker on C- and

M-ends) disclosed herein are non-limiting examples of suitable ones, and that the present invention may include any suitable linker fragment. Thus, some embodiments of the present invention comprise a homo- or heterodimeric peptide inhibitor consisting of two monomeric subunits selected from the peptides shown in any of the tables herein or containing or consisting of the sequence presented in any of tables of this document, where the C- or M-ends of the corresponding monomer subunits (or internal amino acid residues) are connected by any appropriate linker fragment to form a chimeric peptide inhibitor with activity to inhibit II/-23K. In some embodiments, the linker binds to the M- or C-terminus of one monomer subunit and an internal amino acid residue of another monomer subunit, forming a dimer. In some embodiments, the linker binds to an internal amino acid residue of one monomer subunit and an internal amino acid residue of another monomer subunit, forming a dimer. In additional embodiments, the linker is linked to M- or

C-terminus of both subunits. 00533) In specific embodiments, the peptide inhibitor of this invention contains two or more polypeptide sequences of the monomeric peptide inhibitors described herein. (00534) In one embodiment, the peptide dimeric inhibitor of the present invention contains two peptide monomer subunits connected by one or more linker fragments, and each peptide monomer subunit contains or consists of 7-35 amino acid residues, 8-35 amino acid residues , 9-35 amino acid residues, 10-35 amino acid residues, 7-25 amino acid residues, 8-25 amino acid residues, 9-25 amino acid residues, 10-25 amino acid residues, 7-20 amino acid residues, 8-20 amino acid residues, 9 -20 amino acid residues, 7-18 amino acid residues, 8-18 amino acid residues, 9-18 amino acid residues or 10-18 amino acid residues and contains the sequence of formula Ia as described herein. 00535) In specific embodiments, one or both of the monomer subunits contain a sequence of any one of the formulas: formula X, formula Y, II, IP, IM or M, as described herein. 00536) In some embodiments, the peptide dimeric inhibitor comprises two peptide monomer subunits connected by one or more linker fragments, where each peptide monomer subunit is 8-20 amino acids in length and contains the sequence of any one of the formulas described in this document, for example, formula X, formula I, II, PI, IM, or M. In some embodiments, the peptide dimeric inhibitor comprises two peptide monomer subunits connected by one or more linker fragments, where each peptide monomer subunit has 8-20 amino acids in length and contains the sequence of any one of formula X, formula I, II, PI, IM or M.

I00537| In some embodiments, the peptide dimer inhibitor has the structure of Formula

MI: (8'-X-A2)2-I. (MI), 00538) or a pharmaceutically acceptable salt or solvate thereof,

IІ00539| where each K' is independently absent, represents a bond (eg, a covalent bond), or K' is selected from hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl, C1-C6 alkyl,

C1-C20 alkanoyl, and includes PEGylated variants alone or as spacers of any of the above;

І00540| every VN? independently absent, is a bond (for example, a covalent bond) or selected from OH or MH"; 00541) And is a linker fragment; and

I00542| each X is an independently selected peptide monomer subunit containing or consisting of 7-35 amino acid residues, 8-35 amino acid residues, 9-35 amino acid residues, 10-35 amino acid residues, 7-25 amino acid residues, 8-25 amino acid residues , 9-25 amino acid residues, 10-25 amino acid residues, 7-20 amino acid residues, 8-20 amino acid residues, 9-20 amino acid residues, 7-18 amino acid residues, 8-18 amino acid residues, 9-18 amino acid residues or 10 - 18 amino acid residues in length, each containing or consisting of the sequence of formula Ia as described herein. In specific embodiments, each peptide monomer subunit contains or consists of a sequence of the formula Ih, Pa, IB,

Is, Ta, Te, IE, 19, IN, Ii, y, IK, 1i, Tt, Ty, Io, Ir, Id, Id", Iv, I, Pa, Pr, Ps, Pa, Sha, ShB, Shs , Sha, She, IMa, IM 60 or Ma-My as described in this document.

00543) In some embodiments, one or both peptide monomer subunits of the peptide dimeric inhibitor are cyclized, for example, by means of an intramolecular bond between X4 and XU. In some embodiments, where both peptide monomer subunits are cyclized, the intramolecular bond may be the same or different in the two peptide monomer subunits. In some embodiments, one or both intramolecular bonds are a disulfide bond, a thioether bond, a lactam bond, a selenoether bond, a diselenide bond, or an olefinic bond.

I00544| In one embodiment, X4 and XO of one or two cyclized peptide monomer subunits are independently selected from Sub, Rep, pSukh, Y-Rep, YO-Sub, and O-pSukh, and the intramolecular bond is a disulfide bond.

I00545)| In one embodiment, X4 and XO of one or two cyclized peptide monomer subunits are independently selected from Sim, Avr, Gu, Ogp, Yuar, bab, O-Oar, O0-raj, p-

Ar, O-Cys and OB-H bonds, and the intramolecular bond is a lactam bond.

I00546| In one embodiment, each of X4 and XO of one or two cyclized peptide monomeric subunits is independently selected from B-azido-Aia-OH, propargylglycine, and the peptide dimer inhibitor is cyclized using a triazole ring. In one embodiment, each of X4 and XO of one or two cyclized peptide monomer subunits is independently selected from 2-allylglycine, 2-(3'-butenyl)glycine, 2-(4-pentenyl)glycine, 2-(5'-hexenyl) uglycine, and the peptide dimer inhibitor is cyclized using a ring-closing reaction to obtain the corresponding olefins / "cross-linked peptides".

I00547| In one embodiment, X4 of one or two cyclized peptide monomer subunits is 2-chloromethylbenzoic acid, mercaptopropanoic acid, mercaptobutyric acid, 2-chloroacetic acid, 3-chloropropanoic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid, or p5eg(SiI), ХУ of one or two cyclized peptide monomer subunits is p5eg(Si), Su, Rep, pSuz, O-Rep, O-Suz or p-

Su, and the intramolecular bond is a thioether bond.

I00548| In one embodiment, X4 of one or two cyclized peptide monomer subunits is 2-chloromethylbenzoic acid, 2-chloroacetic acid, 3-

C chloropropanoic acid, 4-chlorobutyric acid, C-chloroisobutyric acid, p5eg(Si) or Zes, X9 of one or two cyclized peptide monomer subunits is pZeg(SiI) or ec, and the intramolecular bond is a selenoether bond. 00549) In some embodiments, one or both intramolecular bonds represent a diselenide bond. 00550) In some embodiments, one or both of the peptide monomer subunits are linear or noncyclized.

І00551| In specific embodiments of the peptide dimeric inhibitors, each X7 and each X11 is a MU. In some embodiments, each X7 and each X11 is a MU, each X10 is a Y, and each of X4 and XO is a C. In some embodiments, each X7 and each X11 is a MU, each X10 is a Y, and each HA and

ХУ is an amino acid capable of forming an intramolecular bond, which is a thioether bond, a lactam bond, a triazole, a selenoether bond, a diselenide bond, or an olefin bond. 00552) In some embodiments of peptide dimeric inhibitors, one or both of the peptide monomer subunits have a structure shown herein, e.g., in Tables ZA-3I, or contain an amino acid sequence shown herein, e.g., as indicated in Tables ZA-3I , or where the peptide dimer inhibitor has the structure shown herein, for example in Table 3E, or contains the amino acid sequence shown in this document, for example as shown in Table 3E.

Y00553| In specific embodiments, each K' is independently a bond (e.g., a covalent bond) or selected from hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl, C1-C6b alkyl, C1-C20 alkanoyl, and including PEGylated variants alone or as spacers of any of the above. In specific embodiments, the M-terminus of each subunit includes a moiety selected from hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl,

C1-C6 alkyl, C1-C20 alkanoyl, and including PEGylated variants alone or as spacers of any of the above. 00554) In some embodiments of any of the peptide inhibitors having any of the various formulas specified herein, each K' (or M-terminal fragment) is selected from methyl, acetyl, formyl, benzoyl, trifluoroacetyl, isovaleryl , isobutyryl, octanyl, and 60 conjugated amides of lauric acid, hexadecanoic acid, and y-Si-hexadecanoic acid. 00555) In specific embodiments, each HB: (or C-terminal fragment) independently represents a bond (eg, a covalent bond), or is selected from OH or MH." 00556) In specific embodiments, any of the peptide inhibitors having any of the various formulas specified herein, each X contains or consists of 7-35 amino acid residues, 8-35 amino acid residues, 9-35 amino acid residues , 10-35 amino acid residues, 7-25 amino acid residues, 8-25 amino acid residues, 9-25 amino acid residues, 10-25 amino acid residues, 7-18 amino acid residues, 8-18 amino acid residues, 9-18 amino acid residues or 10 -18 amino acid residues.

I00557| In specific embodiments, one or both of X contains or consists of a sequence of any one of the formulas described herein. In some embodiments of any of the peptide inhibitors, including dimers, or formulas specified herein, X does not contain or consist of the amino acid sequence specified in US patent application publication MegO52013/0029907. In some embodiments of any of the peptide inhibitors, including dimers, or formulas specified herein, X does not contain or does not consist of the amino acid sequence specified in patent application publication MeO52013/0172272.

I(00558| In specific embodiments of the peptide inhibitors of this invention (both monomers and dimers) containing Su5 in the XA position and Su5 in the XO position, Sub in the position

XA and Suz in position X9 are connected by a disulfide bridge. 005591 In specific embodiments of the peptide inhibitors of this invention, each X7 and each X11 are not MU. 00560) In specific embodiments of the peptide inhibitors of this invention, each X7 and each X11 is a MU.

I0O561| In specific embodiments of the peptide inhibitors of this invention, each X7 and each X11 is MU, X10 is Y, and both X4 and XO are C.

I00562| In some embodiments, at least two cysteine residues of the peptide dimeric inhibitor are linked by a disulfide bridge or intramolecular or intermolecular bridge.

Zo 00563) In specific embodiments of any or both monomer subunits (for example, Ix, Ia-Yi, where permitted), found in a peptide dimeric inhibitor, both X4 and XU are Suv. 00564) In specific embodiments of any or both of the monomeric subunits (eg, Ix, Ia-Y, where permitted) found in the peptide dimeric inhibitor, both X7 and X11 are MUs. 00565) In specific embodiments of any or both of the monomeric subunits (e.g., Ia-YiY, where permitted) found in a peptide dimeric inhibitor such as X7, such

X11 is MU, X10 is "U, and both XA and XU are Sub. 00566) In specific embodiments, any or both of the monomer subunits (eg, Ia-Ii, where permitted) located in the peptide in a dimeric inhibitor, X15 is Su or Zeg. 00567) In specific embodiments of any or both monomer subunits (eg, Ia-Ii, where permitted) found in a peptide dimeric inhibitor, X1b6 is AEA or AEP. 00568) In specific embodiments, any or both of the monomeric subunits (eg, Ia-Ii, where permitted) found in a peptide dimeric inhibitor, WHICH is Tug or Ppe or an analog of Tug or Re. 00569) In specific embodiments of any or both monomer subunits (for example, Ia-Ii, where allowed) found in the peptide dimer inhibitor, X11 is Ttgr.

IІ00570| In specific embodiments of any of the peptide dimer inhibitors described herein, one or both EC! are hydrogen. 00571) In specific embodiments of the peptide dimer inhibitors of this invention, the linker fragment, () is any of the linkers described herein or shown in Table 2A or 2B. In some embodiments, I is a lysine linker, a diethylene glycol linker, a linker based on iminodiacetic acid (ICA), a linker based on B-AlIa-iminodiacetic acid (B-AlIa-ICA), or a PEG linker. 005721 In various embodiments of any of the peptide dimeric inhibitors, each of the peptide monomer subunits is attached to the linker fragment by means of its M- or C-terminus or an internal amino acid residue.

00573) In some embodiments of any of the peptide dimer inhibitors, the M-end of each peptide monomer subunit is connected by a linker fragment. 00574) In some embodiments of any of the peptide dimer inhibitors, the C-terminus of each peptide monomer subunit is connected by a linker fragment. 00575) In some embodiments of any of the peptide dimeric inhibitors, each peptide monomer subunit is connected by a linker fragment attached to an internal amino acid.

I00576| In some embodiments of peptide dimer inhibitors, the linker fragment is a diethylene glycol linker, a linker based on iminodiacetic acid (ICA), a linker based on B-AIa-iminodiacetic acid (B-AIa-ICA), or a PEG linker.

IІ00577| In some embodiments of the peptide dimeric inhibitors, one or both peptide monomer subunits have the structure shown in any of the tables in the examples or contain the amino acid sequence shown in any of the tables in the examples.

І00578| In some embodiments of any of the peptide inhibitors, including dimers, or formulas specified herein, X does not contain or consist of the amino acid sequence specified in US patent application publication MeO052013/0029907. In some embodiments of any of the peptide inhibitors, including dimers, or formulas specified herein, X does not contain or consist of the amino acid sequence specified in US patent application publication MegO52013/0172272. 005791 In specific embodiments of the peptide inhibitors of the present invention, each X7 and each X11 is MU, X10 is Y, and both X4 and XO are Rep.

In some embodiments, at least two cysteine residues of the peptide dimeric inhibitor are linked by a disulfide bridge or intramolecular or intermolecular bridge.

Peptide Inhibitor Conjugates and Biopolymers 00580) In some embodiments, the peptide inhibitors of this invention, including both monomers and dimers, contain one or more conjugated chemical substituents, such as lipophilic substituents, and polymeric moieties that may be referred to herein documents with fragments that extend the half-life period. Without being bound by any specific one

In theory, the lipophilic substituent is believed to bind to albumin in the bloodstream, thereby protecting the peptide inhibitor from enzymatic degradation, and thus increasing its half-life. In addition, polymer fragments are believed to increase half-life and decrease clearance in the bloodstream. 00581) In additional embodiments, any of the peptide inhibitors, for example, peptides of formulas (Ma)-(MII), additionally contain a linker fragment attached to an amino acid residue present in the inhibitor, for example, the linker fragment can be linked with the side chain of any amino acid of the peptide inhibitor, with the M-terminal amino acid of the peptide inhibitor or with the C-terminal amino acid of the peptide inhibitor. 00582) In additional embodiments, any of the peptide inhibitors, e.g., peptides of formulas (Ma)-(MI), further comprise a half-life-prolonging moiety attached to an amino acid residue present in the inhibitor, e.g., a half-life-prolonging moiety half-life, can be connected to the side chain of any amino acid of the peptide inhibitor, to the M-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, for example, peptides of the formulas (Ma)-(MI), additionally contain a half-life-extending fragment attached to a linker fragment that is attached to an amino acid residue present in the inhibitor, for example, a fragment extending the half-life can be connected to a linker fragment that is connected to the side chain of any amino acid of a peptide inhibitor, to the M-terminal amino acid of a peptide inhibitor, or to the C-terminal amino acid of a peptide inhibitor. n-0-24 00584) In specific embodiments, the analogue of I./2Z3K contains a half-life-extending fragment with the structure shown below, where n-:0-24 or n-14-24: vya n-e0-24

KOVO hesn, son, MN ON 3 eh Z o . 00585) In some embodiments, the II 23K analog of the present invention comprises a half-life extending fragment shown in Table 7.

Table 7

Typical half-life-prolonging fragments

Me | 11111 Fragments extending the half-life.:.-/:/ ////:Z: a

Stra pe a to Ku cha

Si12i (Lauric acid o

C14 (MPrysteinov knslotai o sZ ra

Sib (Palm or palmitic acid) f:

Sa la aa a a o a more -

SIV (Stearic acid! 6)

С5 ря/юУ У У У

C20 o

Н СИ12 (dinoic acid) o

C7 is heavier than СІ14 (diacid) and is heavier than Sbdiacids

Table 7

Typical half-life-prolonging fragments

Me | Fragments that extend the half-life of SIV (diacid) o por y | HELL

Its SO (butaneic acid)

I00586| In some embodiments, the half-life-prolonging moiety is linked directly to the peptide inhibitor, while in other embodiments, the half-life-prolonging moiety is linked to the peptide inhibitor via a linker moiety, e.g., any of shown in tables 6 or 8. 00587

Table 8

Typical linker fragments

Me 17777771 Fragment link.7//://:65С:(://СС (in)

M

"-

And r ka dream

IvoSly

MN"

M

AND

I2 o shi

Rara - vk oh M

From Nn

Ah iv)

Lipid linkers:

DI var. cook

I4 from her a n- 1-24

Table 8

Typical linker fragments me | 77777711 Frapmentlinnkvr../.7./:/:/./.:/:/.:.: g: - o 7 t they

IB N o RESI

N tr pera le a o RES2 zh o i

M. and named Tit l

Ge) n-11

PEG11 (40 atoms), also known as PEG12

From "Gi: I. zh" In p. 1-25

Linkers based on PEG shr ra rchu , and OEO (6)

N

My entire river

IiO N dream |);

IvoSITy-Aibh son of Fr

Z o M (9) and

RO M ma a kit

N

111 | AND

IboC1-OEO-OEO

Table 8

Typical linker fragments

Me 17777771 Fragment link.7//://:65С:(://С (е)

M (c) o) o ra t B burned i ik 2 son o

IvoSip-REO5 (o)

Nrya Mo)sia and M

Driving - 125 hours per day

IvoSPSH-RESp (in; (o) 14 years, m o M

N N

VAIA-REO2

Iv. 19. - that in U kt o. i ry 15 -- V "y ge t ; Shsh-- hSh

No!

VAIV-AVEST1 (40 atoms)

I00588| In specific embodiments, a peptide inhibitor of the present invention comprises any of the linker moieties shown in Table 8 and any of the half-life extending moieties shown in Table 7, including any of the following combinations shown in Table 89a.

Table ba

Typical combinations of linker and half-life-prolonging moieties in peptide inhibitors

Fragment that Fragment that Fragment that

Linker extends the half-life Linker extends the half-life Linker extends the half-life half-life half-life

Table ba

Typical combinations of linker fragments and half-life-extending fragments in peptide inhibitors ee |do |lee «dor le «sin

Linker extends the half-life Linker extends the half-life Linker extends the half-life half-life half-life

AND THEN ED

Linker extends the period Linker extends the period Linker extends the period half-life half-life half-life ee | oh lee bosu le |NKOKh

Linker extends the half-life Linker extends the half-life Linker extends the half-life half-life half-life

Fragment that Fragment that Fragment that

Linker extends the period Linker extends the period Linker extends the period half-life half-life half-life 00589) In some embodiments, multiple linkers can be present between the peptide and the conjugated fragment, for example, a fragment that extends the half-life, for example, as depicted in Table 9p.

Table 9r0

Typical combinations of linker fragments and half-life prolonging fragments in peptide inhibitors

Fragment that Fragment that lengthens

Linker prolongs the period Linker rap , tsu d U and half-life half-life 1-2 1-2

I2-15-I3 I2-15-IZ (3-18 3-18

И1-12-13 И1-12-И3 15-13-1-3-1-3 и5-3--3-13 00590) Typical examples of peptide inhibitors of this invention, including those having linker conjugates and/or of the half-life-extending fragment are shown below. All amino acids are I-amino acids, unless otherwise indicated. The present invention also includes salt forms of any of these peptide inhibitors, including, but not limited to, their acetate salts. Oh. MN" Ge)

MN Mne o) i Go) d (o) o 9) (o! uv. (o)

N N N N

M M M M

M M M M To me

N u N N y oyi. MN (c) (c) (e) (in 5 NM

MN F no7 Zo n on M (in) MN r: o o. us" co

Example 1: Cyclo|(AbBsh-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyran|I-EMM-MH)" (ZEO 10 MO:1290)

about MN Go)

MN Mn" o

N N N N

M M M M

M M M M Mn» n u n n y oh. MN o (c) (c) (c) 8 nom t d y i

MN F no7 Zo n on M o MN (c) o r: Z nom" o MN

Nm MA sha nu

Example La: /Ac-MCO)-Ago|-cyclo|(AbBssch-OTUMOSI-(P pe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyran)|- EMM-MN" (ZEO 10 MO 1415)

Mn» o, their Fe Mne o and o (c) (c) (c) (o)

N N N no

M M M Oh. MN O v (v (o) o Mne shko (I !

She eats at 8

N on M MNAs (c) MN yiv. oh oh (in)

Example 2: Ac-IRepI-"MTUMO-(RepI-I(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyrani-(H uv(Ac)I- MM-MN" (ZEO IO MO:1185)

Fragment that

Btosrvave peri reapaveotvata

She young Z a CHI Se. I'm Not Yet : / HE ; and MN

KT ST y "shk ! vok y z Z o b o o what M M se MS Ж ХК. Ж et Ж Же y. A. "M kim ne m GT I chni I still sovav Y I shk sht 8 naya t " vk n G S i na" ge y M s she SCHI "Mn:

I be oh nimbus bo

Example 3: CycloGAbBssh-OTUOSI1-IRNe|(4-(2-aminoethoxy)-(linker-fragment extending the half-life) 1|-(2-Ma1!|-(4-amino-4-carboxytetrahydropyran|i-EMM) -MN" (ZEO OO MO:1467)

A fragment of half-dissolved dreams

S. rent sh y

Su when in | mno and m ksh; In St. Kk "M. a re and u ze, Z i

Zh. that in Tros Su Zh

In M n N I de. MN ge. a shi a : В т вн Г to nebo shchi ЧА МИ шх в; those "jan Z sk pnya Iv na o ik tv

Beh she a cha tyu ne

Example For: As-MCO)-Ago| amino-4-carboxytetrahydropyran|-EMM-MHg (5EO 10

MO:1468) » y 5 eh ze Ey spro: s - se VI y ge zh s a u o X, o n ! n N

ХХ щу ХА А, t M T M Y i: M v yo ssh. YAN from B. still about ; hey

I | and nya re | | It's yours. not the lion of them Ev. ry " s and Fragment. Still half-rosyalt

And on

Example 4: Cyclo|(AbBsh-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4- carboxytetrahydropyrani-I-uh) (linker-fragment that extends the half-life)) |-MM-MN" (ZEO IU MO:1469)

ШЧи pa шчи ОО. "MM and Kv

S che DI SCHE O Mn," and shk: in NO: A oo still m

N. V. K. n

Ass la MN O dy shi and CHO: SHY no

ON. M i: and TI Pinkev E a she

S І Repair, BIO date: extends the period of non-arbitrary recognition

Mm hi z w she shcha

No

Example 4a: Ac-(0)-Ago|-cyclo|(AbBshsh-OTUMOSI-(P pe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4-carboxytetrahydropyrani-I) -uh (linker-fragment that extends the half-life)

Gu-nn Sho j? nn" G

KE и A и сх Й No " g Й v о v Й | 2 and as і і -- M;

UA AK. Even AH zhi I

OA ee MN IZ same zda same E s, she ov E . And | yo, y 7 kg pe sh shiya shk "vy h y vi o

Example 5: Cyclo|(AbBsch-OTUMOSI-(Rpe(4-(2-aminoethoxy) |-(2-Ma|-(4-amino-4- carboxytetrahydropyrani-EMM-I)(Suv(linker-fragment extending the period half-life)|-МН»2 (5EO IO MO:14713)

sfrodement, pa lengthens pero i ojj y r y t ia sei T DT "o I y

IA STA STA j shk t y syam nya k svinn "Ya v T Y i CHE p: YN" VDry vo. y ra Od sho tek y ko In sven sha shchi would be on I» and uch

Example ba: AsCO)-Ag9|-cyclo((ABshI-O HMOSI-(P He(4-(2-aminoethoxy)|-(2-Ma|-(4-amino-4- carboxytetrahydropyrani-EMM-I) (linker-fragment extending the half-life)|-МН»2 (5EOIIU MO: 1472)

Me

I. gu, se. МН р ши | ih i - z - a chto be 8 I Z y e ol v

С С, this is l Ж DAH on Ж Ж A and gr vish shoesh be. MM o o Shi s o She N m she she she sha y h (S -ey | neba y shi y che y - o x - . Document, by

Yalishker G extends the perigee

Example 6: A half-life-prolonging fragment-linkerI-(cyclo(Arshsh-OTUOSI1-

IRpe(4-(2-aminoethoxy)|-(2-Ma1|-(4-amino-4-carboxytetrahydropyran|i-EMM-MH)" (ZEO IU MO 1473)

sht Y i i Se "kn z Y iya reve shk kn

Kk t ST o» iy y in shkh o g Z wd ( | a g z ov ko A S S y AJ ron y Zh. r: M. A pon V. Zh t sor u rogo ytru b y U ny e a y ke | de 1 va |" bno shk mn i a x IR na a V t shk

In! von Ko | catches the period

Example ba: |Fragment that extends the half-life period-linkerI-K0)-Ag91I-Icyclo|HAbc|-

OTMOSI-(Rpe(|(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|i-EMM-MNa) (5EO 10

MO 1474)

G

En ya schu shik h ia p ia sk she still yo s G o Z od Z o G b" o nak t - And i same what. t ZK. z AK d, po. MN y o y o y Z y o i

OZashii vh pory t nan Y p sh | and - CHI: I And oh he mm! g che

ON rat i INas still shi shk ze nan. ooo ut, bryapeent, that iy tp 4 Linkev p

Example 7: |Fragment extending the half-life-linker|-IRepI-M PM O-(RepiI-IRNne(4-(aminoethoxy)|-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani-(H) uz(As))-MM-MN" (ZEO IU MO 1475)

"ragment, which reshukhuvovye ktevi vEaKivtOZshalu

Gu kv zi i sia chn penya fi | and shk: M 2 d) y z g o I Z a me a A y Do o M MI dzhe mV Zh y A. A kov M. AJ What: MNH

M Y I S SH I I in I Bi

I M m M V ge

Fe I MN g" Still c) still still And Gk "mny Z t Oh I ti t vn t still Y t 9 "still 1. | Mnas we nn still and

Example 8: Ac-IRepI-"MTUMO-|RepiI-(Rpe(4-(aminoethoxy)|-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani-(H uv(Ac)|-MM-( Huz (linker-fragment that prolongs the half-life)|-МНе (ZEO IYU MO:1476) вкятЕВ ron тн) mn pri ol chne: o. i | o i o o o o Z o mya o

E |. o m p : n et g

Yes, MN with. ch o ho ; Not chn -B yet. o no MnAye he uya mn te

What about us?

Example 9: As-IRepI-MPUO-|RepiI-IRne(4-(aminoethoxy)-(linker-fragment extending the half-life)|-(2-Ma(|-(4-amino-4-carboxytetrahydropyrani-( uz (As)|-MM-MNa. (5EO Ir

MO:1477)

Mn z Ye Ol MN Ye nn, or else: soya uch

And oh oh oh oh

LJ ND is | HOW и и и : IF

Oz. MM about вх ГК -ш -х about МН; and B! | What and with. |Eragment, nko

ОН ей В.

MM, about " I a

Example 10: As-IRepI-«MTUMO-|RepyI-(Rpe(4-(aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyrani-I-uh) (linker-fragment extending the period half-life) 1|-MM-MH" (ZEO I MO:1478). 00591) In some embodiments, the half-life of the peptide inhibitor of the present invention, which includes a conjugated chemical substituent, i.e., a fragment extending the half-life, is at least 10095, at least 12095, at least 150 95, at least 20095, at least 25095, at least 30095, at least 40095, or at least 500 95 half-life of the same peptide inhibitor but without a conjugated chemical substituent In some embodiments, lipophilic substituents and/or polymer fragments increase permeability of the peptide inhibitor through the epithelium and/or retention in the lamina propria of the mucous membrane In some embodiments, the permeability through the epithelium and/or retention in the lamina propria of the peptide inhibitor of the present invention, which includes is a conjugated chemical substituent, is 100 95, at least 12095, at least 150 95, at least 200 95, at least 250 95, at least 300 95, at least 40095, or at least 50095 of the half-life of the same peptide inhibitor, but without a conjugated chemical substituent . 00592) In one embodiment, the side chain of one or more amino acid residues (for example, Guz residues) in the peptide inhibitor of this invention is conjugated (for example, covalently attached) to a lipophilic substituent. The lipophilic substituent may be covalently bound to an atom in the side chain of the amino acid, or alternatively may be conjugated to the side chain of the amino acid by means of one or more spacers. A spacer, if present, may provide distance between the peptide analog and the lipophilic substituent. In specific embodiments, the peptide inhibitor contains any of the conjugated fragments shown in Tables 2-5. 00593) In some embodiments, the lipophilic substituent may contain a hydrocarbon chain with 4-30 C atoms, for example, at least 8 or 12 C atoms, and preferably 24 C atoms or less, or 20 C atoms or less. A hydrocarbon chain can be

Z is linear or branched and can be saturated or unsaturated. In some embodiments, the hydrocarbon chain is substituted with a moiety that forms part of the attachment to the amino acid side chain or spacer, such as an acyl group, a sulfonyl group, an M atom, an O atom, or a 5 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.

I00594| The lipophilic substituent can be conjugated to any side chain of the amino acid in the peptide inhibitor of this invention. In some embodiments, the side chain of the amino acid contains a carboxy, hydroxyl, thiol, amide, or amine group to form a complex ether, complex sulfonylether, complex thioether, amide, or sulfonamide with a spacer or lipophilic substituent. For example, a lipophilic substituent can be conjugated to Avp, Ar, Sim, Sp, Nivb, Gu, Ago, Zeg, TAg, Tug, Tgtr, Su5 or Yuri, Org or Ot. In some embodiments, the lipophilic substituent is conjugated to Huz. An amino acid shown as uh in any of the formulas specified herein may be replaced by, for example, OBy, Org, or Op, where a lipophilic substituent is added.

I00595| In some embodiments, the peptide inhibitors of this invention can be modified, for example, to increase stability, increase permeability, or increase medicinal properties, by conjugation of a chemical fragment with one or more amino acid side chains in the peptide. For example, M(epsilon) lysine M(epsilon),

VPcarboxyl of aspartic acid or γHcarboxyl of glutamic acid can be functionalized accordingly. Thus, to obtain a modified peptide, the amino acid in the peptide can be modified accordingly. In addition, in some cases, the side chain is acylated with an ading organic compound selected from the group consisting of: trifluoropentyl, acetyl, octonyl, butyl, pentyl, hexyl, palmityl, trifluoromethylbutyric, cyclopentanecarboxylic, cyclopropylacetic, 4-fluorobenzoic, 4-fluorophenylacetic, 3 -phenylpropionic, tetrahydro-2H-pyran-4-carboxylic acid, succinic acid, glutaric acid or bile acids. One skilled in the art will appreciate that a number of conjugates can be joined, for example, PEGA, isodimes and combinations thereof. One skilled in the art will appreciate that an amino acid with a peptide can be isosterically substituted, for example, Guh can be replaced by

Bar, bab, o-MeG uh or Ogp. Examples of modified residues in the peptide are shown in Table 18.

Table 18

Examples of modified lysine, A5p and Azp in peptide c) (c) no no 14 on on

NOM NM

) (is)

Me-I uv(As) Me-I uv(Rai!t) (in) n Ge! N ni r nos o 14 o 14 sleep on on

NhM NM o O me uv-ivosish-Ra

Me-II uz-datasiy-Rait t uz-zosits-gat o N o c son

M on on

HNM:

NhM 0 Me-I U(RES2-As) 2 is) Me-Huv(RESA4-isoSiIc-Rai!t)

Her M i m, Z

Nm oi chi vm 5 at 14 th V! in

He;. Roar!

Nam i o o me-I uB(RES)5-Rait M oiled knelotya!

Table 18

Examples of modified lysine, A5p and Azp in the peptide sv:

Mo he not ooo r I her

JSC am. H OM o o

M uz (glutaric acid) M uziroglutarov knelot)

E vi y: Huh

With t Be

Y Y | In Nm shi S an ON ni vo

C (c)

M oenozoic acid) Me-Huv(MA)

M y / 4779 nm

Y r

And | at

And I am HIM

Y S and NM HER

M HER SH

And about | LErgI 4 liaminobutane)

M Euyoctanoic acid! b a che A i 5, r not y

A ul uch g ni g GK i z M poshi, MN i i natr Y on Z iz KY . OO

In additional embodiments of the present invention, alternatively or additionally, the side chain of one or more amino acid residues in the peptide inhibitor of the present invention is conjugated to a polymeric moiety, for example, to increase solubility and/or half-life ip mimo (eg in plasma), and/or bioavailability. Such modifications are also known to reduce clearance (eg, renal clearance) of therapeutic proteins and peptides.

I00597| As used herein, "polyethylene glycol" or "PEG" is a polyether compound of the general formula H-(O-CH2-CH2g)p-OH. PEGs are also known as polyethylene oxides (PEOs) or polyoxyethylenes (POEs), depending on their molecular weight

REO, REE or ROS as used herein refers to an ethylene oxide oligomer or polymer. The three names are chemical synonyms, but PEG generally refers to oligomers or polymers with a molecular weight below 20,000 Da, REO to polymers with a molecular weight above 20,000 Da, and ROE to a polymer of any molecular weight. PEG and REO are liquids or solids with low melting points, depending on their molecular weight. In this description, Z names are used interchangeably. PEGs are obtained by polymerization of ethylene oxide, and they are commercially available in a wide range of molecular weights from 300 Da to 10,000,000 Da. Although PEGs and REOs with different molecular weights find use in different applications, and have different physical properties (eg, density) due to the effect of chain length, their chemical properties are approximately identical. The polymer fragment is preferably water-soluble (amphiphilic or hydrophilic), non-toxic and pharmaceutically inert. Suitable polymer fragments include polyethylene glycols (PEG), homo- or copolymers of PEG, monomethyl substituted PEG polymer (ptPEG) or polyoxyethylene glycerol (ROS). See, for example, Yipi. U. Nepthaiiodu 68:1 (1998); Viosopitsdaige Spet. 6:150 (1995); and

Stop. Kew. Tpegar. Ogyd Sagtieeg st. 9:249 (1992). Also covered are PEGs that are obtained for the purpose of extending the half-life, for example, mono-activated polyalkylene oxides with an alkoxy terminal (POA), such as polyethylene glycols with a mono-methoxy terminal (ptPEG); bis-activated polyethylene oxides (glycols) or other PEG derivatives are also considered. Suitable polymers will have widely varying masses ranging from about 200 Da to about 40,000 Da or from about 200 Da to about 60,000 Da, which are generally chosen for the purposes of this invention. In some embodiments, PEG with a molecular weight of 200 to 2000 or 200 to 500 Da is used. Different forms of PEG can also be used, depending on the initiator used for the polymerization process - a common initiator is monofunctional methyl ether PEG or methoxypoly(ethylene glycol), abbreviated as tPEG.

IІ00598| Low molecular weight PEGs are also available as pure oligomers, called monodisperse, homogeneous or discrete. They are used in some embodiments of this invention.

I00599| PEGs are also available in different geometries: branched PEGs have three to ten PEG chains emanating from a central backbone; star-shaped PEGs have 10-100

From PEG chains, which come from the central main group; and comb PEGs have many PEG chains grafted normal to the polymer backbone. PEGs can also be linear. The numbers that are often included in the names of PEGs indicate their average molecular weights (for example, a PEG with n-9 would have an average molecular weight of about 400 daltons and would be labeled as PEG 400). 00600) As used herein, "PEGylation" is the act of covalently attaching a PEG structure to a peptide inhibitor of the present invention, hereinafter referred to as a "PEGylated Peptide Inhibitor." In some embodiments, the PEG of the PEGylated side chain is a PEG with a molecular weight of from about 200 to about 40,000 Da. In some embodiments, the separator of the peptide of formula I, formula I" or formula I!" is

PEGylated. In some embodiments, the PEG of the PEGylated separator is

PEGZ, PEG4, PEG5, PEGb, PEG7, PEG8, PEGO, PEG1O or PEG11. In some embodiments

The PEG of the PEGylated separator is PEGZ or PEG8.

Other suitable polymeric moieties include polyamino acids such as polylysine, polyaspartic acid, and polyglutamic acid (see, e.g., Sotroi, et al. (1995), Physopypdaie Spect., my. 6: 332-351; Niedesya, et al.). (1992), Viosopiidaye Spet., my. 3, 49-57 and T5ikKada, her ai. (1984), 9. May!. Sapseg Ip5i., mine. 73: 721-729. The polymer fragment can have a straight chain or a branched chain. In some embodiments, it has a molecular weight of 500-40,000 Da, for example, 500-10,000 Da, 1,000-5,000 Da, 10,000-20,000 Da, or 20,000-40,000 Da. 00602) In some embodiments, a peptide inhibitor of the present invention may contain two or more such polymeric fragments, in which case the total molecular weight of all such fragments will typically be within the ranges indicated above.

IІ00603| In some embodiments, the polymer fragment is connected (covalently) to an amino, carboxyl, or thiol group of an amino acid side chain. Some examples are the thiol group of Sub5 residues, and the epsilon amino group of Huz residues, and the carboxyl groups of Azr and Sim residues may also be included.

I00604| One of ordinary skill in the art will know the appropriate techniques that can be used to carry out the coupling reaction. For example, a PEG fragment bearing a methoxy group can be coupled to the thiol group of Suz via a maleimido bond using reagents commercially available from McCiag TPpegareshisz5 AG. See also UMO 2008/101017 and reference 60 above for detailed information on the relevant chemistry. Functionalized with maleimide

PEG can also be conjugated to the sulfhydryl group of the side chain of the Su residue.

IІ00605| As used herein, oxidation of a disulfide bond may occur in one step or is a two-step process. When used herein for a single oxidation step, the trityl protecting group is often used in coupling, providing removal of the group upon cleavage, followed by oxidation of the solution.

When a second disulfide bond is needed, each has the option of native or selective oxidation. For selective oxidation that requires orthogonal protecting groups, trityl esters are used as protecting groups for cysteine. Cleavage results in the removal of one cysteine protecting pair, allowing oxidation of this pair. The second stage of oxidative deprotection of the cysteine protected by the Ast group is then performed. For native oxidation, a trityl protecting group is used for all cysteines, which allows natural assembly of the peptide. One skilled in the art is well aware of the appropriate techniques that can be used to perform the oxidation step.

ИЙ0О60б6| Several chemical moieties, including poly(ethylene) glycol, react with functional groups found in twenty naturally occurring amino acids, such as the epsilon amino group in lysine amino acid residues, the thiol present in cysteine amino acid residues, or other nucleophilic side groups chains of amino acids. When many naturally occurring amino acids are reacted in a peptide inhibitor, these nonspecific chemical reactions yield a ready-made peptide inhibitor that contains many isomers of the peptide conjugated to one or more poly(ethylene) glycol strands at various locations in the peptide inhibitor.

I00607| One advantage of some embodiments of the present invention includes the ability to add one or more chemical moieties (such as PEG) by incorporating one or more unnatural amino acids that have unique functional groups that react with activated PEG using chemistry that is unreactive with naturally occurring amino acids. , which are in the peptide inhibitor. For example, azide and alkyne groups are unreactive with all naturally occurring protein functional groups. Thus, an unnatural amino acid can be incorporated into one or more specific sites in a peptide inhibitor where PEG or other modification is desired without unwanted non-specific reactions. In some embodiments, the particular chemistry involved in the reaction provides a stable, covalent bond between the PEG strand and the peptide inhibitor. In addition, such reactions can be performed under mild aqueous conditions that do not affect most peptides. In some embodiments, the unnatural amino acid residue is ANA. (00608) Chemical fragments attached to natural amino acids are limited in number and size. In contrast, chemical moieties attached to non-natural amino acids can employ a much wider range of suitable chemistries by which to attach the chemical moieties to the target molecule. Essentially any target molecule, including any protein (or part thereof) that contains an unnatural amino acid, such as an unnatural amino acid containing a reactive site or side chain where a chemical moiety can attach, such as an aldehyde or ketone derivatized amino acid , can serve as a substrate for attaching a chemical fragment. 00609) A number of chemical moieties can be attached or linked to a specific molecule by various methods known in the art. A number of such methods are described in US Pat

Mo8568706. As a typical example, azide moieties may be useful in the conjugation of chemical moieties such as PEG or others described herein. The azide moiety serves as a reactive functional group and is absent from most naturally occurring compounds (thus, it is unreactive with the native amino acids of naturally occurring compounds).

Azides also undergo selective ligation with a limited number of reaction partners, and azides are small and can be introduced into biological samples without significantly changing the size of the molecule. One reaction that allows the introduction or incorporation of azides into molecules is the copper-mediated |3-2| cycloaddition of azide according to Huysgen. This reaction can be used for selective PEGylation of peptide inhibitors. (Togpoe ei ai., U. Og9.

Spent 67: 3057, 2002; Voviomivem eyi ai!., Apdem/. Spet., Ipi. Hey. 41: 596, 2002; and Umapo ei ai., ».

At. Spent Boss. 125: 3192, 2003, 5 reegz eyi a!., U. At. Spent 5os., 2003, 125, 4686).

Typical Peptide Inhibitors and Peptide Dimeric Inhibitors and Methods of Their Preparation 00610) The present invention thus provides various peptide inhibitors that bind or associate with II-23 to disrupt or block binding between II-23 and II-23B. 00611) Typical peptide inhibitors and peptide dimer inhibitors of the present invention, shown in Tables 3A-3H, 4A, 4B, 5A-5C, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, provide amino acid sequence of selected monomeric peptide inhibitors and peptide dimer inhibitors and show the linker fragment found in the peptide dimer inhibitors. According to the protocols discussed herein, a series of peptide inhibitors and peptide dimer inhibitors shown in the accompanying tables were synthesized and cyclized.

Tables EZA-EZN, EYAA, E4B, EBA-E5C, Eb, E7, E8, E9, E10, E11, E12, E13, E14 or E15 provide IC50 values for selected monomeric peptide inhibitors and peptide dimeric inhibitors in the inhibition of II-23 zv binding with II-23E, or in the inhibition of signaling 1-23, as determined by measuring changes in the levels of phospho-ZTATZ, as described in the accompanying examples. Typical peptide inhibitors of this invention are shown in formulas (US) 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 this invention can be synthesized by many techniques known to those skilled in the art. In some embodiments, the monomeric subunits were synthesized, purified, and dimerized using the techniques described in the accompanying examples. In some embodiments, the present invention provides a method for producing a peptide inhibitor (or a monomeric subunit thereof) of the present invention, comprising the chemical synthesis of a peptide comprising, consisting of, or consisting primarily of a peptide having an amino acid sequence described herein, including but not limited to without limitation, any of the amino acid sequences specified in any of the formulas I, II, PI, IM, M or MI or tables herein. In other embodiments, the peptide is recombinantly synthesized, instead of chemically synthesized. In some embodiments, the peptide inhibitor is a dimer, and the method includes the synthesis of both monomer subunits of the peptide dimer inhibitor, and then dimerization of the two monomer subunits to obtain the peptide dimer inhibitor. In various embodiments, the dimerization is performed using any of the various methods described herein. In specific embodiments, methods of obtaining a peptide inhibitor (or its monomeric subunit) also include cyclization of a peptide inhibitor (or its monomeric subunit) after its synthesis. In specific embodiments, cyclization is performed using any of the various methods described herein. In some embodiments, the present invention provides a method for obtaining a peptide inhibitor (or its monomeric subunit) of the present invention, which includes the introduction of an intramolecular bond, for example, a disulfide, amide, or thioether bond, between two amino acid residues in a peptide containing with or consisting primarily 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, I, IM, M, or MI or the accompanying examples , tables or a list of sequences.

I00613) In related embodiments, the present invention includes polynucleotides that encode a polypeptide with the sequence indicated in any of formulas I, II, PP, IM, M, or MI or the accompanying examples, tables, or sequence listings. 006141) In addition, the present invention includes vectors, for example, expression vectors containing the polynucleotide of the present invention.

Methods of treatment 00615) In some embodiments, the present invention includes methods of inhibiting IL-23 bound to IL-23E on a cell, comprising contacting IL-23 with a peptide inhibitor of this invention. In some embodiments, the cell is a mammalian cell. In specific embodiments, the method is performed by ip myo or ip mimo. Binding inhibition can be determined by various standard experimental methods and assays known in the art. 00616) In some embodiments, the present invention includes methods of inhibiting signaling

And/-23 cell, which include contact 1-23 with the peptide inhibitor of this invention. In some embodiments, the cell is a mammalian cell. In specific embodiments, the method is performed by ip miigo or ip mimo. In specific embodiments, the inhibition of IL-23 signaling can be determined by measuring changes in the levels of phospho-5TATZ in the cell.

I00617| In some embodiments, the present invention provides methods of treating a subject affected by a condition or symptom associated with 1-21 or 1-23. (for example, activation of the II-2Z3/I-23K signaling pathway), and the method includes the administration of the peptide inhibitor of this invention to the subject. In one embodiment, a method is provided for treating a subject afflicted with a condition or symptom characterized by inappropriate, dysregulated, or increased I/-23 or I/-23EE activity or signaling, comprising administering to the subject a peptide inhibitor of the present invention in an amount, sufficient to inhibit (partial or complete) binding of II-23 with I/-23K in the subject. In specific embodiments, the inhibition of the binding of 1-23 to II-23E occurs in specific organs or tissues of the subject, for example, the stomach, small intestine, colon, intestinal mucosa, lamina propria, Peyer's patches, intestinal lymph nodes or lymphatic ducts. 00618) In some embodiments, the methods of the present invention include providing a peptide inhibitor of the present invention to a subject in need thereof. In specific embodiments, the subject in need has been diagnosed or determined to be at risk of developing a disease or disorder associated with II-23/LI-23K. In specific embodiments, the subject is a mammal. 00619) In some embodiments, the disease or disorder is autoimmune inflammation and related diseases or disorders, such as multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease (IBD), juvenile IBO, adolescent IBO, Crohn's disease, sarcoidosis, systemic lupus erythematosus, ankylosing spondylitis (axial spondyloarthritis), psoriatic arthritis or psoriasis. In specific embodiments, the disease or disorder is psoriasis (eg, plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, palmoplantar psoriasis, psoriasis vulgaris, or erythrodermic psoriasis), atopic dermatitis, inverse acne, ulcerative colitis, Crohn's disease, gluten disease (non-tropical Sprue), enteropathy associated with seronegative arthropathies, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis/oesophagitis, colitis associated with radiotherapy or chemotherapy, colitis associated with disorders of innate immunity such as adhesion disorders leukocytes-1, chronic granulomatosis, glycogenosis type 16, Germansky-Pudlak syndrome, Chediak-Higashi syndrome, Wiskott syndrome-

Aldrich's, postproctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral enteropathy, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, uveitis, or "transplant versus host" reaction.

І00620| In some related embodiments, the present invention provides a method of selectively inhibiting 1-23 or 1I-23K signaling (or binding of 1I-23 to II-23K) in a subject in need thereof, which comprises administering to the subject a peptide inhibitor of this invention. In specific embodiments, the present invention includes a method of selective inhibition of 1-23

Zo or II-23B signaling (or binding of 1-23 with II-23E) in the SI tract of a subject in need thereof, which includes administering to the subject the peptide inhibitor of this invention by oral administration. In specific embodiments, the release of the administered peptide inhibitor in these tissues (eg, 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 release into the blood. In specific embodiments, the present invention includes a method of selectively inhibiting I/23 or II23K signaling (or binding of II/23 to I/23K) in the C tract of a subject in need thereof, which includes administering to the subject a peptide inhibitor, wherein the peptide inhibitor does not block the interaction between 1Y--6 and II-6K or does not antagonize the signaling pathway of ЙЙ-- 12. In additional related embodiments, the present invention includes a method of inhibiting SI inflammation and/or neutrophil infiltration into SI, which includes administering sub subject in need of this peptide inhibitor of the present invention. In some embodiments, the methods of the present invention include administering a peptide inhibitor of the present invention (ie, a first therapeutic agent) to a subject in need thereof in combination with a second therapeutic agent. In some embodiments, the second therapeutic agent is administered to the subject before and/or simultaneously with and/or after administration of the peptide inhibitor to the subject. In specific embodiments, the second therapeutic agent is an anti-inflammatory agent. In some embodiments, the second therapeutic agent is a non-steroidal anti-inflammatory drug, a steroid, or an immunomodulating agent. In another embodiment, the method includes administering a third therapeutic agent to the subject. In some embodiments, the second therapeutic agent is an antibody that binds II-23 or II-23B.

I00621| In specific embodiments, a peptide inhibitor or a pharmaceutical composition containing a peptide inhibitor is suspended in a sustained-release matrix. A sustained-release matrix as used herein is a matrix derived from materials, usually polymers, that degrade by enzymatic or acid-base hydrolysis or dissolution. When introduced into the body, enzymes and body fluids act on the matrix. The sustained-release matrix is preferably selected from biocompatible materials such as liposomes, polylactides (polylactic acid), polyglycolide (a polymer of glycolic acid), polylactide-co-glycolide (copolymer of lactic acid and glycolic acid), polyanhydrides, poly(ortho)ethers, because of polypeptides, hyaluronic acid, collagen, chondroitin sulfate, carboxylic acids, fatty acids, phospholipids, polysaccharides, nucleic acids, polyamino acids, amino acids such as phenylalanine, tyrosine, isoleucine, polynucleotides, polyvinylpropylene, polyvinylpyrrolidone, and silicone. One embodiment of the biodegradable matrix is a matrix of one of polylactide, polyglycolide, or polylactide-co-glycolide (copolymers of lactic acid and glycolic acid). (00622) In some embodiments, the present invention includes pharmaceutical compositions containing 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, semisolid, or liquid excipient, diluent, encapsulating material, or formulation excipient of any type. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenolsorbic acid and the like. It may be desirable to include isotonic agents such as sugars, sodium chloride, and the like.

I00623| In some embodiments, the compositions are administered orally, parenterally, intracisternally, intravaginally, intraperitoneally, intrarectally, topically (as powders, ointments, drops, suppositories, or transdermal patches), by inhalation (such as an intranasal spray), intraocularly (e.g., in the eye), or buccally The term "parenteral" as used herein refers to modes of administration that include intravenous, intramuscular, intraperitoneal, supraperitoneal, subcutaneous, intradermal, and intra-articular injection and infusion. Accordingly, in some embodiments, the compositions are formulated for delivery by any of these routes of administration. (00624) In some embodiments, pharmaceutical compositions for parenteral injection contain pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions or sterile powders for dilution into sterile injectable solutions or dispersions prior to use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents, or media include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), carboxymethyl cellulose and their respective mixtures, β-cyclodextrin, vegetable oils (such as olive oil), and injectable organic ethers such as ethyl oleate. Adequate fluidity can be maintained, for example, by means of coating materials such as lecithin, by maintaining the desired particle size in the case of dispersions, and by means of surfactants. These compositions may also contain excipients such as preservatives, wetting agents, emulsifiers and dispersants.

Prolonged absorption of the injectable pharmaceutical form may be due to the inclusion of agents that delay absorption, such as aluminum monostearate and gelatin. (00625) Injectable depot forms include those obtained by forming microencapsulating matrices of the peptide inhibitor in one or more biodegradable polymers such as polylactide-polyglycolide, poly(orthoethers), poly(anhydrides) and (poly)glycols such as PEG. Depending on the ratio of peptide to polymer and the nature of the specific polymer used, the release rate of the peptide inhibitor can be adjusted. Injectable depot formulations are also obtained by entrapping the peptide inhibitor in liposomes or microemulsions compatible with body tissues. (00626) Injectable formulations can be sterilized, for example, by filtration through a bacteria-retaining filter or by including sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injection medium prior to use.

I00627| Topical administration includes administration to the skin or mucosa, including the surfaces of the lungs or eyes. Compositions for topical use in the lungs, including those for inhalation and intranasal, can include solutions and suspensions in aqueous and non-aqueous formulations, and can be prepared as a dry powder that can be pressed or unpressed. In non-pressed powder compositions, the active ingredient may be in finely divided form, and may be used in admixture with a pharmaceutically acceptable inert carrier of larger size containing particles of, for example, up to 100 micrometers in diameter. Suitable inert carriers include sugars such as lactose. (00628) Alternatively, the composition may be compressed and contain a compressed gas, such as nitrogen, or a liquefied propellant gas. The liquid propellant medium, and of course the entire composition, may be such that the active ingredient does not dissolve in it to any significant extent.

The pressed composition may also contain a surface-active ingredient, such as a liquid or solid non-ionic surface-active ingredient, or may be a solid anionic or surface-active ingredient. It is preferable to use a solid anionic surfactant

active ingredient in the form of sodium salt.

I00629| An additional form of local administration is administration into the eye. A peptide inhibitor of the present invention can be delivered in a pharmaceutically acceptable ophthalmic medium such that the peptide inhibitor is in contact with the surface of the eye for a sufficient period of time to allow penetration of the peptide inhibitor into the cornea and internal regions of the eye, such as the anterior chamber, posterior chamber, vitreous, intraocular fluid, vitreous, cornea, iris/ciliary body, lens, choroid/retina and sclera. A pharmaceutically acceptable ophthalmic medium may, for example, be an ointment, a vegetable oil, or an encapsulating material. Alternatively, the peptide inhibitors of this invention can be injected directly into the vitreous and intraocular fluid. 00630) Compositions for rectal or vaginal administration include suppositories which may be prepared by mixing the peptide inhibitors of this invention with suitable non-irritating excipients and carriers such as cocoa butter, polyethylene glycol or suppository wax which are solid at room temperature but liquid at body temperature and thus melt in the rectum or vaginal cavity and release the active substance. 00631) Peptide inhibitors of this invention can also be administered in liposomes or other lipid carriers. As is known in the art, liposomes are usually derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-layered 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. Compositions of the present invention in the form of liposomes may contain, in addition to the peptide inhibitor of the present invention, stabilizers, preservatives, excipients, and the like. In some embodiments, the lipids comprise phospholipids, including phosphatidylcholines (lecithins) and serines, both natural and synthetic. Methods of forming liposomes are known in the art.

I00632| Pharmaceutical compositions useful in the present invention suitable for parenteral administration may contain sterile aqueous solutions and/or suspensions of peptide inhibitors that are isotonic to the recipient's blood, generally by

From sodium chloride, glycerin, glucose, mannitol, sorbitol and the like.

IІ00633| In some aspects, the present invention provides a pharmaceutical composition for oral delivery. The compositions and peptide inhibitors of this invention can be prepared for oral administration according to any of the methods, techniques and/or delivery media described herein. Additionally, one skilled in the art will appreciate that the peptide inhibitors of the present invention can be modified or integrated into a delivery system or medium not disclosed herein that is already known in the art and compatible for use in oral peptide delivery. (00634) In some embodiments, oral formulations may contain excipients (eg, resorcinol and/or nonionic surfactants such as polyoxyethylene oleic ether and n-hexadecyl polyethylene ether) to artificially increase permeability through the intestinal wall and/or enzymatic inhibitors (eg, pancreatic trypsin inhibitors, dipropylfluorophosphate (DPO) or trasitol) to inhibit enzymatic degradation. In some embodiments, the peptide inhibitor in a solid oral dosage form 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 semi-synthetic polymers or glyceride. These dosage forms may also contain other type(s) of additives, such as an inactive diluent, a lubricant such as magnesium stearate, paraben, a preservative such as sorbic acid, ascorbic acid, alpha-tocopherol, antioxidants such as cysteine, disintegrants, binders, thickeners, buffers, pH adjusters, sweeteners, flavors or perfumes. 00635) In specific embodiments, oral dosage forms or unit doses compatible for use with the peptide inhibitors of this invention may include a mixture of the peptide inhibitor and non-drug components or excipients, as well as other non-reusable materials that can be considered either as an ingredient or as packaging .

Oral compositions may include at least one of liquid, solid and semi-solid dosage forms. In some embodiments, an oral dosage form containing an effective amount of a peptide inhibitor is provided, wherein the dosage form comprises at least 60 one of a pill, tablet, capsule, gel, paste, drink, syrup, ointment, and suppository. In some cases, an oral dosage form designed and formulated to provide sustained release of the peptide inhibitor in the small intestine and/or colon of a subject is provided. 00636) In one embodiment, an oral pharmaceutical composition containing a peptide inhibitor of the present invention contains an enteric coating that is designed for sustained release of the peptide inhibitor in the small intestine. In at least some embodiments, a pharmaceutical composition comprising a peptide inhibitor of the present invention and a protease inhibitor such as aprotinin in a sustained release pharmaceutical formulation is provided. In some cases, the pharmaceutical compositions of this invention contain an enteric coating that is soluble in gastric juice at a pH of approximately 5.0 or higher. At least one embodiment provides a pharmaceutical composition comprising an enteric coating comprising a polymer with dissociating carboxyl groups, such as a cellulose derivative, including hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and cellulose trimellitate acetate and similar cellulose derivatives and other carbohydrate polymers.

I00637| In one embodiment, a pharmaceutical composition containing a peptide inhibitor of the present invention is provided in an enteric coating, wherein the enteric coating is designed to protect and release the pharmaceutical composition in a controlled manner in the lower gastrointestinal tract of a subject, and to avoid systemic side effects. In addition to enteric coatings, the peptide inhibitors of the present invention may be encapsulated, coated, incorporated, or otherwise associated with any compatible oral drug delivery system or component.

For example, in some embodiments, the peptide inhibitor of this invention is provided in a lipid carrier system containing at least one of polymer hydrogels, nanoparticles, microspheres, micelles, and other lipid systems.

I00638| To overcome cleavage of the peptide in the small intestine, some embodiments of the present invention contain a polymeric hydrogel-based carrier system in which the peptide inhibitor of the present invention is contained, while the polymer-hydrogel protects the peptide inhibitor from proteolysis in the small intestine and/or colon. Peptide inhibitors of this invention can also

To be formulated for simultaneous use with a carrier system, which is designed to increase the kinetics of dissolution and increase absorption in the intestines of the peptide. These methods include the use of liposomes, micelles and nanoparticles to increase the penetration of peptides into the SI tract. 00639) Various biologically active systems can also be combined with one or more peptide inhibitors of this invention to provide a pharmaceutical agent for oral delivery. In some embodiments, the peptide inhibitor of the present invention is used in combination with a biologically active system, such as hydrogels and mucoadhesive polymers with hydrogen-bonding groups (e.g., PEG, poly(methacrylic) acid |(PMAA)Y, cellulose, Etzagadif, chitosan and alginate) to provide a therapeutic agent for oral administration. Other embodiments include a method of optimizing or extending drug retention time for a peptide inhibitor disclosed herein, wherein the surface of the peptide inhibitor is modified to have mucoadhesive properties through hydrogen bonding, polymers with bound mucins, and/or hydrophobic interactions. These modified peptide molecules may exhibit an increased retention time of the drug in the subject in accordance with a desirable feature of the present invention. In addition, targeted mucoadhesive systems can specifically bind to receptors on enterocytes and M-cell surfaces, while also increasing the uptake of particles containing a peptide inhibitor.

I00640| Other embodiments include a method for oral delivery of a peptide inhibitor of this invention, wherein the peptide inhibitor is administered to a subject in combination with penetration enhancers that activate the transport of peptides across the intestinal mucosa by increasing paracellular penetration or penetration through skin cells. Various penetration enhancers and methods for oral delivery of therapeutic agents are described in Vgaudep, 0.9., Mizpu, K.)., 2011.

She Ieadipu Tesppoiodiev5. Tag. Oeyimegu 2 (12), 1567-1573. (00641) In some embodiments, pharmaceutical compositions and formulations of the present invention comprise a peptide inhibitor of the present invention and one or more penetration enhancers. Examples of absorption enhancers may include bile salts, fatty acids, surfactants (anionic, cationic, and nonionic), chelators, zonular OTs, ethers, cyclodextrin, dextrin sulfate, ozone, crown ethers, EOTA, sucrose ethers, and phosphotidylcholine, for example. Although absorption enhancers are typically not carriers themselves, they are also widely associated with other carriers to improve oral bioavailability by transporting peptides and proteins across the intestinal mucosa.

Such substances can be added to the composition as excipients or included in the form of non-specific interactions with the indicated peptide inhibitor. (00642) Dietary components and/or other naturally occurring substances that have been shown to enhance tight junctions for penetration and are generally recognized as safe (OKAF5B) include, for example, glycerides, acylcarnitines, bile acid salts, and medium-chain fatty acids chain Sodium salts of medium-chain fatty acids (MCFA5) have also been considered as penetration enhancers. Sodium caprate, a salt of capric acid, which contains 2-3 96 fatty acids in the milk fat fraction, has been studied in detail by MSEAZ. At present, sodium caprate is mainly used as an excipient in suppositories (boKiasiliip"M) to improve the absorption of ampicillin in the intestine. The penetration properties of other dietary MSEABZ sodium caprylate (8-carbons) have been shown to be lower when compared to sodium caprate. Sodium caprylate and a peptide drug were formulated as a mixture with other excipients in oil to obtain an oil suspension (05) that increases permeability (Thymia, 5. ei aiYi,, Rpagtasecissa!

Veseaigs, Moi. 31, Mo. 8, 2010-2021 (2014).

Y00643| For example, in one embodiment, the penetration enhancer is combined with a peptide inhibitor, wherein the penetration enhancer comprises at least one of a medium chain fatty acid, a long chain fatty acid, a bile acid salt, an amphiphilic surfactant, and chelating agent. In some embodiments, medium chain fatty acid salts activate absorption by increasing paracellular permeability across the intestinal epithelium. In one embodiment, the penetration enhancer contains sodium

M-I(Hydroxybenzoyl)amino|caprylate is used to form a weak non-covalent association with the peptide inhibitor of this invention, and the agent for increasing penetration promotes transport through the membrane and also dissociation upon reaching the bloodstream. In another embodiment, the peptide inhibitor of this invention is conjugated with oroligoarginine, thereby increasing the penetration of the peptide into cells in various cell types. Additionally, in at least one embodiment, a non-covalent bond is provided between a peptide inhibitor of the present invention and a permeation enhancer selected from the group consisting of cyclodextrin (CO) and dendrimers, wherein the permeation enhancer reduces peptide aggregation and increases stability and solubility for a peptide inhibitor molecule.

I00644| In some embodiments, the pharmaceutical composition or formulation comprises a peptide inhibitor of the present invention and transient penetration enhancers (TPEs). Penetration enhancers and TPEs can be used to increase the oral bioavailability of the peptide inhibitor. One example of a TRE that can be used is the composition of an oil suspension that disperses a powder containing sodium caprylate and a therapeutic agent (Timia, 5. eyi a)I., Rpaptaseciisa! Rezeeagsp, Moi. 31, Mo. 8, 2010-2021 (2014).

I00645| In some embodiments, the pharmaceutical composition and formulations may include a peptide inhibitor of the present invention and one or more absorption enhancers, enzyme inhibitors, or mucoadhesive polymers. 00646) In specific embodiments, the peptide inhibitors of this invention are formulated in a formulation medium, such as, for example, emulsions, liposomes, microspheres, or nanoparticles.

I00647| Other embodiments of the present invention provide a method of treating a subject with a peptide inhibitor of the present invention with an increased half-life. In one aspect, the present invention provides a peptide inhibitor with a half-life of at least several hours to one day ip migo or ip mimo (eg, when administered to a subject-/human) sufficient for once-daily (d.4.) or twice-daily dosing per day (B..a.) therapeutically effective amount. In another embodiment, the peptide inhibitor has a half-life of three days or more, which is sufficient for once-weekly (DM) dosing of a therapeutically effective amount. Additionally, in another embodiment, the peptide inhibitor has a half-life of eight days or more, which is sufficient for biweekly (B.ilmu.) or monthly dosing of a therapeutically effective amount. In another embodiment, the peptide inhibitor is derivatized or modified to have a longer half-life compared to an underivatized or unmodified peptide inhibitor.

In another embodiment, the peptide inhibitor contains one or more chemical modifications to increase the serum half-life. (00648) When used in at least one of the treatments or delivery systems described herein, the peptide inhibitor of this invention can be used in pure form or, if such forms exist, in a pharmaceutically acceptable salt form.

I00649| The total daily dose of peptide inhibitors and compositions of this invention can be specified by a doctor within the scope of medical judgment. The specific therapeutically effective dose levels for any particular subject will depend on various factors, including: a) the disorder being treated and the severity of the disorder; p) activity of a specific compound used; c) specific composition used, age, body weight, general state of health, gender and diet of the patient; 4) the time of administration, the route of administration and the rate of elimination of the specific peptide inhibitor used; f) duration of treatment; Drugs used in combination or together with a specific peptide inhibitor used and similar factors well known in medicine.

І00650| In specific embodiments, the total daily dose of the peptide inhibitors of the present invention administered to a human or other mammalian host in single or divided doses may be amounts, for example, from 0.0001 to 300 mg/kg body weight daily or 1-300 mg/ kg of body weight daily.

Non-invasive detection of intestinal inflammation

I00651| Peptide inhibitors of this invention can be used to detect, evaluate and diagnose intestinal inflammation using microPET imaging, wherein the peptide inhibitor is labeled with a labile group or detectable label as part of a non-invasive diagnostic procedure. In one embodiment, the peptide inhibitor is conjugated to a bifunctional chelator. In another embodiment, the peptide inhibitor is radiolabeled. The labeled peptide inhibitor is then administered orally or rectally to the subject. In one embodiment, the labeled peptide inhibitor is included in drinking water. After absorption of the microPET peptide inhibitor, the image can be used to visualize inflammation in the subject's gut and digestive tract.

Identification of Peptide Inhibitors That Inhibit II-23 Signaling 00652) As described herein, in some embodiments, the peptide inhibitors of this invention preferentially bind to II-23E. human and/or 1-23 rats compared to HER - 23 mice. Mouse I-23K contains additional amino acids compared to human II-23E or rat II-238 in a region corresponding to about amino acid residue 315 to about amino acid residue 340 of the mouse I/23K protein, e.g., the amino acid region

From MUMORMZZREMNOTZOETOKK (see, for example, Fig. 4). In specific embodiments, the peptide inhibitors bind to the human IL-23E region from about amino acid residue 230 to about amino acid residue 370.

Y00653| The present invention provides a new method of identifying an inhibitor (for example, a peptide inhibitor) of I/-23K based on the identification of an agent (for example, a peptide) that preferentially binds to II-23E. human or rat II-23E compared to mouse II-23K. In some embodiments, the method includes: (a) determination of the amount of binding of the candidate agent to human polypeptide I/-23K or rat polypeptide I/-23K; (b) determination of the amount of binding of the candidate agent to the mouse I/Y/-23K polypeptide and (c) comparison of the determined amount of binding to human I/-23K polypeptide or rat I/Y/-23K polypeptide with the determined amount of binding with polypeptide II/-23K of the mouse, and if the determined amount of binding to polypeptide II/-23K of man or polypeptide I/-23K of the rat is greater than the amount of binding to polypeptide 1 -23K of the mouse, the canididate compound is an inhibitor of 1I- 23K. In specific embodiments, the canididate compound is identified as an I/-23E inhibitor if the determined amount of binding to the human II/-23K polypeptide or the rat 1-238 polypeptide is at least 1.5-fold, at least 2-fold, at least 3 times, at least 4 times, at least 5 times, at least 10 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times, at least 100 times, at least 200 times, at least 500 times or at least 1000 times higher than the determined value of binding to polypeptide I/-23K of the mouse. In specific embodiments, the canididate compound is a peptide. In specific embodiments, the peptide is a peptide of one of the formulas described in this document. In specific embodiments, the human II-23K polypeptide or the rat II-23K polypeptide contains or consists of a full-length human I/-23K or rat II/-23K protein, respectively. In other embodiments, the human I-23K polypeptide is a fragment of the full-length human III/-238A protein containing 8 or more amino acid residues in the human I/-23K region from about amino acid residue 230 to about amino acid residue 370. In other embodiments, the rat I/-23K polypeptide is a fragment of a full-length protein

Rat I -23K containing 8 or more amino acid residues in the rat II -23E region from about amino acid residue 245 to about amino acid residue 385. bo (00654) In another embodiment, the present invention provides a new method of identifying an inhibitor (eg, a peptide inhibitor) of I/-23K based on the identification of an agent that binds to the region of I/-232; human or rat II/-23 that is disrupted in mouse III/-23K by the presence of additional amino acids from about amino acid residue 315 to about amino acid residue 340 of the mouse I/23K protein, e.g., the amino acid region

MUMORMIZZREMNOTZOETOKK (see, for example, Fig. 4). In some embodiments, the method includes: (a) determining the amount of binding of the candidate agent to a human II/-23E polypeptide fragment that falls within the range of about amino acid residue 230 to about amino acid residue 370 or to a rat 1-23 polypeptide fragment, which falls within the range of about amino acid residue 245 to about amino acid residue 385; (B) determining the amount of binding of the candidate agent to a negative control (for example, a negative control peptide that is not related to II -238 human or 1 -23K rat); and (c) comparing the determined amount of binding to the human I/-23K polypeptide fragment or the rat I/-23K polypeptide fragment with the determined amount of binding to the negative control, and if the determined amount of binding to the I-23K polypeptide fragment human or rat 1-23 polypeptide fragment is less than the value of binding to the negative control, the canididate compound is an inhibitor of 1-23. In specific embodiments, the canididate compound is identified as an I/-23K inhibitor if the determined amount of binding to the human I-23E polypeptide fragment or the rat I-23K polypeptide fragment is at least 1.5 times, at least 2 times, at least 3 times , at least 4 times, at least 5 times, at least 10 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times, at least 100 times, at least 200 times, at least 500 times or at least 1000 times higher than the determined value of negative control assay.

In specific embodiments, the canididate compound is a peptide. In specific embodiments, the peptide is a peptide of one of the formulas described in this document. In specific embodiments, the human 1I-23K fragment contains at least 8, at least 12, at least 20, at least 50, or at least 100, or all amino acid residues in the human I.-23E region from about amino acid residue 230 to about amino acid residue 370. In other embodiments, the fragment of polypeptide I is rat 23K

Zo contains at least 8, at least 12, at least 20, at least 50, or at least 100, or all amino acid residues in the rat II-23E region from about amino acid residue 245 to about amino acid residue 385. 00655) Methods for determining the binding of a candidate compound to polypeptide 1-23 are known in the art and include, but are not limited to, ip miigo binding assays and cellular assays, including those described herein. For example, a labeled candidate compound can be incubated with recombinantly produced II/-23K polypeptide or a negative control bound to a solid support under conditions and for a time sufficient to ensure binding, and binding is then determined by measuring the amount of label, associated with the bound polypeptide 1 -238B.

Non-Invasive Detection of Intestinal Inflammation (00656) Peptide inhibitors of the present invention can be used to detect, evaluate and diagnose intestinal inflammation using microPET imaging, wherein the peptide inhibitor is labeled with a labile group or detectable label as part of a non-invasive diagnostic procedure. In one embodiment, the peptide inhibitor is conjugated to a bifunctional chelator. In another embodiment, the peptide inhibitor is radiolabeled. The labeled peptide inhibitor is then administered orally or rectally to the subject. In one embodiment, the labeled peptide inhibitor is included in drinking water. After absorption of the microPET peptide inhibitor, the image can be used to visualize inflammation in the subject's gut and digestive tract.

Animal models of IVF

I00657| The present invention includes animal models of disease including inflammatory diseases and disorders such as inflammatory bowel diseases such as Crohn's disease and colitis. As described in the accompanying examples, several animal models of inflammatory diseases and disorders have been developed.

I00658| In one embodiment, the present invention includes a method for evaluating the ability of a candidate compound to inhibit or reduce a disorder in an inflammatory disease, which comprises: 00659) (a) administering to a rat an amount of dextran sulfate sodium (055) sufficient to cause IVO; bo 00660) (b) administering to the rat an amount of the candidate compound; and

(00661) (c) measuring the magnitude of IVI symptoms present in the rat after administration of 055 and the candidate compound;

I00662| further, if the magnitude of IVI symptoms measured in (c) is significantly lower than that measured in a control rat given an amount of 055 and/or an amount of control compound or no peptide (eg, medium control), the candidate compound inhibits or reduces an inflammatory disease or disorder. 00663) In some embodiments, the rat is administered U55 for about 5-12 days, such as about 9 days. In specific embodiments, the rat is administered О55 by administering to the rat a b drinking water containing 055, for example, from about 1 95 to about 1095 055, from about 2 95 to about 595 055, or from about 956 055. In specific embodiments, the rat is administered test compound at a level of 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 specific embodiments, the rat is administered the test compound orally, for example, in drinking water. In some embodiments, testing with p55 is performed as described in the accompanying examples. (00664) In another embodiment, the present invention includes a method for evaluating the ability of a candidate compound to inhibit or reduce an inflammatory disease disorder comprising:

I00665| (a) administration to a rat of an amount of 2,4,6-trinitrobenzenesulfonic acid (TMV5) sufficient to cause IVI; (00666) (b) administering to the rat an amount of the candidate compound; and

I00667| (c) measuring the magnitude of IVI symptoms present in the rat after administration of TMB5 and the candidate compound;

I00668| further, if the magnitude of IVI symptoms measured in (c) is significantly lower than that measured in a control rat given an amount of TMV5 and/or an amount of control compound or no peptide (eg, medium control), the candidate compound inhibits or reduces an inflammatory disease or disorder.

І00669| In some embodiments, the animal is administered from about 10 mg/kg to about 200 mg/kg of TMV5, for example, 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

Co) 80 mg/kg, about 90 mg/kg, about 100 mg/kg, about 120 mg/kg, about 150 mg/kg or about 200 mg/kg TMV5. In some embodiments, TMB5 is in alcohol, for example, in 4595-5095 ethanol. In specific embodiments, TMB5 is administered intrarectally. In specific embodiments, the rat is administered a test compound at a level of from about 5 mg/kg to about 100 mg/kg, or from about 10 mg/kg to about 50 mg/kg, or from about 20 mg/kg, or from about 30 mg/kg . In specific embodiments, the rat is administered the test compound orally, for example, in drinking water. In some embodiments, testing with TMB5 is performed as described in the accompanying examples. 00670) In specific embodiments, IVI symptoms are measured immediately after administration of re or TMV5 and the candidate compound (or test compound or no compound), or at a later time, e.g., approximately 3 days, 5 days, or 9 days after the initial administration of U55 or TMV5 and candidate compound (or test compound or no compound). In specific embodiments, measured IVI symptoms include one or more of percent body weight loss, stool consistency, blood culture quantification, and colon mass:colon length ratio. In some embodiments, IVO symptoms are measured using a disease activity index (OA!) and/or the colon mass:colon length ratio, and the UA! consists of data from three parameters, including percent body weight loss, stool consistency, and blood culture quantification, and can reach a maximum of three units. 00671) In some embodiments, a neutralizing antibody against II -23p19 is used as a comparator or positive control drug.

I00672| In some embodiments, to assess the magnitude of the inflammatory response, the animals were observed, for example, daily for clinical signs, which included percent body weight loss and signs of loose stools or diarrhea. After a period of time after inoculation with 055 or TMB5 (eg, 5 days, 6 days, or 7 days), rats were sacrificed and their entire colon length and colon mass from cecum to rectum were recorded. The severity of colitis can be assessed by a pathologist who does not have information regarding the identity of the treatment. In addition to colonic wall thickness, gross colonic damage can be graded based on a 0-4 scale according to Table 19 below, and histopathological scores were determined based on the following parameters (Tables 20 and 21). because I00673| In some embodiments, IVI symptoms were measured in three groups of rats,

each of at least 3 animals, for example, each of six animals, and the three groups included: medium, 055 or TMB5, and 055 or TMB5 with a positive control (eg, sulfasalazine was administered at 100 mg/kg PO, 00).

Examples

Example 1

Synthesis of peptide monomers

I00674| Peptide monomers of this invention were synthesized using the technologies of solid-phase synthesis of Maggiyeeidy on a multi-channel synthesizer Zutrpop from the company

Rgoieip Tesppoiodu. Peptides were collected with the help of NVTI (O-benzotriazole-M, M,M",M'-tetramethyluronium hexafluorophosphate), diisopropylethylamine (OIEA) coupling conditions. For some amino acid couplings, the conditions of RudoOR'(7-azabenzotriazol-1-yloxy)utripyrrolidinophosphonium hexafluorophosphate were used ) and OIEA.Kipk Atide MVNA resin (100-200 mesh, 0.57 mmol/l) was used for the peptide with C-terminal amides and Ulapd resin preloaded with M-α-Ethos protected amino acid was used for the peptide with acids at the C-terminus. Coupling reagents (premixed NVTI and OIEA) were prepared at a concentration of 100 mmol. Analogous solutions of amino acids were prepared at a concentration of 100 mmol. Peptide inhibitors of the present invention were identified based on medicinal chemistry optimization and/or phage display and selected to identify those having the best binding and/or inhibition properties.

Collection

IІ00675| Peptides were collected using the standard Zutrpop protocol. Peptide sequences were collected as follows: the resin (250 mg, 0.14 mmol) in each reaction vessel was washed twice with 4 ml of UOME, followed by treatment with 2.5 ml of 20 95 4-methylpiperidine (Etos deprotection) for 10 min. The resin was then filtered and washed twice with HME (4 mL) and retreated with M-methylpiperidine for an additional 30 minutes. The resin was washed again three times with UME (4 mL), and then 2.5 mL of amino acid and 2.5 mL of the HBTO-SIEA mixture were added. After 45 min of vigorous stirring, the resin was filtered and washed three times with UME (4 mL each time). Double conjugation was performed for a typical peptide of this invention. After the resin coupling reaction is complete

Zo was washed three times with UME (each time 4 ml) before transferring to the next amino acid combination.

Ring closing reaction with the formation of olefins

I00676| The resin (100 μmol) was washed with 2 ml of OSM (3 x 1 min) and then with 2 ml of OSE (3 x 1 min) before treatment with 2 ml of 6 mM catalyst solution

Grubbs of the first generation in OSE (4.94 mg ml-1; 20 mol. 95 in relation to resin substitution). The solution was refluxed overnight (12 h) under nitrogen before decanting. The resin was washed three times with UME (each 4 ml); OSM (4 ml) before drying and digestion.

Splitting

I00677| After completion of peptide collection, the peptide was cleaved from the resin by treatment with a cleavage reagent such as reagent K (82.5 96 trifluoroacetic acid, 5 95 water, 5 90 thioanisole, 5905 phenol, 2.595 1,2-ethanedithiol)d. The cleavage reagent is able to successfully cleave the peptide from the resin, as well as all other side chain protecting groups.

I00678| 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 was repeated. The crude peptide was dissolved in a solution of acetonitrile:iodide (7:3 3 1595 TEA) and filtered. The quality of the linear peptide was then confirmed by electrospray ionization mass spectrometry (EBI-M5) (Misgotazzl/Maset5 203) before purification.

Formation of a disulfide bond by oxidation 00679) A peptide containing a free thiol (for example, diRep) was collected on Kipk Atide resin

Ministry of Internal Affairs using the general procedure Eitos-5RR5. The peptide was cleaved from the resin by treatment with a cleavage reagent of 9095 trifluoroacetic acid, 595 water, 2.590 1,2-ethanedithiol, 2.595 triisopropylsilane. 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 was repeated. The crude peptide was dissolved in a solution of acetonitrile:water (7:3 with 1 95 TPA) and filtered to obtain the desired unoxidized crude peptide. 00680) Unpurified, cleaved peptide from XA and XO, containing either Suv, Rep, pSuz, (C0)Rep, or (0)Suz or (0)pSuz, was dissolved in 20 ml of water:acetonitrile. Saturated iodine in acetic acid was then added dropwise with stirring until a yellow color was obtained. The solution was stirred for 15 minutes and the reaction was monitored by analytical NRIS and

ISM5. After completion of the reaction, solid ascorbic acid was added until the solution became clear. The solvent mixture was then purified first by diluting with water, and then by loading into a machine for reverse-phase NRI C (Hypa C18 media, 10 μm, 100A, mobile phase A: water containing 0.1 95 TEA, mobile phase B: acetonitrile (АСМ) , containing 0.1 to TEA, the gradient starts at 5 95 V, and changes to 50 95 V in 60 minutes with a flow rate of 15 ml/min). Fractions containing the pure product were then lyophilized in a lyophilizer.

Lactam bond formation

I00681| 100 mg of crude, cleaved peptide (approx. 0.12 mmol) was dissolved in 100 ml of anhydrous dichloromethane. NOVI (1-hydroxybenzotriazole hydrate) (0.24 mmol, 2 equiv) was added, followed by OSIEA (M,M-diisopropylethylamine) (1.2 mmol, 10 equiv) and TVTO (0-(benzotriazol-1-yl)- M, M, M", M'-tetramethyluronium tetrafluoroborate) (0.24 mmol, 2 equivalents).

The mixture was stirred overnight, followed by NRI C reaction. After completion of the reaction, the dichloromethane was evaporated and diluted with water and acetonitrile, and then loaded into a reverse-phase NRI C machine (I pa C18 media, 10 μm, 100A, mobile phase A: water, which contains 0.195 TEA, mobile phase B: acetonitrile (ACM) containing 0.195 TEA, the gradient starts at 5 95 V and changes to 50 95 V in 60 minutes at a flow rate of 15 ml/min). Fractions containing the pure product were then lyophilized in a lyophilizer.

Formation of a triazole bond

I00682| The purified peptide containing the relevant alkyne and azide amino acids was stirred at room temperature in phosphate/MeOnH (2:21) at pH 7.4 (1 mg per 2 ml). SiBO4:5H2H2O (10 equiv.) and sodium ascorbate (10 equiv.) were added and the mixture was stirred at room temperature for 36 h. MeOH was removed and the solution was acidified to pH 3 with an aqueous mixture of 1 95 TEA. The solution was then filtered before loading onto the NRI C to purify the peptide.

Formation of a thioether bond (00683) A peptide containing a free thiol (e.g. Sus) and pzZecOoTvoOM5) was collected on resin

Vipk Atide-MVNA by means of the general procedure ERitos-5PP5. Chlorination was carried out by treating the resin with RRIAZ (10 equiv.) and SIZSSM (10 equiv.) in OSM for 2 h.

The peptide was cleaved from the resin by treatment with a cleavage reagent consisting of 90 95 trifluoroacetic acid, 595 water, 2.595 1,2-ethanedithiol, 2.595 triisopropylsilane. 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 was repeated. The crude peptide was dissolved in a solution of acetonitrile:water (7:3 with 1 95 TEA) and filtered to obtain the desired uncyclized crude peptide.

I00684| A crude peptide containing a free thiol (e.g., Su, Rep, pSus, (0)Rep, (0)Sus, or ()pSus) and an alkyl halide (pZeg(CI)) either at the X4 position, or at the XU position, or at position of XO and X4 were dissolved in 0.1 M TKIZ buffer, pH 8.5. Cyclization was carried out during the night at a temperature of The solvent mixture was then purified by first diluting it twice with water and then loading it into a reverse-phase NRI C machine (Hypa C18 media, 10 μm, 100A, mobile phase A: water containing 0.1956 TEA, mobile phase B: acetonitrile (АСМ ), containing 0.1 95 TEA, the gradient starts at 5 95 V, and changes to 50 95 V in 60 minutes at a flow rate of 15 ml/min). Fractions containing the pure product were then lyophilized in a lyophilizer.

Formation of a selenoether bond

І00685| The crude peptide containing a thiol-protected selenium amino acid and an alkyl halide on XA and XU was dissolved in 0.1 M sodium phosphate buffer, pH 5.5, containing OTT (40 equiv.). Cyclization was ensured within 24 hours. at c.t. The solution was then diluted twice with water, and the finished cyclized peptide was purified by KR-NRI C to give the selenoether.

Formation of a diselenide bond

I00686| The diselenide precursor was dissolved in a solution of 0.1 M phosphate buffer pH 6.0 and isopropanol containing OTT (40 equiv.), and the reaction mixture was incubated at 370C. After 20 hours additional OT (10 equiv.) was added to the reaction mixture. After a total of 32 hours, the cyclization reaction was then diluted twice with water, and the resulting cyclized peptide was purified using

VR-NR'IS, giving a diselenide.

Cleaning

I00687| Analytical reversed-phase, high-performance liquid chromatography (HPLC) was performed on a Setipi C18 column (4.6 mm x 250 mm) (Rpepotepeh). Semi-preparative reverse-phase NRI C was performed on a Setipi 10 μm C18 column (22 mm x 250 mm) (Rpepotepeh) or a Uirieg 10 μm column, 300 A g C18 (21.2 mm x 250 mm) (Rpepotepeh). Separation was achieved using linear gradients of buffer B in A (mobile phase A: water containing 0.15 95 TEA, mobile phase B: acetonitrile (ACM) containing 0.1 95 TEA) at a flow rate of 1 mL/min. (analytical) and 15 ml/min (preparative). Separation was achieved using linear gradients of buffer B in A (mobile phase A: water containing 0.15 95 TEA, mobile phase B: acetonitrile (ACM) containing 0.1 95 TEA) at a flow rate of 1 mL/min. (analytical) and 15 ml/min (preparative).

Linker Activation and Dimerization (00688) Peptide monomer subunits were linked to form peptide dimer inhibitors as described below. (006891) Small-scale bis linker activation procedure: 5 ml of MMP was added to a glass container containing ISA diacid (304.2 mg, 1 mmol), M-hydroxysuccinimide (MH, 253.2 mg, 2.2 equiv., 2.2 mmol) and a stirrer. The mixture was stirred at room temperature until complete dissolution of solid starting materials. M, M'-dicyclohexylcarbodiimide (OSS, 453.9 mg, 2.2 equiv., 2.2 mmol) was then added to the mixture. Precipitation occurred within 10 min and the reaction mixture was further stirred at room temperature overnight. The reaction mixture was then filtered to remove precipitated dicyclohexylurea (DCI). The activated linker was kept in a closed container before use for dimerization. The nominal concentration of the activated linker was approximately 0.20 M. 00690) Dimerization using PEG linkers does not require a preliminary activation stage.

Commercially available preactivated bifunctional PEG linkers were used.

I00691| Dimerization procedure: 2 ml of anhydrous OME was added to a container containing peptide monomer (0.1 mmol). The pH of the peptide was adjusted to 8-9 with OSIEA. Activated linker (BA or PEG13, PEG25) (0.48 equiv 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 by analytical NRI C. The time for completion of the dimerization reaction varied depending on the linker. After completion of the reaction, the peptide was precipitated in cold ether and centrifuged. The ether layer of the supernatant was discarded. The deposition step was repeated twice. The crude dimer was then purified using reverse-phase NRI C (Hypa C18 media, 10 µm, 100A, mobile phase A: water containing 0.1 95 TEA, mobile phase B: acetonitrile (ACM) containing 0.1 95 TEA , gradient from 15958 and

From change to 4595 V in 60 min, flow rate 15 ml/min). Fractions containing the pure product were then lyophilized in a lyophilizer.

Example 2

Characterization of peptide inhibition of interleukin-23 binding to the interleukin-23 receptor

I00692| Peptide optimization was performed to identify peptide inhibitors of II signaling. - 23, which were active at low concentrations (for example, IC50 "10 NM), while showing stability in the gastrointestinal tract (I). Some peptides were tested to identify peptides that inhibit the binding of I/-23 to human 1-23 and inhibit the functional activity of I/-23/LI/-23K, as described below. Tested peptides included peptides containing a number of different cyclization chemistries, including, for example, cyclic amides (side chain cyclizations), peptides containing a disulfide bond, for example, between two residues

Rap, and peptides containing a thioether bond. Peptide inhibitors of this invention include, but are not limited to, peptides with any of the structures shown herein. In addition, the peptide inhibitors of the present invention include those having the same amino acid sequence as the peptides or structures described herein, without the need for the same or any of the "cap groups" at the M- or C-terminus , such as, for example, As or MN".

I00693| The analyzes performed to determine the activity of the peptides are described below, and the results of these analyzes are presented in tables EZA-EZN, E4A and E4B, EBA-E5C, Eb, E7 and E8.

Human EHIZBA shows the I/23-I/23K competitive binding assay described below, rat EHIZA shows the rat EHIZBA 1/-23K competitive binding assay described below, and regazzntTEe shows the cellular analysis of retTATZ II -23K OV cells , described below. The peptides shown in the EZE-EZE tables are cyclized using a disulfide bridge formed between two cystetic residues in these peptides. Peptides shown in Table EE are dimerized via a linker fragment or through internal cysteine fragments as indicated. The peptides shown in Tables E4A and E4B are cyclized using the two Rep residues present in each of these peptides. The peptides shown in Table E5A are cyclized using a thioether bond between the indicated amino acid residues. Table E5B provides a typical structure showing a thioether cyclization, which is indicated in the table by the term "cyclo", with the cyclic region indicated in parentheses immediately thereafter. The monomer subunits of the 60 peptide dimers shown in Table E5C are cyclized as indicated by the term "cyclo" and linked to each other by the indicated linker. The peptides shown in Table Eb are cyclized using the ring-closing reaction of the indicated residues. Table E7 provides two typical structures depicting side chain cyclizations using cyclic amides, and the peptides in this table are cyclized as indicated after the term "cyclo." Table E8b shows peptides cyclized with a cysteine residue and a Rep residue. 00694) Peptide inhibitors of this invention include both cyclized forms of the peptides shown in this document and non-cyclized forms. For some peptides, an Aby residue is present where indicated, while in other embodiments referring to the non-cyclized form, the Aby may be referred to as a pZeg(CI) or pPotobeg residue.

Competitive binding analysis of EGIZA 1.23-I 2313 00695) ItthiopF 4NVH plate was coated with 50 ng/well I/23K piEs and incubated overnight at 4 "C. The wells were washed four times with RVZT, blocked with РВ5 containing Z 96 skim milk, for 1 hour at room temperature, and washed again four times with PB5T Serial dilutions of test peptides and 1-23 with a final concentration of 2 nM diluted in assay buffer (PB5 containing 1 95 skim milk), was added to each well and incubated for 2 hours at room temperature.After washing the wells, bound II-23 was detected by incubation with 50 ng/well goat anti-p40 polyclonal antibody (850 Zuziet5 MoAEZ309) diluted in assay buffer for 1 hour at room temperature. The wells were again washed four times with RVB5T. Secondary antibodies, NKR conjugated donkey anti-Ids antibody (daskzop IttipokKezeagsi I arogafogie5 Me705-035-147), diluted 1:5000 in b Uferi for analysis, then added, and incubated for 30 minutes at room temperature. The tablet was finally washed as described above. Signals were visualized using TMB of a one-component NKR membrane substrate, quenched with 2 M sulfuric acid and read spectrophotometrically at 450 nm. The IC50 values for the various test peptides determined from these data are shown in the tables

EZA-EZN, E4A and 4EB, E5A-E5C, Eb, E7 and E8.

Competitive binding analysis of rat EGISA 1I--23K

I00696| The assay plate was coated with 300 ng/well of I/-23K rat pES and incubated overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions

Of the test peptides and 1-23 with a final concentration of 7 nM was added to each well and incubated for 2 hours at room temperature. After washing the wells bound 1-23 was detected using polyclonal goat anti-p40 antibodies, and then HER conjugated donkey anti-dO goat antibodies. The signals were visualized with the help of single-component TMB

HER of the membrane substrate and quenched with 2 M sulfuric acid. IC50 values for various test peptides determined from these data are shown in Tables EZO, EZN, E4A, E4B, E5B, E5C and E8.

Cellular analysis of retTATZ II 23K OV cells

I00697| I--23 plays a central role in maintaining TP17 IP mimo differentiation. This process appears to be mediated mainly through transmitter and activator of transcription signals (TTATZ), phosphorylation of 5TATZ (to produce roTATZ) leads to up-regulation of COX and pro-inflammatory 1-17. This cellular assay shows the levels of ROtTATZ in OB expressing cells

I/-23E, when simulated with I-23 in the presence of test compounds. OB cells (ATS Moscow -2289), cultivated in KRMI-1640 medium (ATSS Mo30-2001), supplemented with 1095 EV5 and 1 95 glutamine, were seeded at a concentration of 5 x 10E5 cells/well in a 96-well plate for tissue cultures. Serial dilutions of test peptides and I/-23 with a final concentration of 0.5 nm were added to each well and incubated for 30 minutes at 37 "С in a humid chamber with 5 95 СО2.

Changes in phospho-5TATZ levels in cell lysates were detected using the Cibrio NTP pRAZTATZ cell assay kit according to the manufacturer's protocol for a two-plate assay.

IC5O values determined from these data are shown in tables EZE, EZO, EZN, E4A, E4B, E5B, ES and

E8 in the form of absolute values or ranges. Where not shown, data were not determined.

EZA table

Typical non-cyclic peptides and activities

ENZA II 238 / I 23

ZEOIIUO MO. Sequence in nmol

ISBO

EZA table

Typical non-cyclic peptides and activities

ENZA II 238 / I 23

ISBO

16.

TABLE

Typical peptides containing the motif СХХХХС (5EO IU MO:1479) with IC50О »1 µM in the competitive binding analysis of EGISA II 23-I, 231 89 |NuUSOB5MESUMUNUMUMNII SS 890 |NuUsVOMVASUMNURYAMNII SS 96 |NuUsvTMUUSUMNUvgaMNIi СССО98 -marusuUmntvayemNI 77777771 899 NU SAS-(-VIREMSUMUNTRYAMNIILGS//777771111111111111111111111111111

TABLE

Typical peptides containing the motif СХХХХС (5EO IU MO:1479) with IC50O »1 µM in competitive binding analysis EGISA II 23-I, 231

ESS TABLE

Typical peptides containing the CXXXXX motif (ZEO IU MO:1479) with IC50 from 500 nM to 1000 nM in the competitive binding analysis of EGISA II 23-I 238

EZO TABLE

Typical peptides containing the CXXXXX motif (5EO IU MO:1479) with IS5O "500 NM in the competitive binding analysis of EGISA 1 23-I. 238

EZO TABLE

Typical peptides containing the CXXXXX motif (5EO IU MO:1479) with IS5O "500 NM in the competitive binding analysis of EGISA 1 23-I. 238

EZE table

IC50 of typical peptides containing the CXXXXS motif (5EO IU MO 1479), with activities of 5EOU. . EPBA 1238 / raaiz NTRE v

NU-SAOMUSUMNTESV-MN"

As-SAOM SUM NTEO-TSO) in ON

As-SAOMUSUMNTESAR-(About UVI ON

As-SAOMUSUMNTESAGA2O- (0) in ON

AS-STOMKSUMNTEO-MN"

As-SADMMSUMI-KO)NivI-THEO-(AEAI-(O) ug|-MN» 281 ris dimerization through lysine at the M-end yyyyyyyyyyyyyy

As-KMTM OVU MO V-MN")" 284 ris dimerization through lysine at the C-end yyyyyyyyyyyyyy

As-AMTM OM MOK-MNg)" i--"10 NM; -10-25 NM yah - 25-100 nM, ex - 100-1000 nM, tee-1000-10000 NM

EZE table

IC50O of typical peptide dimers

EPISODE

5 EOI. . . n 2g3vlI23

Mo. Linker fragment Human sequence

NM cysteine grew through lysine NU-IVATZY5SAYUM SUM NT ES-OH) 20105 510,000 grew through lysine As-KO)Huz|- ZSADM USUMNTEO-OH) 2010 510,000

IS through lysine (then under the control of SAVMLUSUMNTESON) 10,000 rose through lysine NU-AEA-SAYUDM SUM NT EO-ON) 2010 510,000 rose through lysine As-KO)Huz|-SAYUM/ MSUMUNTEO-ON) 2010 510,000 rose through lysine As-SKOMUUSUMNTES-OH) gRIS 510,000 ris through lysine As-SASMUXUM NTES-OH) gris 510,000 ris through lysine As-SADMUSMMKTEO-OH) 2010 nin rose through lysine As-SAVMUUSUMNKES-OH) 2010 510,000 ris through lysine As- SADM SUM NTKO-ON) 2010 rose through lysine As-SAVMUUSUM NTEOK-ON) 2010 510,000 rose through lysine As-SADMUSUM NTEaOK) g0IS

IS through lysine (lo-saOMUSUMNTE OV AIvuKO uv GON)

IS through lysine (ps SAOMLUSUMNTEOTABANKO IN NON)

KI pizinzSvna | (nu -sARM/USUMNTROeK-ON) 20

PEG25 through lysine NUu-IVAIaVI-ZSAOMUSUMNTRO-ONI LEGO | 000

PEG25 through lysine As-KO) ug|-6ESADM USUMNTEO-OH) 2 ni

PEG25 through lysine As-(0)I uv)-IVAai-SASUMUSMUMNTRa-ON» Her

PEG25 through lysine NU--(AEAI-SAOM SUM NTEI-ON)»2 ni

PEG25 through lysine As-KO) uv|I-CAOM/ MSUMNTEO-ON) 2 n

PEG25 through lysine As-SKOMUSUMNTES-ON)» ny

PEG25 through lysine As-SAOMKSUMNTES-ONI2 in

EZE table

IC50O of typical peptide dimers

EPISODE my Fragment-linker The sequence of the lurine.

NM

PPE |PEGho5perezlisin | (As-SAYUMSUMKTRO-ON»y: SS: 5 ///|i.7777yu 314 |PEGho5cerezlysine | (As-SAYUMSUMNKRa-OH): С LS/://////і1Is720 315 |PEGho5cerezlysine | (As-SAYUMUSUMNTKO- OH»: І С/::: 17777777 316 |PEGO5pereslysine | (As-SAOMUSUMUNTE-COILUESONE» ХГ 317 |PEGO5pereslysine | (As-SAOMUSUMNTROTSOMUEVON» -b5 |: 318 |PEGO5pereslysine |(As-SAOMUSUMUNTESrAaGoIOMuUErON» 5 | PE) As-SAOMUUSUM/NTESTAEAN(OUuUVION" se DON ruoyuchstntko 17 x-"10 nm; -10-25 nM and - 25-100 nM, and - 100-1000 nM, 7y5-1000-10000 nm

EZO table

IC50 of typical peptides containing the motif СХХУХХХХХХ-(О уз| (ZEO 10 MO:1480)

EI5A EIP5BA reiaiz

ZEO I Sequence 23/11 231 23/ I 238 NTVE

Mo. human rat (nm)

NM NM

16 p. As-SOOMOSUMUVASpageOiAEArOHuyerMna. | 113 | 77777177 17 As-SOPMOSUMUAIOoCTEOTABAN(OUVIMN | 206 | g 18 AsSOpMOsSUMUK-Sario|AEATSIOMuNMNa.Yi | 32 | i 19 AsSSOpMOSUMNIOSariRoiABAN(OubeMnN. | 49 | | 59

AS-SOPMOSUMVIROCHABANOOUVMNII | 51 | 1 21 AssOpMOsSUM PA rariRo-iABAIOzhHuMna | 25

As-SOpMOSU-TisOTIKRa-AEATSIOMUZIMNI | 530000 26 AS-SOPMOSMUARAVRAIABAN (OUUMNNNNA | 37 28 AS-SO-SO-SUMMARYUMSUIUNIUNIAS 77777 220 | Sh (D 29 AS S-S-S-S-Tu-Suppur 1 B zhf8 31 As-SM-MeliaGOMUSUMuNTESTAEAROuvrMNna | 183 33 AS-SAOMUUSUM Si KEo-IV-Aar(OzhMubrMNnI | 52 | 1 29 34 AS-SAOMUUSUM Si pere V-AarOzuvmMna | 518 | 9 AS-SAOMUUSUM Si tyareo-m-AnaIomuvr . | 153 36 AS-SAOMUUSUM SY Spareo-V-AaromuvrmnMnai | 223 37 As-SAOMUUSU-P-mardistruga-v-AaromuvrmnMna.i | 79 | 22 38 AS-SAOMUUSUM SY MEo-IV-Aar(OzhMurMNnI | 124 | (1 ) -O)AarURsCHABATIOMuVIMN | 232 44 As-SOPMOSUM VAD MEOLAEATIOUVMNaY | 2207 | g

ASSOPMOSUM-(Opets UROo|ABAC(OMuIrMNn | 188 46 (As-SOPMOSUM-(O)RPeGDMRODABAN(OUVIMNa | 848 | her

EZO table

IC50 of typical peptides containing the motif СХХУХХХХХХ-(О уз| (ZEO 10 MO:1480)

EPOA EPIZA reiaiZ 5EO IU Sequence p-23/ p 2ЗАИ23/23ВИ DtTVe

Mo. human rat M

NM NM (nm)

As-SOPMOSUM-(O)А5пИМЕСАЕАЦОУВМНАЙ | 6 | 717

As-SOTMOSUMI-(O) GiP-MES-AEAY- (ОЙ ug|-MNeg 3662 ІІ

As-SOPMOSUM-(O)A5rI MES AEATSSOKHUZMN.Y | 129 | her

As-SOTUMOSUMI-(SISH-(O)» eshES-(AEATOMUuYEMNa | 0709 Her

As-SOTUMOSMUMI-(СЩ-(О)Рпе|-EO-(AEAI- (ОЙ uz|-МН» 1304 1

As-SOTUMMOSMMM-(SISH-(O)A5pI-ha-ABAI OM UVMNa. | 0026911

AS-SOTMOSUMU-(SSHAO) GAI-EYA-(AEAI- (OS UgI-MN" 1214

As-SOTMOSUM-I (AorIi-UMO-(AEAN (OS UvI-MN) g | 1

As-SOTUMMOSM-(a-Me TtrI-VUMO-(AEAI- (OH uUz|-MN) "vovoy

As-SOTMOSU-Ta Me TtriI-(St-(pi esh-MO-(AEAY- 56 V uvI-MNH -6000

As-SOTMOSUM-|SISH-UMO-IAEANO) Suz|-МНе 75383

As-SOTMOSMM-(Aori(SariMO-(AEAIOiueMN. 10088011

As-SOTUMMOSMMUM-(SISH-ME-(OAanAEAROyuguvMNa 10897. 60 fAs-SOPMOSUMU-ISSH-ME-(Omzesh-(AEBAYUOMUuUZeMN. | 0444011

AS-SOTMMOSMMM-(SSH-ME-(ORAEMAEAROguUVMNa | 0784011

As-SOTMMOSMMUM-(SSH-ME-(O3AZpAEATOUuUeMNaY 1009511

As-SOTUMOSUMI-ISSH-ME-(O)TIY-AEBAN (OzhUVMN. | 518 Her

AS-SOTUMOSUMM-(SSH-ME-(O)ZAZrIAEATSNOiUuUZEMNII | OB

As-S-IM-MeAga| HMOSUM/ VMES-IAEAI- (ОЙ uUv|I-MN» 066 | As-S-IM-MeOip-TUMOSUMUVMEO-AEAOMgUZIMNa | 069 | 85 | 101

As-S-ISE-TUOSUMVURO-IADEAIN(O)S UVI MN" 68 fAs-SAOMUMSUMI-(Ogpi-(Oari-gO-IAEBAIOiUEMna. 0198821

As-SAOM/MSU-(11-MaP-IOgpI-(Oar|-PO-IAEAI-KO) uzi-

Mne 302 to OMS teLo tar EOTAEANKO UVI; 530000 i sauce tepenO ti bari koTABANKO Uvi 80000

As-SADM/MSU-IViri-OtiI(SariEs-AEAN(OYUUEMna) AND 530,000 OF IT

As-SAOM/MUSU-(Rpe(3,5-E2)-(OgpI-(IOSarI-RO-IAEAY- 73 -6000 )suz| МН» 74. | AS-SAOMUSU-IRpe(SOMNg) BUT those (OarI- RO-IAEA)- 8000 )suz| MN" 75. | AS-SAOM/USU-IRpe(4-SEzNO ti (bari-RO-IAEA)- 51000 )suz| MN"

As-SAOM/MSU-(Rpe(2,4-Meg)-IOgti-IOarI-RO-IAEAY- 76 o uv-MH 1525

As-SMTMOSUUM Mav-IAEAI (ON UvI-MN» 898 | /!

NuU-SMTUMOSMMI Ma V-GAEAI- OII uv|I-MNg 30000 Her

As-SAOMMSU-|VPTtrI(Oti-(OarI-RO--(AEAI-(O) uv|- 78 MN -6000 tv OM USTA teme oo ROTABAN(OV UVI 6000

As-SAOM/MSUMI-IOgti-(D-spiral-pip|-PO-I(AEAI-KO)Y uzi- 79

MN" to her

Vi As-SAYUMUUSU-(4-Phenylcyclohexylalanine|-(OgpI-(Oari|- 3000

ES-IAEAIN(O)uUgI-MN 7

As-SADM/MSUMU-(Ogpi-IAiVI-Ea-GAEAIN (OS ug|-MN" tov

As-SOMMSUMI-(Ogpi-IDiethylIuU|-EO-IAEAI-(O)Yi uv1- 83 МН -6000

EZO table

IC50 of typical peptides containing the motif СХХУХХХХХХ-(О уз| (ZEO 10 MO:1480)

EPOA EPIZA reiaiZ vka IIU Sequence p-23/ p 2ЗАИ23/23ВИ DtTVe. human rat (nm)

NM NM ovo AosAI IOM a Merlos, PNO OarneOTAEAI, yuyu 85 |As-SOTMOSU|VpRIerVUMO-IAEAIOM UVI MN | 530000 | HER 86 |As-SOTMOSU-|Y-ma)d vUMo-iAEAN(OMuzrMNna | 530000 | І 321 fAssSOTMOsSU|VptuTAUMo-AEATsOMuyeIMNa | 530000 | Her! 322 |As-SOTMOSU-|VpRpe(-R)-VUMO-AEAINOmuyeIMNn. | 30000 | J. 777 zaz | OTMOSU VKM Fenig NUMO TABANKO uyu yuyu 324 Sh|AssSOPMOSURpe(34- Si) vUMO|ABAC(OduzIrMNn|Y 530000 | -.(/O/ HC 325 Sh|AssSSOgMOSU TaarvUMO|AEAC(OMuvrmMna | 530000 | ЇЇ 326 Щ|АсССОпМОСУМУвіВпіецМоАБАЦОлуєрМНна | 224 327 Щ|АССОПМОСУМУВІАвІМОе|АБАН(ОМуЗрМНа | 10656 | :Г 328 ЩфАсССОгМОСУМУвіВпАаІМОо|АБАр(ОдугрМНа | 457 329 Щ|АсССОпМОСУМУвіВпМармо|АЕАр(ОлуєрМНне | 328 зво о ОТМОСУУНТВ спіралеіп МОТАЕАНКО Уві; аю

МН» 31 ШфАСССОГМОСУМУВСИМОАЕАРОМугМне. | 250 | |! 932 Sh|ASSOPMOSUM Ve UMo|ABAN(OLuvrmMna.d | z | sh(! 9333 Sh|ASSSOPMOSUMVAI UMO |ABAr(OiLugrMNn. | 2903 | / 334 Sh|AssSOpMOSUMVpliarUMoCAEATC(OLuermne. | 355 335 Ш|AssSOpMOSUMVyMarumoi|Aeats. | 50 | !/ 336 C|ASSOPMOSUM-V-spiral-pip UMODAEAN(OMLuUZrMNYA »b00o | І 337 Щ|ASSOPMOSUM VA UMO AEAR(OMugMne. | 922 938 Щ|AsmMATMOi|MesSuZI UM vKESIAEATCI(OuviMnna | 4251 9339 TsKROVK|TAASOMADUS (Oluvmne | 60 | 9 340 C | A5 Nallobumzkrozatzarozharozhmn | 2816 | ..: G O Z41 (Assomum Suinvkrozabatzoluumnnnn. 777 | 664 342 : | 132 345 Ts|ASSOTMOSUM pe EMOCHAEATS(OdMuerMNaYi | 222 346 Sh|ASS5PMUESUMVUUSIABATSOMubrMNna 7 | 47 | HER 347 |AssOTrTUOSMUVURO|ABAN(OMuZrMN. | 22 | 69 | 55 348 Sh|AssSSOgGMOSUM OtArye Otr. 349

Zo (fAsS|M-Mesug|TUOSUMVURO|AEAN(OLugrMNnai | 80 | /

ZB ShfAssSraBrtmOsSUMVURSIAEAETSOMueIMne | 23 | 51 | 99 352 Sh|AssSSOTMOSUMOTIOSariRo|AeAr(OMugrMNai | lo | / 353 Sh|AssSS5PUOSUM Oti (rarrusiAEAROduvrMNn | 37 | |! 354 Sh|ASSZPUESUM SI OariusiaAeAr(OLuvMna.i | 74 | / 355 Sh|ASSOTMOSEREOtIOar(igouv42AMEARr) Sh|ASSRPIUOSUMVURSTABAD(OMUVMN | 422 9347 Ts|ASS5PMUESUM Ot rarrus|AEAr(OdluzrMNna | 3388 | / 358 Sh|ASSSZPMUESUMVUROTABAN(OMUrMNe.Yi | 48 359 Ts|AssITUUOSUMVURO|ABAN(OLUVMNe. | 134 | OarihiiiAear (Omtormne | 1885 461 Sh | Assentmoumuzurozabatzomnnnnnn | 21 | 79 | 96 9362 | ASC-OUARATMUMUMUSUMUSIABURSIAMMNE | 31 | 363 363

EZO table

IC50 of typical peptides containing the motif СХХУХХХХХХ-(О уз| (ZEO 10 MO:1480)

EIPZA EPZA reiaiz

ZEO I Sequence 23/23 23/11 238 NTVE

Mo. human rat (nm)

NM NM

365 C | Assortmosimvisisisisisispispoxro | Aean (Ouvrmne. 51 17777711 (370 56

EZN table

IC50 of typical peptides containing the motif СХМУХХХХХ (5EO IU MO:1481)

ENZA II 23/LEG IA 1Y 23, reiaiz

BO Sequence pШоЗА | eZA | Ntve

Mo. human rat (nm)

NM NM

371 ASSZPUESUMVTRO-MNY 77777777 11252 | 7 372 ASSSOBMESUMATUEMNa 77777771 11366 |. HER 374 ASSSKlUTSUMNTUO-MN.Y 77777771 1131 | |Її11 375 АССВТМЕСУМНЕУЗАМН.ЇГ////77777777777777717 11416 ЇЇ 376 АсССВТМ/ТСУМНЕМО-МНЇГ///777777777777771717 11434 377 АССЕПМОСУМНЕУВАМНЇ 77777771 1155 ЇЇ 379 АССОЛУОС-МН 77777771 1530000... |: о З80 АССВТМОС-МНе 77777771 1530000... |:

ZV ASSAOMUSIMNI 77777771 1530000... |: 382 ASSAOMUSUMNAMNa 77777777 1530000 |......7.STU 383 ASSAOMUSUMNAMNa 77777777 15300001 Her 384 ASSAOMUSUMNI-MN 77777777 |114795 -:: о З85 АССАОМУСУМНТЕМНе 77777771 13277 386 АССМІМОСУУУЄУаВМНЇ 77777771 1163 ЇЇ 387 АССВТМОСУМНЕВО-МН.ЇЛГ/З/77777777777717 11111111 Її їг1 388 АССВТМУЕСУМНТРЯ-МНІЇд///777777777777717 ї1111111111ї1111ї1 389 АССОПУОСУМНЕРО-МНеЇГ//777777777171171ї111111111Ї11111г1 390 АсССВТМОСУМООРОСЕМНЇ 77777777 11781 Її 391 АССВБУОСММСМРаРО- МН.Я //-/-//777777777717171111711 Her Я11 392 AsSSVATMOSUUMKMarV-MN 77777777 11739 Her 393 AsSSOTMOSMMKArOs-MNne 77777777 117167 | HER 395 ASSZPUESUMZOVARO-MN 77777777 1240 | ЇЇ 396 АССОПМУЕСУМАТЕОРЕО-МН.Ї 77777777 11581111 397 АССВАТМОСУМОЕКОТО-МН 77777777 1171186 Її 1 398 АсССОпПУОСММСОВІЯО-МН 77777777 117193 ЇЇ 399 АССВТМОСУМТКРОЗЕР-МНад//-/-777777777717171187 11111115 340 АССВЗУУОСУМУМКРаАСО-МНе 77777777 177142 | 7 341 ASSNTMOSUUMMEOOEE-MN.Y 77777777 1323 342 ASSVTMOSUMMROMEO-MNe 77777777 117127

I 345 |ASSNIMOSUMUZTOREA-MN.Y 77777777 1222 | (

EZN table

IC50 of typical peptides containing the motif СХМУХХХХХ (5EO IU MO:1481)

ENZA ІІ 23/LEG ІА 1І 23, reiaiz my Sequence pЩоЗА | eZA | Ntve. human rat (nm)

NM NM

346 AsSSZPUOSUMZKOZOO5-МНе 77777777 1771933 | 204 | 89 347 АССНІМОСУУМММатТВО-МНе 77777777 13 ЇЇ 348 АССНІМОСУМВАМОСНО-МНеЇ 77777777 1210 Її 11 349 АСЗОСВТМОСУМНЕВО-МНЇ 77777777 1390 ЇЇ 350 АСМКСВлУОСУМНЕМО-МН.Ї 77777777 11712 351 АСЗОСВТМЕСММУНЕМА-МНаЇГ/-/77777777711111257 352 АСОАСВТМЕСУМНКРЯ-МНЇ 77777777 1171656 | HER 353 ASRESNTMESUMNKERO-MN.YIL///777777777777717 11197 | 7 354 OC ASOMSOTMESUMUVERYA-MNaY 77777771 117145 | 7 355 ASOVSUTMUESUMUVERYA-MNaYidG////77777777777717 1217 | 1 356 ASAROSNTMOSUMNERO-MNY 77777777 1228 357 OC ASKEMSVTMESUMVERO-MN.Y 77777777 17148 | 7 358 Ts|ASMOBS5PUOSUMVTRA-MNYI 77777777 17138, | 77777717 359 AsSEESZTMOSUMUVKRO-MNe 77777777 17153 | 77717117 24 360 Asra5sSATMOSUMNOga-МНе 77777777 1240 | HER 361 AS-MAOSNOMUESUMVERO-MNe 77777777 171872 | HER 362 ASEVMSZTMUESUMVARO-MN. 77777777 171855 363 As-VUOS5TMESUMVERO-MNaYidG//-:777777777/ 1147 | 1 364 ASKAMSVTMOSUMUAKRE-MN////7777777777/ 1142 | 7 365 AsUEOSVTMOSUMEMEO-МНе 77777777 11280 | ЇЇ 366 АсССОпПУОСУМАМЕОО8-МН.Їд/////7777777777777/ її Їг1 367 АсССОПУОСУМАМРЕВО-МН.ЇГ/:77777777777/ 17111111 її 368 АсССОРМОСУМВЕРОРО-МНЯЇГ/77777777117 11111111 г1 369 АсССОрМОСУМвБРаРО-МНаЇГ//:/777777/ ї177111111171ї111111Їг1 370 АсССОпПУОСУМвТІаРВ- MNaYIG/: 77777777 и1111111111Ї1111Йг1 371 АСССВТМОSUMОМЕО-МНе 77777771 11235 | Y / 372 | As-SsaTMOSUMVvTRORO-MNYI 77777777 11176 HER 373 As-SePUOSUMNKROaME-MNe 77777777 118 | 7 374 OC As-SVTMESUMUVTUYARB-MN.YI 77777777 1116 HER 375 As-SVTMOSUMMEMBOM-MNe /////77777777777171і199 HER 376 AsSSOPUOSUMVEROVO-MNY 77777777 171656 | 7 377 ASSSOpUOSUMvTNeoV-MNh 77777777 1783 | HER 378 AsSSVOMOSMUMyaARAMNaY 77777771 1330 HER 379 AsSSOPUOSUMK(Ratsemo-Mn.

ZV AsSSOPUOSUMnetsEOs-MN 77777777 11128 | HER 382 ASSOPUSAVOS-(O)TUTMUvserEMO-MN" 1 530000 | Y .YUG( (|: 383 AsSSOpUOS-(M-MetumpetsEMO-MN. 1 530000 | : 384 AsSSOpUOS-isoNiMuChvpeEMO-MNa 1530000 | Y ...yuYUC( |: 385 AsSSOPUOSEMpeEMO-MNa 77777777 1530000 |. Y ..:: (| Euzhks 386 Association-Mn. 77777777777777777777777 (OzhuvMNa 7777/1121 Her 391 AsSSOpUOSUMChnNetsEMO-ON 777777777777771711317 | 1 393 AsSSOpUOSUMChneEMAV-MNa 77777777 11193 Her 394 AsSSOpPUOSUMChNeEME-MN. 777777182 | 17182 | 17182

EZN table

IC50 of typical peptides containing the motif СХМУХХХХХ (5EO IU MO:1481)

ENZA II 23/LEG IA 1Y 23, reiaiz

ZBO about Sequence 123 | LeZA | Ntve

Mo. human rat (nm)

NM NM

96 Тs|AssOopMOSUMpecEMO-МНе.І 77777711 347 1777771 397 І|АсСсОпМОСUMPецЕМН 77777777 1 45 11 399 І|АсСсСОпМОСUMPеНО-СМНе.І 77777777 | 67 1777771 401 Ts|AssOopMOSUMm nev eMNn: 77777771 | 158. 17777771 402 ЦС|АСССОпМОСУМПЕТО-МН 77777777 | 88 17777711 403 Ts|AssSsOpMOSUMPetsemMamMne. 77777771 | 395 1. :( to her with 404 c | Assassompmospetsrmo-mneum. 77777777 . 77777771 1 7109 17777771 408 C | Assassin-MNN 777777777777777

А fАсССОгпМосСУМТЕМО-МНИИСЛС///77777777777771 | 714 17777771 42 fASSOPMOSUMEEMO-MNYUY 77777777 | 147-177 17 413 fAssOTMESUM pe EMO-MNa.Yid 77777777 | 112 7777/1777 414 фАсСОТМРСУМЧНешЭМО-МНа 77777777 | 2795 |Y.:::ЖЙЙ ГГ | : X A15 Fassopmumum (Piezzhem-Mne. 777777777 МН 77777777 | 164 17777771 419 ЦфАссОоТаОсСУМпецЕМО-МНе 77777777 | 00001777 Її 420 Ц|АсССОТРОСУМ-ецЕМО-МНаЇ 77777777 | 00001777 Її 421 Ц|АсСОТМОСУМпецЕМО-МНа 77777777 | мб 177711 422 Ц|АсСОТВОСУМ- пе ЕМО-МНа 77777777 | мб 17777 Її 423 C | Association-Chnpetsum-MNA 7777777 77777777| .id 77777771 | 205 и.Й.Й...7/ДГ(-/ 451 TsfAsSsSRTMOSUM Not EMO-MNY 77777777 | 27412 1...7.7./(.(Х 452 ІС|АсССМлУОСУМ pe EMaMNYU.Й 77777777 | 61 171 453 Ts|AssSotmOsSUMPetsEMO-MNe.Y 77777777 | 167 17777771 455 Ts|AsSSETMOSUMNetseEMO-MN 77777777 | 1 1717111 456 ЦС|АССсСОпMOSUMIM-МесецЕМО-МН | 56000 17777771 459 ТС|АсССОпМОСИОМЕРпеИМ/|(tecEMO-МН | «300001... 461 ТС|АССОпМОСИПТутм пред еМО-МНе. | 60001... 462 Ц|АСССОпМОССИВРИМнецЕМО-СМН | 77777 | ЦИЙ... 2ГЙ... 2ГЙ 4 337 1 ASSSSOpMOSUMODREMO-MNa 77777777 | 166 | 163 | 76

EZN table

IC50 of typical peptides containing the motif СХМУХХХХХ (5EO IU MO:1481)

ENZA II 23/LEG IA 1Й 23, reiaiz my Sequence 123 | LeZA | Ntve. human rat (nm)

NM NM

466 Ts|AssOopMOSUMpecEMOR-MNY 77777777 1 797 1 1 467 Ts|AssOopMOSUMpecEMOV MN 7777777 | 180 of her! 468 Ts|AssSOpMOSUMPetsEMO-(r)bSHMNn | 188 17777771 469 C | Assosopmos (O Merpezmo-MNNE 0 | 300001 ... 470 C | Assassompmospetsmoron 777777777 7777777 | 174 17777717 473 Ц|АсССсОпМОСУМпецЕМОРМН 77777777 | 131 ї77777171Г1 474 Ц|АсСсОпМОСУМпецЕМОВ МН 7777777 | 129 17777771 475 |АсССсОпМОСУМпецЕМОММНа. 77777777 | 66 1 4 ДЮ 23 476 Ц|АсСсОпМОСУМпецЕМОТ МН. 77777777 | 1во 17777771 477 Ц|АсССсОпМОСУМптмецЕМОВаМНе. 0 | 10000177 | 1000 478 (|АС-РСОТМОСУМ ве ЕМО-МНаЇ 77777777 17117197 | 11117171 481 Ц|АСЕСОТМОСУМЧНецЕМО-МНеЇ 777 Ї7777711117111111Гр 482 Ц|АсМСОпМОсСУМ пе ЕМО-МНе.Їд 77777771 Ї77777117117111111Г 483 Ц|АсСвсСОпМОсСУМ-пецЕМО-МНе.Ї 77777777 Ї77777171717171711171СГ 484 Ц | Assxopmoza2-Matsneum-Mne. 77777 | 126 17777771 490 Ts 1.Y.Y...77 17 491 Ts|AssSSOpMOSsUNpecEMO-MNa 77777777 | 398.1... 492 Ts|AsSsOopMOsS-u(oMe) m pecEMO-MNe | 300001... 494 Ts|AssOopMOSsUu(OoMe)(pesh-EMA-MNYI | 998 Y." 2 ЖБж5ф 495 Ts|AssSSOpMOSsnnNipetsEMO-MNaY 77777777 | 148 17777777 17 496 Ts|AsSSOpMOsSU(aMettrupttetsEOs | 90 150 3H 40... Ts|AsSOTM(K(PEGVDSUUMEMO-MN.Y 7 | 212 1... 498 Ts|AsSSOpMOSUMLIMo-MNe 77777777 | 800 171

As-SOTM/-(K(PEGODSMUU-(K(PEGVTS-EMO-MN)" 753 500 TsassSOTMK(RatusSUMEMO-MN 777 | "30000171 501 fAsSsSOgMOSUM Ot K(Rat)umMeMNn | 56000 17777771

As-SIu-KO)Avp|(0)С1y-(O ei-(0)TGtr-(0B)Tug-(0)Suv-oo em v nn A es: NI NI 5OZ TSasSsSOpMOSUM (Ot) uK(pEGVD MO МН | 169 17777771 504 ЦфАССВЛУОСУМНЕВО-МНЇЛ//7777777777777771 | 7166 17777711 505 ЦфАсССвлуУєСУМНТРО-МНЇ 77777777 | 33 1777771 506 ЦфАсССОпМОСУМНЕРО-МН.Ї 77777771 | 16917771 507 Ц|АсСсСОпМОСУМАМЕСО5-МНе 77777777 | 196 1 щЩДщ ЇЇ 508 ЦфАсСсСОпМОСУМАМРЕБО-МНаЇ 77777777 | 315 17777771

TSasSSOOMOSUMVERORO-MN.YIG///77777777771 | 82177771 50 TsfAsSSOOMOSUMABROROMN.Y 77777777 | 717 17771711 511 fАсСsOTpMOSUMVTORUMN. 77777777 | 66 1771 512 Ts|AssSOpMOSUM(O)ROREMO-MNa 7 | 53000011.

EZN table

IC50 of typical peptides containing the motif СХМУХХХХХ (5EO IU MO:1481)

EPBA I 23/ENBA 23 reiaiZ my Rat Man Sequence NTVE

NM NM (NM) 516 C | Assosopmos (I-Marodzpremo-MN | 7145 | Vrchshch | 98 517 C | Associationsumlek (Rant) SMMNN. 777777777777 | 252 177777 of the 52nd TsfAsSSOBMESUMVTUO-MNI 77777777 | 366 17777171

Table E4A

IC50 of typical examples of peptide dimers containing the motif Ac-IRep|-XXMUX-IRep|-XXXXX (ZEO 10

MO:1482), and analogues

FEOYU | | EPIBA | BPBA | tore

MO Consistency of a person | rat NTVE and (nm) (nm) (nm)

Ias-I(RepI-OTUMO-(RepiI-(Rpe(4-OMe)I-(2-MaC-(o-Me! uz|- sent

EMa-MNgr 0IS

Ias-I(RepI-OTUMO-(RepiI-(Rpe(4-OMe)I-(2-MaC-(o-Me! uz|- field

EMOa-MNa|» PEG25

IAs-I(RepI-OT M O-(RepiI-(Rpe(|4-(2-aminoethoxy) |-(2-Mas|- posle a-Me-Iesch-OMM-MNhi|» IS

IAs-I(RepI-OT M O-(RepiI-(Rpe(|4-(2-aminoethoxy) |-(2-Mas|- field

Is-Me-esh-OMMm-MNg|r» PEG25

IAs-I(RepI-OT M O-(RepiI-(Rpe(|4-(2-aminoethoxy) |-(2-Mas|- if

АиВИ-(сув(Ас)|-МО-МНг|» 01С

IAs-IRepi-SUTMO-(RepiI-(Рпе|4-(2-aminoethoxy)|-(2-MaC-posle)

AIBI-(suv(Ac)|Y-MO-MHg|g PEG25

Ias-I(RepI-OT M O-(RepiI-(Rpe(4-OMe)|-(2-Mai-(o-Mema!|- pol she

And uv(As)|-MM-(O) uz". 10 p kn o tables o PO PO

MacC- (d-MemaP-(Suz(Ac3-MM-(O) uz|g OS i acetylaminovto i

Maa-Memats-kMm-MNh|» 012 pase ogne no pos acetylaminovtoyu MA Hn

Mats-k-Isuv(As)|-MMm-MNgr 01

Ias-I(RepI-OTUMO-(RepiI-(Rpe(4-OMe)I-(2-MaC-(o-Me! uz|- field

And uv(As)I-MM-MANg» BIS oovza street I in her somneinya field

Maip-Ta-Memaii-P uz(As)|-MM-MNgi". O1C

I(As-I(RepI-OTUMO-(RepiI-(Rpe(4-SOMHn)I-(2-Ma|-(a-

Me! uzI-ISuv(As)-MM-MNg|» 012 ov M epitepes. doubtful May

KMM-MNg|» 012

I(As-IRepi-MTMO-IRepi-(Rpe(4-SOMHn)|-(2-MmaP|-I4-amino-pi and 4-carboxytetrahydropyran|-KMIM-Mnhy). O1S wa? oeM mer elitepesomna Te Mindstoi, half a year

KMM-MNg|» 012 oovzvo | ooielEM ote elitepog Somnai ne Myn Asmoi;

KMM-MNg|» 012 539 As|IReprmtm/OiRepTsROPe(4-SOMNOde-mMatse | 7/7 Y177777171171177

Table E4A

IC50 of typical examples of peptide dimers containing the motif Ac-IRep|-XXMUX-IRep|-XXXXX (ZEO 10

MO:1482), and analogues

FEOYU | | EPIBA | BPBA | tore

MO Consistency of a person | rat NTVE and (nm) (nm) (nm) 11 mesedkmmmnarv Her //77111111111111111111111111111111gr

I(As-IRepIi-MTMO-(Rep-(Rpe(4-OMe)I-(2-MaP-(AiVI-KMM)

Mn IS

IAs-(RepIi-MTMO-(RepI-(Rpe(4-OMe)|-(2-Ma/|-(4-amino-4-polshe carboxytetrahydropyrani-KMM-MNa|» OS ov potr epitepes copper cana)

Mngr IS ov potr epitepes copper ditch

Mgr IS

I(As-IRepIi-MTMO-IRepy-(Rpe(4-OMe)|-(2-Mai|-(a-Mei ec|- pol

KMM-MNg|» 012

I(Ac-I(RepI-OTUMO-(RepiI-(Rpe(4-SOMHn)I-(2-Ma|-(a-pol

Me uzI-(ISuv(As)-MM-MNag|» YuA

I(Ac-I(RepI-OTUMO-(RepiI-(Rpe(4-SOMHn)I-(2-Ma|-(a-pol

Me! uzI-(Suv(As)|-MIM-MNgi|2 POA-VAia i--«10 nm; 2-10-25 NM yah - 25-100 nm, yah - 100-1000 NM, tiie-1000-10000 nm

Table E4B

IC50 of typical peptides containing the As-IRep|-XXM/X-IRep|-XXXU motif and their base analogs

ZEO IU MO. Human sequence | rat | NTAVE (nm) (nm) (nm) 548 AND ASACREPIOM/MIREPIUMUAKRST|AEAN(O)- in MNa | 530000| | 2 Zuv (I 549 and Ascreyrepopmusurope Um (MEMMMME 11111 550 Iasireppotmoremoremu (M-Meltosmo-MN 71530000, 551 .І 11111 ov, warm ome)ne property of Meguvi

EMO-MN" oval ep epesgome) does not have the purpose of sl

I uv(As)|-MO-MN»g 563 AsiRepPOTMOREpI MU o-MeguvI(suvAsuMa-MNaY | 77 17717111.

Ac-(RepIi-OTUO-(RepIi-Irpe-(4-OMe)|lm-(a-Me! uz -

And uv(As)|-MO-MN»g oovvbo Te epilogue oMme)ne minena Meguvi

And uv(As) |-MO-MN»g

Ac-(RepI-OTUO-(RepiI-I(Rpe(4-OMe)1-11-Ma|-(o-Me uz1-

And uv(As) |-MO-MN»g

Table E4B

IC50 of typical peptides containing the As-IRep|-XXM/X-IRep|-XXHU motif, and analogues are 00000000000000000000000000

ZEO IU MO. Human sequence | rat | NTAVE (nm) (nm) (nm) ov, ee OTO trep Viv Ne Magtsoemes uv uv movo! 1 oovvvo|lotRTgo S echepepo(you see Mais Meg in; if

I uv(As)|Y-MO-MN» ooovveoloieepge PM reprle( vo) Mayo Meguvi; dog

And ув(Ас)|Й-MO-МН»2 ovo lovli pa repepesichnae meto Meguvi; dog

And uv(As)|Y-MO-MN»2

Bl di epTa tlo rap mainoemes uv uv(doyomo: ES ov irepnepe(va seIte Mao Messiah pes

EMO-MN"

Ac-(RepI-OTMO(RepiI-(Rpe(4-CM)1-(2-May-(o-MeOgpi- pes

EMO-MN" vm aiKepneme(ve tata maina meoti; dog

EMO-MN"

As-(RetT-OTUMOG(RepiI-I(Rpe(4-CHSO2H)1I-(2-Ma-(a- po

MeOgpI-EMa-MN"

As-(ReptT-OTUMO(H(RepiI-I(Rpe(4-СНаСОЕ2)И-(2-Май-(а- po

MeOgpI-EMa-MN» vl Zibepiteme (penta- RIO Mao Meoti; by

EMO-MN" ov" Zibepnepe sg Myna menuvi po

EMO-MN"

Ac-(RepI-OTMO(Repi-(Rpe|4-(2-aminoethoxy)|-(2-Ma|-(a- pok

Me! uzI-EMY-Mng

As-IRepI-OTMO(Repi-(Rpe(4-(2-aminoethoxy))-(2-Mai|-(a- po

Me! uzI1-ЕМЯ-МНг vv op Mypeshomeine property mes in pes

K(imrae)-MO-MH" succinic acid-IRepI-SPMO(RepiI-(Rpe(4-OMe)I-(2-

MaC-(a-MeH uzI-(Huz(Ac)|-Ma-MNe glutaric acid)-(RegpI-STMO(RepI-(Rpe(4-OMe)|-(2-

MaC-(a-Me!H uz|I-(Huz(As)|-Ma-MNe ovo oMoylorolya in C epitenes

OMe)|-(2-MaC-(o-Me! uz|-(Suv(Ac)-Mma-MNeg pyroglutamic acid-(Repi-OTUO(Repi-IPpe(4-

OMe)|I-(2-MaC-(o-Me! uz|-(Suv(Ac)-mMa-MNeg isovalerianova o ucha t p p PO 2-MaC-(a-MeH uzI-(Suz(AsDL-Ma -Mneg gallic acid-(RepIi-STUMO(RepI-Irpe(4-OMe)|-(2-Mas- psla (o-Me!uziI)-(Huv(Ac)D-mMa-MNeg octanoic acid-(RepI- OTMO(RepiI-(Rpe(4-OMe)|-(2- pes

MacC-(a-Me! uz|--(Guv(Ac)-Ma-MNeg oovveoacetic acid-I(RepI-STUMO(RepiI-(Pne(4- pes

OMe)|-(2-MaC--(c-Me!ugI-(Suv(Ac3-Ma-MNeg ovo oophenynovtic acid-IRepI-STUMO-(RepiI-I(Pne(4-

OMe)1-2-MaipP-Ta-Me! uziI-P .uz(As)3-Ma-MNeg 591 NugRepiAOMU/M|REP UUNTRO-MnY | 6000 | ..../G("HER

Ac-(RepI-OTMS-|(RepiI-(Rpe|4-(2-aminoethoxy) |-(2-MaC-(a- post

Me! uzI1-EMЯa-МНг

I 593 |As-RepttM/C-IRep|Cryee|y-(2-aminoethoxy)Ce-madoY " | |"

Table E4B

IC50 of typical peptides containing the Ac-IRep|-XXM/X-IRep|-XXU motif and analogues

EPBA | EEPBA | reaiz (nm) (nm) (nm) 1111 pmesuvrEmMamMniYidG///7111111111111111111111111111С111g

As-I(RepI-5TMO-(RepI-(Rpe(4-(2-aminoethoxy)|-(2-MaP-(a- post

Me! uzI-EMO-MN»g ooovevo oo all GMO vel Rpe r (o aminovtoxy)

MapP-(a-MeH ugI-EMa-MH» ooovavo 0 |Aoirop i Moi TU depieper aminoethoxyyi; pes 2-MaP-(a-Me uz|I-EMa-MH»

As-IRepI-MTUO-|Repi-Irpe(|4-(2-aminoethoxy)|-(2-MacC-(a- poch

Me! uzI-EMO-MN»g

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-aminoethoxy)|-(2-MaC-(a-

Me! uzi-P uv(As)-Ma-MNa

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-aminoethoxy) |-(2-Ma/|-(a-

Me! uziI-P uv(Ac)1-MM-AMN» voi Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-aminoethoxy)|-(2-MaC-(a- post

Me! uzI-EMO-MN»g

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-aminoethoxy)|-(2-MaC-(a-

My university-EMA-MN"

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-aminoethoxy)|-(2-MaC-(a-

Me esh-P uv(As)-MM-AMN"

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-aminoethoxy)|-(2-MaC-(a-

Me esh-OMIM-MN» ovo eMR per aminoetokomy T2Mai, poh

AIV-EMM-MN" oovovo oo p el P per aminoetokomy T2 Mai, poh

AiB-(suv(Ac)|-MM-MH» oovovo0AoTreO PUSTevo g (per aminoutoxyu Ya Mai; pokh divI-Isuv(Ac)|-MO-MH» acetylaminoethoxy)|-(2-MaC-(o-Mei!uv (Ac)-EMa-MH"

Ac-(RepI-I(c-MeOg(Ac)|- TUMO-(RepI-(Rpe(4-(2-pes acetylaminoethoxy)|-(2-MaC-(o-Mei! uv(Ac)-EMa- МН» voi Ac-(RepI-OTHUO-(RepI-IRpe|4-(2-acetylaminoethoxy) |-(2- poch

MaC-(a-MeH uz(As)|-(uv(As)|-Ma-MHg).

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-acetylaminoethoxy) |-(2- poch

MaC-(o-Me! uz(Ac)|-(Suv(Ac)|-MIM-MHg).

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-acetylaminoethoxy) |-(2- posl

MaC-(a-MeH uz(Ac)-EMIa-MH»g

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-acetylaminoethoxy) |-(2- posl

MaC-(o-MeH uv(As)-EMA-MH»g

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-acetylaminoethoxy) |-(2- poch

MaC-(o-MegH eshiI-(Suz(Ac)|-MM-MH»

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-acetylaminoethoxy) |-(2- poch

MaC-(a-MeH esh-OMM-MN"

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-acetylaminoethoxy) |-(2-posts map-(AivI-EMM-MH)

Ac-(RepI-OTHUO-(RepiI-Irpe|4-(2-acetylaminoethoxy)|-(2- poch map-(AivI-(suv(Ac)|-MM-MH»

Ac-(RepI-OTUO-(RepiI-Irpe|4-(2-acetylaminoethoxy) |-(2- poch map-AivI-(suv(Ac)-MO-MH») oovivo|doibep KO chep of element maitAiremm: 2 each

I 619 |AsiRepPOTM/ORepIRpe|d-(2-aminoethoxy)Ce-Mad | | |"

Table E4B

IC50 of typical peptides containing the As-IRep|-XXM/X-IRep|-XXXU motif and analogues

ZEO IU MO. Human sequence | rat | NTAVE (nm) (nm) (nm) 1111 This EMAEMNIIG/G//777111111111111111111111111111C1111g oovgoAsRot t M Rep Rper aminoetokoy Ne Maiyi; by divI-(suv(As)|Y-MM-MN»

Ac-(RepIi-OTUO-(RepiI-Irpe(4-OME)I-(2-Map-H(AIBI-poshe)

Guv(Ac)-MA-MH»g ovo |Aoirolt rel epor (b aminoethoxy Ne Maii; by divI-(suv(Ac)Y-MO-MH»

Ac-(RepIi-OTUO-(RepiI-IRpe(4-OME)I-(2-Map-H(AIBI- po

I uv(Ac)|-MO-MN» obsya |ool Op TRepMrper about amino-etocomy T2Mai, on divI-(suv(Ac)|Y-MA-MN»

Ac-(RepIi-OTUO-(RepiI-IRpe(4-OME)I-(2-Map-H(AIBI- po

GG uv(Ac)-MM-AMN" was not directly TEpeg about T2Mai amino flow, according to pHetsi-(Suv(Ac)|-M-|VAЯa|-МН»

As-IRep-OTUMO-(RepI-(Rpe(4-OMe)|-(2-MaP-(pi ec|- po

And uv(Ac)|-M-IVATa|-MNg ovo ooo PA ve Key aminoetokomy T2Mai, on diVI-(suv(Ac)|-M-(VATa|-MN»

Ac-(RepIi-OTUO-(RepiI-IRpe(4-OME)I-(2-Map-H(AIBI- po

Гув(Ас)|-M-VATA|-MNeg ovo |deibepim lot epitepesoMmenYa maindeneMn: po

МН» va lv m now aminoethoxyi Ne Mai; by pseshch-EMA-MN" oovva0 | Aoeeli lMTRean ele aminoutoxyi -Mai; dibI-(suv(Ac)|Y-MM-MN»

As-(Rep-MTUO-(Repi-(Rpe(4-OMe)|-(2-Mai-IAiVI|- po

And uv(As)|-M-IVATa|-MHg review in oepegaminoethoxy Ne Mai; by divI-(suv(As)Y-MO-MN"

As-IRepI-MTU/O-|Repi-IRpe(4-OMe)I-(2-MaP-(AIIB|- po

ГГ ув(Ас)-МА-МН»г оовзво0 Ас iРолЕ M Meteor of aminoethoxy No Mai; by divI-(suv(As)|Y-MA-MN»

As-IRepI-MTU/O-|Repi-IRpe(4-OMe)I-(2-MaP-(AIIB|- po

GG uv(As)-MM-AMN"

As-IRepI-MTU/O-|Repi-IRpe(4-OMe)I-(2-MaP-(AIIB|- po

And uv(As)|-MO-MN" oovze0 | AstrolE M does not contain aminoethoxy; OSI diVI-(suv(As)|-M-(VATa|-MN)»

As-IRepI-MTUO-|RepiI-IRpe(4-OMe)-I(2-MapP-(pi ec|- po

I uv(As)|-M-IVATa|-MNg oval lotvti moreli GBpeg about aminoethoxy NE Mai; by pHetsi-(Suv(As)|-M-|VAYa|-MN»

As-E-(RepI-YUTUMO-(Repi-IRpe|4-(2-aminoethoxy)|-(2-Mas|- po dbVI-(suv(Ac)|Y-MM-MH»

Ac-(0)Azr-IRepI-S TM O-(RepI-(Rpe(4-(2-aminoethoxy)|-(2- poshe mac-(AivI-(suv(Ac)-MM-MH)

As-B-(RepI-OTMO-(Repi-IRpe|4-(2-aminoethoxy)|-(2-Ma!|- po diVI- (c uv(Ac)|Y-MM-MH»

I 645

Table E4B

IC50 of typical peptides containing the As-IRep|-XXM/X-IRep|-XXHU motif and their base analogs

ZEO IU MO. Human sequence | rat | NTAVE (nm) (nm) (nm) 11111 pmaNAvTsruasrmmMMmNne.І С//77777777777777711111171і1111111171С1111171g oovavo operel opo eptenernoaminoetokoy NU. by maps(livI-(suz(As)-MM-MN"

Ac-(0)Rpe-IRepI-YUTUMO-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-poshe)

Mmap-(AlivI-(isuv(Ac)-MM-MH)

Ac-(2-MaP-I(Repi-STUO-(RepI-(Rpe(4-(2-aminoethoxy)|-(2-po map(AivI-(uv(Ac)-MM-MH)

As-T-IRepI-OTMO-|Repi-(Rpe(4-(2-aminoethoxy) I-(2-Ma/|- po divI-(Suv(Ac)|-MM-MH»

Ac-I - Repi-OT O-(RepI-/(Rpe|4-(2-aminoethoxy) |-(2-Mas-po divI-(Suv(Ac)|-MM-MH»

Ac-(0)SIP-IRepI-OTMO-(RepI-(Ppe(4-(2-aminoethoxy) |-(2- po

Mmap-(livI-(uv(Ac)-MM-MH») ovva ovo el Ol ele via aminoethok; by 2-Maps-HAiVI-(Suv(Ac)|-MM-MH» ovva lo ie relay elegome) do not have Memai by

I uv(As) I-MM-KOH ug|-MN"

Ac-(RepI-OTHUO-(RepiI-IRpe|4-(2-acetylaminoethoxy) |-(2- po

Maya-MemaTs-kMM-MN"

Ac-(RepI-OTUO-(RepiI-IRpe|4-(2-acetylaminoethoxy)|-(2-p more mat-k-(Suv(Ac)|-MM-MH» oovvv Ko pes oMme)ne minena Meguvi po

GG uv(As)-MM-AMN"

As-KO) uzI-(RepI-YUTUMO-(RepiI-I(Rpe(4-SOMHn)I-(2-Mas-(a- p more

Memay!-P uv(As)-MM-MNg

As-IRepI-SOTUMO-IRepI-(Rpe(4-SOMNg)|-(2-maiCh(a-Me! uz|- p

Guv(Ac)-MM-AMN» vve As-(Rep-OTUO-(RepiI-I(Rpe(4-SOMN?g)I-(2-May-(o-Memac|- OSI)

GG uv(As)-MM-AMN» this put per somneinepe (moMeg on a-MemaiiP- GP uv(As)-MM-MNg mo pe peraminovtoki and map-(AivI-(suz(As)|-MM-MH» Tue.

MIM-MN" me per amine flows and

Mats-TAsysI-P uv(As)-MM-MH» ov sel M Khoroli pog aminoethokyuy by 2-Ma(|-(4-amino-4-carboxytetrahydropyran--СЩщ-АММ-МН» ov ole per o aminoethoky; by 2-Ma-(AspsiI-I(SiSh-AMM-MH) both see in ele Mloeya (leg aminoethoxy; by 2-Mapc-HAiVI-(Suv(Ac)|-M-(VATa|- МН» ovo vol relay m motels terminal on amino-4-carboxytetrahydropyran-P uz (Ac)-MM-МНg ovo TO ee ku otbepnepesnomeya ma pok

Aspsii-I uv (Ас)-MM-АМН» ovok lek reli MM Ot opi posome ema po amino-4-carboxytetrahydropyran-"СЩ-MM-МН» oovvolova ve M pMOtep pes omela mai po

AspsiI-ISSH-AMM-MN"

Table E4B

IC50 of typical peptides containing the Ac-IRep|-XXM/X-IRep|-XXU motif and analogues

EPBA EIZA | rea

ZEO IU MO. Human sequence | rat | NTAVE (nm) (nm) (nm) 681 As-KO)RPpeI-(RepI-MTUMO-(Repi-(Pne(4-OMe)I-(2-Mas|-

Asps|-EMM-MN»

As-I(Rep-MTUuO(Repi-(Rpe(4-SOMHn)I-(2-Ma-H(AIBI- pok

Guv(Ac)|-MM-MNg v83 As-(Rep|I- MTM OGRepyI-IRpe(4-СОМНг)I-(2-Mas|-(4-amino-4-carboxytetrahydropyrani-I uz(Ac)|- MM-MH» vva As-(Rep|I- MTM OGRepiI-IRpe(4-SOMNHg)I-(2-MatC-(AsnsiI-

H uv(Ac)|-MM-MHg 685 Ac-(Rep|I- MTM OGRepiI-IRpe(4-SOMNHg)I-(2-MatC-(Asrsi-

H uv(Ac)|-MM-MNg 686 As-I(RepI- MTM OGRepI-IRpe(4-SOMNh)I-(2-Mas|-(o-MegHecy|-

G uv(As)|-MM-MHg

As-I(Rep|-« MTM OGRepiI-IRpe(4-OMe)I-(2-MaC-(AiBI-(Huz(Ac)|- 687 | mm-mn 688 As-(Rep|I- MTM OGRepiI- Irpe(4-OMe)I-(2-MaP-(4-amino-4-carboxytetrahydropyrani|-(Guv(Ac)-MM-MH»g 689 As-(Rep|- MTM OGRepiI-Irpe(4-OMe) |-(2-MaC-(Apsi|-

H uv(Ac)|-MM-MNg 670 As-I(RepI-M PU O(Repi-IRpe(4-OMe)|-(2-MaC-(Asre|-

H uv(Ac)|-MM-MNg 671 As-(Rep|I- MTM OGRepiI-IRpe(4-OMe)I-(2-MaP-(a-Meg ecy|-

H uv(Ac)|-MM-MHg i-10 nm; 7-10-25 nm 77 - 25-100 nm, 777 - 100-1000 nm, 7777-1000-10000 nm

Table E5A

IC50 of typical peptide inhibitors (thioether)

ZEO I. . EPZA

Sequence/Structure o)

IM-MeAIa|-OHMUMUSUMNTES-(AEA1-KO)SUv| "МН" 672 v8-- -6000 (F) (M-MeAIa|-OMU-(Rep|-U MUNTEO-|(AEA1-((O)GUuv| -МН»о 673 - - »30000 v)

IM-MeAIa|I-OMZHMU-KO)Rep|-U IN NTEO-(AEA1-KOGUuvI| "-MN"o 674 in-i- »30000 o IM-Melia|-Okh/U-(vSuv1-UUNTES-I (ABA1-OSUvI "MN" 675 8-4 "6000

Table E5A

IC50 of typical peptide inhibitors (thioether) and APGMUUSUMNTEO-|AEA1-(O)Uv| "МН 676 8- -3000 o ARMZHU-IRepI-UZHMUNTES-(AEA1-(O) in -"МНо 677 5--К- 530000 (Ф)

APUU-KO) Rep|-UK/NTEO-IAEA1-KO)UvI| -MNo about ARCHZHU-(VSuv|-UKHUNTES-(ABA1-(O)Uuvi -MNo 679 8th -6000 (Ф) vvO frame itevvnoya -MNo 6000 with

F)

In the ovnodtnnno environment many,

F) 5 (o) and RMOSUMVEMO-IAEA1-O) Uuvi "MN. and A | and 8 o ORZHOSUMVEMO-IAEA1-(O Uvi "МН 684 в- -30000 9 ORZHOSUKHKEMO-|AEA1-(O)UvI -"МНо 685 8- »6000

Z RMO-(VSuv| UM KEMO-(AEA1-KO)Uvi -MN. vv С O-(VSuvi- -(AEA1-(O)Suv| -МН» 6000 8-- is)

OMO-(vSuvI- UM VEMO-(ABA I-I in -MN es ochno) (AVANFUCHI MN, 8B-Sh838ISH and ORZHO-(vSuvIi- UMVEMO-(AEAT-((O Uvi -MN» 688 8-4 »6000

Table E5A

IC50 of typical peptide inhibitors (thioether)

ZEO I. . EPZA

Sequence/Structure (o)

ORMO-(NSuv|- IN MKEMO-(AEA1-KO)SUv| -"MN"o 689 8---3 -30000 9 ORZHOSUKHMVEMO-IAEAI-(O uv) "MN u "30000 8 o ORZHO-(VSUVI- SUMVEMO-(AEA1-(O uv "MN" 691 Sh, »30000 8

Table E5B

IC50 of typical peptide inhibitors (thioethers) is

Aby I shi --TRpeb-Omenie-marhhhkhmn» she shchi i I sing AVK KA GESTURE wa I OmMe I 12A Ma ЦК ХА.

Asetsikpo PANA ST Rv OMEGA Ma HA ХК g (5EO1O MO: 1483)

EIPZA reiaiz my Sequence of man pa coca (NM) NTVE (m) SG (nm)

As-cyclo-PABCSHA TUUOSI-MUU AKRa-(AEA|- jjjjjjjjjjjj 692 r)Sug|-MN»g

As-cyclo-ISA TUMO-TABy|- M AKRa-(AEAY- kzhzhzh yazhzhzh yazhzh 693

O)Suv|- M.Sc

As-cyclo-ABSH-OTUMOSI-MUM VEMA-(AEAI- kzhzhzh yazhzhzh yazhzh 694

B) Suv|- M.Sc

As-cyclo-TsAby-A TU O-(Repi|- Z/M VKRa-I(AEA|- yazhzhzhzh 695

O)Suv|- M.Sc

As-cyclo-(RepI-ATUO-IABy|-yM/AKRa-(AEAY-zhzhzhzh

O) GuvI-Mng

As-cyclo-((O)Suv|-ATUMO-(АВy|- UM AKRa,-(АЕА|- жкжжж 697 0)-GuviI- MNeg 698 As-cyclo-PABShSH-O TM OSI-IMI-(Ogti-( bar|-Ma- zhk

AEAII-(O) Huz|- MNeg 699 C|Ac-cyclo-(dByrOtMOsSgUM (pieEMO-MNaDH | 7771177

As-cyclo-I(AbyY|-OTUO-(0)SuvI|-yM-(p esh-EMa-«zhkzhzh 700 МН»g

As-cyclo-PABSh-O GTM O-(Repi|-UMU-(pHesh-EMa- kzhzhzhzh 701 Mne 702 As-cyclo-PABShSh-Ogtumosi-(P; pe(4-OMe)|-(2-MaP-( a-yyyyyyyyyyyyyyyyyyyy

Me! uz|-EMa-MN»

As-cyclo-PABSH-OTUMOSI-MMU-(a-Mei esh-EMO-yah 703

МН»г

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia by KK urn "Depe(i men 2 May xxx chn.

N Y N Her de AV XXX Re CM - Z- Ma UHKHAMV.

Aecyclo-C AB XXX 5-OMets- 2 MaC- XX KHAN" (BEO 10 MO-1483)

EIPZA region: (nm) (nm)

PES vt

EMO-MN"

As-cyclo-HABC-OTUCOSI-(Rpe(4-OMe)|I-(2-ma!-(a-

Me! uzI1-EMЯa-МНг

As-cyclo-HABC-OTUCOSI-(Rpe(4-OMe)|I-(2-ma!-(a-

MeOgpI-EMa-MN"

MeOgpI-EMa-MNeg

As-cyclo-ABISH-OTMOSI(Rpe(4-OMe)1-2-Mma!Time

Me! uzI1-EMЯa-МНг

Me! uzi-P uv(As)|-Ma-Mng

Me! uzI1-EMЯa-МНг

As-cyclo-HABC-OTUCOSI-(Rpe(4-OMe)|I-1-ma!-(a-

Me! uzi-P uv(As)-Ma-Mng

As-cyclo-GABSH-OTUKOSI-(Rpe(4-OMe)|I-(2-ma!(a-

Me! uzi-P uv(As)|-Ma-Mng

And uv(As)|-Ma-MN» asla nok cottage cheese asMenegnome)nya ma

О)Ав5пи-П uz(Ас)И1-МОа-МНг ovo

MaC-(a-Me!H uz|I-(Huz(As)|-Ma-MNe).

As-cyclo-GABSH-OTUCOSI-(pRNe(3,4-dimethoxy)|- pesto HO 2-MaC-(a-MeH uzI-(Suz(AsDL-Ma-MNeg

Me! uzi-P uv(As)|-Ma-Mng

As-cyclo-HABCSH-OTUOSI-IR; pe(4-SOMNg)I-(2-Mat-a-Mei uziI-(-uv(As)3|Ma-MNe le |odiklo TA og OSreegv in ov Mayo: send us ee

Me! uzi-P u(As)Ma-MN»eg ocho oko ini opo relinenepevnoMeinYa.

MmapP-Go-Mei uzI-EMIa-MN" (to: (cocyclo TAB AND TRelipe Med:

MapP-Go-Me! uzi-P uz(As)iMa-MNg tva |to iklo Tretvo ploTo TepesnoMeinekh pol OO ОН

MapP-Go-Me! uzi-P uz(As)iMa-Mng

As-cyclo-PABSH-O TU OST-IR ne(4-OMe)|-

Prov tritretbuil Me ememn | 01

As-cyclo-GABSHSH-OTMOSI-|(P pe(4-OMe)|- |Ppe(4- post poly

Oalil)|-(a-Me! ug|-EMa-MN» ootBoroiklo Aa A SMEpesnoMe) tu

IVSHI-(a-Me! uz|I-EMIa-MH" (726 | As-cycloCSABCOTUOSuRae(-OMe) Red | 77171711

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia KK urn Tele OMeno- Main.

M Y N Her

Ae-cyclo PAH ХУ ХСН ОмМец-АМЯАТС- ХХ ХАМНЯ (BEO 10 МО- 1483)

EPZA Shchaiz

ZE o Sequence of human EPZA ren

Mo. (NM) rat (NM) (nm) 771 PVoshNo-mesubreMO-MNeidG///7777111111111Й1111111111171С111111g that |nocyclo Theo OTM OS pes oMe)Ne pes posly poly guanidino)|-(с-Me! ug|I-EMSIa-MN» Mr

Rpe(B21I)-(a-Me! uz|I-EMa-MN»

As-cyclo-CSABSH-OTUOSI-(Tuk(Z3-IVy)1-UM-(a-

Sea 161

Me! uzI-EMI-MNg tvo clo le POS peg tuanidinod M (o-Me! uz|-EMOa-MN»g aminoethoxy)|-UU-(a-Me! uz|I-EMa-MN»g otv a TO pmasnemern osn that the ambassadors left

Me! uzI1-EMЯa-МНг

As-cyclo-GABSHSH-OTHUOSI-IR pe(4-phenoxy) |-UM-|(a-

Me! uzI1-EMЯa-МНг

Me! uzI1-EMЯa-МНг

Me! uzI1-EMЯa-МНг

Me! uzI1-EMIa-MNg opened it OM pesnemoenesya sent poly

Me)-(a-Me! uzI1-EMOa-MHg

As-cyclo-HABC-OTUCOSI-(Rpe(4-OMe)|I-(1-ma!-(a-

Me! uzI1-EMЯa-МНг

As-cyclo-HABC-OTUCOSI-(Rpe(4-OMe)|I-(2-ma!(a-

MeOgpi-P uz(Ac)I1-MOa-MHg

MeOgtpi-(Suz(As)|-Ma-MNe

As-cyclo-GABSH-OTUKOSI-IVIRI-(2-MaP-o-Me!uzi|- post poly SHO

And uv(As)|-Ma-MN» otv |pochiko DAK Tato SEspate myno metsuv pesto BUT

And uv(As)|-Ma-MN"

Me! uzi-P uv(Ac)|-Ma-MHg tav eye in op ridilalaninite. the ambassadors

MaC-(a-Me!H uz|I-(Huz(As)|-Ma-MNe).

As-cyclo-ABSH-OTUMOSI-(B-poto GupP-(2-MaP-(a- ote honey)

Ac-cyclo-HABSHSH-OTMOSI(Rpe(4-SOMNHgY-2-Mas- (o-Me!uzyI-(Huv(Ac)-Ma-MHg

Me! uzI1-EMЯa-МНг

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia by KK urn "Depe(i men 2 May xxx chn.

N Y N Her that AKA KK me IM XX KHAN

As-cyclo PAN XX U HOSE HF OMep- A MaC- XX KHAMN" (BEO 10 MO-1483)

EIPZA reiaiz i (nm) (nm)

As-cyclo-GABsh-OT-(2-mapy-ost(Rpe(4-OMe)|I-(2-postly shi SHA)

MypP-Go-Me! uzi-P uz(Ac)1-Ma-Mng

As-cyclo-GABSH-OT-P1-mapc-Oost(Rpe(4-OMe)|I-(2- posly shi SHA

MypP-Go-Me! uzi-P uz(Ac)1-Ma-Mng

As-cyclo-ABSH-OTMOSI-(Pne(4-OMe)|-(2-Ma!|-(a- ovo mere) 611

As-cyclo-GABSH-OTUMOSI-I(Rpe(4-OMe)1-(2-maC-(a- polo o

Me! uzI-(Suv(As)|-Ma-MNeg

As-cyclo-HABSH-OTUOSI-(P pe(4-OMe)|-(2-may-(a-posts according to NA)

Me! uzI-ISuv(As)|-ME S E-MN"

As-cyclo-GABSH-OTUMOSI-I(Rpe(4-OMe)1-(2-maC-(a-pol OO OH)

Me! uzi-P uz(Ac)-MEABE-MN"

As-cyclo-HABSHSH-ZTHUMOSI-(Rpe(4-OMe)|-(2-may-(a-pol OO OH)

Me! uzI-Iuv(As)|-ME S E-MN»

Me! uzI-Iuv(As)|-ME S E-MN» ovo? | pochi TA I POS UTe Maiu Me pol OO ON

And uv(As)|Y-MOSE-MN"

As-cyclo-GABSH-OTUMOSI-I(Rpe(4-OMe)1-(2-maC-(a-

Me! uziI-P uv(As) |-М5-МН»

As-cyclo-GABSH-OTUMOSI-I(Rpe(4-OMe)1-(2-maC-(a-

Me! uziI-P uv(As)I-MA-MNg ovo oko wav o M OSMR dog mistletoe may, divI-Isuv(As)|-Ma-MNe vo v pe menya Magne,

Me! uzi-P uv(As)|-Ma-Mng

As-cyclo-GABSH-OTUMOSI-I(Rpe(4-OMe)1-(2-maC-(a-

Me! uzI-P uz(Ac)1-0OS-Mnh

As-cyclo-GABSH-OTUMOSI-I(Rpe(4-OMe)1-(2-maC-(a- polo o

Me! uzi-P uz(Ac)-TSSH-c2-MNeg

As-cyclo-GABSH-OTMOSI(Rpe(4-OMe)1-2-ma!Chas-

Me! uzI-MMYa-MNg ovi |docyclo Teo o OSnepes mistletoe mat, send shi SHA

Oti-P uz(Ac)1-Ma-MNeg oovivo | pocyklo Tov PMOSNR pes memela mat, posly shi SHA

Ot!i-Yushari-MA-MNe

As-cyclo-HABSHSH-MTUMOSI(Rpe(4-OMe)I-(2-Mai-(a-

Me! uzi-P uv(As)|-Ma-Mng

As-cyclo-CABsh-OT-(VirI-OCI-(Rpe(4-OMe)1I-(2- ov ikaeme sem 011 oovyu dopsiv agtosnenegnom)nya me

Spa!-I uv(As3l-Ma-MNeg oovgo | ocyclo PAvo o hMOSnRpes mistletoe may, poskhly lo NYA

Spai-I uv(Ac3l-Ma-MNeg (821 |Ac-cyclo-CSABC OT OsyuurOosSiIRpe(4-OMe)tsa-| 510000 | "

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia t KKU r "Penegi OMei-2-Mai-xxxh mn. g Y M Her

Asetsivloi TANKU Rv AS Me TZ -MaC-kih.

Heh o PANA ZHAE EV I OMetsA2-MaTs- HA HAMN". (ZO 10 MO-1483)

EIPZA reiaiz

ZE TO Human sequence EPVA NTVE

Mo. (NM) rat (NM) (nm) 1177 TmaNo-meguzTsuv(Ac)Ma-MN» shin"shiin shi 822 As-cyclo-ABSH-O GTM OSI-(Osidiu|-(2-MaC-(а- -10000)

Me! uzI-(Guv(As)|-Ma-MNeg

As-cyclo-PABSHSH-OTUMOSI-(P; pe(4-OMe)-(Osta!uI|- y 823 To-Meguvi-P uv(ASL-MO-MH» 10000 824 As-cyclo-PABShSH-OHTUMOSI-( P; pe(4-OMe)|-(2-MaP-(а- яжж яжж ж

Me! uzi-P uv(As)|-MEE-MN»g

Me! uzI-(-uv(Ac)-MAE-MH" 826 As-cyclo-CAbBy-5 TM OCI-(P; ne(4-OMe)I-(2-MaC-(a- "zhk z zhzhzh)

Me! uzi-P uv(Ac)|-MEE-MH»g 827 Ac-cyclo-HAVSH-O HMOSI-(P; pe(4-OMe)|-Ж/-Іа- жхжжж

Me! uzi-P uv(Ac)3-MaE-MH»g 828 Ac-cyclo-ABSH-O GTM OCI1-X-(2-Ma!|-(c-Me! uzI|- yazhzh

I uv(Ac)|-MOE-MHg 829 Ac-cyclo-HAVSH-O HMOSI-(P pe(4-(2- « « « aminoethoxy)||-(2-MaC-(o- Me!ug|- EM-M.Sc

As-cyclo-ABSH-OTOHOSI-(Rpe(4-(2-830 aminoethoxy)|-(2-mai-Cha-Mei in EMa-MH) "3000

As-cyclo-TsABSH-OTNOSI-|РНе(4-(2-831 aminoethoxy)|-(2-ma-a-Mei uvIEMa-MNe "3000

As-cyclo-TsAbBSh-OT-(pRNe|-OCI1-(P He(4-(2-832 aminoethoxy)|-(2-mai-Cha-Meg in EMC-MH) "3000

As-cyclo-CabBSh-OT-(SiC(B213-OCI1-(РНе(4-(2-833 aminoethoxy)|-(2-mai-a-Mei uv|-EMO-MNe "3000

As-cyclo-CABbBsh-OT-(VirI-OCI-(PHe(4-(2-

VZA aminoethoxy)|-(2-mai-Cha-Meg in EMa-MN" "3000

As-cyclo-CabBSh-OT-Pis|-HOS1-(PHe(4-(2-835 aminoethoxy)|-(2-Mai-Ch(a-Mai in EMO-MH) "3000

As-cyclo-CabBSh-OT-(PHe|(4-(2-aminoethoxy)|-OCI|- 836 | (Ppe|4-(2-aminoethoxy)|Y-I2-MaNa-Me! ugI-EMO- » 3000

МН»г

As-cyclo-CABSH-OT-(РНе(3,4-СИ2Л-ОСІ-(РНе((4-(2-837 aminoethoxy)|-(2-mai-Cha-Me! in EMO-MN) "3000

As-cyclo-CabBSH-OT-(Rpe(4-OMe)|I-OCI1-(РНе(4-(2-838 aminoethoxy)|-(2-Mai-Cha-Mei in EMO-MH) "3000

As-cyclo-CABy-OT-(Ogp(Benzyl)|I-OCI-(RHe(4-(2-839 aminoethoxy)|-(2-may-(a-Mei uv|-EMO-MH) "3000

As-cyclo-CABy-OT-(Ogp(benzaldehyde)|1-OC1- 840 IRpe(4-(2-aminoethoxy))I-(2-MaP-(α-Me!uz|-EMa-

МН»g val As-cyclo-IABSH-OTUOSI1-(РНЕОСН2СНаМНАсиI- 2-МапП-(а-Me!uzI-EMIa-МНг 84? As-cyclo-PABSH-OTUMOSI-(P pe(4-(2- aminoethoxy) |-(2-MaC-(c-MeH ets-EMIa-MH»

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia KK urn Tele OMeno- Main.

Ehh! Y M Her

Asetsivlo ANA KAZHAN I SMT GAMA AN, (ZO 10 MO-1483)

EIPZA reiaiz

I (nm) (nm) was formed aminoethoxy) EM-M.Sc

As-cyclo-CabBshSh-OT-(M-Me TtrI-OCI-(Rpe(4-(2- ) ono oo Me MOM. || 1 846 | tetrahydronorharmani-OCI1-(РНе(4-(2- aminoethoxy) ||-(2-MaC-(o-Me!ug|-EMa-MHg

As-cyclo-CABSH-OT-(Rpe(4-СО2ND-ОСІ-(РНе(4-(2- vat |aminotoy oaeMeerem || 1

As-cyclo-GABSHSH-OT-IRN(4A-SOMN2H-OXI-(P pe|4-(2- aminoethoxy)||-(2-MaC-(o-Me!ug|-EMa-MHg)

As-cyclo-HABSHSH-OT-IRN(4A-SOMN2H-OXI-(P pe|4-(2- aminoethoxy)||-(2-MaC-(o- Me!ug|-EMa-MHg oovvo od Ave) tele in OoMe) SOMY lege Dt 2-aminoethoxy)||-(2-MaP|-(c-Me! ug|I-EMIa-MH»g oovvio | docyclo PA ti More Osg ee posly shi SHA aminoethoxy)||- (2-MaC-(o-Me!ug|-EMa-MHg)

As-cyclo-CabBSh-OT-(Pne(4-48y1-OCI-(Pne(4-(2-

WE ARE NOT LEADING BY HIM

As-cyclo-HABSHSH-OT-(Rpe(2,4-Me2)1-OXI-(Rpe(4-(2-posyl sia aminoethoxy)||-(2-MaC-(o-Me!ug|- EMa-MHg aminoethoxy) |-(2-MaC-(o-Me! uzI-I-uz(benzoic x x acid)|-Ma-MNeg 858 aminoethoxy))|-(2-MaC-(o-Me! uzI-I-Uz(succinic x their x acid)|-Ma-MNeg 859 aminoethoxy)|I-(2-MaZ-(o-Me! uzI-(Iuz(glutaric x x acid)|-Ma-MNeg 860 aminoethoxy)||-(2-MaZZ -(o-MegH uz|- x x

I uz (pyroglutamic acid)|-Ma-MNeg 861 aminoethoxy)||-(2-MatC-(o-MegH uz|- x - x

And uh (isovaleric acid)|-Ma-MNeg

И 8б2 7/7 17777

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia by KK urn "Depe(i men 2 May xxx chn.

Ehh! Y M Her to KATA HK Re Me Na KHAN

Asetsivlo ANA KAZHAN I SMT GAMA AN, (ZO 10 MO-1483)

EIPZA reiaiz. (nm) (nm)

And aminoethoxy)|-(2-MaP|-(a-Me! uzI-( uz(Ra!t)|-Ma-pol OO OH)

МН»г

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-863 aminoethoxy))|-(2-Ma!c|-(o-Me!uzI-H UZ (PEGI1)|-Ma-

МН»г

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-864 | aminoethoxy))I-(2-Ma!|-(o-Mei! uzI-(ISuUz(PEG2)|-Ma-

МН»г

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-865 aminoethoxy))|-(2-MaC-(o-Me! uzI-Isar(benzoic acid)|-Ma-MNeg)

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-866 aminoethoxy)|I-(2-MaC-(o-MegH uz|-

IOSar (succinic acid)|-MIa-MNeg

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-867 aminoethoxy)||-(2-MatZ-(a-Me/ uzI-(Sar(glutaric acid)|-Ma-MNeg)

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-868 aminoethoxy)|I-(2-MaC-(o-MegH uz|- - x)

IOar (pyroglutamic acid) |-МСиа-МНг aminoethoxy) ||

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-870 aminoethoxy))|-(2-Map|-(o-Mei! uzI-(Sar(PEG1)|-Ma-

МН»г

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-871 aminoethoxy))|-(2-Map|-(o-Mei! uzI-(Isar(PEG2)|-Ma-

МН»г

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-872 aminoethoxy))I-(2-MaC-(o-Me! uzI-ISar(PEG2-Ac)|- what - ma-MNeg)

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-873 aminoethoxy))|-(2-MaC-(o-Mei!uziI-( uz(Ac)|--Ma- x x

AEAI-KO) uv|-Mneg

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-874 aminoethoxy))|-(2-MaC-(o-Me!uziI-( uz(Ac)-Ma-x x p)Sug|- МН»г

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-875 aminoethoxy))|-(2-MaC-(o-Me!uziI-( uz(Ac)-Max-x)

AEA|-MNg aminoethoxy)I|-(2-MaC-(AiVI-(Suv(Ac)-OS-MNeg aminoethoxy)I-12-MaP-TAIVBI-OMa-MNeg (878 |Ac-cyclo-CAvyOTMOSCREIDg-. 777771 Her 11111111

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia KK urn Tele OMeno- Main.

Ehh! Y M Her

Asetsivlo ANA KAZHAN I SMT GAMA AN, (ZO 10 MO-1483)

EPBA req

ZEO about Human Consistency EPVA NTAE

Mo. (NM) rat (nM) (nm) 111 |aminoethoxyuue-maiavreMO-MNaDH71Й7771111111Й1111111с11 aminoethoxy)||-1-MaH(AIVI-(Huz(Ac)|-Ma-MNeg aminoethoxy)||-(2-MasC-HAiVI- (Suv(Ac)|-MA-MNg aminoethoxy)|-(2-MaC-(Aiv|I-KMa-MNeg 882 aminoethoxy)|-(Rpe(4-СО2Н)|-(α-Mei! uziI-( uz (Ac)|- yach ma-MNeg 883 aminoethoxy)||-I(Rpe(4-phenoxy)|-(c-MeH uv |- yach

Guv(Ac)|-Ma-MNeg 884 aminoethoxy)||-(Rpe(4-(2-aminoethoxy))|-(o-Me! uz|- yach

Guv(As)|-Ma-MNeg

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2- contents o Me esumeme OO aminoethoxy)|-(pRAe|-(a-Me!H uzI-(Huz(Ac)|-Ma-MNe 887 aminoethoxy) ))|-(C1ch(B21)1-(o-Mei! uziI-(H uz(As)|-Ma- 23000

МН»g aminoethoxy)|Y-UM-(a-Me-Ogp|-EMa-MH» aminoethoxy)|-UM-(a-Me!H uzI-(Suz(Ac)-Ma-MNe aminoethoxy)|-UM -(a-Me-OgpiI-(Suz(AsD-Ma-MNeg 891 aminoethoxy))|-(2-MaC-(o-Me-Ogtpi-(H uz(Ac)|-Ma- х х

МН»g aminoethoxy) -MNeg aminoethoxy)|-UM-(Ogt|I-EMa-MNg aminoethoxy)|-UM-(Ot|-(bar|-Ma-MH»g aminoethoxy)|-UM-(Ot|-(bar(AcC- Ma-MHg aminoethoxy)

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia KK urn Tele OMeno- Main.

Ehh! Y M Her

Asetsivlo ANA KAZHAN I SMT GAMA AN, (ZO 10 MO-1483)

EPBA req

ZEO about Human Consistency EPVA NTAE

Mo. (NM) rat (nM) (nm) 111 |aminoethoxyuue-mazoOtuOarasrMmayemne.D | 77 G77777111171G1 aminoethoxy)|-UM-(pSesh-EMY-MN»

Ac-cyclo-PABSHSH-OTUMOSI-(PHe(4-(2-«(acetyl-aminoethoxy))|-(2-MaC-(o-Mei! uz(Ac)I-( uv(AcD-Max-xx) h

MH»g aminoethoxy)|-UM-(a-Me-Heshsch-EMa-MH»

Zyssissipu!-cyclo-CSABSh-OTUOSI-IRpe(|4-(2-aminoethoxy)||-(2-MaC-(o-Me! uz|I-(uz(Asu-Mma-MNe aminoethoxy)|-UM- (a-MeH uzI-(Huz(Ac)I-(Sar|-a-MH» 904 aminoethoxy)||-UM-(a-Me!uzI-(Guv(Ac)|-(b-amino- p x 1,4-diazepan-2,5-dione|-MNeg aminoethoxy)|-UM-Spa-uz (Ac) 1-MO-MH»g (acetylaminoethoxy))|-(2-MaC-(o-Mei uz( As)|-EMa- x x x

MH»g 907 aminoethoxy)|-(Pne(4-SOMH)|-(α-Mei! uz|- yach

Guv(As)|-Ma-MN"

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-aminoethoxy)||-(Pne(3,4-OMegy-(a-Me/ uz|-

Guv(Ac)|-Ma-MNeg aminoethoxy)||-(TisIi-(c-MeH uzI-(uz(Ac)|-Ma-MNe)

Ac-cyclo-CAbBi|-bartuosi-(Ppe(4-(2- aminoethoxy)|I-(PNe(3,4-C12)1-(o-Me!ugI--(H uz(Ac)|- o ma-MNeg aminoethoxy) -(2-MaC-(o-Me!ug|-EMa-MNeg 914 aminoethoxy)| )|-(2-MaC-(c-MemayP-(Suv(Ac3-Ma-MNeg aminoethoxy)||-(2-MaC-(c-Mesep-(Suz(AcD-Mma-MNe) (917 |Ac-cyclo -TsavyrOtrarosSCRIed-2- 0 | 53000 | .:(X GG SSi

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia t KKU r "Penegi OMei-2-Mai-xxxh mn.

Ehh! Y M Her

AS "AN AKA TR YAMA GAMA A. khs-tsivlo TAN AK KS TR I OMetsA 2-Mats- HA KHAMN" (ZO 10 MO-1483)

EIPZA reiaiz

ZE TO Human sequence EPVA NTVE

Mo. (NM) rat (NM) (nm) 11111 |aminoethoxyue-madio-mesuzuvAsu menya GG 918 As-cyclo-PABSH-OTUMOSI-(P pe(4-(2- 53000 aminoethoxy)I-(Ouari-(a-Me! uzi-P uz(Asi-Ma-MN»g

Ac-cyclo-CSABSH-OTVOSI-IR e(4-(2-919 | aminoethoxy)|-(2-mayCha-Meg uz|I-(-uv(Ac)u-me-mng, 7000

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-320 aminoethoxy)|-B-(a-MeH uz |I-(uz(Ac)D-Ma-MNe 73000 321 aminoethoxy)I|-( OariI-(a-Me GG uvgI-ISuv(As)-mMa-MNeg 73000

Ac-cyclo-CSABSH-OTROSI-IR He(4-(2-922 aminoethoxy)|-(2-maiCa-Me uzI-Iuv(Ac)-ma-mn| 7000

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-323 aminoethoxy)|-O-(a-MeH uz |I-(uz(Ac)D-Ma-MNe 73000

As-cyclo-TsABSH-OTrOSI-IR He(4-(2-324 aminoethoxy)|-O-(a-MeH uz |I-(uz(As)D-Ma-MNe 73000 925 As-(0)H ubz -(Icyclo-PABBYA-OTUMOSTI-(Ppe(4-OMe)|- « eat x 2-MaC-(a-MeH esh-EMa-MHg 926 As-cyclo-PABSH-OTUMOSTI-(P pe(4-(2 - yaz x aminoethoxy) |-(2-MaC-(o-Me! uz|-(Ogp|-Mma-MNe 928 As-cyclo-PABSH-OTUMOSI-(P pe(4-(2- « x aminoethoxy)||-(2- MaC-(o-Me! uz |-KMa-MHg 929 As-cyclo-PABSH-OTUMOSI-(P pe(4-(2- « x aminoethoxy)||-(2-MaC-(o-Me!H uz) |-p A! Ma-MNeg

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-930 |aminoethoxy))|-(2-MaPC-(y eshI-( uz(Ac)I-M-|BAa1- х х х

МН»г aminoethoxy)|-(2-MaЦ-(СщЧ-(Сар|-Мма-МНг 932 As-cyclo-DCABy|-(c-Me-Ogp|I- HMOSI)-(РНе(4-(2- aminoethoxy) MaC-(o-Me! ug|-MMa-MH»g 934 As-cyclo-CAbBy-Z TM OSI-(PHe(4-(2-zhk aminoethoxy)||-(2-MaC-(c-Me! G uz|-KMas E-MN»g

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-935 (acetylaminoethoxy))|-(2-MaC-(o-Mei uz(Ac)|-EMO- х х х

МН»г 936 As-cyclo-PABShSH-O HUMOS-(PHe(4-(2-«(acetyl- « « « aminoethoxy)||-(2-MasC-(a-MeGG uz(Ac)|-EMIM- МН» 937 As-cyclo-CABi|-TUMOSI-(Rpe(4-(2-aminoethoxy) ||- 2-MapP-(a-Me ugI-EMa-MNg 938 As-cyclo-ABSH-OTUMOSI-(Р pe (4-Me)|-(2-MaC-(a- « «

Me uzgI-(Suv(As)|-ma-MN»

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia KK urn Tele OMeno- Main.

Ehh! Y M Her

Asetsivlo ANA KAZHAN I SMT GAMA AN, (ZO 10 MO-1483)

EIPZA reiaiz

And (NM) (NM)

Hey, I have something to say

Me! uzI-(Guv(As)|-Ma-MNeg for this PA atmasnyt not vanemey i

Guv(Ac)|-Ma-MH» 941 aminoethoxy)||-(c-Me TtrI-(o-Mei! ugI-( uv(Ac)-Ma- -3000

MN"

As-cyclo-GABy|-(-Mebep- TOUCHOSI-(Rpe|4-(2- more aminoethoxy)||-(2-MaC-(o-Me! uz|I-(uz(AsD-Mma- I don't

As-cyclo-CAbBi|-O-(o-Mezep-Um OCI1-(P pe(4-(2- amino Ma to-Mei 51- ii As Sn yuyu 944 aminoethoxy)||-(c-MeRHe|-( s-Me! uzI-(Guz(As)-Ma- 23000

МН»g aminoethoxy)|-UM-(АЙВБИ-ЕМЙа-МНг aminoethoxy)|-(2-MaЦ-(АивI-(-ув(AsCD-Ma-MNeg aminoethoxy)|-(2-MaЦ-(АивИ-Е- (Sar(Ac)|-C-MH»g aminoethoxy)|-(2-MaC-(AivI-E-(Sab(Ac)|--MH»g aminoethoxy)|-(2-MaC-(AivI-E) -(Huz(Ac)-a-MNeg aminoethoxy)||-UM-(AIVB|I-EMM-MH» aminoethoxy)||-(2-MaC-(-MeGSecsh-EeEMM-MH» aminoethoxy)|-(Рпе (3,4-OMeg)I-(AIVB-EMa-MH» aminoethoxy) MeH ets)-(СЩ-MM-МН» aminoethoxy)||-(2-MaP|-(o-MeH ets|-(Suv(As)|-MM-MNeg oats in POS dog Mene ma; posy seh)

AIV-EMO-MN»g ev vno PMOSNR lem EN ka posli shi she

AIV-EMO-MN»g

As-cyclo-GABSH-OTUOSI-IRpe(3-SOMN)|I-(2-Ma!|- posly shi SHA

AIV-EMO-MN»g

ESE ambassadors of the United States of America

AIV-EMO-MN»g (960 |Ac-cyclo-TsAvy OTO SuRe(Z-Medda-Mad.DG HER s17 g 7

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennia KK urn Tele OMeno- Main.

N Y n Her

Asetsivlo ANA KAZHAN I SMT GAMA AN, (ZO 10 MO-1483)

EPISODE

ZEO about Human Consistency EPVA NTAE

Mo. (NM) rat (NM) (nm) 00000 TSABREMO-MNIISS////11111111111111111Ї111111111Ї11111g

As-cyclo-HAVSH-OTUOSI-IR pe(4-C1)1-(2-MaP-HAIBI- posy lyshe

EMO-MN»g

As-cyclo-HABSH-OTUMOSI-I(P pe(4-P)I-(2-Mapz-HAIBI-postly shi SHA

EMO-MN»g

As-cyclo-GABSHSH-OTUMOSI-IRpe(2,4-Si", van

Matsp-(AivI-EMY-M.Sc

As-cyclo-GABSH-OTUMOSI-IRpe(4-OMe)1-(2-MaC-(a- post

MeGesh-EMOa-KO) uz|-MHg aminoethoxy)||-(2-MatC-(a-MeHuz|-EMM-MH» aminoethoxy)||-(2-MatC-(a-MeHuz|-EMM-MH» amino-ethoxy) (a-MeHuz|-EMM-MH» aminoethoxy)||-(2-MatC-(a-MeHuz|-EMM-MH» aminoethoxy)||-(2-MatC-(a-MeHuz|-EMM-MH» amino-ethoxy) (α-MeHuz|-EMM-MH» aminoethoxy)||-(2-MmaC-(Asre|-EMM-MH»g aminoethoxy)||-(2-MmaC-(Asrs|-EMM-MH» aminoethoxy)| |-(2-MaC-(Asps|- EMM-MH»g aminoethoxy)||-(2-MaC-(Asms|-EMM-MH» 979 aminoethoxy)|I-(2-MaC-(4-amino- 4-x carboxypiperidine-EMM-MH» g 980 aminoethoxy)|I-(2-MaC-(4-amino-4- x x x carboxytetrahydropyrani-EMM-MH» aminoethoxy)||-(2-MaC-(o- Me!H ets|-(Suv(As)-Ma-MNa

Table E5B

IC50 of typical peptide inhibitors (thioethers) of rennion in KKU r "Penegi OMei-2-Mai-xxxh mn.

Ehh! Y M Her

Asesivlo- PAIV KA AS Ve ASOM NA -Mats- AK KHAMY.

MO AN KHAKI R Y SMT GAMA AN, (ZO 10 MO-1483)

EIPZA reyaiz my Sequence of human pa coca (NM) NTVE (m) (I (nm) 982 As-cyclo-PABSH-OTUMOSI-(P pe(4-(2- aminoethoxy)|-(2-MaC-(c- MeH ec-EMIa-MH" 983 Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2- aminoethoxy)||-(2-MaC-(c-MeH ech-OMa-MH)" 984 Ac-cyclo -PABSH-OTUMOSI-(P pe(4-(2- aminoethoxy)||-(2-MaC-(c-Me!H!ec|-OM-(VATa|-MH)» 985 Ac-cyclo-PABSH- OTUMOSI-(P pe(4-(2- aminoethoxy))|-(2-MaC-(-MeH esch-Ora-MNe 986 As-cyclo-CSABS-OTUOSI-cycloCRPpe(4-(2- aminoethoxy)| |-(2-MaC-(c-MeH esChI-O01-2-MNeg 987 As-cyclo-PABSH-OTUMOSI-(P pe(4-(2-aminoethoxy)|-(2-MaC-(AivI-OM) -(VAIa|-MN»

As-cyclo-PABSH-OTUMOSI-(P pe(4-(2- 988 aminoethoxy)||-I(1,2,3,4-tecanpuago-pogpathtapi|- dIB-OMa-MNeg 989 As-cyclo-PABSH- OTUMOSI-(P pe(4-(2- aminoethoxy)||-(5-hydroxy Tgr|-(AIVSH-OMa-MNeg)

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-aminoethoxy))|-(2-Mai| --Mei!uziI-(H uv(Ac)|-

IAzp(isobutyl)|-c-M-MHg

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-991 aminoethoxy))|-(2-MaC-(o-Mei!uzI-(uz(Ac)|-

Azri(1,4-diaminoethane)|-c-MNeg

As-(0)Rpe-cyclo-CAVsh-OTUMOSI-(Rpe(4-(2-992 aminoethoxy)|I-(2-MaC-(4-amino-4- carboxytetrahydropyrani-EMM-MH))

As-KO)Ago|-cyclo-CSABSCHI-OTUOSI-(P pe(4-(2-993 aminoethoxy)|I-(2-Ma1|-(4-amino-4- carboxytetrahydropyrani-EMM-MH)» i-« 10 nm; -10-25 nm i - 25-100 nm, i - 100-1000 nm, 75 -51000 nm

EC table

IC50 of typical synthesized thioether peptide dimers

EPZA reiyaiz my tragent Sequence of a person and a coke (NM) NTVE and (m) | (nm)

IAs-KO)H uv|-cyclo-ABSHSH-OTUMOSI- 994 YN IRpe(4-OMe)-2-May-(a-Me!

In EMO-MN|» ОЙ grew through IАс-cyclo-PAВБШЩ-ОТУМОСИ-ИР pe(4-995 2 (|РНе|4-(2- (2-aminoethoxy)|I-(2-MaP-IAiV-OMa- and - aminoethoxy)| | MNa|g OIS

EC table

IC50 of typical synthesized thioether peptide dimers

EPZA reiaiz my tragent Sequence HUMAN and coca (NM) NTVE and (nm) (YAZ (nm) 1 TSas-cyclo-AVTSSH-OTUMOSI-(P Ne(4- rischerez- |OMmee-maiNa-meg uzi EMO-MNr , - ,

Me" uz BIS "PAs-KO) Huz|-cyclo-CavschSh-OTUOSI- 997 MB through a Trne(4-OMe-2-Mai|-(a-Me! uziya- ia ia

In EMO-MH PEG25 998 grew through IAs-cyclo-TsAVBShSh-OTUMOSI-IR pe(4- "

B) Guv OV8213-MU-(a-Me! ugI-EMA-MNeg|» 1

PEG25 through |(Ac-cyclo-PAVBSH-OTUOSI-Z(B21)-M- « p)H uz (o- Me! uz|-EMIa-MHg|g PEG25

AIekha488-PEGA | (0-Aga|-cyclo-PABSHSH-OTUMOSI-zh through (O-Aga Rpe(4-2ae)I-(2-MaC-(TNRIEMM-MH) i--«10 nm; 2-10-25 NM i - 25-100 nM, i - 100-1000 nM, eek-»1000 nM

Table E5O

Typical thioether peptides

EPIBA II 238 /

ZEO IU MO. Sequence I/ 23 people

NM oovez VE cycloitavoga PMOSN pes vena MaittnereMn,

МН» 1416 As-(O-Ago|-cyclo-TsAvSh-OTumMOSI-(Rpe(4-2ae)I-(2-Map-(TNRII-EMO-

МН» зи? in Ak cycloiTdvora PMOSm pes oveine Matner,

МН» 1418 As-(O-Ago|-cyclo-TsAVshSh-O TU ESI-IR pe(4-2ae)I-(2-MaC-PT NRI-EMM-

МН» 1419 As-(O-Ago|-cyclo-TsAvsh-ETMOSI-(P pe(4-2ae)I-(2-MaC-P HRI-EMM-

МН» 1420 As-(O-Ago|-cyclo-TsAvSh-O TM OSI (Rpe(4-2ae)I-(2-may-(TNRI-EOO-

МН» 1424 As-(O-Ago|-cyclo-TsAVshSh-O TU ESI-IR pe(4-2ae)I-(2-MaC-PT NRI-EMO-

МН» 1422 As-IO-Aga|-cyclo-АВЩ-ЕТУМОСИ-(Рпе(4-2аве)|-(2-Мац|- ях)

Ihetrahydropyran-AI-EMO-MN»g

Ac-10-Ago|-cyclo-ABsh-O PM ESI-(P pe(4-2ae)|-(2-MaC-(TNRI-EOM-yazzh 1423 МН

As-IO-Aga|-cyclo-TsABSH-ETUMOSI-(P pe(4-g2ae)I-(2-MaP-(TNRI-EOM-yaz 1424 МН 1425 As-(O-Aga|- cyclo-(IABy- ETUMESI-(Rpe(4-2ав)Д-(2-Мац-(ТНРИЕММАМНИ 000 оовезо0/ OSI Ak cycloitavora PMOSN rpei vena MaittnereMn, (on 1416 Ac-(O-Ago|-cyclo-TsAvSh-O TM OSI (Rpe() 4-2ae)I-(2-may-(TNRI-EMO- (on

Ac-IO-Agao|-cyclo-CSABSh-OTUOSI-IRpe(4-gae)-(2-Mas-(TNRI-EOM-yaz 1426 OH 1425 As-(O-Ago|-cyclo-ABSh-OTUMESI-IRpe( 4-2аез-2-МацтНРИЕММ-ОНИИ 00

Ac-(O-Ago|-cyclo-PASCHETUMOSI-(Rpe(4-2ae)-(2-MaC-PT HRI-EMM-OH)

Table E5O

Typical thioether peptides

EPZA I 23 /

ZEO IU MO. Sequence I/ 23 people

NM ho o« 1 NM; 1 pM-10 nm; 7 - 10 PM - 100 nm

Table Eb

IC50 of peptide inhibitors (ring closing reaction)

EPBA sh Sequence/Structure of man and (nm) (0) N o

Мне М 1000 our UM NTEO-MN, - 20000 s) domn. where 1001 AOZHMU UMNTEO-MNO -30000 o demn. | goes 1002 (ETMO AND UHUVKEO-(AEAI-O) in -"МНо яжжжж with --ШЧ Z is) ds-pl. where 1003 ( ВТМ ) UMZHEKEO-I (AEA1-KO uv) - which MNo

Z - 2 is) deMmn. And where 1004 U e) I UMUVKEO-IAEA1-KO Uvi "MN" of which --ь- Z is) ds-pl. and 1005 (who is in UVKEO-IAEA1-KO)І UVI -MNo janzhkh 3 pp o domn. | where 1006 ( 59) ) УХ/ВКЕО-(АЕА1-((О)Г ув) "МН" яжжж а -- 2 е) don. | where 1007 ху, UUVKEO-(АЕА1-ЦО Uvi "МН. янжх ( is) domn. I 1008 ВТМ УХЕКЕО-(АЕА1-((О)Гуви| -МНо "- ---0 Из я--«10 NM; 2-10-25 NM yah - 25-100 nM, ex - 100-1000 NM, ie-1000-10000 NM

Table E7

IIS50 typical peptides containing cyclic amides (cyclization of side chains)

N R Z N

M M ) ( 12 12 ( 12 12

As XXIX. УМХХХХ-АЕА-(Ю уз-МН» Ас--М ХХХ. AL МХХХХ-АЕА-(О)Я uz-МН2 no no No No

ZEO and MO:1484 that is 000-000

ZEO IU MO. Human sequence (nm)

Table E8

IC50 of typical peptides containing the motif As-IRep|-ХХМУХХХХХХ (5EO IU MO:1485) and analogues

As-ХХХМХ-IRep|-ХХХХ (5EO 10 MO:1486)

EO | | Epza Epza Rea B Mr. Kadsuk NTEE I (NM) (NM) (NM) L020 |As-ARepIOMUSUMVAKEODAEAN(OUVIMN.Yi | and 1111111 1027 |As-A-pSuzIOMUM- (Rep UMUVKRSOAEAITO)-SuvrMNa | 30000, 1028 |AsS-SOTMUS Rep uma MesetsEMO-MN.Y 7777711 (1029 |As-SOTMUSN Rep UMu- (O)AvpreEMO-MNaYIDG 77111111 111111 t-10 nm; 77-10-25 NM 7 - 25-100 nm, 7 - 100-1000 nm, 7775-1000-10000 nm (00698) BAK analysis of the tested activities of peptide inhibitors showed, that disulfide

СХХХХО (5ЕО ИО МО:1479) is associated with high activity. Two Tgtr residues and a Ppe residue are also associated with high activity, but it is recognized that these amino acids can be easily replaced with similar homologues (eg, 1-Ma! replaced by Tgr and/or Ppe replaced by

Longing). In addition, the data confirmed that the presence of one or more basic residues at the C-terminus is associated with high activity. Niz-9 can also be replaced with Agod or another homologue and the activity can be maintained or increased. The scheme below provides one typical consensus sequence showing some of the residues associated with high activity. 1 I 3 and I Es t 5 Z that of their i3 Ii

Su Khkh-Ahk- sin Su 1 3- PYU-Niv- Zhkh-Rbe-zhhh-Hkhh- PL huya- ON and shhhshsh (ZEO IYU MO:275)

Example C

Stability of peptide inhibitors in simulated intestinal fluid (5IR), simulated gastric fluid (35OE) and under redox conditions

I00699| Studies were carried out in simulated intestinal fluid (SIV) and simulated gastric fluid (5OBE) to assess the stability of the peptide inhibitors of this invention in the stomach. In addition, studies were conducted to assess the stability of the peptide inhibitors of this invention under redox conditions.

I00700| 5IE was obtained 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 Mmaon.

A stock solution of OM5O (2 mM) was first prepared for the test compounds. Aliquots of solutions

PM5O was dosed into 6 separate test tubes, each containing 0.5 ml of ZIE, which was preheated to 37 "C. The finished concentrations of the test compounds were 20 μM. The containers were kept in a tabletop Tpeptotiheg during the experiment. At each time point (0, 5, 10 , 20, 40, 60 or 360 minutes, or 24 hours) 1.0 ml of acetonitrile containing 1 95 formic acid was added to one container to end the reaction. The samples were kept at 4 "C until the end of the experiment. After the final moment of sampling, the tubes were mixed and then centrifuged at 3000 rpm. within 10 minutes. Aliquots of the supernatant were removed, diluted 1:11 in distilled water containing an internal standard, and analyzed using I CM5/M5. The percentage remaining at each time point was calculated based on the ratio of the peak area to the response for the compound relative to the internal standard.

Time 0 was set as 100 95 and all other time points were calculated relative to time 0. Half-lives were calculated by fitting to a first-order exponential decay equation using Ssgarprey. Stability in 5IE assays is shown in Tables E9 and E10.

I00701| 5OE was obtained by adding 20 mg of Masi, 32 mg of porcine pepsin (MR Viospetisai!5, catalog 02102599) and 70 μl of HCl in 10 ml of water (final pH-2). Aliquots of BOE (0.5 ml each) were previously heated to 37 "C. To start the reaction, 1 μl of the initial peptide solution (10 mM in

OM509) was added to 0.5 ml of 5OE and vigorously mixed so that the final concentration of the peptide was 20 µM. The reaction mixtures were incubated at 37 "C with gentle shaking. At each time point (0, 15, 30, 60 min) 50 μl aliquots were removed and added to 200 μl of acetonitrile,

Of which contains 0.1 96 formic acid, to complete the reaction. Samples were kept 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 in distilled water containing an internal standard, and analyzed using I CM5/M5. remains at each time point were calculated from the peak-to-response ratio for the compound relative to the internal standard. Time 0 was set as 100 95 and all other time points were calculated relative to time 0. Half-lives were calculated by fitting a first-order exponential decay equation with the help of Sgarpraa.

Stability in 5OE analyzes is shown in Tables E9 and E10.

Table E9

Stability of typical peptides containing the As-IRep|-XXM/X-IRep|-XXXX motif (5EO IO MO:1482) and analogues in simulated intestinal fluid (5IRE) and simulated gastric fluid (ZORE) 549 AsCRep OPO Rep um yetsEMO -MNAID 7777777 7030 (AU | Repotusnrepi UUUM-WUM-WEMNAID 777777111 551 Assyrops Otmusnrepimm-Piemo-Mn777111 Ї // 7777777777771171111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111 месуврЕМа-МНне.у 7777111 Ї111111Ї1и 558 Ас|РепОТМУСнРеп2-майг-мафіо-МмесуєрЕМО-МНЇ ЇЇ" 559 Ас|РепОТМУСнРепіу-2-Машіоа-меОтрЕМО-МНеЇ:д 7777717 Ї17711171Ї1 560 Ас|РепОТМУСнРепі МУу-а-МеОтрЕМО-МНед 777777777111Ї1111111Ї1и ( 561 TSA|RepOtMUSnIRepi u-P-MafiameOtreMO-MneYi:d 7777717 Y17711171Y1

Table E9

Stability of typical peptides containing the motif As-IRep|-XXM/X-IRep|-XXXXX (5EO IO MO:1482) and analogs in simulated intestinal fluid (5IRE) and simulated gastric fluid (ZORE)

As-IRepI-STUMO-(Repi-(Rpe(4-OoMeL(OMe)|-(2-May-(a-MeoOgpisha)

I uv(As)|-Ma-MN" 1032 |As-IRep OTMU/S-IRepi(Rpe(4-OMe)rm-o-MesuzNiuv(Asu Mene! 17" web | ep Olmoteepiepei mistletoe Maitoye Me in (home: 2 vv.

Me! uzi-P uv(Ac)-MIa-MHg pyroglutamic acid-(RepI-OTHUO(RepiI-("Rpe(4-OMe)I-(2-Map-(a-

Me! uzi-P uv(Ac)-MIa-MNg tin in ep eper o aminoethoxy Do not have Meguvi;

And uv(As)-MM-MAN" in Otepieper about aminoethoxy Do not have Meguvi;

EMA-MN" this episode about aminoethoxy Do not have Megetsi

And uv(As)-MM-MAN" ovo tep peri about aminoethoxy Do not have Megetsi

OMM-MN" ovo Otepieperi about aminoethoxy Ne Mag Aich I uv (Asy

2 more vov | Ac-IRepI-SOTMS-(RepiI-(Rpe|4-(2-aminoethoxy)|-(2-maP-HAiYVI-( uv(Ac)|-

MO-MNe ovo set as Ni ope per acetylaminoethoxy I Mai; (o-MeH uv(Ac)|-EMa-MH»g vov | Aoirepi mes As Orel peg o acetylaminoutoxy, 2-MaC-(a-MeiH uz(Ac)|-EMOa-MH»g - As-IRepI-SOTMSO -(RepiI-(Rpe|4-(2-acetylaminoethoxy)|-(2-Ma-(a-

Me! uz(Ac)I-P uv(Ac)I-MOa-Mng

Ac-(RepI-YTUMO-(Repi-IRpe|4-(2-acetylaminoethoxy)|-(2-MaC-(a-

Me! uz(As)|I-P uz(As)-MM-MN"

Ac-(RepI-YTUMO-(Repi-IRpe|4-(2-acetylaminoethoxy)|-(2-MaC-(a-

Me! uz(Ac)1-EMIa-MHg

Ac-(RepI-YTUMO-(Repi-IRpe|4-(2-acetylaminoethoxy)|-(2-MaC-(a-

Me! uv(Ac)1-EMA-MN»g

Ac-(RepI-YTUMO-(Repi-IRpe|4-(2-acetylaminoethoxy)|-(2-MaC-(a-

Me! eci-P uz(Ac)-MM-AMN"

Ac-(RepI-YTUMO-(Repi-IRpe|4-(2-acetylaminoethoxy)|-(2-MaC-(a-

Me! esh-ОММ-МН»g led Teplyo with acetylamino flow T2 May

EMM-MN" operated with T2 acetylaminoethok May

And uv(As)-MM-MAN" in the ele peri about acetylaminotokom T2 Mai

I uv(As)|-MO-MN» vag EepPOPMOTEpepesnoMayte Mayte MeguzNEMS MNor via eieLKO POT r peri o aminoetokoi Te maitli en EM: 2

Table E9

Stability of typical peptides containing the motif As-IRep|-XXM/X-IRep|-XXXXX (5EO IO MO:1482) and analogs in simulated intestinal fluid (5IRE) and simulated gastric fluid (ZORE) 5EO I p vakn/gi | in H/2

As-I(RepI- GTU O-(RepiI-IRne(4-(2-aminoethoxy)|-(2-MaC-(AlIVI-(Huz(Ac))|- « « 620 | Mm-mne

As-IRep-OTMS-(Rep|-(Rpe(4-OMe)|-(2-Map-(AiVI-(Suv(Ac)|-MM-MH))

Ac-(RepI-OTUMO-(Repi-IRpe|4-(2-aminoethoxy)I-(2-map-(AIVI-( uv(Ac)|- І І

M-TVAIa1-MN"

As-IRepIi-MTU/O-IRepy-(Rpe(4-OMe)-(2-macC-(AivI-EMM-MH)" (ovzy Aoirepictuschelienov (in aminoutoxide in-maint ots EMA)

MN"

Ac-I(RepI-«MTUM/O-(Repi-(Pne(4-(2-aminoethoxy)|-(2-MaP|-(AIVI-(H uv (Ac) |- « « 632 | Mm-mne at the eiepem mor elitepesnoMe)nYa mag section VA,

MN"

Ac-I(RepI-«MTUM/O-(Repi-(Pne(4-(2-aminoethoxy)|-(2-MaP|-(AIVI-(H uv (Ac)) |- « « 6534 |Mo-Mne

Ac-I(RepI-«MTUM/O-(Repi-(Pne(4-(2-aminoethoxy)|-(2-MaP|-(AIVI-(H uv (Ac) |- « « 636 | MA-MHn

Ac-IRepI-MTM/O-(Repi-(Rpe(4-OMe)-(2-MmapP-IAivI-(uv(Ac)|-MM-MH))

Ac-(IRepi-MTUM/O-(Repi-(Rpe(4-OMe)|-(2-MapC-H(AiBI-( uv(Ac)Y-MO-MH»

Ac-(RepI-MPTMO-|Repi-(Rpe((4-(2-aminoethoxy)|-(2-maP-(AIVI-( uv(Ac)|- І І

M-(ВАТа|-МН»

As-IRepi-MTUO-(Repi-I(Rpe(4-OMe)|-(2-Map-(pi esI-(uv(Ac)|-M-(BAIa|-

MN"

As-IRep|-MTUS-(Repi-IRpe|4-(2-aminoethoxy)|-(2-MaC-(yi ec|- zzhkzhh pzhkzhh

I uv(As)|-M-(VATA|-MN» vve Ov ele somNaTe meto Me uv(As

MIM-MN"

I(Ac-(Rep-OTUMO-IRep|-(Rpe(4-SOMHng)I-(2-MaP-(a-Me! uziI-( uv(Ac)|- uch; 5ZA)

Mm-MNaeoa 1035. | AE-KO)Rpe (Rep "MTmO-Repy-(Rpe|4-(2-aminoethoxy)|-(2-maPChAiLi-); ;

And uUv(As)-MM-MAN"

As-KO)RpeI|-(RepIi-MPMSO-(Repi-Irpe|4-(2-aminoethoxy)I-(2-MaP-I(Aib|- y

And uv(As)|-M-(VATa|-MNeg

As-IRepy-MTM/O(Hrepy-(Rpe(4-SOMHng)I-(2-Map-AIVI-(uv(As-MM-MH)

As-IRepi-MTUO(Repi-I(Rpe(4-SOMNHg)|-(2-MaP|-(4-amino-4-uh; carboxytetrahydropyrani|-Huz(As)|-MM-MH) vva o epEMTUsirelinepegn oon Magndspoi p inods)Nmm:

MN" 1036. | As-(Rep|-MPMUO(Repi-(Rpe(4-SOMNg)I-2-Ma|Chasusi(Suv(AsuMMMNna, eat mo epim plates dog soma me et in

MN"

As-IRepi-MTUO(Repi-I(Rpe(4-OMe)|-(2-Ma|-(4-amino-4-ІІ carboxytetrahydropyrani-(H uz(Ac)|-MM-MH»

Ac-IRepI-MTM/O(Repi-(Rpe(4-OMe)-(2-MmaPC-(AspsIi-( uv (Ac)-AMM-MH»

Ac-(Irepi-MTM/O(Hrepi-(Rpe(4-OMe)|-(2-MaP-(Asucy-(Sus(Ac)|-MM-MH) t eirepemtmsibelinepernomein Meioemes oo uv(ds)NMK:

MN"

As-IRepIi-MTM/O-(Repi-(Rpe(4-SOMNHg)I-(2-MaP-(AivI-KMM-MNHg) IS (As-(Repi-M TU (Repi-(Rpe(4-SOMNHg) I-(2-MatZ-(4-amino-4-; ; 536 carboxytetrahydropyran-KMM-MNai|» О1С

As-IRepIi-MTM/C-(Repi-(Rpe(4-SOMNHg)I-(2-MaP-(Asps|-KMM-MHg|» 01

Ias-I(RepIi-M' TM O-(RepiI-I(Rpe(4-COMNHg)I-(2-Ma-(a-MeH esChI-KMM-MNa|» ris

Table E9

Stability of typical peptides containing the motif As-IRep|-XXM/X-IRep|-XXXXX (5EO IO MO:1482) and analogs in simulated intestinal fluid (5IRE) and simulated gastric fluid (ZORE)

ZEO I. . final 5IE n/2 matrix used is a 100-fold dilution of the standard concentration of BIR x-»360 min; 77-180-360 min; 77-120-180 min; and --60-120 min; and -"60 min

Table E1O0

Stability of typical peptides containing thioether motifs and analogues in simulated intestinal fluid (SID) and simulated gastric fluid (Za)

ZIR zak my Sequence np/2 n/2 and (min) (min)

As-cyclo-DABCHTV TMOSI-ZhMAKES-(AEAI-OYI uUv|I-MN" now

As-cyclo-DABy|-STUOSI- UM VEMO-|(AEAI-(O)І uv|- МН» now

Ш- As-cyclo-CABi|-OTUMOSI-ZhMU-(pHec-EMa-MH»

As-cyclo-IABSH-OTUO-(0)SuzCAIM-(pi esh-EMO-MH» i

As-cyclo-TsABshsh-STUO-(Rep| HA iMm-(pi esh-EMO-MN" now

As-cyclo-DABy|-STUOSI-IM/-(a-Me emI-EMO-MH» now

As-cyclo-(ABy|-STUOSI-X-(2-MazC-a-Me uz|I-EMOa-MH») of this |ecycloidene g OtmasieperMme has a uvEems:

MN»g tin |doshchylo About olUasieneoMelne Mayo meoti emo:

MN"

As-cyclo-DAVsh-OTUKOSI-IRpe(4-OMe)-m-(a-MeOgp-EMa-MH" (that

МН»г

Ac-cyclo-CSABSH-OTUCOSI-(Rpe(4-OMe)|- M -(a-Me! uzI-C uz(Ac)|-Ma-

МН»г

As-cyclo-DABsh-STUOSI-(Ppe(4-OMe)|-M-(a-Mei!ug|-EMO-MH» p As-cyclo-CAbBi-O TU OSI1-I(Ppne(4-OMe) I-(11-Ma!|-(s-Me! uzI|- « yyyyyy

Guv(Ac)-Ma-MH»g 712 As-cyclo-CAbBi-O TU OSI1-I(Pne(4-OMe)|-(2-Ma!|-(c-Me! uzI|- yazh kzhzhzhzh

Guv(As)-Ma-MN»g

As-cyclo-DABsh-STUOSI-MM -(a-MeOgpi-(uv(Ac)-MO-MH" powder

As-cyclo-HABy|-O TU OSI1-I(Rpe(4-OMe)I-(2-MaC-KO)Avpi1-(H uz(Ac)|- «

Pa molmn 715 As-cyclo-CABi-OTUMOSI1-IRNe(4-phenoxy)|-(2-MatZ-(o-Meg! uzI|- «

Guv(Ac)-Ma-MH»g 716 Ac-cyclo-CABy|-OTUMOSI1-(pPe(3,4-dimethoxy)I-(2-MaP-(a-MegGuvi|-)

Guv(As)-Ma-MN»g tt |dedicloiden g otmosioM te have MeguvNi uv(dsinmo: EH

МН»г 718 As-cyclo-AbBi-O TU ОСИ1-(Рпе(4-СОМН2)И-(2-МаП-(о-Мей! уз|- яжж кжжжж)

Guv(Ac)|Ma-MH»g 719 As-cyclo-AbBi-O TU OSI-Rpe(3,4-С122-МацЦ-(o-Mei! uzi|- yazh

Guv(As)|Ma-MN»g

As-cyclo-TsABy|-OTUMO-(Repy|-(Рпе(4-ОМе)|-(2-Мац-(o-Meguz1-yzh yzhzh 720

EMOa-MH»g 794 As-cyclo-CAbBi|-O TU O-(Repi|-(Rpe(4-OMe)|-(2-MaC-(o-Mei! uv|- eat same)

Guv(As)|Ma-MN»g

As-cyclo-PAVshsh-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-UM-(a-Me!uz |-

Table E1O0

Stability of typical peptides containing thioether motifs and analogues in simulated intestinal fluid (SID) and simulated gastric fluid (Za)

CIE vaye and (min) (min) 1 EMEEMNIA S/g

As-cyclo-CAVSH-OTUMOSI-IRpe(4-OMe)I-(2-Ma-(o-MeOgpi-

And uv(As)|-Ma-MNe (oto doshchikloTSAeni oto Mav mario-Meogi and uv(Asd MO,

MN" of data ootea|dolikloiden OT mOSI Te Myte megoeMe in uv(As) we eat:

MN" data

As-cyclo-D(Arsh-OTHUOSI-(Rpe(4-SOMN")1-(2-MazC-(a-Me! uzI-

And uv(As)|-Ma-MN"

Ac-cyclo-CABi-OTUOSI1-(2-MaC-(2-MaC-(o-Me!H uz|-EMa-MH» ds-cyclo ParyHOTMOSI(Rpe(-OMeda Mai TATII PUv(AS MO: ЭХ 2 ds -cyclo PAryg OTO (Reya oMed2 may Oti p uv(As MO: EX 2 dsgcyclo PARygOTMOSI(Rpe(ya- Omez Ma Spo uv(As MO: kN 2 vag | dolicloylene OTO CO seed a MeichoyeMe in Uv(AsLMO- LY 2

As-cyclo-DCABSH-OTUMOSI-IRpe(4-OMe)I-(Osidio|-(o-Me!uz|- SL)

And uv(As)|-Ma-MN"

As-cyclo-DCABSH-OTUMOSI-IRpe(4-OMe)I-(Osidio|-(o-Me! uz|- LY)

And uv(As)|-Ma-MN"

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Me! uzI-EMa-MN»g

As-cyclo-DHAVSH-OTUHOSI-(Rpe|4-(2-aminoethoxy)||-(2-May-a-

Me! uzI-(Suz(benzoic acid)|-Ma-MNeg

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Me! uzI-(Suz(isovaleric acid)|-Ma-MNeg oovuvo lopat moseneg o aminoethoxy I Maindyu

Huv(As)-O0-MNe ovo ok otile g atmosiene ho aminoethoxy I Maindyu

ОМа-мНе оовтво вок о лег атмосиене г aminoethoxy I Maindyu

EMO-MN"

As-cyclo-CAVSH-OTUMOSI-(Rpe|4-(2-aminoethoxy)||-1-Ma|(AIBI-

And uv(Ac)|-Ma-MH» oovvo|lolist o OTMOSIENE ho aminoethoxy Ya Maindyu

And (Ac)L-MA-MN» ooveio |to diko log about MaSIEne ho aminoethoxide of PM? Maicho"me;

Ot!-P uv(As)I-MOIa-MNg

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Me! uzi-P uv(Ac)-MIa-MNg oovezo | Loly Ta Otuosiene ho aminoethoxy Pa MainOti; LI

I uv(As)|-Ma-MH» ooveiao|Aoshchyklo PAro ho pMosITenegi o aminoethoxy t MO EMo; sl 2

As-cyclo-CABy-OTUMMOSI-(Pne(4-(2-aminoethoxy)||-UM-(Othi|i-(Oarikzhzhzhzh ovo one

As-cyclo-PAVshS-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-UU-(Ogp|- LY)

Rar (Asl-Ma-MNg

Table E1O0

Stability of typical peptides containing thioether motifs and analogues in simulated intestinal fluid (SID) and simulated gastric fluid (Za)

CIE works

Mo. (min) (min) ooveo | pocyclo Pav Op UOSITeneg about aminoethoxyh Ta MaiCHOti; sl

Rari-Ma-MN»g oovevo | opisok OTUasipe g aminoethoksid I MainOti; LI

Rar(Asl-Ma-MHg ds-cyclo Pary OTO SI(Rpega-(2-aminoethoxyuI M/-(pi-eoI EMO: 2

I Ac-cyclo-CSABSH-OTUMOSI-(Rpe(4-(2-(acetyl-aminoethoxy))|-(2-Ma/|- (α-Mei! uz(Ac)|-(Sus(AsD-Ma- МНег вой роколен отмасиТепег о аминовтоций МогМетеми;

EMO-MN"

Succinylcyclo-GABSHSH-OTUMOSI-(Rpe(4-(2-aminoethoxy))|-(2-Mas-(a-

Me! uzi-P uv(Ac)-MIa-MHg ovo As-cyclo-PABshS-OTUMOSI-IRpe(4-(2-(acetylaminoethoxy))|-(2-Ma/|- (o-MeH uv(Ac)|- EMa-MH»g dsgcyclo PARIGOTMOSI(Rpe(ia- omega Ma Spo uv(As MO: 2

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Me! UGI-EMO-MN"

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Me! uzI-EMM-MN"

As-cyclo-DABi|-TTUMOSI-(Rpe|4-(2-aminoethoxy))I-(2-MaC-(a-

Me! uzI-EMYa-MN»g eta | dol Po oliavcenegn o aminoethoxykh o MaichioyeMe, siu(ethyl)| Suz(As)|-Ma-MNe

As-cyclo-DHAVSH-OTUHOSI-(Rpe|4-(2-aminoethoxy)||-(2-May-a-

Mema!y!-P uz(Ac)1-MOa-Mng

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Mezep-P uv(As)-MIa-Mng

Ac-(0) uz-(Icyclo-ABsch-O HUMOSII-(P pe(4-OMe)|-(2-MaC-(o-MegG ecy|- жкжжж жжжж)

МЕС amines BUT PO s в дихло PAVOG Ома раси оМмельнЯ MainaiMmene ee nn

EMOa-MNg|2 BIS: dimerization through (B) in ooevo | Lola Po Ot MOSIeteg o aminoethoxyuPch o Mainitsoeia;

And uv(As)|-M-(VATa|-MNeg data).

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Me! uzI-MMSY-MN»g oovavo | shares PT OTMOSIENe ho aminoethoxy Ya Maindyu

And uv(As) |-MO-MN»g

As-cyclo-DABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy)||-(2-MaP|-(a-

Me! eci-P uz(Ac)-MM-AMN"

I(As-cyclo-HABSHSH-OTUMOSI-Z(B21)-UM-(a-Mei uz|I-EMO-MHg|): PEG25 through (a-MeH uv vv i OpMOSNRpen aminoutoxyi Mine

Me! uzI-EMM-MN"

ALSO Ac-(0)c1y-(Icyclo-ABSHSH-OTUMOSI-(P pe(4-(2-aminoethoxy)||-(2-Ma||- a-Mei uz|-EMM-MH)) introduced Av apMasm pore aminoethoxy NOT Maine"

Me! uzI-EMM-MN"

As-KO)Agd-cyclo-PABSH-OPMOSI-I(P pe(4-(2-aminoethoxy))|-(2-Ma!|-

Yo- Me! uz|-EMM-MH» 969 |Ac-E-cyclo-PABSH-OTU OSI Rpe|4-(2-aminoethoxy))|-(2-MaC-(a-

Table E1O0

Stability of typical peptides containing thioether motifs and analogues in simulated intestinal fluid (SID) and simulated gastric fluid (Za)

ZIR zak

Mo. (min) (min) 11 fmeuvrEMMAMNYI 11111111 po KOINEi chyklo PAVYNO PMOSITEneg and aminoethoxy Na nn a-Mei! ug|I-EMM-MNg vla ik rat MOSI pore aminoethoxy Ne Mane»

Me uz |-EMM-MN" uz ro tape t Osi Tepeg o aminovtoxyuio-Meicho;

Me uz|-EMM-MN"

As-CO)OHIIp|-cyclo-CASH-OTUMOSI(Rpe(4-(2-aminoethoxy)||-(2-Mac|- (a-Me!ug|-EMM-MH)) Meyidoroi;

EMM-MNg ovuvo o len otmasitepeg o aminoethoxyuich o Meini Asosi;

EMM-MNg loz ve o len otmasitepeg o aminoethoxyuich o Meiidoroi;

EMM-MNg ovuvo vo o leg atmosiene g aminoethoxy I MainAsmsi

EMM-MNg dost in le aminotoxyl a Maittamnoi 51 4-carboxypiperidine|I-EMM-MN» vla ie ap MOsieperi o aminoethoxy S Mains»

Me uz|I-EMM-MN" matrix used is a 100-fold dilution of the standard concentration of BIR "-5360 min; "7-180-360 min; 77-120-180 min; 77-"60-120 min; 77 - "60 min

IІ00702| For each tested peptide, the OTT stability analysis was performed by adding 5 μl of a 10 mM initial solution of the peptide in OM5O to 1 ml of 100 mM Tris-CI, pH 7.5 (the final concentration of the peptide is 50 μM). At time 0 min, 5 μl of freshly thawed 5,100 mM OTT solution was added to the incubation tube containing the peptide, so that the final concentration of OTT was 0.5 mM. Reaction mixtures were incubated at room temperature. At different time points up to 120 minutes (20 min, 40 min, 80 min, 120 min), 50 μl aliquots were removed, the reaction was terminated by adding 10 μl of 5M acetic acid. To measure the disappearance of the initial peptide, cooled samples (30 μl) were analyzed by reverse-phase NRI C and UV absorption at 2209 nm. The oxidized fraction remaining was plotted against time, and half-lives were calculated by fitting a first-order exponential decay equation using Echsei. The results of these tests are shown in Table E11. All peptides with a half-life of 2120 min are considered stable.

Table E11

Stability of typical peptides in OTT analysis

OT (min)

Table E11

Stability of typical peptides in OTT analysis

OT (min)

As-cyclo-DGABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy))|-(2-Ma/|-(4-amino-4-ES) . . 5120 carboxytetrahydropyrani-EMM-MH» "-10-120 min.

Example 4

Cross-reactivity of peptide inhibitors 00703) The amino acids of the human extracellular domain 1/-23K are identical at 95 95, 77 95 and 70 95

I/-23K dog, I/-23E rat and I/-23K mouse, respectively. Interestingly, the mouse receptor contains a 21-residue insert that is absent in the human, mouse, chimpanzee, dog, and cow receptors. These additional amino acids are located in the region where human II-23E is believed to bind to

I. -23.

I00704| To identify peptide inhibitors that cross-react with species other than human II/-23K, the ability of some peptide inhibitors to inhibit human II/-23K,

I/-23K of dog, P/-23K of rat and I/-23E of mouse are determined using the EGISA analysis.

According to the observation regarding the sequence difference between human I/-23K and mouse IS-23v8, the tested peptide antagonists showed no or very weak inhibitory activities in EGISA II -23E mice (see Table E12). In contrast, antagonists tested to date have shown comparable potency at the rat receptor and somewhat less activity at the dog receptor. 00705) Various bioassays performed to determine the potency, cross-reactivity, and selectivity of I--23E antagonists are described below.

Analysis of the selectivity of specific II -238 antagonists

EPZA 1 -12K81 of a person

I00706| The assay plate was coated with 100 ng/well of human I.-12K81 pESC and incubated overnight at 4 °C. Wells were washed, blocked, and washed again. Serial dilutions of test peptides and I-23 with a final concentration of 2.5 nM were added to each well. and incubated for 2 hours at room temperature. After washing the wells, bound 1-23 was detected using polyclonal goat anti-p40 antibodies, followed by NCR conjugated donkey anti-goat dO antibody. Signals were visualized using TMB one-component

HER of the membrane substrate and quenched with 2 M sulfuric acid.

Competitive binding analysis of mouse EGG IZA 1-23K

I00707| The tablet for analysis was covered with 50 ng/well of I/-23K piBS mouse and incubated

Overnight at 4°C. The wells were washed, blocked, and washed again. Serial dilutions of the test peptides and I/-23 at a final concentration of 4 nM were added to each well and incubated for 2 hours at room temperature. After washing the wells, bound 1 -23 was detected using polyclonal goat anti-p40 antibody, followed by NCR conjugated donkey anti-goat dO antibody. Signals were visualized using TMB one-component

HER of the membrane substrate and quenched with 2 M sulfuric acid.

Competitive binding analysis of rat EGISA 1I--23K

I00708| The assay plate was coated with 300 ng/well of I/-23K rat pES and incubated overnight at 4 °C. The wells were washed, blocked, and washed again. Serial dilutions of the test peptides and II-23 at a final concentration of 7 nM were added to each well and incubated. for 2 hours at room temperature. After washing the wells, bound 1-23 was detected using polyclonal goat anti-p40 antibody followed by NCR conjugated donkey anti-goat dO antibody. Signals were visualized by TMB one-component

HER of the membrane substrate and quenched with 2 M sulfuric acid.

Competitive binding analysis of dog EIG I5A II -23K

IІ00709| The assay plate was coated with 50 ng/well of dog I/-23E piES and incubated overnight at 4 °C. Wells were washed, blocked, and washed again. Serial dilutions of test peptides and I/-23 at a final concentration of 2 nM were added to each well and incubated for 2 hours at room temperature. After washing the wells, bound 1-23 was detected using polyclonal goat anti-p40 antibodies, followed by NCR conjugated donkey anti-goat dO antibody. Signals were visualized using TMB one-component

HER of the membrane substrate and quenched with 2 M sulfuric acid.

Table E12

Cross-reactivity of typical peptide inhibitors

Dog connection number (NM)

EPZA Cell analysis EPIZA 1 23A Ts|EGIZA 23 EGIBZA II 23 I 23 nnitliinininninchinyInnsnnishyshn shi 1117197. | the same | no data | - - | i | unmayedanykh 07169 Y z. | in- 1 - Her - | it shows 0-250 nm it shows 251-1000 nm it shows 1001-10000 nm it shows » 25000 nm

Example 5

Cell analysis of MK 00710) Natural killer (NK) cells, purified from human peripheral blood of healthy donors by negative selection (Minnepui Wioyesi, Mo under catalog 130-092-657), were cultured in complete medium (KRMI 1640 containing 10 95 ЕВ5, I -glutamine and penicillin-streptomycin) in the presence of II -2 (KpO, Mo according to catalog 202-II -010/SE) at 25 ng/ml. After 7 days, the cells were centrifuged and resuspended in complete medium at 1 Eb cells/ml.

Recombinant 1-23 with predefined EC50 to EC75 and 1-18 (KpO, Mo according to the catalog

BO03-5) at 10 ng/ml was mixed with different concentrations of peptides and added to MK cells seeded at 1E5 cells per well. After 20-24 hours, IEM in the supernatant was evaluated using Otsapiikipe EGIZA (Kp, Mo according to the OIE50 catalog).

Table E13

IC50 of typical peptide inhibitors in a primary cell line (MC cell analysis) len

MK sequence (nm)

As-cyclo-HAVSHSH-OTUMOSI-IRpe(4-OMe)1-(2-Ma|-(o-Me! uz|I-EMO-MH" (5EO 10

MO:705

As-cyclo-GABSH-OTUKOSI-(Rpe|4-(2-aminoethoxy)|-M/-(α-Me!uz|-EMO-MH»

ZEO and MO:259

As-cyclo-DABSH-OTUCOSI-IRpe|4-(2-aminoethoxy))|-(2-MaC-(α-Me!uzi-

ISuz (isovaleric acid)|-MO-MH" (ZEO IU MO:443

As-cyclo-GABSHSH-OTUMOSI-(Rpe|4-(2-aminoethoxy))I-I(2-MaP-(AiIVB-OMa-mH»

ZEO IU MO:1487

Ac-cyclo-GABSH-OTUCOSI-IRpe(4-(2-aminoethoxy))I-(2-mapP-(AIVI-P uv(Ac)-MA-

MN" (ZEO IO MO:447

As-cyclo-GABSH-OTUMOSI-IRpe|4-(2-(acetylaminoethoxy)||I-(2-Mas-(a-

Me uv(As)|-(Suv(As)|-Ma-mMmN" (ZEO 1O MO:432

As-cyclo-HABSH-OTUCOSI-IRpe(4-(2-aminoethoxy)I-IRpe(3,4-OMeg1-(o-Me! uv|-

Гув(Ас)|-Ма-МН" (ZEO 1О MO:908

Table E13

IC50 of typical peptide inhibitors in a primary cell line (MC cell analysis)

Cell analysis

MK sequence (nm)

As-cyclo-PABSH-OTUMOSI-IR pe(4-(2-aminoethoxy))I-(2-MaP-(a-Me uzI-EMO-MH)

ZEO IU MO:437

As-cyclo-GABSHSH-OTUKOSI-(P pe|4-(2-aminoethoxy)||-(2-MaP-(a-Mei uv|1-EMM-MH» 5ZEO IU MO:912

Ac-cyclo-GABSHSH-OTUKOSI-(Rpe|4-(2-aminoethoxy))|-(2-MaP-(o-memapP-(Cuz(Ac)|-

MOa-MH" (ZEO and MO:660 (Ac-cyclo-CSABSH-OTumMOSI-(P;pe(4-OMe)-(2-Mai-(a-Me! uvI-EMO-MHg|2"; (ZEO

I MO:258) BIS through a-Me! uz

As-cyclo-DABSH-OTUCOSI-IRpe|4-(2-aminoethoxy))|-(2-MaC-(a-Mei esh)-(SSH-MM-

MN" (ZEO IO MO:665

As-KO)RPpe|-cyclo-solvent-OTUMOSI-(RPe(4-(2-aminoethoxy)|I-(2-MaC-(α-MeGuvi|-

EMM-MN" (ZEO 10 MO:970

As-T-cyclo-GABSH-OTUMOSI-(PHe|4-(2-aminoethoxy))I-(2-Ma!/|-(c-Me!uz|-EMM-"

МНг (ZEO IU MO:972

Ac-cyclo-PABSH-OTUMOSI-(P pe(4-(2-aminoethoxy))I-(2-MaP-(AcbcI-EMM-MH))

ZEO IU MO:253

As-cyclo-PABSH-OTUMOSI-IR pe(4-(2-aminoethoxy))I-(2-Ma-(Asrs|- EMM-MH)

ZEO IU MO:975

As-cyclo-CABSH-OTUMOSI-(P pe(4-(2-aminoethoxy))I-(2-MaPC-(Asps|I-EMM-MH»)

ZEO IU MO:754

As-cyclo-DGABSH-OTUMOSI-(Rpe(4-(2-aminoethoxy))|-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|i-EMM-MH)»g (ZEO 1O MO:260

As-cyclo-GABSH-OTUKOSI-IRpe|4-(2-aminoethoxy) 1I-(2-maP-(a-Mei esch-OM-

IVAIa|-MN" (ZEO 1 MO:1488

Ac-(0)Rpe-cyclo-CavshS-OTumMOSI-(Rpe(4-(2-aminoethoxy))|-(2-MaC-(4-amino-4-carboxytetrahydropyrani-EMM-MN)" (ZEO 10 MO:992

Ac-((0)Aga|-cyclo-TsABSH-OTUMOSI-IR pe(4-(2-aminoethoxy)||-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)» g (ZEO 1O MO:993 i--"25 NM

Table 14

IC50 of typical peptides containing the motif As-IRep|-XXM/X-(Rep|-XXXXX (ZEO I MO:1482) and analogues (cellular analysis of MK)

Cellular

Sequence analysis MK (nm)

Ac-(Rep-OTUMO-|RepiI-IRpe|4-(2-aminoethoxy)|-(2-MaP-(a-Mei esI-( uv(AcL-MM-MH)" (ZEO

IU MO:256

Ac-IRepI-MTU/O-|RepiI-IRpe(|4-(2-aminoethoxy)|-(2-MasP-(AIV1-(uv(Ac)|-MM-MH)" (ZEO 10

MO: 255

Ac-(Rep-MTUS-(Repi-Irpe|4-(2-aminoethoxy)|-(2-Map-HAiLi-( uv(Ac)|1-M-(BATa|-MH))

IU MO:639

Ac-IRepI-OTUMO-(RepiI-(Rpe(4-OMe)|-(2-MaP-(a-Mei uz |-(Suv(Ac)|-MM-MN)" (ZEO 10 MO:532

Ac-(RepI-OTUMO-(RepiI-IRpe(4-SOMNHg)1-(2-May-(o-Me! uzI-(Sus(Ac)-MM-MH)" (EC 10

MO: 257

Ac-(RepI-OTUMO-(RepiI-IRpe(4-COMNHg)1-(2-MaP-(o-MemapP-(Suz(Ac)|-MM-MH)" (ZEO 1U

MO:669

IAs-I(RepI-OT M O(Hrepi-(Rpe(4-(2-acetylaminoethoxy)|-(2-Mai-(o-Mema!|-KMM-MHg|» BIS

ZEO IU MO:530

Table 14

IC50 of typical peptides containing the motif As-IRep|-XXM/X-(Rep|-XXXXX (ZEO I MO:1482) and analogues (cellular analysis of MK)

Cellular

Sequence analysis MK (nm)

IAs-I(RepI-OT M O(Hrepi-(Rpe(4-(2-acetylaminoethoxy) I-(2-MasC-K-( uv (Ac) |-MM-MHg|» 012

ZEO and MO:531 (As-IRepy-STUO-(Repy-(Rpe(4-OMe)|-(2-mai-(a-Me uz1-( uv(Ac)|-MM-MNeg|» 01С (5EO 10

MO:532

IAs-I(RepI-OTUMO-(RepiI-(Rpe(4-SOMN?g)I-(2-Ma-(a-Me! uzI-(uz(Ac)|-MM-MHg|g» 012 (ZEO M

MO:257 oo a reg pesnomelne Maty amino-k carboxytetrahydropivani 5

SSHCHAMM-MN" (ZEO 10 MO: 679 yt-10 nm; 777-10-25 nm

Example 6

Determination of characteristics of peptide inhibitors by means of bioanalysis

IІ00711| The potency, cross-reactivity and selectivity of some peptide inhibitors were determined using various bioassays developed for this purpose and described below.

Analysis of rat splenocytes

I00712| The newly developed analysis was an analysis of rat splenocytes. This assay detected I-17A levels in activated rat splenocytes after stimulation with 1-23 in the presence of test compound. 00713) Briefly, splenocytes freshly isolated from the rat were plated in 96-well tissue culture plates in complete medium containing II/-13f8. Serial dilutions of the test compounds were injected into each well along with rat II-23 with a final concentration that is between the EC5O and EC80 values; the tablets were then incubated for 3 days at 37 "C in a humid incubator with 5 95 CO2. Changes in II-17A levels in the supernatants were detected using EG IZA.

Colitis model in the rat: 9 days of drinking water containing Z 95 055 (00714) There is a body of evidence in the literature that supports the pathogenic role of II-2ZLI-231 signaling: in animal models of colitis. For the IL-23 ligand, this requirement has been shown in many models, including the I--10-/- spontaneous colitis model, the Neussobasieeg Peraisiv5-mediated colitis model, the CO40-induced congenital colitis model, and the chronic CO4-C045EVPdp T cell transfer model. For the II-23 receptor, the requirement for the development of colitis was shown in acute models of colitis caused by 055 or anti-СО40, as well as in the model of chronic transfer of T cells СО4-С045ЕВпидп. Since some peptide inhibitors of this invention do not cross-react with the 1-23 receptor from the mouse, but recognize one from the rat, a rat IBO model relevant to the 1-23 pathway was developed. 00715) In this model, colitis was induced in 560 rats by the administration of 9 days of drinking water containing C 96,055. rats/group): medium, 395,055 and 395,055 with a positive control (sulfasalazine was administered at 100 mg/kg PO, 00). The BAI indicator consisted of ratios of three parameters,

Zo including the percentage loss of body weight, stool consistency and the quantitative indicator of blood cultures, and could reach a maximum value of Z units. Animals injected with Yu55 showed a significantly increased WAI (compared to medium) from day 4 onwards, with WAI values peaking at approximately 2.5 at the end of the trial (day 9). Treatment of rats injected with U55 with a positive control (sulfasalazine) reduced the disease index (compared to 055 alone) from day 5. Differences found in the final colon mass:colon length ratio were also significant for animals with O55-induced disease with or without sulfasalazine treatment.

Activity and stability ex mimo 00716) Two peptides (compound A and compound B) were selected for use in additional biological studies (shown below). One contained a thioether bond and the other contained

Rep-Rep disulfide bond. The activity, selectivity and external stability profiles of the two compounds are provided herein.

I00717| Peptide inhibitor selectivity assays included human I-12K61 EGISA and measurement of I-12 production in activated human PBMC RNA, described briefly below.

EPZA 1 -12K81 human 00718) The tablet for analysis was coated with 100 ng/well of human I--12K0B1 psEsS and incubated overnight at 4 "C. The wells were washed, blocked and washed again. Serial dilutions of test peptides and I-23 with a final concentration of 2 .5 nM was added to each well and incubated for 2 hours at room temperature. After washing the wells, bound 1-23 was detected with polyclonal goat anti-p40 antibody followed by HER conjugated donkey anti-goat dO antibody. Signals were visualized using ТМВ single-component

HER of the membrane substrate and quenched with 2 M sulfuric acid. Data from these analyzes are provided in this document.

Production of IEM 1--12 in activated RNA of human PBMC 00719) This analysis revealed the ability of Y/-23E antagonists to neutralize protein production

IEMUu in stimulated 1-12 human RVMS. Peptide inhibitors of I--23K, specific for the II-2Z3LI-23K pathway, are not believed to change the levels of IEM produced. Compound A and Compound B were tested in this assay and a graph showing that they do not alter IEM levels! produced at most tested concentrations is provided in fig. 2.

M o

WITH

(in)

Ж for И m о тм сх M Ж m Е M 2-МН, c) c) c) : c)

Compound A (5EO IU MO:258)

M o

B-- -5 (in)

Ж І s, t M pa M Ж m E M 2-МН, (c) (c) (c) : (c)

Compound B (BEO IU MO:282)

Activity of ip mimo 00720) Acute colitis was induced by feeding female Sprague-Dawley rats with Fo (w/v) O55 dissolved in drinking water. For nine days, starting on the same day as 055, compounds A or B were administered orally three times a day at a concentration of 20 mg/kg or 30 mg/kg. Compound A was also administered intraperitoneally three times a day at a concentration of 30 mg/kg.

Zo Neutralizing antibody against 1IS-23p19 was used as a comparison and was administered intraperitoneally at a concentration of 4 mg/kg on the same day and five days after the start of administration of Yu55. To assess colitis for clinical activity, the disease activity index (DIA) was determined daily for each animal as the average of three parameters: changes in body weight (scale 0-3), stool consistency (scale 0-3) and hemoculture in blood (scale 0-3) , as shown in table E15.

At necropsy, the entire colon was removed from the cecum to the rectum. The length of the colon was measured, washed with PB5 to remove feces, weighed and cut longitudinally for macroscopic parameters. Visible colonic damage was measured on a scale of 0-3 as shown in Table E16.

I00721| Table E17 shows that on the 7th day, treatment with compounds A and B significantly improved SAI indicators compared to the group treated with medium. Fig. 1 shows the results for the values of UA! from the 7th day. In addition, a significant decrease was also found in the ratio of colon mass to colon length, and macroscopic parameters of the colon (Fig. 3). The reduction in inflammation seen with orally delivered peptides was similar to the effects seen with a neutralizing monoclonal antibody against I./23p19. Statistical analysis for significance was compared to the medium-treated group and determined using the Student's t test (Student's t-test).

Differences were marked as significant "p" 0.05, "p" 0.01, p" 0.001, and хр-0.0001.

Table E15

Estimates of the disease activity index

Stool consistency | Indicator of blood cultures 77071771 no 17777 Norm | / norm//

Table E16

Assessment of macroscopic morphological damage to the large intestine

Macroscopic morphology 000 |Normai////7771111111111111111111111111111111111

Erythema, slight edema, small erosions

Two or more bleeding ulcers, inflammation, moderate adhesion

Severe ulcers, stenosis with dilations, severe adhesion

Table E17

Indicators of the disease activity index and evaluation of individual parameters on day 7, ratio of mass to length of the colon and macroscopic indicators of the colon on day 9 1 1111111111111day/////////////////////// / | A day. necropsy/ y y y Mass/length | Macroscopic

Percentage change Consistency! Indicator. : RAI of the large intestine | indicators of the body weight of the stool, hemocultures and (g/cm) of the large intestine

ZO

Average- (state- Average- Average- Average- Average- Average-

Group -- | Dart schi 5O schi ZO schi ZO schi 5O si ZO nii i nii nii nii nii deviation)

Without zhk zhk zhk zhk zhk no no po ayuvit o oh o |oihi o on | your

From rB55, ser- -6.39 1.11 2.00 10.58 1.50 10.50 1.72 | 0.45 |124.36| 17.11| 1.00 | 1.00 more tA against -0.05 11.92 1.00 0.587 0.50 | 0.57. | 0.67 0.437) 99.96 | 16.19" 0

And 2Zr19 tue but wow? oh oh oh oh | ov yav noy weight ot zones of stents obi ov, sito vet tya zako ot

Example 7

Ip Migo and Surface Plasmon Resonance (SPR) analyzes (007221) Ip Migo and BRC were performed to further determine the characteristics illustrating compound C:

M o tn,

WITH

Ги (c) реш т M сх M Ж m Е M 2-МН, (c) (c) (c) : (c) soy

M

N

As-cyclo-PABSH-OTUMOSI-IR pe(4-(2-aminoethoxy)|-UM-(a-MeH uzI-EMa-MH)" (ZEO I MO:259)

Compound C 00723) The assays described in the previous examples were performed to demonstrate that compound C is a potent, selective, and competitive inhibitor of I/-23A, showing potent inhibition of I-23-dependent up-regulation of phosphor-5TATZ (p5TATZ) in OV cells human and IEM production in the cells of natural killers of human peripheral blood (RBM).

In addition, compound C is selective, showing little inhibition in cell-free EHI5ZA for

I.6K of a person, or in the IY-12-dependent production of IEMd in RVMSO. The data are shown below in Table E18A. Compound C also cross-reacts with II -23E. cynomolgus macaque (IC50 7 nM) and rat I-23 (IC50 17 nM), and inhibits II-23-dependent production of II-17A in rat splenocytes (IC50 130 nM) (data not shown).

Table E18A

Determining the characteristics of the compound S voi kos

IEMu/RV MK IEMulLi-12

THIS CHE I it and cellular EIPZA cellular 238 1281 analysis. . analysis analysis

I00724| The effect of exposure to compound C was also limited to Si after oral administration of PO to rats at a concentration of 20 mg/kg, with AOC values of 355 μg.h./g for the small intestine mucosa; 77 mcg.h/g for colonic mucosa and 0.3 mcg.h/ml for plasma, with 40 95 excreted in feces. 00725) Compound C was also stable in various SI liquids and a reducing medium, having a half-life of ZIB » 24 h.; and the half-life of 5OE » 24 hours. the elimination half-life from human intestinal fluid is 24 hours. and the half-life of g? 2 hours in the analysis

Ot.

I00726| 5RK experiments were carried out using the Viasoge 2000 apparatus and T100 optical biosensors, equipped with Viasoge SM4 and Hapies NS1500t sensor microcircuits.

Recombinant human I -23K psEsS (Kp) or recombinant human I/-12KD81 pis (Kp) or a mixture of these two receptor subunits were fixed on the surface of antibodies to (DO) of a person.

Recombinant human 1I/-23 (Nitaplute) or compound C was used as an analyte.

The sensorgrams of 5RK corresponded to a mutually exclusive model of interaction, which determines the approximate estimation of the association rate constant (Kop), the dissociation rate constant (Koi) and the dissociation constant (KO) of the complexes, as shown in Table E11. The data show that compound C does not bind to I/-12K81, but binds to II/-23K and the mixed surface of III/-12K81 and I/-23K with similar strength, at 2.42 nM and 2.56 nM, respectively. This affinity for 1I-23K is comparable to that of 1-23. In contrast, the affinity of I--23 to the mixed surface is about 14 times faster than that of compound C.

Table E18B8

Binding characteristics of II -23 and compound C for I -12281, II -23K or mixed

I--12E81 and I-23KE, determined using Z5RE. 1-31 Spolulas/7/7/7/:U

Example 8

Effectiveness of I-23K antagonists in TMB5-induced colitis in rats

I00727| To further evaluate the effectiveness of P/-23K antagonists in an animal model of the disease, acute colitis was induced by administering to 7-week-old female Sprague-Dawley rats 60 mg/kg of 2,4,6-trinitrobenzenesulfonic acid (TMV5) in 45-5095 ethanol (TMV5/ethanol ) intrarectally on day 0. Compound C (described in Example 7) was administered orally three times daily at a concentration of 20 mg/kg or 6.7 mg/kg and provided in the drinking water at a concentration of 0.6 mg/ml or 0.2 mg/ml, respectively, for 8 days, starting approximately 24 hours (-1 day) before TMB5 inoculation. A neutralizing antibody against IH-23p19 was used as a comparison and was administered intraperitoneally at a concentration of 4 mg/kg on day 1 and again on day 3. All animals received an oral medium with РВ5 (pH 7.4), which was used to make compound C. The scheme of the experiment is shown in fig. 5. (00728) To assess the degree of 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 TMB5 inoculation, rats were sacrificed and their entire colon length and colon mass from cecum to rectum were recorded. The severity of colitis can be assessed by a laboratory diagnostician who does not have information regarding the identity of the treatment. In addition to colonic wall thickness, gross colonic damage can be graded based on a 0-4 scale according to Table E19 below, and histopathological scores were determined based on the following parameters (Tables E20 and E21).

Table E19

Definition for macroscopic parameters of the colon 000 |nNorma////11111111111111111111111111111111111111

Table E2O0

Definition for histopathology

The degree and severity of inflammatory cell infiltration, localization and/or diffusion, cells include polymorphonuclear leukocytes (neutrophils), mononuclear cells (macrophages and lymphocytes), fibroplasia and revascularization. mucous by products of cell decay; measured as the length of the lesion per the total length of the portion of the colon to determine the 95 affected plane

BU nn en pini niy bath

Loss of gland. shell or without it

Thickness Total colonic thickness measured transmurally (full thickness) from

Table E21

Classification criteria 0010110 |Normal tissue, non-inflammation.//-/:///////:(К4СС:/СС"СС)Ї " parts of the large intestine approximately 2-10 95 parts of the large intestine

A moderate degree of multifocal infiltrates in the mucosa, submucosa 2 membrane, external muscle group and serous membrane affecting approximately 11-year-olds

The average degree of multifocal infiltrates in the mucosa, submucosa

From the shell, the external muscle group and the serous membrane, which affects approximately 26- o reve euro

A noticeable degree of multifocal infiltrates in the mucosa, submucosa 4 membrane, external muscle group and serous membrane affecting approximately 51-o sieve

A severe degree of multifocal infiltrates in the mucosa, submucosa, outer muscle group and serosal membrane affecting approximately »75 95 parts of the 0000000 | Beznecrobu///////////777777777711111111111111111111111111111111111111111111 colon colon colon colon colon colon 5

1110 | No losses, normal crypt mucosal epithelia. suffered from acute weight loss, showed an increased frequency of loose stools, and an increased colonic mass-to-length ratio. These findings are supported by macroscopic colon experiments, which reveal moderate colonic damage characterized by erythema, edema, and small erosions. Compound C treatment reduces these changes compared to the TMB5 colitis group At the high dose, compound C was significantly effective in reducing colonic mass-length ratio, decreasing colonic wall thickness, and more importantly, improving macroscopic colonic pathology scores to normal in 7095 animals.

Statistical significance was found at the low dose in all of the above indicators except for the thickness of the colon walls, although the trend was obvious. The reduction in inflammation that was found with oral delivery of compound C was similar to the effect that was found with the neutralizing monoclonal antibody against II -23p19 (Fig. b). 007301 Histological studies of hematoxylin-eosin-stained distal parts of the colon showed that most of the lesions detected in the environment group were transmural, characterized by necrosis with inflammatory cells crossing the entire thickness of the colon, the presence of necrotic tissue remnants on the lumen surface, and mucosa without crypts Compound C-treated animals generally showed localized lesions confined to the mucosa and submucosa, with colonic tissue showing probable signs of healing at sites of necrosis. In particular, animals treated with 160 mg/kg/day of compound C showed a significant reduction in inflammation, mucosal necrosis, and colon wall thickness, leading to a significant reduction in the overall histological score compared to the control with anti-I-23p19 antibody (Fig. 7).

IІ00731| Analysis of the concentration of samples collected 1 hour after the last dose of PO showed that the plasma concentrations of compound C detected in all animals were “-2X below the IC75 of the compounds, as determined in an assay based on rat splenocytes/LiI -17A cells or EIHIZA 1-23 rat, confirming that the effectiveness that was shown at

From oral treatment, probably occur due to its local activity in the large intestine (see Fig. 8). Together, these data show the protective effect of the II -23K antagonist in the development of colitis caused by TMV5. (00732) These studies have shown that the peptides of this invention are potent, selective and orally effective peptide antagonists of II-23K, which are promising therapeutic agents for the treatment of IVF and other disorders. As shown in this document, the present invention provides peptides that are: strong blockers of 1--23/LI - 23K signaling in a human cell line and in primary human cells; selective for II-23K and do not inhibit binding of II-6K or signaling through II-12E; cross-reactive with rat and macaque homologues rather than mouse homologues, facilitating ip mimo studies in these species; resistant to proteolytic and reducing environments of Si, resulting in high levels of drug in intestinal tissues and limited drug concentrations in the bloodstream, providing strong safety advantages over systemically administered therapeutics; and effective and comparable to the monoclonal antibody against I./23p19 in alleviating colitis in the TMB25-induced colitis model in rats, probably due to limited SI activity.

Example 9

IP Miigo determination of characteristics of typical antagonists II -238 00733) To evaluate the properties of the peptide antagonist I/-23K 5EO IO MoMo: 980 (peptide 980), 993 (peptide 993) and 1185 (peptide 1185), experiments were conducted to determine the strength, selectivity and peptide stability as described above. IC50 values of peptides measured by quantitative EGISA for II-23/I-23K competitive binding assays (which were performed as described above in Example 2) for human (Ni), cynomolgus macaque (Supo) and rat (Ba) The 1st-23rd linkages of II-23E are shown in Table E22. Peptide potencies were also assessed by II-23K activity assays as described above. IC50O value of peptides, as determined by the decrease in the levels of phospho-ZTATZ (p5TATZ) in human OB cells treated with II-23 (Ni OB Sei! (roTATZ); carried out as shown above in example 2); by reducing IEMugH, which is produced by human MK cells, which are affected by I--23 (Ni MK cells; carried out as shown above in example 5); and by reducing I/-17A, which is produced by activated splenocytes, which are affected by 1-23 (Kakzrivep); carried out as shown above in example 6). Selectivity was assessed by measuring IC5O peptides for inhibition of II-23/I/-12K beta interactions! of a person (see example 4) or of the interaction of ІІ/-6/Л/-6К of a person (see example 6). Peptide stabilities were determined by measuring the half-life of peptides exposed to simulated intestinal fluid (SIF), simulated gastric fluid (SSF) or human intestinal fluid (SIF).

Table E22

Properties of typical peptide antagonists I -23A. and Selectivity Stability (y/",

I EMS (nM) Cell analysis (nM) (EM8A, NM)

Not OV

Peptide | Ni Supo| Wow Sey pk (vribeg) vv i-6/p-6v| VIE | 5ОЕЕ | NO oZTATZ and

The same in zo|2o| ov 22 yav looho| 5 ше 1 гег ве ге ге ге field є є є є є є ше 1 Oh

The structure of peptide 993 is shown below:

Me aa Oh. MN is the day and the day. . o 4 y 2 y t zho tom M km ni y pe y Z o

Oh MN Oh IYA y a a B o o t, 5 o Z nach -e ay "yun | yy a r A | va y I

ON. и AK ak shk MM p y her ke Her m ia | and in N M shk o k nab bo not that r nm sn

Ac-(0)-Agao|-cyclo(Absch-O HMOSI-(P pe|4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|)-EMM-MH » (ZEO IO Mo: 993)

The structure of peptide 1185 is shown below:

Mn; kn o I. ts i z cad ran chn.

B Oh | | і z still fay is a Sword: še z -і o Ka o kashe m z | | from yah Za o

N Her Y yn TSI Y n Kv N I n IZ rshe AKA v o d schi E. AMOAM, y y y y a o o tav ovs V polo Y g z S sa g beat, I Z y pe

FOR N g! SHE seutchyu shiy ey o notoo a t n i g on Z. I I G zro vu i chn de

Oh! dyasya ras in

As-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani|-

ISUuz(As)|-MIM-MN" (ZEO IO Me: 1185)

The structure of peptide 980 is shown below:

Her" osv her m. r. 1 th i s shi MV res Ya

N ee Sho " Or Mne ; chi | pshshe ni rn sya y re zhe lezh o y o a | | a tota o ; Y ! THIS Y ! M Go y | in I. o tsa M v - For My re y. ven nya -M what cancer . pi: ie p V o v v mn ny: shi m n E 5 N | V N Y x H 1 a and b. MN bo s voshch: ChchN M e shysheYa o 5 M 7 A b EN a a schi She i Vch i lu g 7 Sni i m A nob oso U s Y ry YAM, yayu ho r dl t M y o r o y sya what

CS

KI and

As-cyclo-HABBshsh-O HUMOS-(Rpe(4-(2-aminoethoxy))I-(2- Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)" (ZEO IO Mo: 980 ) 00734) The results shown in Table E22 show that the peptides potently and selectively inhibit II-23/I-23E binding compared to II-23/LI-12K beta! or II-6/LI-68 interactions .

This inhibition is confirmed by cell culture assays that measure II -23B-dependency, such as 5TATZ phosphorylation, IEM production, and I--17A production. Peptides have also been found to have a high degree of stability when exposed to simulated intestinal fluid, simulated gastric fluid, or human intestinal fluid.

IІ00735| The data for the experiment OV Seyi (reBTATZ) were used in the Schild analysis (see Fig. 17). For the Schild assay, concentrations of 0.3 nM, 1 nM, 3 nM, 10 nM, 30 nM, 100 nM of peptide 993 were tested. The slope of the Schild curve 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 ZEO IO Mo: 1169, which is very similar to the structure of peptide 1185. The slope of the curve

Schild was determined to be 0.91, indicating that peptides with a similar structure, including peptide 1185, likely behave as a simple competitive antagonist. 56 Schild analysis was also performed on a peptide with the structure 5EO IU Mo: 1211, which has a structure similar to peptide 980. The slope of the Schild curve was determined to be 0.76. However, when the slope was fixed at 1, the value of 82 was 0.975. These data confirm that peptides with a similar structure, including peptide 1185, can behave as a simple competitive antagonist.

Example 10

IP Mimo pharmacokinetics of typical antagonists II-238A (00736) Pharmacokinetic properties of typical peptides were measured by IP Mimo. Breed rats

Sprague-Dawley was administered peptide 993 at a concentration of 10 mg/kg R.O.

I00737| A single oral dose of peptide 933 was administered to normal female rats of the breed

Sprague-Dawley (M-Z3 rat at time point) either with or without a dose of drinking water provided by aa irrit (see Fig. 11). After oral dosing, the effect of peptide 993 was determined in plasma at 0.25, 0.5, 1, 3, 6, 8, and 24 hours after dosing. Peptide 993 levels were also determined in the small intestine, large intestine, small intestinal mucosa, colonic mucosa, small intestinal mucus, Peyer's patches, and intestinal lymph node (MI-M) at 1, 3, 6, 8, and 24 hours after dosing. Urine and feces were collected after 6 and 24 hours to determine the excretion of peptide 993.

Samples of plasma, feces and tissues were kept at -80 P 107 C before analysis. For plasma, 50 μL of the sample was used for compound extraction by precipitation of proteins using a cooling solution (MeoOH:.АСМ with 0.195 formic acid, 50:50 vol.) with an internal standard. For feces, samples were homogenized with 0.195 formic acid in water (water:faeces ratio 4:11) before extraction. 50 μL of faecal homogenate was used for compound extraction by precipitation of proteins using a cooling solution (MeOH:IASM with 0.195 formic acid, 50:50 v/v) with an internal standard. For tissues such as colon or small intestine, samples were homogenized with 0.1 96 formic acid in water (water:tissue ratio 3:11) before extraction. For tissue such as Peyer's patches and intestinal lymph nodes, samples were homogenized with 0.1 95 formic acid in water (water:tissue ratio 20:11) before extraction. 50 μl of the tissue homogenate was used for compound extraction by precipitation of proteins using a cooling solution (MeOH:ACM with 0.1 95 formic acid, 50:50 v/v) with an internal standard. The precipitated protein was removed with a filter plate and the collected supernatant was dried and reconstituted.

The processed samples were analyzed on a mass spectrometer AB/MO5 5x АРИ 4000. Positive ions were monitored in the mode of monitoring multiple reactions (MEM). Characterization was carried out through the ratio of peak areas.

IІ00738| No detectable levels of peptide 993 were detected in the plasma of rats between 0 and 24 hours after administration (see Fig. 11A). In contrast, detectable levels of peptide 993 were present in the Peyer's patches and small intestine at least six hours (see Figures 118 and 112) and at least 8 hours after dosing in the colon (see Figure 1103). levels

More than 5% of the total administered dose of peptide 993 was recovered in the feces of rats 24 hours after administration, also showing that peptide 993 has a high degree of oral stability.

Taken together, these results indicate that peptide 993 is an orally stable C-restricted peptide that exhibits high C content and limited systemic distribution after oral administration.

I00739| Sprague-Dawley rats were injected with peptide 1185 at a concentration of 10 mg/kg R.O. A single oral dose of peptide 1185 was administered to normal female Sprague-Dawley rats (M-Z rats per time point). After oral dosing, the effect of peptide 1185 was determined in plasma samples collected up to 8 hours after dosing. Urine and feces were collected up to an hour to determine the excretion of peptide 1185 (Fig. 18).

I00740| Sprague-Dawley rats were injected with peptide 980 at a concentration of 10 mg/kg R.O. A single oral dose of peptide 980 was administered to normal female Sprague-Dawley rats (M-3 rats at time point). After oral dosing, the effect of peptide 980 was determined in plasma samples collected up to 8 hours after dosing. Urine and feces were collected up to one hour to determine the excretion of peptide 980 (Fig. 19).

Example 11

Safety profile of typical antagonists II -23A

I00741| The safety profiles of typical peptide inhibitors were characterized. Peptide 993 and peptide 1185 were evaluated according to safety panel tests associated with a panel of 44 targets. Targets included C-protein-coupled receptors (CPRs), transporters such as the dopamine transporter (DTP), and ion channels. For all targets, these peptides showed no activity as determined by variable (inhibitory or stimulatory) target activity greater than 25 95. The targets tested in the safety panel are shown in Table E24. For each target, peptide 993 and peptide 1185 were determined to be inactive at concentrations up to 10 µM. The safety profile of peptide 980 was evaluated using test compounds selected from Table E24. For all compounds tested, peptide 980 showed only moderate activity in the acetylcholinesterase assay (33 9b), and otherwise showed no activity, as determined by variable target activity greater than 25 95.

Table E24

Peptide 993 and peptide 1185 are inactive in the 111 Me security panel | 7 Mneuronnia4va///7// | 77777777 is 4::4:4:SCC

Example 12

Effects of a typical peptide inhibitor in a rat model of acute colitis 00742) To evaluate the effectiveness of a typical peptide inhibitor peptide 1185 in an animal model of the disease, acute colitis was induced by intrarectally administering 64 mg/kg TMV5 in 50 95 ethanol to 7-week-old female Sprague-Dawley rats at 0 day. Peptide 1185 was administered orally at a concentration of 37 mg/kg/day (both PO and drinking water), PO IV, from day -1 to day 7.

A placebo group not exposed to TMV5 and a TMV5-injected group treated with medium were used as control groups. For comparison, a neutralizing antibody against I--23p19 was administered intraperitoneally at a concentration of 4 mg/kg on day 1 and again on day 3, and prednisone was administered at a concentration of 10 mg/day PO. All animals received water as the medium used for the assembly of peptide 993.

I00743| As described above, animals were observed daily for clinical signs, which included percent body weight loss and signs of loose stools and diarrhea. Six days after inoculation

TMV5 rats were sacrificed and total colon length and colon weight were recorded for each animal. The severity of colitis was assessed by pathologists. In addition to colonic wall thickness, macroscopic colonic lesions were graded on a scale of 0-5 according to Table E29, and histopathological grades were determined based on the parameters listed in Table EZ0.

I00744| Treatment with peptide 1185 significantly reduced several disease parameters in a TMB5-mediated rat model of acute colitis. Although rats in the placebo group continued to gain weight throughout the study, rats exposed to TMV5 and treated with medium had weight loss. Oral treatment with prednisone or systemic treatment with anti-II/-23p19 antibody prevented weight loss in rats given TMV5.

Treatment with orally administered peptide 1185 did not significantly prevent weight loss in rats treated with TMV5 (see Fig. 13). A significant decrease was also found in the ratio of colon mass to colon length after treatment with prednisone or anti-I-23p19 antibody compared to treatment with medium. Oral administration of peptide 1185 produced similar reductions in colon mass to colon length ratios and

From the macroscopic parameters of the large intestine in rats given TMV5. Larger macroscopic parameters of the colon showed a higher degree of colon pathology. Colonic macroscopic score was determined by adding scores for adhesion, stenosis, ulceration, and colonic wall thickness, all of which were significantly reduced by treatment with prednisone, anti-II/-23p19 antibody, or peptide 1185 compared with vehicle-treated controls. These data showed that oral administration of peptide 1185 has comparable efficacy to systemic administration of monoclonal antibody against I -23p19. 00745) Pathological features of colon tissue sections taken from rats in the placebo group, the medium group, the anti-II/-23p19 antibody group, and the 1185 peptide group were investigated. Mucosal inflammation, transmural inflammation, glandular loss, and erosions were evaluated according to the criteria shown in Table E29, for all of these signs, treatment with anti-II/-23p19 antibody or prednisone reduced the histopathological parameters associated with the effect of TMV5. Treatment with peptide 1185 did not significantly reduce histopathological parameters.

Example 13 effects of a typical peptide inhibitor in a rat model of acute colitis

I00746| To evaluate the effectiveness of the typical peptide inhibitor peptide 993 in an animal model of the disease, acute colitis was induced by injecting 7-week-old female Sprague-Dawley rats with 64 mg/kg TMV5 in 50 95 ethanol intrarectally on day 0. Peptide 993 was administered orally twice daily at a concentration of 10 mg/kg, for a total of 42 mg/kg per day, for 8 days beginning approximately 24 hours (-1 day) prior to TMB5 inoculation. A placebo group not exposed to TMB5 and a TMB5-injected group treated with medium were used as control groups. All animals received water as the medium used for the assembly of peptide 993.

I00747| As described above, animals were observed daily for clinical signs, which included percent body weight loss and signs of loose stools and diarrhea. Six days after inoculation

TMV5 rats were sacrificed and total colon length and colon weight were recorded for each animal. The severity of colitis was assessed by pathologists. In addition to colonic wall thickness, macroscopic colonic lesions were graded on a scale of 0-5 according to Table E29, and histopathological grades were determined based on the parameters listed in Table E20.

I00748| Treatment with peptide 993 significantly reduced several disease parameters in a TMB5-mediated rat model of acute colitis. Although rats in the placebo group continued to gain weight during the study, rats exposed to TMV5 and treated with medium had weight loss. Treatment with orally administered peptide 993 also prevented weight loss in rats given TMV5 (see Fig. 12). In addition, a significant decrease was also found in the ratio of colon weight to colon length after treatment with oral administration of peptide 993. Larger colon macroscopic indices indicated a higher degree of colon pathology and were significantly reduced by treatment with peptide 993 compared to vehicle-treated controls. Oral administration of peptide 993 had comparable efficacy to systemic administration of monoclonal antibody against I-23p19, which served as a positive control. Histopathological indicators were significantly reduced in

From the colons of rats treated with peptide 993 compared to the vehicle group.

Example 14 effects of a typical peptide inhibitor in a rat model of acute colitis

I00749| To evaluate the effectiveness of the typical peptide inhibitor peptide 980 in an animal model of the disease, acute colitis was induced by injecting 7-week-old female Sprague-Dawley rats with 64 mg/kg TMV5 in 50 95 ethanol intrarectally on day 0. Peptide 980 was administered orally at a concentration of 37 mg/kg/day (both PO and drinking water), PO VIO, from day -1 to day 7.

A placebo group not exposed to TMB5 and a TMB5-injected group treated with medium were used as control groups. All animals received water as the medium used to assemble peptide 980.

IІ00750| As described above, animals were observed daily for clinical signs, which included percent body weight loss and signs of loose stools and diarrhea. Six days after inoculation

TMV5 rats were sacrificed and total colon length and colon weight were recorded for each animal. The severity of colitis was assessed by pathologists. In addition to colonic wall thickness, macroscopic colonic lesions were graded on a 0-5 scale according to Table E29, and histopathological grades were determined based on parameters listed in Table E30. Treatment with peptide 980 significantly reduced all these parameters, which were detected in the mediated model

TMV5 of acute colitis in rats.

I00751| Treatment with orally administered peptide 980 prevented weight loss in rats treated with TMV5 (see Fig. 14). In addition, a significant decrease was also found in the ratio of colonic mass to colonic length after treatment with oral peptide 980. Larger colonic macroscopic parameters indicated a higher degree of colonic pathology and were significantly reduced by peptide 980 treatment compared to vehicle-treated controls ( see Fig. 14).

I00752| Pathological features of colon tissue sections taken from rats in the placebo group, the medium group, and the peptide 980 group were examined. Mucosal inflammation, transmural inflammation, loss of glands and erosions (see Fig. 140) were evaluated according to the criteria shown in Table EZ30. The sum of histopathological indicators was significantly reduced by treatment with peptide 980 compared to the medium.

Example 15 Biomarker levels after treatment with peptide inhibitors in a model of acute colitis in rats

I00753| Levels of inflammatory markers were examined in colons. Tissue samples from the distal end of the colon designated for protein expression analysis were snap-frozen after collection. For protein extraction, the samples were thawed, weighed, and homogenized in the extraction buffer (PB5, pH 7.2, supplemented with protease inhibitors, 3 vol.:wt.). The homogenates were centrifuged at 13,000 rpm. at 4 "C for 15 minutes, only twice to remove residues. Supernatants were stored in multiple aliquots at -80 "C, and then used for analysis of protein expression by EGISA. Total protein in each sample was quantified by BSA analysis. Protein expression of MPO, 1-18, 1-6, II-17A and 1-22 in samples of the distal end of the large intestine was analyzed using a commercially available EGISA kit for rats.

I00754| Treatment with peptide 993 reduced the levels of inflammatory markers present in the colon. Disease markers (MRO, 1-6 and II-1beta) and 1-23-directed biomarkers (I/--22 and 1H-17A) were reduced by treatment with peptide 993 compared to controls treated with medium (see Fig. 15). These data show that the introduction of peptide 993 in amounts that can reduce the pathology of ip mimo also reduce the levels of biomarkers present in the colon that are associated with II/-23K activity. Treatment with peptide 980 reduced levels of MPO and 1-22 compared to controls treated with medium (see Fig. 16). Treatment with peptide 1185 at the dose tested did not significantly reduce MPO, 1II--22, or 1-17A levels.

Table E29

Macroscopic indicators of the colon of the colon (maximum value - 12).

Adhesions: none - 0 minimal - 1 include several intestinal loops - 2

Stenoses: none - 0 minimal - 1 moderate - 2 severe, expansion of near ones - Z

Ulcers: no focal hyperemia, without ulcers:- 1 ulcer without significant inflammation (significant and thickening of the intestinal wall) - 2 ulcers 1- "Z cm - Z ulcer 3- "6 cm - 4 ulcers b cm - 5

Wall thickness:

Wall thickness: less than 1 mm - 0 1-3 mm - 1 »ZmMmm:-2

Table EZba

Histopathology - Indicator of mucosal/submucosa inflammation

The degree of infiltration of macrophages, lymphocytes, neutrophils and other inflammatory infiltrates was evaluated according to the following criteria: separation of the glands, may be mainly in the areas of edema of the submucosa or mesentery, focal or multifocal separation of the gland, without separation in most areas

Table EZba

Histopathology - Indicator of inflammation of the mucosa/submucosa with multifocal separation of glands by infiltration of inflammatory cells, more moderately in other areas of the mucosa with some areas without separation of glands due to inflammation 4-Visible, 51-7595 mucosa is affected, with moderate-moderate separation of glands by infiltration of inflammatory cells, minimal- moderate in other areas of the mucous membrane, but all glands have some separation with an infiltrate

B-severe, 76-10095 of the mucosa is affected, with medium-visible zones of gland separation by infiltration of inflammatory cells, moderate-moderate in other zones of the mucosa

Table EZOB

Mucous membrane thickness index

The thickness of the mucosa was assessed in the large intestine in the non-tangential region of the section, which better presents the entire thickness of the mucosa. This parameter is an indicator of gland elongation and mucosal hyperplasia. The hyperplasia index was determined as follows. - t No mucosa 0 - normal 1- minimal, 5-1095 thicker than the control mucosa 2 moderate, 11-2595 thicker than the control mucosa

C-medium, 26-5095 thicker than the control mucosa 4-marked, 51-7595 thicker than the control

EZOs table

Transmural inflammation

The presence of infiltrates of inflammatory cells in the mucous membrane of the muscles and an increased number of fibroblasts/fibrocytes with perpendicularly located blood vessels (granulation tissue) probably reaches the serous membrane.

O-norm 1- minimal, 5-10 9o infiltration 2 moderate, 11-25 95 infiltration 3- medium, 26-50 95 infiltration 4-noticeable, 51-75 Fo infiltration 5-severe, infiltration reaches the serous membrane and mesentery

EzOba table

Rate of gland loss

Cryptic epithelial loss and other loss of glandular epithelium were estimated based on the approximate percentage of mucosa affected as follows:

O-none 1- minimal, 1-10 95 of the affected mucosa 2 moderate, 11-25 95 of the affected mucosa 3- medium, 26-50 to the affected mucosa 4- noticeable, 51-75 9o of the affected mucosa bB-severe, 76-100 95 affected mucosa

Table EZb0e

The rate of erosion is affected as follows.

EZOI table

The sum of histopathological indicators

Example 16 determining the characteristics of additional peptide inhibition or binding of interleukin-23 to the interleukin-23 receptor 00755) Peptide optimization was carried out to identify additional peptide inhibitors of I-23 signaling that were active at low concentrations (for example, IC50 "10 nM), while showing stability in the gastrointestinal (GI) tract. Some peptides were tested to identify peptides that inhibit the binding of I/-23 to human I/-23K and inhibit the functional activity of I/-23/LI/-23K, as described below. Tested peptides included peptides containing a number of different cyclization chemistries, including, for example, peptides containing a disulfide bond, for example, between two Rep residues, and peptides containing a thioether bond. Peptide inhibitors of the present invention include, but are not limited to, peptides with any of the structures shown herein. In addition, the peptide inhibitors of the present invention include those having the same amino acid sequence as the peptides or structures described herein, without the need for the same or any of the "cap groups" on the M- or

C-ends, such as, for example, As or MH". (00756) Assays performed to determine the activity of the peptides were performed as described in example 2 above. Human EGISA shows the II 23-II 23K competitive binding assay described below, rat EGISA shows the rat EGI5ZA 1/-23K competitive binding assay described below, and regag(znNtTKkeE shows the cellular analysis of reTATZ I/-23K OV cells described below.

The peptides shown in Table EZ31 are cyclized using a disulfide bridge formed between two cysteine residues in these peptides. The peptides shown in Table Ez32 are cyclized using a thioether bond between the indicated amino acid residues.

Table E32 provides a typical structure showing a thioether cyclization, which may also be indicated in the table by the term "cyclo", with the cyclic region indicated in parentheses immediately following.

Table EZ31

Typical peptides containing the motif As-IRep|-XXMUH-IRep|-XXXXX (ZEO IU MO:1482) and analogs. . EPZA EIPZA rea

W (nm) (nm) (nm)

IRa!ti-(isosSiICH-IPEGAI-(RepIi-MTUUO-(Repi-(Rpe|4-(2-po aminoethoxy)|-(2-MatC-(AIVI-(Suv(Ac)-MM-MH)) tvo orel) o epi rpegk i aninovtoxi Mai; GO SHE

AIVI-(SUZ(PEGA-isosti-Rait)|-MM-MN»

Ac-(RepI-STUMO-(RepI-Rpe(4-SOMNHg)-(2-MaC-(a- pOX C

Me! uz(Ac)|-(Suz(Ac)-MM-MH» otv ani pove Meth Mk ved evne: pOX C aminoethoxy)|-(2-MatC-(AIVI-(Suv(Ac)-MM-MH»)

IOctanilI-IPEGAY-(RepI-MTUO-(RepiI-(Rpe(4-(2- present

Table EZ31

Typical peptides containing the motif As-IRep|-XXMUH-IRep|-XXXXX (ZEO IU MO:1482) and analogs. . EPISA EPIBAUS | rai 7 (nm) (nm) (nm) 11 |aminoethoxy)Ce-macyuvAsurmmMmamne:D//1Г177711111Г111g a ve rapper bami 11 2-MaP-(AiVI-(Suv(Ac)|-MM-MN) leto orel o Raleigh Lege t yaminotoxisia Yama; POD

ABI-(SU(PEGA-octanyl)|-MM-MH» ha |AooepEo epi kpode(aminoethoxy Do not have; poHO PO

AiVI-(Su(PEGA-Rait)|-MM-MN" theses You refer to the change flow (PEGYA pi I

Rait)1I-2-MaPp-TAiYVI-P y(Ac)uMM-MH» hal lov vp o ep Nv aminoethoky (PEGY pi I lauryl)|-(2-MaP|-HAiVI-(Suv(Ac)|-MM) - МН»г

As-IRepI-STUMO-(RepI-Rpe(4-SOMNHg)-(2-Mma|-(a- poHO PO

Me! uz(PEGA-Rai1t)-P uv(As)|-MM-MN»

As-IRepI-STUMO-(RepI-Rpe(4-SOMNHg)-(2-Ma-(a- poHO PO)

MeHuz(PEG4-Lauryl)|-(Guv(As)|-MM-MN» tat athlete and aminoetokovy (PLEGYA pi I

Ivos1y-Rait)1-H2-MaiPP-HAiVI-P uz(As)I1-MM-MN»g

As-IRep|-MTUO-(Repi- (Rpe|4-(2-aminoethoxy)-(PEGA- py I

Ivocyyl-lauryl)|-(2-MaC-(AIVI-(Suv(Ac3-MM-MH)

As-IRepI-STUMO-(RepI-Rpe(4-SOMNHg)-(2-Mma|-(a- pOX C

Me! uz(PEG4-Ivosti-Rait)1I-P uz (Ac)1-MM-MN»g

As-(RepI-OTUMO-|RepI-Rpe(4-SOMN?g)-(2-MaC-a-Me- poHO PO

K(PEGA-IsoSi-lauryl)|I-(-uz(AsD-MM-MH»g

As-IRepI-STUMO-(RepI-Rpe(4-SOMNHg)-(2-Mma|-(a- pOX C

Me uv(IMAT-(Suv(As)-MM-MN"

As-IRepI-STUMO-(RepI-Rpe(4-SOMNHg)-(2-Mma|-(a-

Me! uz(biotin)|-(uv(Ac)|-MM-MH»

As-IRep OTUMO-(RepiRpe(4-SOMNg)-2-ma!Na- pOX C

Me! uz(octanyl)|-P uv(Ac)-MM-MH» tva TA vyY U mele per aminoethoky pOX C 2-MaP-(AIV|-(Suv(Ac)|-MM-MH» zv ov Me Teep ele ( about Maya's amino acid; poHO PO

AB uv(Ac)I-(SuUv(IMA)D-M-MN"

Ac-(RepiI-ISuv(biotin)|- GMO-(RepI-(Rpe(4-(2- pOH C aminoethoxy)|-(2-MatC-(AIVI-(Suv(Ac)-MM-MH) yavu oo trep logs (t aminoethoxy Maya; po

AIVI-(Huz(Ac)I-(Suz (biotin) |-M-MH»

Ac-(RepiI-Isu(Octanyl)|- HTUO-(RepiI-(Rpe(4-(2-po aminoethoxy)|-(2-MatC-(AIVI-(Suv(Ac)-MM-MH» otze | Aooepg Metro lay (aminoethokoi Maya; on the hole-(Suz(Ac)|-(Suz(octanyl)|-M-MH»

As-IRepiI-I«-uv(Ra!t)I-TU/O-(Repi-(RHne(4-(2-aminoethoxy)|- ha A As рр

As-IRepiI- MTM O-|(Repi-(Рпе(4-(2-aminoethoxy)|-(2-MaЦ|-

DA uv ratu LEM: swarm

Ac-IRepI--ISUz(PEG8)I- GMU/SU(Repi-(Rpe(4-(2-aminoethoxy)|- by 2-Ma--(AlivI-(Suv(Ac)|-MM-MH) laz by the field of sweat lay (eaminovtoxi May POD she

ABIS uv(As)|-(Suz(PEG8)I-M-MN"

As-IRep|-K(IPEG11-Rait) GMO-|RepiI-(Rpe(4-(2-po aminoethoxy)|-(2-MatC-(AIVI-(Suv(Ac)-MM-MH)" (1145 | As-IReprmtMus-IRep|(Rpe|4-(2-aminoethoxye-Mad- | /!/ "

Table EZ31

Typical peptides containing the As-IRep|-ХХМХ-IRep|-ХХХ motif (ZEO IU MO:1482) and analogues of EPOA | EP5A I raz shchi (nm) (nm) (nm) o TSABCSUV(ASIuv(PEGI1-ratumMamNnaD/77777111111Ї11111Г1111g chav | MOTO PASMO nega aminovtoksid Ya. pi i

Mats--IAivI-(uv(As)-MM-MN»

Ac-IRepy-(H uv(Ac)|- HMM-ISSH-(RepyI-(Rpe|4-(2-aminoethoxy)|- pi and 2-ma|CHAIVI-(suv(Ac)-MM-MH»

As-IRepI-MT-(Rpe(3,4-OSHz)21-O-(Repi-/Rpe|4-(2-ovo aminoethoxy)I-T2-MaP-HAiYivI-P uz(AsL-MM-MH»

As-IRepI-MT-IRne(2,4-CHz)2I-O-IRepI-(Rpe(|4-(2- po ee aminoethoxy)I-T2-MaP-HAiYivI-P uz(AsL-MM-MH»

Ac-IRepIi-MT-IRpe(3-CHz)-O-(RepiI-(Rpe(4-(2- po ee aminoethoxy)I-(2-MacC--TAYVI-P uv (Ac)-MM-MHg

As-IRepI-MT-IRpe(4-CH3)-O-(RepyI-(Rpe(4-(2- po ee aminoethoxy)I-T2-MaP-HAiYivI-P uz(AsL-MM-MH»

Ac(O)Aga|-(RepI-MTUO-(RepiI-(Rpe(4-(2-aminoethoxy) |-(2-

Mats--IAivI-( uv(Ac)|-M-(BA1a|-MN»

As-KO)TUP-(RepI-M PM O-(RepiI-(Rpe(4-(2-aminoethoxy) I-(2-mapP-HAiVI-(suv(Ac)|-M-(BAIa|-MH) zva |AooRol lm re ele aminoethoxy)Y-Mei; poHO PO

AdiVI-P uz(Ac)1-OM-MN» оявБ AROMAT e ooo in S eminoethoxy)MYA-Mei, poHO PO

AIVI-P uz(Ac)I-P uv(Ac)-M-AMN»g oyavv AROMATE poi in aminoethoxy)MYA-Mei; POHO PO

AIVI-P uz(Ac)I-M-T uv (Ac)L- MH" yavu |AoRol lm ro per aminoethoxy)n (My; pOH C

AIVI-(suv(Ac)I|-00O-MH»g ochvv, | Aooepg m oven vno (b aminoethoxy may; POD

AIVI-(Guv(Ac)I-O-I(VAia|-MN»g zve, | Astra M per per o aminoethoxy) I: Mei, poHO PO div uv(Ac)|-M-(SiISH-MN» tvo AROK lm ro per aminoethoxy)MYA-Mei; pOH S diru (Ac)-I(SISH-AMMN» ojavi | Aorol lm resler o aminoethoxy)MYA-Mei; poHO PO divI-(suv(Ac)-ISSH-O- MNe tva |AooRolE lm ropy logs (b aminoethoxy)MYA-Mei, po divi-P uz(Ac)I-TSSH-P uUv(As)I-MNHg tva, |AooRolE MM Tee pog, (g aminoethoxy)MYA-Mei , by diVI-P uz(Ac)I-P uUv(Ac)-TSSH-MN»g tva AROK rep Neper aminoethoxy) (My; div-OM-IVATa|-МН» ochvv ASOM rep Neper aminoethoxy)MYA-Mei; POHO PO

АИВИ-Е-ИСХ-О-МН» ochvv AROK TO ReLNeper aminoethoxy)Я-Mei; po I div|-SIMSYMN» tu |AoolEM le el Neper aminoethoxy)n (My; poHO PO divI-(Сщ-О-ИСХ-АМН»

As-IRepi-I(SiSh- TUHO-IRepI-(Rpe(4-(2-aminoethoxy)|-(2-Ma!|- py i di uv(Ac)|-MM-MH» tvo, Area (Rep rper (b aminoethoxy Ne Maii; poko

ABIS uv(As)|-MM-MN" oto |AotrelKA mokrepneper( aminoethoxy)n(-Mei, according to I

AIVBI-OMM-MN" (1171 |As-IReprmtMus-IRepCrpe|4-(2-aminoethoxye-Ma.id | | " |"

Table EZ31

Typical peptides containing the motif As-IRep|-XXMUH-IRep|-XXXXX (ZEO IO MO:1482) and analogues of EPIZA EPBA I rvaiaiz

Shy (nm) (nm) (nm) p GE UTte i tia UNN KONYA KO NO ota lona I about repteper about aminoetokoy No, my,

ABIS uv(As)|Y-MM-MN"

As-IRepI-REUMO-|Repi-Irpe(4-(2-aminoethoxy)|-(2-MatC- and wholesale ota, | oda ik a ener aminoethoxy Mai; po

ABIS uv(Ac)|Y-MM-MN» otv, oo Rele peg o aminoethoxy Ma; POHO PO

ABIS uv(As)|Y-MM-MN"

As-IRepi-M-IAIVI-UHO-|(Repi-IRNe(4-(2-aminoethoxy) I-(2- pte coda dsnK new

As-(Rep|-M PM-(AIVI-IRepI-(Rpe(4-(2-aminoethoxy)|-(2-Mac|- po

AIBI-(uv(Ac)|M-(AIVB|-MN»

Ac-(RepI-YUTMU-(Huz(AcI-(RepI-(Rpe(4-(2-aminoethoxy)|-(2- po I mats-(AivI-(suv(Ac)|-MM-MH))

As-(RepI-(ISuz(Ac)I- PMO-(RepI-(Rpe(4-(2-aminoethoxy)|-(2- poHO PO mapP--(AiVI-( uv(Asu MU MN) tvo in Aoeep) CM about repteper about aminoethoxy No, poHO PO

ABIS uv(As)|Y-MM-MH" vy Tov ma a ep eper (o aminoutoxy: pi I mats-(AiVI-(suv(As)|-MM-MH)" tva ooo ma a Kepler aminoutoxy: pi I mats -(АиВИ-(сув(Ас)|-MM-МН»

As-IRepi-MTUUO-(Repi-Irpe|4-(2-aminoethoxy)|-(2-MacC-(a-

Me! eci-P uz(Ac)-MM-AMN"

As-IRep|-MTUUO-(Repi-IRpe|4-(2-aminoethoxy)|-(2-MatC-(a-

Me! uz|I-ISuv(As)|-MM-MNh

As-IRep|-MTU/O-IRepy-I(Rpe|4-(2-aminoethoxy)|-(2-Mas-(4-amino-4-carboxytetrahydropyrani-P uz(Ac)I-MM-MH»

As-IRepi-MTUO-(Repi-Irpe|4-(2-aminoethoxy)|-(2-MacC-(a-

Me" etsyI-(Suz(Ac)|-M-(VATa|-MNeg

As-IRep|-MTUUO-(Repi-IRpe|4-(2-aminoethoxy)|-(2-MatC-(a-

Me! uzI-(Suv(Ac)|-M-(VAIa|-MH»

As-IRep|-MTUUO-(Repi-IRpe|4-(2-aminoethoxy)|-(2-Mac-I(4-amino-4-carboxytetrahydropyrani-(Hus(Ac)|-M-(BAIa|-MH) »h tva ovo ep tper o aminoetokoi Ne Maii; poHO PO

ABIS uv(As)|-I-M-MN" tvo, op MO Rep per aminoetokoi Ne Maiyi; POHO PO

AdiVI-P uz(As)I1-YAM-MN" tet ulooeit MO (rep tper aminoethokoi Non Maiyi; pOH S diVI-P uz(As)1-5M-MN»g tva oo Orel ele aminoethokoi Non Maiyi; poHO PO

AB ув(Ас)И-И(АИВИ-М-МН» tez, fish etntper o aminoetokoi Ne Maya; poHO PO

AB uv(As)Y-EM-MN"

Ac-(Rep|-M PMU-(SSH-(RepiI-(Rpe(4-(2-aminoethoxy) |-(2-Ma/|-

ABIS ув(Ас)|I-MM-MN» lion ferry PA OTRepM g pei (about aminovtoxy) Do not May; under her

AIVI-(Suv(Ac)I- PT isI-TVATa|-MN» lion |Aooepg Moto pog yaminoethoxyi mai; poHO PO dirI-(Suz(Ac)|-(pSesh-(VATa|-MNg) (1197 |AsiRepiMmtU/ORepRpe |d-(2-aminoeethoxyue-mad. DH | HER 1"

Table EZ31

Typical peptides containing the motif As-IRep|-XXMUH-IRep|-XXXXX (ZEO IU MO:1482) and analogs. . EPISA EPIBAUS | rai 7 (nm) (nm) (nm) 0 ТАбцОубиАСре|ИВАаМНнЮ7777777777777777777717Й1111111711111171Й1 lion, |АооейЛЙО rep per aminoethoxyi Maya; POHO PO

AIVI-(suz(Ac)|-B-IVATa|-MN» tva orel MAO I (pe aminovtoxy May POD she

ABIS uv(Ac)|IM-(VATa|-MN» tallow, | Aoeep A ve cre aminoethoxy) Ta Mai: poHO PO

AiVI-(Suv(Ac)|-5-IVATa|-MN" zovot Hopak ray aminoethoxy) Ta Mai" poHO PO

AB (suv(Ac))-I-IVATa|-MN" lag op MO vel leg (b aminoethoxy) Ta Mai" poHO PO

AivI-(Suz(Ac)I-IAIVI-(VATa|-MN" tin Meel ovi (taminoethoxyh Ta Mai" by ee

AB (suz(Ac)|-(M-Melia|-(VATa|-MH) according to Kepler with aminoethoxy Maya; pOH C

AB (suz(Ac)I-(2-MariI-(IVATa|-MN) tin OT ve per aminoethokoi Maya; pOX C

AiVI-(Suz(As)|-E-IVATa|-MN»

Kk Ka amino clarinet 000000 1206 /)Ma!||- (4-amino-4-carboxytetrahydropyrani-(Guv(Ac)|MM- x

MN"

Table EZ32

IC50 of typical peptide inhibitors (thioethers)

Sya yo Dr.

M her

As-cyclo-TsAV ХК ХСИЕвес ОМеУ З-Мац-ХХХ-MY, (BO | MO 1483)

FEOYU | | EPIBA | EGPIBA Gireiaiz

MO: Human |rat!| sequence NTAE and (nm) | (nM) | (nm)

Biotin-(IPEGA|1-cycloGABsh-OT UM OSI-(Rpe|4-(2-aminoethoxy) I-(2-

MaC-(4-amino-4-carboxytetrahydropyran-EMM-MH"

Ac-cyclo|(ABshI-OTUMOSI-(Rpe(|4-(2-aminoethoxy) |-(2-Ma!|-(4-amino-4-carboxytetrahydropyrani-P uz (Ac)-MM-MHg)) l Mosk per amino Ma M tvo | 51 4-amino-4-carboxytetrahydropyrani-P uz(Ac)-MM-MH» o viagoi cycloi l pes per aminovtuneman 1 4-amino-4-carboxytetrahydropyrani-P uz(Ac)-MM -MN" blades (lo Kozloyi diklotva o posi Rog (t aminoethoxy pi

Ma!|-(4-amino-4-carboxytetrahydropyrani-EMM-MN»

Kk As-(O)A5ri-KO)Ago|-cycloPABshsh-OTUOSI-(Rpe/|4-(2- that 1274 (|aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyran|- EMM-

МН» olatvo |to o oi dicloilvy om os Rem aminoutoxyi:

MaC-(4-amino-4-carboxytetrahydropyran-EMM-MH"

KK As-KO)Aga|-KO)Ago|-cyclo (Absh|-OTUMOSI-(Rpe|4-(2- KU 1276 |aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyran|- EMM-| TV x x

MN"

Table EZ32

IC50 of typical peptide inhibitors (thioethers)

Sha Z She ky KK r "Pepe(i-OMey-o-mai-xxxh- pl.

N I KE, dsikpo PAN AK ASI RVe i Ome NG 2 Ma KM. (ZEO and MO:1483)

EOYU EPZA | EPIBZA IreigaiZ

MO: Human |rat!| sequence NTAE

And (NM) (NM) | (NM) 1277 As-E-KO)Ago|-cycloCGAbBy|-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-

MaC-(4-amino-4-carboxytetrahydropyran-EMM-MH"

As-KO)PpeI-KO)Ago|-cycloHAvshsh-O HTM OSI-(РНе(4-(2- 1278 |aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyran|-EMM-

MH»g 1279 As-I2-MaC-KO)Ago|-cyclo(ArshI-OTUMOSI-(Rpe(4-(2-aminoethoxy) |- x 2-Ma(|-(4-amino-4-carboxytetrahydropyran)-EMM -АМН» 1280 As-T-KO)Ago|-cycloCGAbBa|-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-

MaC-(4-amino-4-carboxytetrahydropyranI-EMM-MH" 1281 As-I-KO)Ago|-cyclo(ABsh-OT U OSI-(Rpe(4-(2-aminoethoxy)I-(2-

MaC-(4-amino-4-carboxytetrahydropyran-EMM-MH"

As-KO)SIPI-KO)Ago|-cycloABsh-O HTM OSI-(P He(4-(2-1282 |aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyran|-EMM-| TV x x

МН»г

As-KO)А5пИ-КО)Ago|-cyclo (АБаШЦС-О ГМОСИ-(РНе(4-(2- 1283 |aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyran|-EMM- x x

МН» 1284 Ac-cyclo(ABA-O HMOSI-(PHe(4-(2-aminoethoxy)-(PEGA-

AIekha488)1-(2-MaZ-(4-amino-4-carboxytetrahydropyranI-EMM-MH) 1285 AIeha4881-(PEG4|-cycloCPAbsch-OTUMOSI-(P pe(4-(2-aminoethoxy) |- х х х -(2-MaC-(4-amino-4-carboxytetrahydropyran|i-EMM-MH» 1286 IAIehab47|-(PEG4|-cycloCPAbsch-OTUMOSI-(P pe(4-(2-aminoethoxy) |- x tvo 2- Ma(|-(4-amino-4-carboxytetrahydropyran-EMM-AMN"

IAIekha-647|-IPEG41-KO)Ago|-cyclo|AbBsch-OTUOSI-(P pe|4-(2-1287|aminoethoxy)|-(2-Ma-(4-amino-4-carboxytetrahydropyrani|-x)

G uv(As)|-MM-MHg

IAIehab47|-IPEG121-KO)Ago|-cycloAbBsch-OTUOSI-(P pe(4-(2-1288|aminoethoxy)|-(2-Ma-(4-amino-4-carboxytetrahydropyran|-x)

G uv(As)|-MM-MHg

IAIekha4881-IPEG41-KO)Agto|-cyclo (ABASh-O TU OSI-(РНе(4-(2-1289|aminoethoxy)|-(2-Ma-(4-amino-4-carboxytetrahydropyran|- х х

Г ув(Ас)|-MM-МНг "10 NM; i» 10 and « 100 nM; and" 100 and " 1,000 nm

Example 17 Stability of Additional Peptide Inhibitors in Simulated Intestinal Fluid (SIM), Simulated Gastric Fluid (SMS) and Redox Conditions

I00757| Studies were conducted in simulated intestinal fluid (SIL) and simulated gastric fluid (SORE) to assess the stability of additional peptide inhibitors of this invention. In addition, studies were conducted to assess the stability of additional peptide inhibitors of this invention under redox conditions.

EZZ table

Thioethers and DiRep

ZIR zak

ZEO IYUO Mo: Sequence n/2 n/2 (min) (min) oolava | Mutin ET cycle in o pMasielegy (o vminoethoxyh 2: ovo 1269 Ma!|-(4-amino-4-carboxytetrahydropyrani-EMM-MH» 790 x180

Ac-cyclo(Arsh|-OTUMOSI-(RHpe(4-(2-aminoethoxy)|-(2-Mac|-(4-amino- 1270 4-carboxytetrahydropyrani-(uv(AsD-MM-MH)) x180 x180 1271 As -KO)Ago|-cyclo(АБшщ-ОТУОСИ-(Рпе(4-(2-aminoethoxy)|-(2-МацЦ- 5180 -180 4-amino-4-carboxytetrahydropyrani-P uz(Ac)-MM-MH» 1272 As-KO)Ago|-cyclo(AbBch1-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-MaC- | »180, 5180 4-amino-4-carboxytetrahydropyrani-P uz(Ac)- MM-MN» »180 »180

IOctanilI-IPEG41-(RepI-MTUMO-|(RepiI-(Rpe(4-(2-aminoethoxy)|-(2- 1119 magic of removal) (AsMM-MHn "two fo" two

IRa!tI-IPEG41-(RepI-MTUM/O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-Ma!|- 1120 CAibusuv(Asmm-Mn "tvo 1284 Ac-cyclo(ABA- О HМОСИ-(РНе(4-(2-aminoethoxy)-(PEGA-180 90 diekha488)1-I2-MaC-(4-amino-4-carboxytetrahydropyran|i-EMM-MNa) |. 7 7

IAIekha4881-IPEG4|Y-cycloHABsh-O HTM OSI-(PHe(4-(2-aminoethoxy) |-- 12385 2-Ma(|-(4-amino-4-carboxytetrahydropyranY-EMM-AMN) x 180 x 180 1286 IAIehab47|-(PEG4|-cycloCPAbsch-OTUMOSI-(P pe(4-(2-aminoethoxy) |- 5180 5180 2-Ma(|-(4-amino-4-carboxytetrahydropyranY-EMM-AMN)

Ac((0)Aga|-(RepI-MTUMO-(RepiI-(Rpe(4-(2-aminoethoxy) I-(2-Mats-- 1152 TAB uv(Ac)Y-M-IVATaY-MH) 180 180

As-KO)TUp-(Repi-"MTUMO-(Repi-IRpe(4-(2-aminoethoxy)|-(2-Mas|- 1159 TairI-uv(Ac)I-M-IVATaY-MH" 180 180 1164 potre Mt Chrepi(Rpera-(2gaminoethoxyh-(2-may) (left: sari 1183 As-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MaP|-( o-Mei! eci|- 2180 2180,

Guv(Ac)-MM-MH» »180 »180 1185 As-I(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-Ma-(4-amino-4- | 5180, 2180, carboxytetrahydropyrans|-(Guv(Ac)D-MM-MH»g »180 »180

Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MaP|-(o-Mei!ecy|- 1186 С uv(AcY-M-IVATa|- MN" will work 5180

Ac-(RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- 1188 carboxytetrahydropyrani)-(Guv(Ac)|-M-( ВАИа|-МН»г x180 x180

As-IRep|I-M GMU-ISSH-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-Ma!|-(AIBI- 1194 g uv/(AST-MIM-MN)) 5180 5180

As-KO)Aga|-(RepI-MTUMO-(RepiI-(Rpe|(4-(2-aminoethoxy)-(2-Ma/|-(4- 1206 amino-4-carboxytetrahydropyrani-P uz (Ac)- MM-MNh x 180 x 180

IAIekha4881-IPEG41-KO)Agto|-cyclo (ABASh-O TU OSI-(РНе(4-(2-1289 aminoethoxy)|-(2-Ma|-(4-amino-4-carboxytetrahydropyran|-) » 180 » 180

Г ув(Ас)|-MM-МНh »90 - less than or equal to 180 min and more than 90 min; 245 min - less than or equal to 90 min and more than 45 min; 10 - less than or equal to 45 minutes and more than 10 minutes; "10 - less than 10 minutes.

Example 18

Cell analysis MK 00758) Natural killer (NK) cells, purified from human peripheral blood of healthy donors by negative selection (Miyepui Vioyesi, Mo under catalog 130-092-657), were cultured in complete medium (KRMI 1640 containing 10 95 ЕВ5, I -glutamine and penicillin-streptomycin) in the presence of II -2 (KpO, Mo according to catalog 202-II -010/SE) at 25 ng/ml. After 7 days, the cells were centrifuged and resuspended in complete medium at 1 Eb cells/ml.

Recombinant 1-23 with predefined EC50 to EC75 and 1-18 (KpO, Mo according to the catalog

BO03-5) at 10 ng/ml was mixed with different concentrations of peptides and added to MK cells seeded at 1E5 cells per well. After 20-24 hours, IEM in the supernatant was evaluated using Otsapiikipe EGIBA (Kp, Mo according to the OBIE50 catalog). The results are shown in Table EZ4.

Most results shown for a single peptide are from different assays.

Table EZ34

Analysis of primary cells (thioethers and diRep)

Cellular

ZEO IU Mo: Sequence analysis MK (nm) 1270 As-cyclo(AbBiI-OTUMOSI-(P pe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- i zj carboxytetrahydropyrani- (H uz(Ac)|-MM-MH» Sho 1271 As-KO)Ago|-cyclo(ABsh-OTUMOSI-(Rpe|(4-(2-aminoethoxy)I-(2-Ma|-(4- zhk zhk amino-4-carboxytetrahydropyrani-P uz(Ac)I-MM-MH» SHY 1286 IAIehab471-(IPEG4|-cyclo(ABSH-O GU OCI-(РНе(4-(2-aminoethoxy) |-(2- yes

MaC-(4-amino-4-carboxytetrahydropyran|-EMM-AMN»' 1152 AC((O)Ago|-(RepI-MHUUO-(RepiI-IRne(4-(2-aminoethoxy)|-(2-Ma| --(AIVI- same

H uv(Ac)I-M-(BATa|-MH»g 1164 Ac-(RepI-MPMO-(RepiI-I(Ppe(4-(2-aminoethoxy)|-(2-MaP-(AlII-OM- |VAa|-

МН»г 1178 As-IRepy-OTMU-(I uv(Ac)I-I(RepI-(Pne(4-(2-aminoethoxy)|-(2-MaC-(AIBI|-

H uv(Ac)|-MM-MH»g 1183 Ac-I(RepI-«M TM O-(Repi-(Pne(4-(2-aminoethoxy)|-(2-MaC-(c-Me!ec) |- «

Guv(Ac)|-MM-MH»g 1185 As-IRepI|I-MTU/O-(RepI-(Рпе|(4-(2-aminoethoxy)|-(2-Ma!/|-(4-amino -4- "carboxytetrahydropyrani-(H uz(Ac)|-MM-MH" 1186 As-IRepI|I-MTU/O-(RepI-(Рпе|(4-(2-aminoethoxy)|-(2-Ma! /|-(4-amino-4- « carboxytetrahydropyrani-(H uz(Ac)|-M-(BAa|-MH»g 1194 As-IRepIi-MPU-ISSH-(RepiI-(Pne(4-(2- aminoethoxy)|-(2-MaP-(AIBI|- «

Гув(Ас)|-MM-МН»г 00759) All the above-mentioned US patents, publications of US patent applications, patent applications

US, foreign patents, foreign patent applications, and non-patent publications referenced in this specification and/or listed in the appendices are hereby incorporated by reference in their entirety.

I00760| It will be understood from the foregoing that although specific embodiments of the present invention have been described herein for purposes of illustration, various modifications may be made without departing from the spirit and scope of the present invention. Accordingly, this invention is not limited except by the appended claims.

LIST OF SEQUENCES

"1105 PROTAGONIST THERAPEUTICS, INC. "1205 ORAL PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR AND THEIR

APPLICATION FOR THE TREATMENT OF INFLAMMATORY DISEASES

"1305 RETN-002/03MO "1505 PCT/)52015/040658 "1515 2015-07-15 "1505 75 14/800,627

From "1515 2015-07-15 "1505 75 62/264,820 "1515 2015-12-08

"1505 75 62/281,123 "1515 2016-01-20 "1605 1114 "1705 RabeprsIp version 3.5 "2105 1 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" holes "2205 "221" MY VE5 "222" (2)..2) "223" holes "2205 "221" MY VE5 "222" (11 )..(11)

From "223" Air "4005 1

Haa Haa TPg Tkgr bi1ip Avr Tug Ter Ietsy Tug Haa Ag4d 1 5 10 "2105 2 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 2

Suv Aia Mesye TPg Ter beep Avr Tug Ter Gay Tuk s1u Ag Suv 1 5 10 "2105 Z "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" hole 60 "2205

"221" MY VE5 "222" (2)..2) "223" holes "4005 Z

Haa Haa TPg Tgr bi1ip Avr Tug Ter Ietsy Tuk S1u Agd 1 5 10 "2105 4 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 4

Aza Mee TBPg Ter bip Avr Tug Ter Tets Tuk s1u Agd Guv 1 5 10 "2105 5 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 5

Zo Suv Aia Mesye TrPg Ter beep Avr Tug Ter Gay Tuk s1u Akud Suv Guv 1 5 10 15 «2105 6 «2115 13

З5 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 6 puv Aza Mee TPg Ter bip Avr Tug Ter Gay Tu s1u Ag4d 1 5 10 "2105 7 "2115 15 "2125 RVT "2135 Artificial sequence "220" "223" Description of the artificial sequence: Synthetic peptide "4005 7 puv Suv Aia Mee TPg Ter sbip Avr Tuk Ter Gay Tuk b1u Agd Suv 1 v; 10 15 "2105 8 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (5)..(5) "223" holes "4005 8

A1ia Mee TPg Tgr Haa Avr Tuk Tgr Gay Tuk s1u Agd 1 5 10 "2105 9 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 9

A1ia Mee TBPg Ter beep Avr Tug Ter Iets Tuk s1u Ag4d 1 5 10 "2105 10 "2115 12 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of artificial sequence: Synthetic peptide "4005 10

A1ia Mee TBPg Ter bip Avr Tug Ter Iets Tuk s1u Ag4d 1 5 10 "210511 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 11

Aza Aza TPg Ter bip Avr o Tug Ter Iets Tuk s1u Ag4d 1 5 10 "2105 12 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 12

A1ia Mee Aza Tgr bip Avr Tug Ter Iets Tuk s1u Ag4d 1 5 10 60 «2105 13

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 13

A1ia Mee TPg Aza bip Avr Tug Ter Iets Tuk s1u Ag4d 1 5 10 "2105 14 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 14

A1ia Mee TBPg Tgr Asia1a Avr Tug Ter Iets Tuk s1u Ag4d 1 5 10 "2105 15 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 15

A1ia Mee TBPg Ter bip Asia Tuk Ter Iets Tuk s1u Ag4d 1 5 10 "2105 16 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (10 )..(10) "223" Spa "2205 "2215 MOR BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR BE5 "222" (14). .(14) "223" 0-Guv "4005 16 (516) Suv beep Avr Ter sip Suv Tug Tgr Agud Haa Rie s1u Haa Guv 1 5 10

"2105 17 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" Osta1uU "2205 "221 » MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 17

Suv bip TPpg Ter bip Suv Tukg Tgr Agud b1u Rpe s1iu Haa Guv 1 5 10 «2105 18

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 18

Suv beep TPpg Ter beep Suv Tuk Ter puv Haa Rpe s1iu Haa Guv 1 5 10 "2105 19 "2115 14 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of artificial sequence: Synthetic peptide "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 19

Suv bip TPpg Ter bip Suv Tukg Ter Niv Haa Rpe s1iu Haa Guv 1 5 10 "2105 20 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "220" "221" MY BE5 "222" (14)..(14) " 223" 0-Guv "4005 20

Suv bip TPpg Ter bip Suv Tukg Tgr Agd Gay Rpe s1iu Haa Guv 1 5 10 "2105 21 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" VAGD "2205 "221" MY VE5 "222" (10)..(10) (516) "223" Rar

"221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 21

Suv bip TPpg Ter bip Suv Tug Tgr Agud Haa Rpe s1iu Haa Guv 1 5 10 "2105 22 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (9). (13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 22

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Haa Rpe Cs1u Haa Gu 1 5 10 "2105 23 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid (516) "220" "221" MY VE5

"222" (14)..(14) "223" 0-Guv "4005 23

Suv bip TPE Ter sip Suv Tug Tgr Akud UMai Rpe sС1u Haa Guz 1 5 10 "2105 24 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (10)..(10) «223» Rar «2205 «221» MY VE5 «222» (11). (13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 24

Suv beep TPpg Ter beep Suv Tug Tgr Agud Haa Haa s1iu Haa Guv 1 5 10 "2105 25 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (8)..(8) «223» Yew «2205 «221» MY VE5 «222» (9). .(13) "223" (2-aminoethoxy)acetic acid

"221" MY VE5 "222" (14)..(14) "223" V-Puv "4005 25

Suv bip TPpg Ter bip Suv Tukg Haa Haa Ppuv RiPe s1u Haa Gu 1 5 10 "2105 26 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (10)..(10) "223" Rar "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14 )..(14) "223" 0-Guv "4005 26

Suv bip TPE Ter sip Suv Tug Tgr Agud Haa Rpe sС1u Haa Guz 1 5 10 "2105 27 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (9)..(9) «223» Ogp «2205 «221» MY VE5 «222» (10). (13) "223" (2-aminoethoxy)acetic acid 60 "2205

"221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 27

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 28 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (14)..(14) "223" r-Guv "4005 28

Suv bip TPpg Ter bip Suv Tukg Ter Niv bij Avp s1u Aia Guv 1 5 10 "2105 29 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0-Guv "4005 29

Suv Agkud TPE Ter sip Suv Tug Tgr Agud bij Avp s1u Aia Guz 1 5 10 "2105 30 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (14)..(14) «223» 0-Guv «4005 30

Suv Akud TPg Ter bip Suv Tug Tgr Agud bi Tuk s1u Aia Guv 1 5 10 60 «2105 31 «2115 14

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" M-MeA1a "2205 "221" MY VE5 "222 (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" p-Guv "4005 31

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1iu Haa Guv 1 5 10 "2105 32 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (13)..(13) "223" Vega-Ai1a "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0-Guv "4005 32

Suv Aia Avr Ter Uaiii Suv Tug Ter Agud Ppuv Rpe s1u Aia Guz 1 5 10 "2105 33 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" sows 60 "2205

"221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a "220" "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 33

Suv A1a Avr Tgr Ua1i Suv Tuk Tgr Haa puv Rpe s1iu Aia Guv 1 5 10 "2105 34 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" sows "2205 "221" MY VE5 "222" (10)..(10)

From "223" Those "2205 "221" MY VE5 "222" (13)..(13) "223" Websa-A1a "2205 "221" MY VE5 "222" (14)..(14) "223" r-Huv "4005 34

Suv A1a Avr Tgr Uai Suv Tuk Ter Haa Haa Ribe cS1u A1z1a Gu 1 5 10 "2105 35 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9)..(9) "223" seeds "2205 60 "2215 MO VE5 "222" (10)..(10)

"223" E-butyl-Ai1ia "221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a "2205 "221" MY VE5 "222" (14)..(14) "223 » 0-Guv «4005 35

Suv A1a Avr Tgr Uai Suv Tug Tgr Haa Aia Rpe s1iu Aia Guv 1 5 10 "2105 36 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (9)..(9) "223" sows

From "220" "221" MY VE5 "222" (10)..(10) "223" Spa "220" "221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a " 2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 36

Suv A1a Avr Tgr Ua1i Suv Tukg Tgr Haa Haa Rpe s1iu Aia Guv 1 5 10 "2105 37 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (8)..(8) (516) "223" May 1

"221" MY VE5 "222" (9)..(9) "223" sows "2205 "221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 37

Suv A1a Avr Tgr Uai Suv Tukg Haa Haa Uai Rpe s1iu Aia Guv 1 5 10 "2105 38 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9)..(9) "223" sows "2205 "2215 MOR VE5 "222" (13)..(13) "223" Vega-Ai1a "2205 "2215 MOR VE5 "222" (14)..( 14) "223" 0-Guv "4005 38

Suv Aia Avr Ter Uaii Suv Tug Ter Haa Uai Rpe cS1u Aia Guz 1 5 10 "2105 39 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" sows 60 "2205

"221" MY VE5 "222" (10)..(10) "223" Seed "220" "221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 39

Suv A1a Avr Tgr Ua1i Suv Tukg Tgr Haa Haa Rpe s1iu Aia Guv 1 5 10 "2105 40 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (9)..(9)

From "223" sows "2205 "221" MY VE5 "222" (10)..(10) "223" Websa-A1a "2205 "221" MY VE5 "222" (13)..(13) "223" Vega-A1a "2205 "221" MY VE5 "222" (14)..(14) "223" r-Guv "4005 40

Suv A1a Avr Tgr Uai Suv Tug Tgr Haa Aia Rpe s1iu Aia Guv 1 5 10 "2105 41 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222 » (9)..(9)

"223" T1e "221" MY VE5 "222" (10)..(10) "223" T1e "2205 "221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 41

Suv A1a Avr Tgr Uai Suv Tukg Tgr Haa Haa Ribe cS1u A1z1a Gu 1 5 10 "2105 42 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (9)..(9) "223" T1e "220" "221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a " 2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 42

Suv A1a Avr Tgr Ua1i Suv Tuk Tgr Haa puv Rpe s1iu Aia Guv 1 5 10 "2105 43 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (9)..(9) (516) "223" R-A1a

"221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 43

Suv bip TPpg Ter bip Suv Tug Tgr Aia Uai1i Rpe s1iu Haa Guv 1 5 10 "2105 44 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" Vega-Al1a "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 44

Suv bip TPpg Ter bip Suv Tug Tgr Aia Uai1i Rpe s1iu Haa Guv 1 5 10 "2105 45 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (9)..(9) "2235 0-Getz "220" "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid (516) "220" "221" MY VE5

"222" (14)..(14) "223" 0-Guv "4005 45

Suv bip TPE Ter sip Suv Tukg Ter Getsh UMaii Rpe sС1u Haa Guz 1 5 10 "2105" 46 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (9)..(9) "223" 0-RIe "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 46

Suv bip TPpg Ter bip Suv Tuk Ter Rpe Uai Rre s1u Haa Gu 1 5 10 "2105" 47 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (9)..(9) "223" 0-Avp "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 47

Suv beep TPpg Ter beep Suv Tuk Ter Avp Uai Rpe s1iu Haa Guv 60 1 5 10

"2105 48 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (9)..(9) "223" 0-TV g "2205 "2215 MOR VEB "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0-Guv "4005 48

Suv bip TPE Ter sip Suv Tug Tegr TPg Uaii Rpe sS1u Haa Guz 1 5 10 «2105 49 «2115 14

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" 0-Avr "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 49

Suv bip TPpg Ter bip Suv Tukg Tgr Avr Uai Rpe s1iu Haa Guv 1 5 10 "2105 50 "2115 14 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (9)..(9) "223" sows "2205 "221" MY VE5 "222" (10)..(10) "223" P-Hets "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" p-Guv "4005 50

Suv bip TPpg Ter bip Suv Tukg Ter Haa gay Rpe s1iu Haa Guv 1 5 10 "210551 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 9)..(9) "223" sie "2205 "2215 MOR VE5 "222" (10)..(10) "223" 0-RIe "2205 "2215 MOR VE5 "222" (13)..(13 ) "223" (2-aminoethoxy)acetic acid "2205 "2215 МОР БЕ5 "222" (14)..(14) "223" 0-Guv "4005 51

Suv beep TPE Ter sip Suv Tug Ter Haa Rpe Rpe sS1Uu Haa Guz 1 5 10 "2105 52 "2115 14 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "220" "221" MY VE5 "222" (9)..(9) "223" seeds "2205 "221" MY VE5 "222" (10)..(10) "223" 0-Avp "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..( 14) "223" 0-Guv "4005 52

Suv bip TPpg Ter bip Suv Tukg Ter Haa Avp Rpe s1iu Haa Guv 1 5 10 «2105 53

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" sie "2205 "221" MY VE5 "222" (10)..(10) "223" 0-TV g "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 " 221" MY VE5 "222" (14)..(14) "223" V-Puv "4005 53

Suv beep TPpg Ter beep Suv Tukg Ter Haa TPg Rpe s1iu Haa Guv 1 5 10 60 «2105 54

"2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Addr "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 54

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Uai Avp s1iu Haa Guv 1 5 10 "2105 55 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 222 (8). MY VE5 "222" (14)..(14) "223" 0-Guv "4005 55

Suv bip TPpg Ter bip Suv Tukg Tgr Agud Uai Avp s1iu Haa Guv 1 5 10 "2105 56 "2115 14 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (8)..(8) "223" airpa-MetTgr "2205 "221" MY VE5 "222" (9)..(9) "223" siye "2205 "221" MY VE5 "222" (10)..(10) "223" pPTeyl "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 56

Suv beep TPpg Ter beep Suv Tukg Ter Haa gay Avp s1iu Haa Guv 1 5 10

From "2105 57 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" sie "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 57

Suv beep TPpg Ter beep Suv Tuk Ter Haa Uai Avp s1u Haa Guv 1 5 10 "2105 58 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" Address "2205 "2215 MOR VEB "222" (10)..(10) "223" Rar "2205 "2215 MOR VEB "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0- Guv "4005 58

Suv beep TPE Ter sip Suv Tug Ter Haa Haa Ap s1u Haa Guz 1 5 10 «2105 59 «2115 14

From "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" sie "2205 "221" MY VE5 "222 (12). "222" (14)..(14) "223" 0-Guv "4005 59

Suv beep TPpg Ter beep Suv Tug Tgr Haa Uai Rpe Aia Haa uv 1 5 10 (516) "2105" 60 "2115 14

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" seeds "2205 "221" MY VE5 "222" (12)..(12) "223" P-Hetz "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 " 222" (14)..(14) "223" district of Guv "4005 60

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Ua1 Rpe Gay Haa uv 1 5 10 "2105 61 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" sows "2205 "2215 MOR VE5 "222" (12)..(12) "223" 0-RIe "2205 "2215 MOR VE5 "222" (13)..( 13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0-Guv "4005 61 (516) Suv bip TPE Ter sip Suv Tug Ter Haa Uai Rpe Robe Haa Guz 1 5 10

"2105 62 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" seeds "2205 "221 » MY VE5 "222" (12)..(12) "2235 0-Avp "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 " 221" MY VE5 "222" (14)..(14) "223" 0-Guv

From "4005 62

Suv bip TPpg Ter bip Suv Tuk Ter Haa Uai Rpe Avp Haa uv 1 5 10 "2105 63 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (9). ..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) (516) "223" B-Puv

"4005 63

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Ua1i Rpe TPg Haa uv 1 5 10 "2105" 64 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (9)..(9) "223" sows "2205 "221" MY VE5 "222" (12)..(12) "223" 0-Avr "2205 "221" MY VE5 "222" (13 )..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 64

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Ua1i Rpe Avr Haa uv 1 5 10 "2105 65 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (2). VE5 "222" (14)..(14) "223" 0-Guv (516) "4005 65

Suv Akud TPg Ter bip Suv Tug Tgr Agud Uai Rpe s1iu Haa Guv

1 5 10 "2105 66 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" M-Mesip "2205 "221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY BE5 "222" (14)..(14) "223" 0 -Huv "4005 66

Suv bip TPpg Ter bip Suv Tug Tgr Agud Uai Ribe s1u Haa Guv 1 5 10

From "2105 67 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" sie "2205 " 221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY BE5 "222" (14)..(14) "223" 0-Huv " 4005 67

Suv Haa TPg Ter bip Suv Tukg Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 «2105 68 «2115 14 «2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" Okhgp "2205 "2215 MOR VEB "222" (10)..(10) "223" Rar "2205 "2215 MOR VEB "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0- Guv "4005 68

Suv Aia Avr Ter Uaii Suv Tug Ter Haa Haa Rpe sS1u Haa Guz 1 5 10 «2105 69 «2115 14

From "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (9)..(9) "223" Okhgp "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13) ..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv 60 "4005 69

Suv A1a Avr Tgr Uai Suv Tug Haa Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 70 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (8). ..(10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) 0) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" ( 14)..(14) "223" V-Puv "4005 70

Suv A1a Avr Tgr Ua1i Suv Tukg Tgr Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 71 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (8)..(8). )

"223" Rar "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223 » 0-Guv «4005 71

Suv A1a Avr Tgr Uai Suv Tuk Rpe Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 72 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (8)..(8) "223" Ver

From "220" "221" MY VE5 "222" (9)..(9) "223" Ogp "220" "221" MY VE5 "222" (10)..(10) "223" Rar "2205 " 221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY BE5 "222" (14)..(14) "223" 0-Huv " 4005 72

Suv A1a Avr Tgr Uai Suv Tug Haa Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 73 "2115 14 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (8)..(8) "223" РПе(3,5-Е2) "2205 "221" MY VE5 "222" (9)..(9) "223" Охгп " 2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid " 2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 73

Suv A1a Avr Tgr Uai Suv Tuk Rpe Haa Haa Rpe s1iu Haa Guv 1 5 10

From "2105 74 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(СОМН2 ) "2205 "221" MY VE5 "222" (9)..(9) "223" Okhgp "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 60 "222" (14)..(14) "223" 0-Guv

"4005 74

Suv A1a Avr Tgr Uai Suv Tuk Rpe Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 75 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (8)..(8) "223" РПе(4-SEZ) "2205 "2215 MOR ВЕ5 "222" (9)..(9) "223" Ogp "2205 "2215 MOR ВЕ5 "222" (10) ..(10) "223" Rar "2205 "2215 MOR BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR BE5 "222" (14).. (14) "223" 0-Guv "4005 75

Suv Aia Avr Ter Uaii Suv Tukg Rbe Haa Haa Rpe cS1u Haa Guz 1 5 10 "2105 76 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (8).

"221" MY VE5 "222" (10)..(10) "223" Rar "220" "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid " 2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 76

Suv A1a Avr Tgr Uai Suv Tuk Rpe Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 77 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) 0) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 77

Suv Mee TPg Ter bip Suv Tuk Ter Gay Tuk s1u Akd Haa Guv 1 5 10 "2105 78 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (8)..(8) "223" Vega-pTgr "2205 "2215 MOR VE5 "222" (9)..(9) "223" Ogp "2205 60 "2215 MO VE5 "222" (10).. (10)

"223" Rar "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223 » 0-Guv «4005 78

Suv A1a Avr Tgr Ua1i Suv Tukg Tgr Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 79 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" Ogp

From "220" "221" MY VE5 "222" (10)..(10) "223" airpa-Megetsy "220" "221" MY VE5 "222" (13)..(13) "223" (2) -aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 79

Suv A1a Avr Tgr Ua1i Suv Tukg Tgr Haa gay Rpe s1iu Haa Guv 1 5 10 "2105 80 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (9)..(9) 60 "223" Ogp

"221" MY VE5 "222" (10)..(10) "223" Vega-5riga1-rir "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy) acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 80

Suv A1a Avr Tgr Ua1i Suv Tukg Tgr Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 81 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (8). ..(10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14) ..(14) "223" 0-Guv "4005 81

Suv A1a Avr Tgr Uai Suv Tug Haa Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 82 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" Ogp "2205 "2215 MOR VEB "222" (10)..(10) "223" holes "2205 "2215 MOR VEB "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0- Guv "4005 82

Suv Aia Avr Ter Uaii Suv Tug Ter Haa Haa Rpe sS1u Haa Guz 1 5 10 «2105 83 «2115 14

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222 (10). "222" (14)..(14) "223" 0-Guv "4005 83

Suv A1a Avr Tgr Ua1i Suv Tuk Tgr Haa s1u Rpe s1iu Haa Guv 1 5 10 (516) "2105" 84 "2115 14

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" Weba-MeRPe (4-E) "2205 " 221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14)

From "223" V-Puv "4005 84

Suv A1a Avr Tgr Uai Suv Tuk Rpe Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 85 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (8)..(8) "223" Vega-pPRIe "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14)..(14) "223" 0-Guv "4005 85 (516) Suv bip TPE Ter sip Suv Tug Rbe Agud Uai Ap s1u Haa Guz 1 5 10

"2105 86 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" Vega-1-May "2205 "221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY BE5 "222" (14)..(14) "223" 0 - Guv "4005 86

Suv bip TPpg Ter bip Suv Tug Haa Agud Uai Avp s1iu Haa Guv 1 5 10 «2105 87

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 87

Suv age Avr Tgr bij Suv Tug Ter Niv I1ie RpPe 1U 1 5 10 "2105 88 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 88

Suv bij TPE Ter siy Suv Tug Ter Niv Bek RPpe 5eg 1 5 10 "2105 89 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "4005 89

Suv beep back Ter fight Suv Tuk Ter Niv Tug Tu U 1 5 10 "2105 90 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 90

Suv vek Avr Tgr Agud Suv Tukg Ter Niv Uaii Roe c1U 1 5 10 "2105 91 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 91

Suv Niv TPE Ter Uai Suv Tug Ter Niv bij RPpe 5eg 1 5 10 "2105 92 "2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 92

Suv TPkgE Avr Ter Ua1i Suv Tukg Ter Niv bij Tuk 5ekg 1 5 10 "2105 93 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 93

Suv bip TPg Ter Uai Suv Tuk Ter Niv TPg Tu U 1 5 10 "2105 94 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "4005 94

Suv b1u AvBp Tgr bij Suv Tuk Ter Niv Uai1i Tukh U

1 5 10 "2105 95 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 95

Suv Guv Avr Tgr Ppuv Suv Tug Ter Niv Iie Tukh schu 1 5 10 "2105 96 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 96

Suv Akud TPg Ter Ua1i Suv Tuk Ter Niv Uai Rpe 1U 1 5 10 "2105 97 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 " (4)..(4) "223" May 1 "4005 97

Suv A1a Avr Haa Ua1i Suv Tukg Ter Niv TP RpPe C1U 1 5 10 "2105 98 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 4)..(4) "223" May 2 "4005 98

Suv A1a Avr Haa Ua1i Suv Tukg Ter Niv TP RpPe S1U 1 5 10 60 «2105 99

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (4)..(4) "223" 1-Vir "4005 99

Suv A1a Avr Haa Ua1i Suv Tukg Ter Niv TP RpPe C1U 1 5 10 "2105 100 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 4)..(4) "223" Yew "4005 100

Suv A1a Avr Haa Ua1i Suv Tukg Ter Niv TP RpPe S1U 1 5 10 "2105 101 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 4)..(4) "223" Vesa-PTEegr "4005 101

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TP RpPe C1U 1 5 10 "2105 102 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" ( 8)..(8)

"223" 1-Vir "4005 102

Suv A1a Avr Tgr Ua1i Suv Tuk Haa Niv TP Rpe C1U 1 5 10 "2105 103 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 8)..(8) "223" Yew "4005 103

Suv A1a Avr Tgr Ua1i Suv Tuk Haa Niv TP Rpe C1U 1 5 10 "2105 104 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 8)..(8) "223" Vesa-PTEgr "4005 104

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TP RpPe C1U 1 5 10 "2105 105 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 105

Suv Aia Avr Ter Uaii Suv Tug Aia Niv TPg Rpe Sh1U 1 5 10 "2105 106 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "4005 106

Aza Suv Avr Tgr Uai Suv Tug Tegr Ni5 TPg Rpe Sh1U 1 5 10 "2105 107 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 107

Aza Suv Avr Tgr Suv Suv Tuk Tgr Suv TPg Rpe Sh1U 1 5 10 "2105 108 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 108

A1a Aza Avr Tkgr Suv Aia Tuk Tgr Suv TPg Ribe Ss1Uu 1 5 10 «2105 109 «2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 109

Suv A1a Avr Tgr Suv Suv Tukg Tgr Suv TPg Rpe C1U 1 5 10 "2105 110 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 110

Suv A1a Avr Tgr Suv Suv Tukg Tgr Suv TPg Rpe C1U 1 5 10 "2105 111 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "4005 111

Suv A1a Avr Tgr Suv Suv Tuk Ter Suv TPg Roe s1U

1 5 10 "2105 112 "211511 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 112

Suv A1a Avr Tgr Ua1 Suv Tuk Ter Niv TPg Rie 1 5 10 "2105 113 "2115 10 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 113

Suv A1a Avr Tgr Ua1 Suv Tuk Ter Niv TEG 1 5 10 "2105 114 "2115 8 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 114

Suv A1a Avr Tgr Ua1 Suv Tuk Tgr 1 5 "2105 115 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..( 1) "223" Websa-A1a "4005 115

A1ia bek Suv Aza Avr Tgr Uai Suv Tug Tgr Ni5 TPpg Rpe Sh1U 1 5 10 "2105 116 "2115 14 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of the artificial sequence: Synthetic peptide "221" MY VE5 "222" (1)..(1) "223" 0-Guv "4005 116

Tpuv bek Suv Aza Avr Ter Ua1 Suv Tuk Ter Niv TPg Roe C1Uu 1 5 10 "2105 117 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (1). Ter Ni5 TPg Rpe SHU 1 5 10 "2105 118 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" (2-aminoethoxy)acetic acid "4005 118

Haa Suv Aza Avr Tgr Uai Suv Tuk Ter Niv TP Rpe C1U 1 5 10 "2105 119 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" (1)..(1)

"223" 0-Guv "4005 119 ace Suv Aza Avr Ter Ua1 Suv Tug Ter Niv TPg Roe c1U 1 5 10 "2105 120 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide " 4005 120

Suv Guv Avr Tgr Ua1i Suv Tukg Ter Niv TP Rpe C1U 1 5 10 "2105 121 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 121

Suv A1a Avr Tgr Ppuv Suv Tug Ter Niv TP Rpe C1U 1 5 10 "2105 122 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 122

Suv Aia Avr Ter Uaii Suv Tug Ter Guv TPg Ribe o1Uu 1 5 10 "2105 123 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 123

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv puv RpPe C1U 1 5 10 "2105 124 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"4005 124

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TPg guv Sh1U 1 5 10 "2105 125 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (12 )..(12) "223" 0-Guv "4005 125

Suv Aia Avr Ter Uai Suv Tug Ter Niv TPg Rpe Guv 1 5 10 "2105 126 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 126

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TP RpPe C1U 1 5 10 "2105 127 "211511 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8 )..(8) "223" May 1 "4005 127

Suv A1a Avr Tgr Ua1 Suv Tuk Haa Niv TPg Riye 1 5 10 "2105 128 "211511 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

"222" (8)..(8) "223" 1-May "2205 "2215 MOR VE5 "222" (11)..(11) "223" M-Me-RBGe "4005 128

Suv Aia Avr Ter Uai Suv Tuk Haa Niv TPg RiGe 1 5 10 "2105 129 "211511 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8) ..(8) "223" May 1 "2205 "221" MY VE5 "222" (10)..(10) "223" bBucks "4005 129

Suv A1a Avr Tgr Ua1 Suv Tuk Haa Niv Haa Riye 1 5 10 "2105 130 "211511 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8) ..(8) "223" 1-May "2205 "221" MY VE5 "222" (9)..(9) "223" M-Me-Niv "4005 130

Suv A1a Avr Tgr Ua1 Suv Tuk Haa Niv TPg Riye 1 5 10 "2105 131 "2115 13 "2125 RVT

Gs10) "213" Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 131

Suv Aia Avr Ter Uaii Suv Tug Ter Niv TPgE Rpe s1UuU Tuv 1 5 10 "2105 132 "211511 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 2)..2) "223" bBucks "2205 "221" MY VE5 "222" (8)..(8) "223" May 1 "4005 132

Suv Haa Avr Tgr Ua1 Suv Tuk Haa Niv TPg Riye 1 5 10 "2105 133 "211511 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (4 )..(4) "223" M-Me-Tgr "2205 "221" MY VE5 "222" (8)..(8) "223" May 1 "4005 133

Suv A1a Avr Tgr Ua1 Suv Tuk Haa Niv TPg Riye 1 5 10 "2105 134 "211511 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

"222" (5)..(5) "223" bBaks "2205 "2215 MOR VE5 "222" (8)..(8) "223" May 1 "4005 134

Suv Aia Avr Tgr Haa Suv Tug Haa Niv TPg RiGe 1 5 10 "2105 135 "211511 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8) ..(8) "223" May 1 "2205 "221" MY VE5 "222" (11)..(11) "223" 0-RIe "4005 135

Suv A1a Avr Tgr Ua1 Suv Tuk Haa Niv TPg Rie 1 5 10 "2105 136 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8 )..(8) "223" May 1st "2205 "221" MY VE5 "222" (12)..(12) "223" bBucks "4005 136

Suv A1a Avr Tgr Ua1i Suv Tuk Haa Niv TPg Rie Haa 1 5 10 "2105 137 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 137

Suv Aia TPg Ter Uai Suv Tug Ter Niv TPg Rpe 1U 1 5 10 "2105 138 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 138

Suv A1a Avr Tgr bij Suv Tukg Ter Niv TP Rpe S1U 1 5 10 "2105 139 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 139

Suv A1a Avr Tgr Ua1i Suv Tuk Tgr Niv Agud Suv s1iu Ter Tgr S1u Suv 1 v; 10 15 "2105 140 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" 1- May "2205 "221" MY VE5 "222" (10)..(10) "223" R-A1a "4005 140

Suv A1a Avr Tgr Uai Suv Tukg Haa Niv Aia RpPe 0Щ1У 1 5 10 "2105 141 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (10)..(10) "223" holes "4005 141

Suv A1a Avr Tgr Uai Suv Tuk Haa Niv Haa Roie c1U 1 5 10 "2105 142 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 8)..(8) "223" 1-May "2205 "221" MY VE5 "222" (10)..(10) "223" rega-Ai1a "4005 142

Suv A1a Avr Tgr Uai Suv Tukg Haa Niv Aia RpPe 0Щ1У 1 5 10 "2105 143 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 1 "4005 143

Suv A1a Avr Tgr Uai Suv Tuk Haa Rpe TPg Rpe S1U 1 5 10 "2105" 144 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (9)..(9) "223" Р-А1а "4005" 144

Suv A1a Avr Tgr Uai Suv Tug Haa Aia TP Rpe C1U 1 5 10 "2105" 145 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (10)..(10) "223" holes "2205 "221" MY VE5 "222" (11). .(11) "223" 0-RIe "4005" 145

Suv A1a Avr Tgr Uai Suv Tuk Haa Ni Haa Rpe 1U 1 5 10 "2105" 146 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 " (8)..(8) "223" May 1 "220" "221" MY VE5 "222" (12)..(12) "223" hole 60 "4005 146

Suv A1a Avr Tgr Ua1i Suv Tuk Haa Niv TPg Rie Haa

1 5 10 "2105 147 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" 1- Mai "2205 "221" MY VE5 "222" (9)..(9) "223" M-Me-Niv "2205 "221" MY VE5 "222" (10)..(10) "223" R- A1a "2205 "221" MY VE5 "222" (12)..(12) "223" holes "4005 147

Suv A1a Avr Tgr Ua1i Suv Tukg Haa Niv Aza RiPe Haa 1 5 10 "2105" 148 "211511 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (10)..(10) "223" AER "4005" 148

Suv A1a Avr Tgr Ua1i Suv Tuk Haa Niv Haa 0Щ1U 1 5 10 "2105" 149 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" M-MeNiv "2205 "2215 MOR VEB "222" (13)..(13) " 223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VEB "222" (14)..(14) "223" 0-Guv "4005" 149

Suv Aia Avr Ter Uaiii Suv Tug Ter Niv TPg Rpe s1u Haa Guz 1 5 10 "2105 150 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (8)..(8) "223" Ais "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 " (14)..(14) "223" 0-Guv "4005 150

Suv A1a Avr Tgr Ua1i Suv Tuk Haa Niv TPg Rpe s1iu Haa Guv 1 5 10 "2105 151 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (8)..(8) "223" Ver

"221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" p-Guv "4005 151

Suv A1a Avr Tgr Uai Suv Tuk Haa Niv TPg Rre s1u Haa Gu 1 5 10 "2105 152 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" M-MeAgd "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14)..(14) "223" 0-Guv "4005 152

Suv bip TPE Ter sip Suv Tug Tgr Agud bij Avp s1u Haa Guz 1 5 10 "2105 153 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" M-MeAgd "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid 60 "2205

"221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 153

Suv bip TPpg Ter bip Suv Tug Tgr Agud Agud Avp s1iu Haa Guv 1 5 10 "2105 154 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" M-Meguvs "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14)

From "223" V-Puv "4005 154

Suv bip TPpg Ter bip Suv Tuk Ter Agud pub Avp o biu Haa Gu 1 5 10 "2105 155 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222 (10). 14)..(14) "223" 0-Guv "4005 155 (516) Suv beep TPE Ter sip Suv Tug Ter Agud Haa Avp s1u Haa Guz 1 5 10

"2105 156 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" 0-с1y "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 156

Suv bip TPpg Ter bip Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 «2105 157

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" P-Ag4d "2205 "221 » MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 157

Suv beep TPpg Ter beep Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 158 "2115 14 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of artificial sequence: Synthetic peptide "221" MY VE5 "222" (9)..(9) "223" 0-Agd "2205 "221" MY VE5 "222" (10)..(10) " 223" 0-c1y "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) ) "223" 0-Guv "4005 158

Suv bip TPpg Ter bip Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 159 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (9)..(9) "223" M-Mesits "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 159

Suv beep TPpg Ter beep Suv Tukg Tgr bij Avp s1iu Haa Guv 1 5 10 "2105 160 "2115 6 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"4005 160

Suv A1a Avr Tgr Uai1i Suv 1 5 "2105 161 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" M-MeAgd "2205 "221" MY VE5 "222" (13)..(13) "223" AER "2205 "221" MY VE5 "222" (14)..(14) "223" 0 -Huv "4005 161

Suv Agkud Avr Tgr bip Suv Tukg Tgr Agud puv Rpe s1iu Haa Guv 1 v; 10 "2105 162 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" 0-Guv "2205 "221" MY VE5 "222" (13)..(13) "223" AER "220" "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 162

Suv Agkud Avr Tgr bip Suv Tukg Ter Agd Ppuv Rpe s1iu Haa Guv 1 5 10 «2105 163 60 «2115 14 «2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" 0-Agd "2205 "221" MY VE5 "222" (13) ..(13) "223" AER "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 163

Suv Agkud Avr Tgr bip Suv Tukg Tgr Agud puv Rpe s1iu Haa Guv 1 5 10 "2105 164 "2115 14 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" 0-Agd "2205 "221" MY VE5 "222" (10) ..(10) "223" 0-Guv "2205 "221" MY VE5 "222" (13)..(13) "223" AER "2205 "221" MY VE5 "222" (14)..(14 ) "223" 0-Guv "4005 164

Suv Agkud Avr Tgr bip Suv Tukg Tgr Agud puv Rpe s1iu Haa Guv 1 v; 10 "2105 165 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" M-MeAgd "2205 "2215 MOR VEB "222" (13)..(13) " 223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VEB "222" (14)..(14) "223" 0-Guv "4005 165

Suv bip TPE Ter sip Suv Tug Tgr Agud bij Avp sb1u Haa Guv 1 5 10 "2105 166 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 166

Suv TPE Avr Ter Ppuv Suv Tug Ter Niv bi Rpe C1U 1 5 10 "2105 167 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 167

Suv Akud TPg Ter TpPg Suv Tukg Ter Niv Uai1i Tukh shSHХU 1 5 10 "2105 168 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 168

Suv Rkgo AvBp Tgr bij Suv Tug Ter Niv Agd RpPe S1U 1 5 10 "2105 169 (516) "2115 12 "2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "4005 169

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TP RpPe C1U 1 5 10 "2105 170 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 170

Suv A1a Avr Ter Mee Suv Tug Ter Niv bij Tu schu 1 5 10 "2105 171 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 171

Suv TPE TP Ter Ppuv Suv Tukg Ter Niv sbip Tukh schu 1 5 10 "2105 172 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 172

Suv vek AvBp Tgr bij Suv Tuk Ter Niv Niv Tu Sh1U 1 5 10 "2105 173 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 173

Suv bek Avr Tgr Uaiii Suv Tukg Ter Niv Uai Tuk schu 1 5 10 "2105 174 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 174

Suv Avr TPg Ter Ppuv Suv Tug Ter Niv Agud bip b5eg 1 5 10 "2105 175 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 1 "4005 175

Suv A1a Avr Tgr Uai Suv Tuk Haa Niv TPg Roe 01U 1 5 10 "2105 176 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (8 )..(8) "223" May 2 "4005 176

Suv Aia Avr Ter Uaii Suv Tuk Haa Niv TPg Rpe 1U 1 5 10 "2105 177 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 177

Suv A1a Avr Tgr Uaiii Suv Tukg Ter Niv TPg Roe 01Uu 1 5 10 "2105 178 "2115 13 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (13)..(13) "223" V-Puv "4005 178

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe cS1u Guv 1 5 10 "2105 179 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 15)..(15) "223" 0-Guv "4005 179

Suv Aia Avr Ter Uaii Suv Tug Ter Niv TPg Rpe s1u Aia Rgo Guv 1 5 10 15 «2105 180 «2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 180

Suv TPE Avr Ter Ppuv Suv Tug Ter Niv TP Rpe C1U 1 5 10 "2105 181 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 181

Suv Agkud Avr Tgr Ua1i Suv Tuk Ter Niv TPg Roe 01Uu 1 v; 10 "2105 182 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "4005 182

Suv A1a Avr Tgr Ua1i Suv Tug Ter Niv bij RpPe S1U

1 5 10 "2105 183 "2115 16 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 183

Suv Asia1a Avr Tgr Ua1i Suv Tuk Ter Niv Rpe Niv sip Gay Agd ABr A1a 1 5 10 15 "2105" 184 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 184

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv bij Niv back bij Agkd Uai s1U 1 5 10 15 "2105 185 "2115 16 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 185

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv Avp Niv bek sbits siu bek 01U 1 5 10 15 "2105 186 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 186

Suv A1a Avr Tgr Ua1i Suv Tuk Tgr Niv Agud bek TPg siu s1u bip Niv 1 5 10 15 "2105 187 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" (1)..(1)

"223" 0-Guv "221" MY VE5 "222" (9)..(9) "223" 1-May "2205 "221" MY VE5 "222" (13)..(13) "223" bBaks "2205 "221" MY VE5 "222" (14)..(14) "223" AER "2205 "221" MY VE5 "222" (15)..(15) "223" 0-Agd "4005 187

Tpuv Suv Agd Avr Tgr beep Suv Tug Haa Niv TPg Niv Haa Haa Agd 1 5 10 15 "2105 188 "2115 16 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 188

TPgE bip Rbe Avr Suv Agd TPg Ter bis Sub Tuk Ter Niv TP Rpe S1U 1 5 10 15 "2105" 189 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 189 си1у b1у UMaii siy Suv Avp Avr Tgr bip Suv Tug Ter Niv TPg Roe 01Uu 1 5 10 15 "2105 190 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 190 (516) Agd biy s1u TBg Suv bek TPK Ter Ppuv Suv Tug Ter Niv TPg Ribe s1U 1 5 10 15

"2105 191 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 191

Avr TPg Rgo Agd Sub Agud TP Ter bi Sub Tug Ter Niv TPgs Rpe S1U 1 5 10 15 "2105 192 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 192 si1u b1u sb1u fight Suv fight Avp Ter fight Suv Tuk Ter Niv TPg Roe 01Uu 1 5 10 15 "2105 193 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 193 s1u Avr Niv Ppuv Suv back bek Tkgr bii Suv Tuk Ter Niv TPg Rpoe 1U 1 5 10 15 "2105 194 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 194 bi1u bek Uai Niv Suv Mee TPg Ter sei Suv Tuk Ter Niv TPg Roe 01Uu 1 5 10 15 "2105 195 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (8) ..(8) "223" May 1

"4005 195

Suv A1a Avr Tgr Uai Suv Tuk Haa Uai TBPg Roe c1Uu 1 5 10 "2105 196 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (9 )..(9) "223" P-Niv "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14 )..(14) "223" 0-Guv "4005 196

Zo Suv Aia Avr Ter Uaii Suv Tug Ter Niv TPg Rpe s1u Haa Guz 1 5 10 "2105 197 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 197

Suv Agkud Avr Tgr bip Suv Tukg Ter Niv puv RpPe С1У 1 5 10 "2105 198 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 198

Suv vek Avp Tgr Ua1i Suv Tukg Ter Niv TPg Tu Sh1U 1 5 10 "2105 199 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (13)..(13) "223" Vega-Al1a "2205 "2215 MOR VEB "222" (14)..(14) " 223" 0-Guv "4005 199

Suv Aia Avr Ter Uaii Suv Tug Ter Niv TPg Rpe cS1u Aia Guz 1 5 10 "2105 200 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 200

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1iu Haa Guv 1 5 10 "2105 201 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 201

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TP RpPe C1U 1 5 10 "2105 202 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

"222" (13)..(13) "223" AER "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0-Agd "4005 202

Suv Aia Avr Ter Uaiii Suv Tug Ter Niv TPg Rpe s1iu Haa Agd 1 5 10 "2105 203 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" AER "4005 203

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1iu Haa Guv 1 5 10 "2105 204 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (13)..(13) "223" bara "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 204

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1iu Haa Guv 1 5 10 "2105 205 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221 » MY VE5

"222" (13)..(13) "223" Nehapois-0-Guv "4005 205

Suv Aia Avr Ter Uaii Suv Tukg Ter Niv TPg Ribe s1Uu Guz 1 5 10 "2105 206 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (13)..(13) "223" (REb)2-0-Guv "4005 206

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe sS1u Guv 1 5 10 "2105 207 "2115 14 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 207

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1u Rgo Guv 1 5 10 "2105 208 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (13)..(13) "223" Ah "220" "221" MY VE5 "222" (14)..(14) "223" 0-Guv 60 "4005 208

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1iu Haa Guv

1 5 10 "2105 209 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (14)..(14) "223" 0- Guv "4005 209

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TPg Rpe s1iu Aia Guv 1 5 10 "2105 210 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (15)..(15) "223" 0-Guv "4005 210

Suv A1a Avr Ter Ua1i Suv Tuk Ter Niv TPg Rbe s1iu Aza Rgo Guv 1 v; 10 15 "2105 211 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (14)..(14) "223" Ah "220 » "221" MY VE5 "222" (15)..(15) "223" 0-Guv "4005 211

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Ribe si1u A1ia Haa Gu 1 5 10 15 "2105 212 (516) "2115 15 "2125 RVT

"2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (15)..(15) "223" 0-Guv "4005 212

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rbe s1iu Aia A1t1a Gu 1 5 10 15 "2105 213 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (13)..(13) "223" AER "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 213

Suv Agkud Avr Tgr bip Suv Tuk Ter Niv Ppuv Rpe s1iu Haa Guv 1 5 10 "2105 214 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 214

Suv A1ia TPg Ter bip Suv Tukg Ter Niv bij Tuhk schu 1 5 10 "2105 215 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 215

Suv Kpuv TPg Ter TpPg Suv Tukg Ter Niv bi Rpe S1U 1 5 10 60 "2105 216

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 216

Suv TPE TPg Ter TpPg Suv Tukg Ter Niv sbip Tukh schu 1 5 10 "2105 217 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 217

Suv Akud TPg Ter bii Suv Tukg Ter Niv bi Rpe S1U 1 5 10 "2105 218 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 218

Suv Akud TPg Ter beep Suv Tug Ter Niv bij Tu schu 1 5 10 "2105 219 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 219

Suv bip TPE Ter sip Suv Tug Tgr Agd bij ABp 1U 1 5 10 "2105 220 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 220

Suv Akud TPg Ter bij Suv Tuk Ter Niv bij Tukh schu 1 5 10 60 «2105 221 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 221

Suv TP TPg Ter bii Suv Tuk Ter Niv bi Tukh Sh1U 1 5 10 "2105 222 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 222

Suv Akud TPE Ter siy Suv Tug Ter Niv bis sbip beg 1 5 10 "2105 223 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 223

Suv TP TPg Ter bij Suv Tuk Ter Niv sbip RpPe СЩ1У 1 5 10 "2105 224 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 224

Suv TP TPg Ter bii Suv Tuk Ter Niv bi Rpe S1U 1 5 10 "2105 225 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 225

Suv bip TPpg Ter bij Suv Tuk Ter Niv Gay Tu Sh1U 1 5 10 "2105 226 (516) "2115 12 "2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "4005 226

Suv bij Avr Tegr Ppuv Suv Tukg Ter Niv Ppuv Tu Sh1U 1 5 10 "2105 227 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 227

Suv TPkgE Avr Ter Ua1i Suv Tukg Ter Niv TP Rpe C1U 1 5 10 "2105 228 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 228

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TPg Tu U 1 5 10 "2105 229 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 229

Suv Asia1a Avr Tgr Ua1i Suv Tukg Ter Ni Agud Nib5 Aza Avr Agud Ua1i Guv 1 5 10 15 "2105 230 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 230

Suv Aia Avr Ter Uaii Suv Tug Ter Niv TPg Ribe s1u siy Agd 1 5 10 "2105 231 "2115 14 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 231

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TpPg No b1u b1y Ag4d 1 5 10 "2105 232 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 232

Avr TPg Rgo Agd Sub Agud TP Ter bis Sub Tug Ter Niv TPg Roe s1U 1 5 10 15 "2105 233 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 222 (13).

Suv bip TPE Ter Uai Suv Tug Tgr Agud bis Avp s1u Haa Guz 1 5 10 "2105 234 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv 60 "4005 234

Suv bip TPpg Ter bip Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 235 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" p-Guv "4005 235

Suv bip TPpg Ter bip Suv Tukg Ter Agud TPg Ap s1u Haa Guv 1 5 10 "2105 236 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 МОР БЕ5 "222" (14)..(14) "223" 0-Guv "4005 236

Suv beep TPE Ter sip Suv Tug Ter Agud pub Avp s1u Haa Guz 1 5 10 "2105 237 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (13)..(13) «223» (2-aminoethoxy)acetic acid 60 «2205

"221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 237

Suv bip TPpg Ter bip Suv Tug Tgr Agud Agud Avp s1iu Haa Guv 1 5 10 "2105 238 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" Rara "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 » (14)..(14)

From "223" V-Puv "4005 238

Suv bip TPpg Ter bip Suv Tukg Tgr Agud Haa Avp s1iu Haa Guv 1 5 10 "2105 239 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (10)..(10) "223" Ogp "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14 )..(14) "223" 0-Guv "4005 239 (516) Suv bip TPE Ter sip Suv Tug Ter Agud Haa Avp s1u Haa Guz 1 5 10

"2105" 240 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy )acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005" 240

Suv Akud TPg Ter bip Suv Tukg Tgr Agud puv Rpe s1iu Haa Guv 1 5 10 "2105 241 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" P-Ag4d "4005 241

Suv bip TPpg Ter bip Suv Tug Tgr Agd bij Avp sb1u Haa Agd 1 5 10 "2105 242 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 60 "2215 MO БЕ5 "222" (14)..(14)

"223" 0-Guv "4005 242

Suv bip TPpg Ter bip Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 243 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 243

Suv beep Avr Tgr beep Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105" 244

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" r-Guv "4005" 244

Suv bip TPpg Ter bip Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105" 245 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 " 222" (13)..(13)

"223" (2-aminoethoxy)acetic acid "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005" 245

Suv bip TPpg Ter bip Suv Tukg Ter Agud TBg Avp o b1iu Haa Gu 1 5 10 "2105" 246 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 222 (13).

Suv bip TPg Ter Ua1i Suv Tuk Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 247 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 247

Suv beep TPpg Ter beep Suv Tuk Ter Agud puv Avp s1iu Haa Gu 1 5 10 "2105" 248 "2115 12 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of the artificial sequence: Synthetic peptide "221" MY VE5 "222" (9)..(9) "223" SakhUu "4005" 248

Suv bip TPpg Ter bip Suv Tuk Ter Haa siy AvBp 01U 1 5 10 "2105" 249 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Wed "4005" 249

Suv bip TPpg Ter bip Suv Tug Tgr Haa bij ABp 1U 1 5 10 "2105 250

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 250

Suv bip TPpg Ter bip Suv Tuk Ter Gay bis AvBp 01Uu 1 5 10 "2105 251 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9 )..(9) "223" pPTey "4005 251

Suv bip TPE Ter sip Suv Tuk Ter Gay fight ABp 1U 1 5 10 "2105 252 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (10)..(10) "223" Ppuv-Ac "4005 252

Suv bip TPpg Ter bip Suv Tukg Ter Agd guv ABp 1U 1 5 10 "2105 253 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 253

Suv Akud TPg Ter bip Suv Tuk Ter Agd puv Roe 01U 1 5 10 "2105 254 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223 » РПе(4-ОМе) "2205 "2215 МОР БЕ5 "222" (8)..(8) "223" 2-May "2205 "2215 МОР БЕ5 "222" (9)..(9) "223" airpa-Me-Guv "4005 254 (516) Haa sip TBg Tgr beep Haa Rope Haa Puv bij ABp 1U 1 5 10

"2105 255 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221 » MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2

From "220" "221" MY VE5 "222" (9)..(9) "223" holes "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 255

Haa Avp o TPg Ter bip Haa Rpe Haa Haa Gpuv Avp Avp 1 5 10 "2105 256 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) 60 "223" Rep

"221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223" 2 - Mai "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As ) "4005 256

Haa bip TPg Tkr bi1ip Haa Rpe Haa Tetsy Guv Avp Avp 1 5 10 "2105 257 "2115 12 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6).. (6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..( 8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 60 "222" (10)..(10) ) "223" Puv(As)

"4005 257

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105 258 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" (1 )..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8).. (8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 258

Haa sip TBg Tgr bip Suv Rbe Haa Puv bij ABp 1U 1 5 10 "2105 259 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe(4-(2-aminoethoxy)) "2205 "221" MY VE5 " 222" (9)..(9) "223" airpa-Meguv 60 "4005 259

Haa beep TPg Ter beep Suv Rpe Ter Guv bij ABp 1U 1 5 10 "2105 260 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9)

Zo "223" 4-amino-4-carboxy-tetrahydropyran "4005 260

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 261 "2115 20 "2125 RVT "213" Myv5 vr. "4005 261

AvpoTer beep Rgo Tgr bek bek Rgo Rore Ua! Niv sbip TPg Bek beep sic 1 5 10 15

TpE o1u Puv Ak4d 20 "2105 262 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep. 60 "2205

"221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 262

Haa beep TPg Ter beep Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 263

From "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY ВЕ5 "222" (6)..(6) "223" Rep "2205 "221" MY ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY ВЕ5 "222" (8)

"221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 263

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 264 "2115 8 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Any amino acid "2205 "221" MY VE5 "222" (3)..(3) "223" Any amino acid "2205 "221" MY VE5 "222" ( 5)..(5) "223" Any amino acid "4005" 264

Suv Haa Haa Tgr Haa Suv Tukg Tegr 1 5 "2105" 265 "2115 4 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1).. (1) "223" airpa-Meguv "4005 265

Tuv 611 ABp 1U 1 "2105 266 "2115 4 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" airpa-Meguv "2205 "221" MY VE5 "222" (2)..2) "223" Puv(As) "4005 266

ТГув Гпув Авп Авп 1 "2105 267 "2115 4 "2125 RVT "2135 Artificial sequence "2205 "223" Artificial sequence description: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" airpa-Megetsy "2205 "221" MY VE5 "222" (2)..2) "223" Puv(As) "4005 267

ТГечп Гпув Авп Авп 1 "2105 268 "2115 4 "2125 RVT "2135 Artificial sequence "2205 "223" Artificial sequence description: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" airpa-Megetsy "4005" 268

Tets 611 ABp sh1U 1 "2105" 269 "2115 4 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" airpa-Megetsy "4005" 269

Tets 611 ABp sh1U 1 "2105 270 "2115 4 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" airpa-Meguv "4005 270

Tuv b1p AvBp Avp 1 "2105 271 "2115 6 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (5)..(5) " 223" 2-May "2205 "221" MY VE5 "222" (6)..(6) "223" airpa-Meguv "4005 271

TER beep Suv Tuk Haa Guv 1 5 "2105 272 "2115 6 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (4)..(4) 60 "223" РПе (4-ОМе)

"221" MY VE5 "222" (5)..(5) "223" May 2 "2205 "221" MY VE5 "222" (6)..(6) "223" airpa-Meguv "4005 272

TER beep Suv Ribe Haa Guv 1 5 "2105 273 "2115 6 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (4)..(4) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (5)..(5) "223" 2-May "2205 "221" MY VE5 "222" (6)..(6 ) "223" holes "4005 273

TEr beep Suv Rie Haa Haa 1 5 "2105 274 "2115 6 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (3)..(3 ) "223" Rep "220" "221" MY VE5 "222" (4)..(4) "223" РПе(4-ОМе) (516) "220" "221" MY VE5

"222" (5)..(5) "223" 2-May "2205 "2215 MOR VE5 "222" (6)..(6) "223" airpa-Meguv "4005 274

Tgr beep Haa Ribe Haa Guz 1 5 "2105 275 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) " 223" Any amino acid "2205 "221" MY VE5 "222" (3)..(3) "223" Any amino acid "2205 "221" MY VE5 "222" (5)..(5) " 223" Any amino acid "2205 "221" MY VE5 "222" (10)..(10) "223" Any amino acid "2205 "221" MY VE5 "222" (12)..(12) " 223" Any amino acid "2205 "221" MY VE5 "222" (13)..(13) "223" Any amino acid "2205 "221" MY VE5 "222" (14)..(14) " 223" 0-Guv "4005 275

Suv Haa Haa Tgr Haa Suv Tuk Tgr Niv Haa Rpe Haa Haa Gu 1 5 10 60 «2105 276 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Tuk(OMe) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" ( 9)..(9) "223" airpa-Meguv "4005 276

Haa bip TPg Ter bip Suv Tugk Haa guv bij ABp 1U 1 5 10 "2105 277 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 277

Rpe Rgo TPg Tgr bij Ter Tug Ter Suv Avp Agud Avr 1 5 10 "2105 278 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 278

A1ia gay TPg Tgr bitsh Rpe Tug Ter Iets Suv Agd s1y 1 5 10 "2105 279 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 " 222 (7). " (9)..(9) "223" airpa-Meguv "4005 279

Haa bip TPg Ter bip Haa Tug Haa guv bij ABp 1U 1 5 10 "2105" 280 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 9)..(9) "223" airpa-Meguv "4005" 280

Haa sip TBg Tgr beep Suv Rbe Ter uv bij ABp 1U 1 5 10 "2105 281 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 281

Tpuv Mee TPg Ter bip Avr Tukg Ter Gay Tu s1u Ag4d 1 5 10 "2105 282 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Me-Gguv "4005 282

Haa bip TPg Ter bip Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 283 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Rep "2205 60 "2215 MO VE5 "222" (6)..(6)

"223" Rep "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" hole "2205 "221" MY VE5 "222" (10)..(10) "223" Puv (Ac) "4005 283

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 284 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 284

A1ia Mee TBg Ter bip Avr o Tuk Ter Gets Tuk s1UuU Guv 1 5 10 "2105 285 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) 10) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 285

Haa bip TPg Tkr bi1ip Haa Rpe Haa Tetsy Guv Avp Avp 1 5 10 "2105 286 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 286

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 60 1 v; 10

"2105 287 "4005 287 oo "2105" 288 "4005" 288 oo "2105" 289 "4005" 289 oo "2105 290 "4005 290 oo "2105 291 "2115 14 "2125 RVT "2135 Artificial sequence 2 "23"2205 " Description of the artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" (1)..(1) "223" Vega-Al1a "4005 291

A1ia bek Suv Aia Avr Tgr Uai Suv Tugk Ter Niv TPg Rpe 1U 1 5 10 "2105 292 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" 0-Guv "4005 292

Tpuv bek Suv Aza Avr Ter Ua1 Suv Tuk Ter Niv TPg Roe C1Uu 1 5 10 "2105 293 "2115 14 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" V-Puv "2205 "221" MY VE5 "222" (2)..2) "223" Vega-A1a "4005 293 pu Ai1a Suv Aza Avr Ter Ua1 Suv Tuk Ter Niv TPg Roe C1Uu 1 5 10 "2105 294 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" (1 )..(1) "223" (2-aminoethoxy)acetic acid "4005 294

Zo Haa Suv Aia Avr Tgr Uai Suv Tug Ter Niv TPg Rpe 1U 1 5 10 "2105 295 "2115 13 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" 0-Guv "4005 295 ace Suv Aza Avr Ter Ua1 Suv Tug Ter Niv TbPg Rbe Sh1U 1 5 10 "2105 296 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Artificial sequence description: Synthetic peptide "4005 296

Suv Guv Avr Tgr Ua1i Suv Tukg Ter Niv TP Rpe S1U 60 1 5 10

"2105 297 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 297

Suv Aia Avr Ter Puv Suv Tug Ter Niv TPg Rpe 1U 1 5 10 "2105 298 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 298

Suv A1a Avr Tgr Ua1i Suv Tuk Ter puv TP Rpe S1U 1 5 10 "2105 299 "2115 12 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of artificial sequence: Synthetic peptide "4005 299

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv puv RpPe C1U 1 5 10 "2105 300 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 300

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TPg guv Sh1U 1 5 10 "2105 301 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 301

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Robe Avr uv 1 5 10 60 «2105 302

"2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 302

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1u Avr uv 1 5 10 "2105 303 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" Vega-Ai1a "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 303

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TPg Rpe s1iu Aia Guv 1 5 10 "2105 304 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 304

Suv A1a Avr Tgr Uaii Suv Tuk Ter Niv TPg Rire s1u Haa Gu 1 5 10 "2105 305 "2115 13 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Artificial sequence description: Synthetic peptide "4005 305

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe cS1u Guv 1 5 10 "2105 306 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Vega-Ai1a "4005 306

Aza bek Suv Aza Avr Tgr Uai Suv Tug Ter Niv TPg Roe s1Uu 1 5 10 "2105 307 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" V-Puv "4005 307

Tpuv bek Suv Aza Avr Ter Ua1 Suv Tuk Ter Niv TPg Roe C1Uu 1 5 10 "2105 308 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1)..(1) "223" 0-Guv "2205 "2215 MOR VE5 "222" (2)..2) "223" Vega-Ai1a "4005 308 (516) puv Aia Suv Aza Avr Tkgr Mai Suv Tug Ter Niv TPg Ribe s1Uu 1 5 10

"2105 309 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" (2-aminoethoxy) acetic acid «4005 309

Haa Suv Aza Avr Tgr Uai Suv Tuk Ter Niv TP Rpe C1U 1 5 10 "2105 310 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1)

Zo "223" V-Puv "4005 310 ace Suv Aza Avr Ter Ua1 Suv Tug Ter Niv TPg Roe c1U 1 5 10 "2105 311 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 311

Suv Puv Avr Ter Uai Suv Tug Ter Niv TPg Rpe 1U 1 5 10 "2105 312 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 312

Suv A1a Avr Tgr Ppuv Suv Tug Ter Niv TP Rpe S1U 1 5 10 60 «2105 313 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 313

Suv A1a Avr Tgr Ua1i Suv Tuk Ter puv TP Rpe C1U 1 5 10 "2105 314 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 314

Suv Aia Avr Ter Uai Suv Tug Ter Niv Ppuv Rpe 1U 1 5 10 "2105 315 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 315

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TPg guv Sh1U 1 5 10 "2105 316 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 12)..(12) "223" 0-Guv "4005 316

Suv A1a Avr Ter Ua1 Suv Tuk Ter Niv TPg Ribe uv 1 5 10 "2105 317 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

"222" (13)..(13) "223" 0-Guv "4005 317

Suv Aia Avr Ter Uaiii Suv Tug Ter Niv TPgE Rpe s1UuU Tuv 1 5 10 "2105 318 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (13)..(13) "223" Vega-Ai1a "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 318

Suv A1a Avr Tgr Ua1i Suv Tukg Ter Niv TPg Rpe s1iu Aia Guv 1 5 10 "2105 319 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 319

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe s1iu Haa Guv 1 5 10 "2105 320 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "4005 320

Suv A1a Avr Tgr Ua1i Suv Tuk Ter Niv TPg Rpe sS1u Guv

1 5 10 "2105 321 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" Vega- bird "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 321

Suv bip TPpg Ter bip Suv Tuk Tug Agud Uai Avp s1iu Haa Guv 1 5 10 "2105 322 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (8)..(8) "223" Vega-BPRIee (4-E) "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid " 2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 322

Suv bip TPpg Ter bip Suv Tuk Rpe Agud Uai Avp s1iu Haa Guv 1 5 10 "2105 323 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (8). .(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VEB "222" (14)..(14) "223" 0-Guv "4005 323

Suv bip TPE Ter sip Suv Tug Haa Agud Uai Ap s1u Haa Guz 1 5 10 "2105 324 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (8)..(8) "223" РПпе(3,4-С12) "2205 "221" MY ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 324

Suv bip TPpg Ter bip Suv Tuk Rpe Agud Uai Avp s1iu Haa Guv 1 5 10 "2105 325 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (8)..(8) "223" Yes

"221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" p-Guv "4005 325

Suv bip TPpg Ter bip Suv Tug Haa Agud Uai Avp s1iu Haa Guv 1 5 10 "2105 326 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (10)..(10) "223" Vega-PppPIets "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14)..(14) "223" 0-Guv "4005 326

Suv beep TPE Ter sip Suv Tug Ter Agd Gay Avp sb1u Haa Guv 1 5 10 "2105 327 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" holes "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid 60 "2205

"221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 327

Suv bip TPpg Ter bip Suv Tukg Tgr Agud Haa Avp s1iu Haa Guv 1 5 10 "2105 328 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" Vega-pA1a "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14)

From "223" V-Puv "4005 328

Suv bip TPpg Ter bip Suv Tug Tgr Agud Aia Avp s1iu Haa Guv 1 5 10 "2105 329 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (10)..(10) "223" Vega-PppPUai "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14)..(14) "223" 0-Guv "4005 329 (516) Suv bip TPE Ter sip Suv Tug Tgr Agkud UMai Avp s1u Haa Guv 1 5 10

"2105 330 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" Vega-5riga1-rir "2205 "221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY BE5 "222" (14)..(14) "223" 0 -Guv "4005 330

Suv bip TPpg Ter bip Suv Tukg Tgr Agud Haa Avp s1iu Haa Guv 1 5 10 «2105 331

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" Vega-c1y "2205 "221 » MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 331

Suv beep TPpg Ter beep Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 332 "2115 14 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of artificial sequence: Synthetic peptide "221" MY VE5 "222" (9)..(9) "223" Vega-PpPIets "2205 "221" MY VE5 "222" (13)..(13) " 223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 332

Suv bip TPpg Ter bip Suv Tuk Ter Ge Uai Avp s1iu Haa Guv 1 5 10 "2105 333 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (9)..(9) "223" Vega-Ai1r "220" "221" MY VE5 "222" (13)..(13) "223" (2) -aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 333

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Uai Avp s1iu Haa Guv 1 5 10 "2105 334 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (9)..(9) 60 "223" Vesa-pA1a

"221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 334

Suv bip TPpg Ter bip Suv Tug Tgr Aia Uai Avp s1iu Haa Guv 1 5 10 "2105 335 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" Vega-PppPUai "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 335

Suv bip TPpg Ter bip Suv Tukg Ter Uai Uai Avp s1iu Haa Guv 1 5 10 "2105 336 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (9)..(9) "223" Vega-5riga1-rir "220" "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid (516) "220" "221" MY VE5

"222" (14)..(14) "223" 0-Guv "4005 336

Suv beep TPE Ter sip Suv Tug Ter Haa Uai Ap s1u Haa Guz 1 5 10 "2105 337 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" Vega-pAgd "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 337

Suv bip TPpg Ter bip Suv Tukg Tgr Agud Uai Avp s1iu Haa Guv 1 5 10 "2105 338 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (6)..(6) "223" MesSuv "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 " (14)..(14) "223" 0-Guv "4005 338

Mee Agud TpPg Ter beep Suv Tuk Ter Agkud pub Rore s1iu Haa Gu 60 1 5 10

"2105 339 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (13)..(13) "223" (2-aminoethoxy)acetate acid "2205 "2215 MOR VEB "222" (14)..(14) "223" 0-Guv "4005 339

A1a Suv Avr Tkgr Uai Suv Tuk Tgr Agd Puv Ribe s1u Haa Guv 1 5 10 "2105 340 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 340 zek Agud TPg Tgr beep back Tug Tgr Agd Guv Rpe si1Uu Haa Guv 1 5 10 "2105 341 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (12 )..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 60 "222" (13)..(13) "223" 0-Guv

"4005 341

Suv Avr Tgr Uai Suv Tuk Ter Agd Puv Rpe siu Haa Guv 1 5 10 "2105 342 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" ( 6)..(6) "223" MesSuv "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14) ..(14) "223" 0-Guv "4005 342

Zo A1a Agud TPg Ter o bip Suv Tuk Ter Agd puv Rbe s1u Haa Guv 1 5 10 "2105 343 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 343

Aza Akud Ts Ter bip Asia Tug Tgr Agd Guv Rpe s1u Haa Guv 1 5 10 "2105" 344 "2115 13 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (9)..(9) "223" Petz "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" r-Guv "4005" 344

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Avp Haa Guv 1 5 10 "2105" 345 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9)..(9) "223" PIE "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14 )..(14) "223" 0-Guv "4005 345

Suv bip TPE Ter sip Suv Tug Ter Gets bis Avp s1u Haa Guz 1 5 10 "2105 346 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (13)..(13) «223» (2-aminoethoxy)acetic acid 60 «2205

"221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 346

Suv bek TPg Ter bii Suv Tukg Tgr Agud Ua1i Tuk s1u Haa Guv 1 5 10 "2105 347 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (2)..2) "223" Ogp "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14)

From "223" V-Puv "4005 347

Suv Haa TPg Ter bip Suv Tukg Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 "2105 348 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9)..(9) "223" Ogp "2205 "2215 MOR VE5 "222" (10)..(10) "223" Rar "2205 "2215 MOR VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 60 "2215 MO БЕ5 "222" (14)..(14)

"223" 0-Guv "4005 348

Suv bip TPpg Ter bip Suv Tukg Tgr Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105" 349 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (2)..2) "223" M-MeAvp "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005" 349

Suv Avp oTPg Ter bip Suv Tug Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 "2105 350 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (2)..2) "223" M-Meguvs "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 " 222" (14)..(14) "223" V-Puv "4005 350

Suv Guv TPg Ter beep Suv Tug Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 60 «2105 351

"2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 351

Suv Haa TPg Ter bip Suv Tukg Ter Agud Uai Rpe s1iu Haa Guv 1 5 10 "2105 352 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13) ..(13) "223" (2-aminoethoxy)acetic acid "220" "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 352

Suv beep TPpg Ter beep Suv Tukg Tug Haa Haa Rpe s1iu Haa Guv 1 5 10 "2105 353 (516) "2115 14 "2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10).. (10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14).. (14) "223" 0-Guv "4005 353

Suv bek TPg Ter bip Suv Tukg Tgr Haa Haa Tuk s1u Haa Guv 1 5 10 "2105 354 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (9)..(9) "223" sows "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13). .(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 354

Suv bek TPg Ter bij Suv Tukg Tgr Haa Haa Tuk s1u Haa Guv 60 1 5 10

"2105 355 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (9)..(9) "223" Ogp "2205 "2215 MOR VEB «222» (10). 222" (14)..(14) "223" 0-Guv "4005 355

Zo Suv bip TPE Ter sip Suv Rrbe Rbe Haa Haa Rpe cS1u Haa Guz 1 5 10 "2105 356 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 356

Suv Rkgo TPg Ter bip Suv Tug Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 "2105 357 "2115 14 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 " 222 (13).

Suv bek TPg Ter bii Suv Tukg Tgr Haa Haa Tuk s1u Haa Guv 1 5 10 "2105 358 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 МОР БЕ5 "222" (14)..(14) "223" 0-Guv "4005 358

Suv bek TPE Ter siy Suv Tug Tgr Agud Uai Ribe s1u Haa Guv 1 5 10 "2105 359 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (13)..(13) «223» (2-aminoethoxy)acetic acid 60 «2205

"221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 359

Suv Gay TPg Ter bip Suv Tukg Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 "2105 360 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (9)..(9) «223» Ogp «2205 «221» MY VE5 «222» (10). (13) 0) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 360

Suv bip TPpg Ter bip Suv Tuk Rpe Haa Haa Rpe siu Haa Guv 1 5 10 "2105 361 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0-Guv "4005 361 (516) Suv Avp o TPE Ter sip Suv Tug Tgr Akud UMai Rpe sS1u Haa Guz 1 5 10

"2105 362 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 362

Suv Haa TPg Ter bip Suv Tukg Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 «2105 363

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" M-Me-A1a "2205 " 221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv " 4005 363

Suv A1i1a TPg Ter beep Suv Tug Tgr Agud Uaii Rre s1u Haa Gu 1 5 10 "2105 364 "2115 14 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of artificial sequence: Synthetic peptide "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14).. (14) "223" 0-Guv "4005 364

Suv Guv TPg Ter bip Suv Tug Tgr Agud Uai Rpe s1iu Haa Guv 1 5 10 "2105 365 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (10)..(10) "223" Spa

From "220" "221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "220" "221" MY BE5 "222" (14)..(14) " 223" 0-Guv "4005 365

Suv bip Avr Ter bip Suv Tug Ter Agud Haa Ribe s1u Haa Gu 1 5 10 "2105 366 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" Od1 "2205 "221" MY VE5 "222" (13)..(13) 10) "223" (2-aminoethoxy)acetic acid

"221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 366

Suv bip TPpg Ter bip Suv Tug Tgr Agud Haa Rpe s1iu Haa Guv 1 5 10 "2105 367 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 " (14)..(14) "223" 0-Guv "4005 367

Suv beep TPpg Ter beep Suv Tuk Ter puv Haa Rpe s1iu Haa Guv 1 5 10 "2105 368 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (10)..(10) "223" Rar "220" "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "220" "221" MY VE5 "222" (14)..(14) "223" 0-Guv 60 "4005 368

Suv bip TPpg Ter bip Suv Tukg Ter Niv Haa Rpe s1iu Haa Gu

1 5 10 "2105" 369 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (13)..(13) "223" ( 2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 369

Suv beep TPpg Ter beep Suv Tukg Tgr Agd Gay Rpe s1iu Haa Guv 1 5 10 "2105 370 "2115 14 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" PAgd "2205 "221" MY VE5 "222" (10).. (10) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14).. (14) "223" 0-Guv "4005 370

Suv bip TPpg Ter bip Suv Tug Tgr Agud Haa Rpe s1iu Haa Guv 1 5 10 «2105 371 «2115 12 «2125 RVT

Gs10) "213" Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 371

Suv back TPE Ter si Suv Tug Ter Agd TPg Rpe 1U 1 5 10 "2105 372 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 372

Suv Avr bek Tgr bij Suv Tug Ter Agd TPg Tugk 1U 1 5 10 "2105 373 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 373

Suv back TPg Ter bii Suv Tuk Ter Niv TPg Tu Sh1U 1 5 10 "2105 374 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 374

Suv Kpuv TPg Ter TPg Suv Tukg Ter Niv TPg Tu Sh1U 1 5 10 "2105 375 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 375

Suv Akud TPg Ter bij Suv Tukg Ter Niv bij Tuk 5ekg 1 5 10 "2105 376 "2115 12 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Artificial sequence description: Synthetic peptide "4005 376

Suv Akud TPg Ter TpPg Suv Tug Ter Niv bij Tu schu 1 5 10 "2105 377 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 377

Suv Rpe TPg Ter beep Suv Tukg Ter Niv bij Tuk 5ecg 1 5 10 "2105 378 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9)

From "223" 3-Rai "4005 378

Suv bip TPpg Ter bip Suv Tug Tgr Haa bij ABp 1U 1 5 10 "2105 379 "2115 6 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 379

Suv beep TPE Ter sip Suv 1 5 "2105 380 "2115 6 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 380

Suv Agkud TPg Ter sbyp Suv 1 5 60 "2105 381 "2115 7

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 381

Suv A1a Avr Tgr Ua1i Suv Tug 1 5 "2105 382 "2115 8 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 382

Suv Aia Avr Ter Ua1i Suv Tuk Ter 1 5 "2105 383 "2115 9 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 383

Suv A1a Avr Tgr Ua1 Suv Tuk Ter Niv 1 5 "2105" 384 "2115 10 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 384

Suv A1a Avr Tgr Ua1 Suv Tuk Tegr Niv TEPg 1 5 10 "2105 385 "211511 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 385

Suv A1a Avr Tgr Ua1 Suv Tuk Ter Niv TPg Riye 1 5 10 "2105 386 (516) "2115 12 "2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "4005 386

Suv Mee TPg Ter beep Suv Tuk Ter Gay Tu c1u Ag4d 1 5 10 "2105 387 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 387

Suv Akud TPg Ter beep Suv Tug Ter Niv bi Rpe S1U 1 5 10 "2105 388 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 388

Suv Akud TPg Ter bii Suv Tukg Ter Niv TP Rpe S1U 1 5 10 "2105" 389 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 389

Suv bip TPpg Ter bip Suv Tukg Ter Niv bi Rpe C1U 1 5 10 "2105 390 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 390

Suv Akud TPE Ter sip Suv Tug Ter b1ip sbip Rpe siu s1iu sitc 1 5 10 "2105 391 "2115 14 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 391

Suv Akud Bek Tgr bip Suv Tuk Ter gay Avp Robe s1u Rgo Avr 1 5 10 "2105 392 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 392

Suv Akud TPg Ter beep Suv Tuk Ter Gay puv Mee s1u Avr 5eg 1 5 10 "2105 393 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 393

Zo Suv bip TPE Ter sip Suv Tug Tgr I1e pub5 Agd ABr sip s1Uu 1 5 10 "2105 394 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 394

Suv back TPg Ter beep Suv Tuk Ter Gets pub Niv s1u C1u s1y 1 5 10 "2105 395 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 395

Suv bek TPg Ter bij Suv Tukg Ter Bek bip Agd A1a ABr sip 1 in; 10 "2105 396 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 396

Suv bip TPE Ter siy Suv Tug Tgr Agud TPg Rpe s1u Rgo 5eg 1 5 10 "2105 397 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 397

Suv Akud TPg Ter beep Suv Tuk Tr beep bij puv b1u TBg Avr 1 5 10 "2105 398 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 398

Suv bip TPpg Ter bip Suv Tuk Ter gay Avr bBekg Gets S1u Avr 1 in; 10 "2105 399 "2115 15 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 399

Suv Akud TPg Ter beep Suv Tukg Ter TPg puv Robe siu bek bij Rgo 1 5 10 15 "2105 400 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Petz "4005 400

Suv beep TPpg Ter beep Suv Tuk Ter Gay bi Rgo Sh1U 1 5 10 60 «2105 401

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 401

Suv beep TPpg Ter beep Suv Tuk Ter Gay sbits Gets c1U 1 5 10 "2105 402 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" pPTey "4005 402

Suv beep TPpg Ter beep Suv Tuk Ter gay sbits TPg o01Uu 1 5 10 "2105 403 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "4005 403

Suv beep TPpg Ter beep Suv Tuk Ter Gay Rpe Ap s1U 1 5 10 "2105" 404 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO ВЕ5 "222" (9)..(9)

"223" pPTey "4005" 404

Suv beep TPpg Ter beep Suv Tuk Ter Gay Rgo Ap 1U 1 5 10 "2105" 405 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 405

Suv beep TPpg Ter beep Suv Tuk Ter Gay AvBp Ap s1U 1 5 10 "2105" 406 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Petz "4005" 406

Suv bip TPpg Ter bip Suv Tuk Ter Gay Gay Up 1U 1 5 10 "2105 407 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9 )..(9) "223" pPTey "4005 407

Suv beep TPE Ter sip Suv Tukg Ter Gay TPg ABp 1U 1 5 10 "2105" 408 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005" 408

Suv beep TPpg Ter beep Suv Tug TeEr Rpe bij A5Bp 1U 1 5 10 "2105" 409 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 409

Suv beep TPpg Ter beep Suv Tuk Ter Rgo bij Ap 1U 1 5 10 "2105 410 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 410

Zo Suv beep TPE Ter sip Suv Tug Ter beep bij ABp 1 5 10 "2105 411 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 411

Suv beep TPpg Ter beep Suv Tug Ter TPg bij Ap 01Uu 1 5 10 "2105 412 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 412

Suv beep TPpg Ter beep Suv Tu Tgr bij bij Ap 1U 1 5 10 "2105" 413 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" pPTey "4005" 413

Suv bip TPE Ter Rpe Suv Tug Ter tey bij ABp 1U 1 5 10 "2105" 414 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 414

Suv bip TPg Ter Rgo Suv Tuk Ter Gay bis AvBp 01Uu 1 5 10 "2105" 415 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" pPTey "4005" 415

Suv bip TPg Ter Avp o Suv Tukg Ter gay bis AvBp 01U 1 5 10 "2105" 416 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (9)..(9) "223" pPTey 60 "4005 416

Suv bip TPpg Ter Agud Suv Tukg Ter Gay bij Ap 1U

1 5 10 "2105 417 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey " 4005 417

Suv beep TPg Ter TPg Suv Tuk Ter Gay fight Ap 1U 1 5 10 "2105" 418 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 418

Suv beep TPpg Ter fight Suv Tuk Ter Gay fight Ap 1U 1 5 10 "2105" 419 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 419

Suv beep TP s1iu beep Suv Tuk Ter Gay fight ABp sh1U 1 5 10 "2105 420 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (9)..(9) "223" pPTey "4005 420

Suv bip TPg Rgo sbip Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105 421 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" pPTey "4005 421

Suv bip TPpg Avp o bip Suv Tukg Ter Gay bij Ap 1U 1 5 10 "2105 422 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (9)..(9) "223" pPTey "4005 422

Suv bip TPpg Agud bip Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105 423 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "4005 423

Suv bip TPpg TpPg o beep Suv Tuk Ter Gay bij Up 1U 1 5 10 60 "2105" 424

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 424

Suv bip TP sei bip Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105" 425 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 425

Suv beep Rpe Ter sbip Suv Tuk Ter Gay bij ABp sh1U 1 5 10 "2105 426 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "4005 426

Suv bip Rho Ter sbip Suv Tuk Ter Gay bij ABp sh1U 1 5 10 "2105 427 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO ВЕ5 "222" ( 9)..(9)

"223" pPTey "4005 427

Suv beep ABp Ter beep Suv Tukg Ter Gay bij Ap 1U 1 5 10 "2105" 428 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 428

Suv bip Agkd Ter sbip Suv Tuk Ter Gay bij AvBp 01Uu 1 5 10 "2105" 429 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Petz "4005" 429

Suv beep bij Ter sbip Suv Tuk Ter gay bis AvBp 01Uu 1 5 10 "2105 430 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ar "2205 "2215 MOB БЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 60 "2215 MO БЕ5 "222" (8). .(8)

"223" 2-May "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 430

Haa beep TPg Ter beep Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 431 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе)

From "220" "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa- MeoOgp "4005 431

Haa beep TPg Ter beep Suv Rpe Haa Haa bij Ap 1U 1 5 10 "2105 432 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) 60 "223" РПе(4-СО2Н)

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 432

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 433 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10). .(10) "223" Puv(As) "4005 433

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 v; 10 "2105" 434 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "2215 MOR WEB "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa - Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005" 434

Zo Haa sip TBg Tgr bip Suv Rpe Haa Guz pub ABp s1U 1 5 10 "2105" 435 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv 60 "2205

"221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 435

Haa bip TP Ter bi1ip Suv Rpe Haa Guv Guv ABp Aia 1 5 10 "2105 436 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8)

From "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) " 223" Tuv(As) "4005 436

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv AvBp Aia s1its 1 5 10 "2105 437 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" Ars "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" Rpe|4-(2-aminoethoxy) "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguv "4005 437

Haa beep TPg Ter beep Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 438 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar

From "220" "221" MY BE5 "222" (7)..(7) "223" Rpe(4-(2-aminoethoxy)) "220" "221" MY BE5 "222" (9)..( 9) "223" airpa-Meguv "4005 438

Haa beep TPg Ter beep Suv Rpe Ter puv bij Ap 1U 1 5 10 "2105" 439 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ary "2205 "221" MY VE5 "222" (7)..(7) 10) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005" 439

Haa beep TPg Ter beep Suv Rpe Haa uv Avr Ap 1U 1 5 10 "2105" 440 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuvivissipis asia) "4005" 440

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 441 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

222 (1). "222" (8)..(8) "223" 2-May "2205 "2215 MOR VEB "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" ( 10)..(10) "223" puv(iditsEagis asia) "4005" 441

Haa sip TBg Tgr bip Suv Rbe Haa Puv iuv ABp 1U 1 5 10 "2105" 442 "2115 12

From "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222 " (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Kuv (ipiroglutamic acid), which is conjugated through side chain 60 "4005" 442

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 443 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9)

From "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" puv(ivoua1egis asiid) "4005" 443

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 444 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Ar "2205 "2215 MOR БЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 60 "2215 MO БЕ5 "222" (8)..(8)

"223" May 2 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv (Ac) "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005" 444

Haa bip TPg Ter bi1ip Suv Rpe Haa Guv Guv Avp s1u GPuv 1 5 10 "2105" 445 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4- (2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "220" "221" MY VE5 "222" (13)..(13) "223 "(2-aminoethoxy)acetic acid 60 "4005" 445

Haa beep TPg Ter beep Suv Rpe Haa Gpuv Ppuv Avp s1iu Haa

1 5 10 "2105" 446 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223 » May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" hole "4005" 446

Haa bip TPg Ter bip Suv Rpe Haa Haa sip Avp 01U 1 5 10 "2105" 447 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" 2-May "2205 "221" MY VE5 60 "222" (9)..(9) "223" holes

"221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005" 447

Haa bip TP Ter bi1ip Suv Rpe Haa Haa Guv ABp Aia 1 5 10 "2105" 448 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" hole "4005" 448

Haa sip TBg Tgr bip Suv Ribe Haa Haa yuv ABp 1U 1 5 10 "2105" 449 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ary "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) 60 "2205

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 " 221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 449

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 450 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "4005 450

Suv Rpe TPg Ter beep Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105 451 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9 )..(9) "223" pPTey "4005 451

Suv Rgo TPE Ter sip Suv Tug Ter tei bij ABp 1U 1 5 10 "2105 452 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (9)..(9) "223" pPTey "4005 452

Suv Avp oTPg Ter beep Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105 453 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "4005 453

Suv b1u TPg Ter beep Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105 454 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9 )..(9) "223" pPTey "4005 454

Suv TPg TPE Ter sip Suv Tug Ter tei bij ABp 1U 1 5 10 "2105 455 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" pPTey "4005 455

Suv bij TPg Ter beep Suv Tuk Ter Gay bij Ap 1U 1 5 10 60 «2105 456 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" M-Megetsy "4005 456

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij AvBp 01Uu 1 5 10 "2105 457 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9 )..(9) "223" airpa-MeoOgp "4005 457

Zo Suv bip TPE Ter sip Suv Tug Tgr Haa siy AvBp 01Uu 1 5 10 "2105 458 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp "4005 458

Suv beep TPpg Ter beep Suv Tug Tgr Haa bij ABp 1U 1 5 10 "2105" 459 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 " 222" (7)..(7) "223" airpa-MeRre

"221" MY VE5 "222" (9)..(9) "223" Petz "4005 459

Suv bip TPpg Ter bip Suv Rpe Tgr Gay bij Ap 1U 1 5 10 "2105" 460 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 9)..(9) "223" holes "4005" 460

Suv bip TPE Ter sip Suv Tug Ter Haa bij ABp 1U 1 5 10 "2105" 461 "2115 12

From "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (7)..(7) "223" PTUYE "2205 "221" MY VE5 "222 " (9)..(9) "223" pPTey "4005" 461

Suv beep TPpg Ter beep Suv Tuk Ter Gay fight Ap 1U 1 5 10 "2105" 462 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 " 222" (7)..(7) "223" Ver

"221" MY VE5 "222" (9)..(9) "223" Petz "4005" 462

Suv bip TPpg Ter sbip Suv Haa Tgr gay sbits AvBp 01Uu 1 5 10 "2105 463 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9 )..(9) "223" Unit 1 "4005" 463

Suv bip TPE Ter sip Suv Tug Tgr Haa siy ABp 1U 1 5 10 "2105" 464 "2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "2205 "221" MY VE5 "222 » (10)..(10) «223» Puv(As) «4005» 464

Suv beep TPpg Ter beep Suv Tuk Ter Gay guv ABp 1U 1 5 10 "2105" 465 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 " 222" (9)..(9) "223" pPTey

"4005" 465

Suv bip TPpg Ter bip Suv Tukg Ter gay bij Avp s1u s1U 1 5 10 "2105" 466 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" (9)..(9) "223" pPTey "4005" 466

Suv bip TPE Ter sbip Suv Tug Ter tey bij AvBp s1Uu Rkgo 1 5 10 "2105 467 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 467

Suv beep TPg Ter beep Suv Tuk Ter Gay bij AvBp s1u s1its 1 5 10 "2105" 468 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (9).

Suv bip TPg Ter bip Suv Tuk Ter Gay bij AvBp s1u s1its 60 1 v; 10

"2105" 469 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (8)..(8) "223" airpa-MeRre "2205 "2215 MOR WEB "222" (9)..(9) "223" pPTey "4005" 469

Suv bip TPE Ter sip Suv Tuk Rbe Tetsy bij ABp s01U 1 5 10 "2105 470 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" pPTey "4005 470

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Avp s1u Rgo 1 5 10 "2105 471 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 471

Suv beep TPpg Ter beep Suv Tukg Ter gay bij Avp s1u s1U 1 5 10 "2105 472 "2115 13 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (9)..(9) "223" pPTey "4005 472

Suv bip TPE Ter sbip Suv Tuk Ter Gay bi Avp s1Uu Гиеч 1 5 10 "2105 473 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 473

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Avp s1u Re 1 5 10 "2105 474 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (9)..(9) "223" pPTey "4005 474

Suv beep TPg Ter beep Suv Tuk Ter Gay bij AvBp s1u s1its 1 5 10 "2105 475 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (9)..(9) "223" pPTey 60 "4005 475

Suv bip TPg Ter beep Suv Tuk Ter Gay bij Avp s1u Avp

1 5 10 "2105 476 "2115 13 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey " 4005 476

Suv beep TPg Ter beep Suv Tuk Ter Gay bij AvBp s1u TEG 1 5 10 "2105 477 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 477

Suv bip TPpg Ter bip Suv Tuk Ter Gets b1its ABp b1u Ag4d 1 5 10 "2105 478 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" pPTey "4005 478

Rkgo Suv beep TPg Tegr beep Suv Tug Ter Te 611 ABp sh1U 1 5 10 "2105" 479 "2115 13 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (10)..(10) "223" pPTey "4005 479

Te Suv bip TPg Ter bip Suv Tugye Ter gay siy AvBp 01U 1 5 10 "2105" 480 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (10)..(10) «223» pPTey «4005» 480

Rpe Suv bip TPg Tegr bi1ip Suv Tug Ter Te 611 ABp sh1U 1 5 10 "2105 481 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

З5 "220" "221" MY VE5 "222" (10)..(10) "223" pPTey "4005 481 bi Suv bip TPg Ter bip Suv Tugye Ter gay siy AvBp 01U 1 5 10 "2105" 482 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" Petz "4005" 482

Avp osuv bip TBPg Tesr bip Suv Tuk Ter Te 611 ABp sh1U 1 5 10 60 "2105 483

"2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (10)..(10) "223" pPTey "4005" 483

Akud Suv bip TBg Tesr bip Suv Tuk Ter Te 611 ABp sh1U 1 5 10 "2105" 484 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (8)..(8) "223" May 2

From "220" "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 484

Suv beep TPpg Ter beep Suv Tuk Haa gay bij Ap 01Uu 1 5 10 "2105" 485 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (9)..(9) "223" Petz "4005" 485

Suv beep TPpg Ter beep Suv Tuk Haa gay fight Ap 1U 1 5 10 60 "2105" 486

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (7)..(7) "223" May 2 "2205 "221 » MY VE5 "222" (9)..(9) "223" pPTey "4005" 486

Suv bip TPpg Ter sbip Suv Haa Tgr gay bij Ap 1U 1 5 10 "2105" 487 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (7)..(7) "223" 1-May "220" "221" MY VE5 "222" (8)..(8) "223" 2- May "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 487

Suv beep TPpg Ter sbip Suv Haa Haa ey bij Ap 1U 1 5 10 "2105" 488 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (7)..(7) (516) "223" May 2

"221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 488

Suv beep TPpg Ter sbip Suv Haa Haa ey bij Ap 1U 1 5 10 "2105" 489 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (7)..(7) "223" Ais "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 489

Suv bip TPpg Ter sbip Suv Haa Tgr gay bij Ap 1U 1 5 10 "2105" 490 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 490

Suv beep TPpg Ter beep Suv Niv Tgr Hey fight Ap 1U 1 5 10 "2105 491 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (9)..(9) "223" pPTey "4005 491

Suv beep TPpg Ter beep Suv Tuk Niv Gay bij Ap 1U 1 5 10 "2105 492 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 7)..(7) "223" Tuk (OMe) "2205 "221" MY VE5 "222" (9)..(9) "223" pPTeiy "4005 492

Suv beep TPpg Ter beep Suv Tuk Ter gay bis AvBp 01Uu 1 5 10 "2105 493 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (8)..(8) "223" Vir "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 493

Suv beep TPpg Ter beep Suv Tuk Haa gay fight Ap 1U 1 5 10 "2105" 494 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (8)..(8) "223" Tuk (OMe) "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 494

Suv beep TPpg Ter beep Suv Tuk Tuk Gay fight ABp sh1U 1 5 10 "2105" 495 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 495

Suv beep TPg Ter beep Suv Niv Niv Gay bij Ap 1U 1 5 10 "2105" 496 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (8)..(8) "223" airpa-MetTgr "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 496

Suv beep TPpg Ter beep Suv Tuk Ter geish bi beep Sh1U 1 5 10 "2105 497 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (5)..(5) "223" KTuv(RESV) "4005 497

Suv bip TPg Ter Ppuv Suv Tuk Ter Gay bij AvBp 01U 1 5 10 "2105" 498 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Any amino acid "4005" 498

Suv bip TPpg Ter bip Suv Tukg Ter Haa gay Ap 1U 1 5 10 "2105" 499 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (5)..(5) "223" KTuv(RESV) "2205 "221" MY VE5 "222" (9)..(9) "223" KTuv(RESV) "4005" 499

Suv bip TPg Ter Ppuv Suv Tuk Ter guv bij ABp 1U 1 5 10 "2105 500 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 5)..(5) 10) "223" Ppuv (Raiyut)

"4005 500

Suv beep TPg Ter Ppuv Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105 501 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(Rait) "4005 501

Suv bip TPpg Ter bip Suv Tuk Ter Haa guv ABp 1U 1 5 10 "2105 502 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 (2). )..(4) "223" P-Getsy "220" "221" MY VE5 "222" (5)..(5) "223" 0-Tegr "220" "221" MY VE5 "222" (6 )..(6) "223" 0-Tukg (516) "220" "221" MY VE5

222 (7). 9)..(9) "223" 0-Tegr "2205 "2215 MOR WEB "222" (10)..(10) "223" 0-TV g "2205 "2215 MOR VE5 "222" (11). .(11) "223" r-s1p "2205 "2215 MOR VE5 "222" (12)..(12) "223" 0-Suv "4005 502

Зо с1у АвБп биц Gay Ter Tug Suv bip Ter TPg sip Suv 1 5 10 "2105 503 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" OGP "2205 "221" MY VE5 "222" (10)..(10) "223" KTuv(RESV) "4005 503

Suv bip TPpg Ter bip Suv Tuk Ter Haa pub AkBp b01U 1 5 10 "2105 504 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"4005 504

Suv Akud TPg Ter beep Suv Tug Ter Niv bi Rpe S1U 1 5 10 "2105 505 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 505

Suv Akud TPE Ter sy Suv Tug Ter Niv TPg Rpe 1U 1 5 10 "2105 506 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 506

Suv bip TPpg Ter bip Suv Tukg Ter Niv bi Rpe C1U 1 5 10 "2105 507 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 507

Suv bip TPpg Ter bip Suv Tukg Tgr Agd Avp Robe s1u Avr 5eg 1 5 10 "2105 508 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 508

Suv beep TPpg Ter beep Suv Tukg Tgr Agd Avp Rbe sitz beg s1Uu 1 5 10 "2105 509 "2115 14 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"4005 509

Suv bip Avr Tgr bip Suv Tug Tgr Agd bis Robe cS1u Rgo c1Uu 1 5 10 "2105 510 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 510

Suv beep Avr Tgr beep Suv Tug Tgr Agud Bek Robe s1u Rgo sip 1 5 10 "2105 511 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 511

Suv beep TPpg Ter beep Suv Tug Tgr Agud TPg Gets s1u Rgo 5eg 1 5 10 "2105 512

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" P-Pgo "4005 512

Suv beep TPpg Ter beep Suv Tuk Ter Rgo bij Ap 1U 1 5 10 "2105 513 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 513

Suv beep TPE Ter sip Suv Tug Tkr bij Gay ABp s1U 1 5 10 "2105 514 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 514

Suv bip TPpg Ter bij Suv Tuk TgEr bij Gay Ap 1U 1 5 10 "2105 515 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 8)..(8) "223" 1-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megeits "4005 515

Suv bip TPpg Ter bip Suv Tuk Haa gay bij Ap 1U 1 5 10 "2105 516 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (8 )..(8) "223" May 1 "2205 "2215 MOR VE5 "222" (9)..(9) "223" 0-Avp "4005 516

Suv bip TPE Ter sip Suv Tug Haa ABp bij ABp s1U 1 5 10 "2105 517 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (11)..(11) "223" Ppuv(Rait) "4005 517

Suv bip TPpg Ter bip Suv Tuk Ter Gay bij guv Sh1U 1 5 10 "2105 518 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 12)..(12) "223" puv(Rai1t) "4005 518

Suv beep TPpg Ter beep Suv Tuk Ter gay bij Avp Guv 1 5 10 "2105 519 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 519

Suv bek TPE Ter siy Suv Tug Ter Agd TPg Rpe 1U 1 5 10 "2105 520 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 520

Suv Avr bek Tgr bij Suv Tug Tgr Agd TPg Tu Sh1U 1 5 10 "2105 521 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 521

Suv bek TPg Ter bij Suv Tuk Ter Niv TPg Tu Sh1U 60 1 in; 10

"2105 522 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (1)..(1) "223" Rep "2205 "2215 MOR VEB "222" (6)..(6) "223" Rep "2205 "2215 МОР БЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 МОР БЕ5 "222 " (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 522

Haa sip TBg Tgr beep Haa Rope Haa Puv bij ABp 1U 1 5 10 "2105 523 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) 60 "2205

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 523

Haa beep TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 524 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Me-Iey "4005 524

Haa bip TPg Tkgr bi1ip Haa Rpe Haa yeetsy bi1ip Avp Avp 1 5 10 "2105 525 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" ( 1)..(1)

"223" Rep "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-( 2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa -Me-Ieiy «4005 525

Haa bip TPg Tkgr bi1ip Haa Rpe Haa yeetsy bi1ip Avp Avp 1 5 10 "2105 526 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 " (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7).. (7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8) "223" 2-May "220" "221" MY VE5 "222 » (9)..(9) "223" holes (516) "220" "221" MY VE5

"222" (10)..(10) "223" Puv(As) "4005 526

Haa sip TBPg Tgr bip Haa Ribe Haa Haa Guv Ap sip 1 5 10 "2105 527 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Artificial sequence description: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 527

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv ABp sip 1 5 10 "2105 528 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222 » (1)..(1) "223" Rep

"221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 " 221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "2205 "221" MY VE5 "222" (13)..(13)

From "223" V-Puv "4005 528

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Gpuv Avp Avp Guv 1 5 10 "2105 529 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) " 223" Rpe|4-(2-acetylaminoethoxy) "2205 60 "2215 MO БЕ5 "222" (8)..(8)

"223" 2-May "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "2205 "221" MY VE5 "222" (10)..(10) "223" Puv (Ac) "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 529

Haa bip TPg Ter bi1ip Haa Rpe Haa Uai Gpuv Avp Avp Guv 1 5 10 "2105 530 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 " 221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2- My "220" "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "4005 530

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Guv Avp Avp 1 5 10 "2105 531 (516) "2115 12 "2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6).. (6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8) ..(8) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 531

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105 532 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 60 "222" (8)..(8) "223" 2-May

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 532

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105 533 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" (1 )..(1) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (2)..2) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) " 223" Rep "2205 "2215 МОР БЕ5 "222" (8)..(8) "223" РПе(4-СОМН2) "2205 "2215 МОР БЕ5 "222" (9)..(9) "223" 2 -Mai "2205 "2215 MOR VE5 "222" (10)..(10) "223" airpa-MeUai "2205 "2215 MOR VE5 "222" (11)..(11) "223" Puv(As) " 4005 533 (516) puv Haa bip TPg Ter sbip Haa Robe Haa Uai Gpuv Avp Avp 1 5 10

"2105 534 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221 » MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2

From "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "220" "221" MY VE5 "222" (10)..(10) "223" Puv( Ac) "4005 534

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105 535 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) 60 "223" Rep

"221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May " 2205 "221" MY VE5 "222" (9)..(9) "223" holes "4005 535

Haa Avp o TPg Ter bip Haa Rpe Haa Haa GPubv Avp Avp 1 5 10 "2105 536 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9).. (9) "223" 4-amino-4-carboxy-tetrahydropyran "4005 536

Haa Avp o TPg Ter bip Haa Rpe Haa Haa GPubv Avp Avp 1 in; 10 "2105 537 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Rep "2205 "2215 MOR VEB "222" (6)..(6) "223" Rep "2205 "2215 MOR WEB "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "2215 MOR ВЕ5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" Asps "4005 537

Zo Haa Avp TPg Tgr beep Haa Ripe Haa Haa Guz ABp Avp 1 5 10 "2105 538 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May 60 "2205

"221" MY VE5 "222" (9)..(9) "223" Asus "4005 538

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 539 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9).. (9) "223" airpa-Megeits "4005 539

Haa Avp o TPg Ter bip Haa Rpe Haa Tetsy Guv Avp Avp 1 5 10 "2105 540 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Rep "2205 60 "2215 MO VE5 "222" (6)..(6)

"223" Rep. "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" A156 "4005 540

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 c) 10 "2105 541 "2115 12 "212" RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221 » MY VE5 "222" (9)..(9) "223" 4-amino-4-carboxy-tetrahydropyran "4005 541

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 542 bo "2115 12 "212" RET

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6).. (6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..( 8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Asps "4005 542

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 543 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" РПе(4-ОМе) "2205 "221" MY VE5 60 "222" (8)..(8) "223" May 2

"221" MY VE5 "222" (9)..(9) "223" Asus "4005 543

Haa Avp o TPg Ter bip Haa Rpe Haa Haa Gpuv Avp Avp 1 5 10 "2105 544 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" ( 1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) " 223" РПе(4-ОМе) "2205 "2215 МОР БЕ5 "222" (8)..(8) "223" 2-May "2205 "2215 МОР БЕ5 "222" (9)..(9) "223 "airpa-Megetsy" 4005 544

Haa Avp TPg Tgr beep Haa Ripe Haa Gay Guv ABp o Avp 1 5 10 "2105 545 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep. 60 "2205

"221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 545

Haa beep TPg Ter beep Haa Rpe Haa Ppuv Gpuv Avp Avp 1 5 10 «2105 546

From "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)

"221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 546

Haa bip TPg Ter bi1ip Haa Rpe Haa Gpuv Ppuv Avp Avp 1 5 10 "2105 547 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (13)..(13 ) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 547

Haa Akd TPg Ter bip Haa Tug Ter Agd Ppuv Rpe siu Haa Guv 1 5 10 "2105 548 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (2)..2) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep (516) "220" "221" MY VE5

222 (13).

A1a Haa Avr Tkgr Uaii Haa Tuk Tgr Agd Puv Ribe s1u Haa Guv 1 5 10 "2105" 549 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9). .(9) "223" pPTey "4005 549

Haa beep TPg Ter beep Haa Tug Ter Gay bij Ap 1U 1 5 10 "2105 550 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 60 "222" (9)..( 9) "223" M-MeAgd

"4005 550

Haa bip TPg Ter bip Haa Tug Tgr Agd bij ABp 1U 1 5 10 "2105 551 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (9)..(9) "223 » pPTey «4005 551

Zo Haa sip TBg Tgr bip Haa Tug Ter tey bij ABp 1U 1 5 10 "2105 552 "2115 12

C5 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222 " (6)..(6) "223" Rep. "2205 "221" MY VE5 "222" (9)..(9) "223" M-MeAgd "4005 552

Haa beep TPg Ter beep Haa Tug Tgr Agd bij ABp 1U 1 5 10 60 «2105 553 «2115 14

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" ( 6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10)..(10 ) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) 0) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14).. (14) "223" V-Puv "4005 553

A1ia Haa Avr Tgr Uai! Haa Tug Ter Haa Haa Rpe s1Uu Haa Guv 1 5 10 "2105 554 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1).. (1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 60 "2215 MO VE5 "222" (9)..(9)

"223" airpa-Megetsy "4005 554

Haa beep TPg Ter beep Haa Tug Ter Gay bij Ap 1U 1 5 10 "2105 555 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9 ) "223" 0-Avp "4005 555

Haa bip TPg Ter bip Haa Tug Tgr ABp bij Ap 1U 1 5 10 "2105 556 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (8)..(8 ) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) (516) "223" airpa-Meguvs

"4005 556

Haa beep TPg Ter beep Haa Tug Haa guv bij ABp 1U 1 5 10 "2105 557 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguv "4005 557

Haa beep TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 558 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep (516) "220" "221" MY VE5

"222" (7)..(7) "223" May 2 "2205 "2215 MOR VE5 "222" (8)..(8) "223" May 2 "2205 "2215 MOR VEB "222" ( 9)..(9) "223" airpa-Meguv "4005 558

Haa sip TBg Tgr beep Haa Haa Haa Puv bij ABp 1U 1 5 10 "2105 559 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (8)..(8 ) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp "4005 559

Haa beep TPg Ter beep Haa Tug Haa Haa bij Ap 1U 1 5 10 "2105 560 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222 » (1)..(1) "223" Rep

"221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meogp "4005 560

Haa bip TPg Ter bip Haa Tug Ter Haa siy AvBp 01U 1 5 10 "2105 561 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (8)..(8) "223 » May 1 "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-MeoOgp "4005 561

Haa sip TBg Tgr beep Haa Tug Haa Haa bij ABp 1U 1 5 10 "2105 562 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep. 60 "2205

"221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 562

Haa beep TPg Ter beep Haa Rpe Haa Haa uv Ap 1U 1 5 10 «2105 563

From "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 563

Haa beep TPg Ter beep Haa Tug Tgr puv puv ABp 1U 1 5 10 60 «2105 564

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" RIe- (4-OMe) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 564

Haa bip TPg Ter bip Haa Rpe Ter Gpuv Ppuv ABp 1U 1 5 10 "2105 565 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7).. (7) "223" РПе(4-ОМе) (516) "220" "221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR WEB "222" ( 10)..(10) "223" Puv(As) "4005 565

Haa sip TBg Tgr bip Haa Rpe Haa Puv yuv ABp 1U 1 5 10 "2105 566 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 1-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 566

Haa beep TPg Ter beep Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 60 «2105 567 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Faith "2205 "221" MY VE5 "222" (8)..( 8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9)

From "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 567

Haa bip TPg Ter bip Haa Haa Haa Gpuv Gpuv ABp 1U 1 5 10 "2105 568 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" РПпе(3,4-С12) "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9 ) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 568

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 569 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Rep

C5 "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(3,5 -E2) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa - Meguv "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "4005 569

Haa beep TPg Ter beep Haa Rpe Haa Gpuv Ppuv ABp 1U

1 5 10 "2105 570 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep " 2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-МН2) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 570

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 571 "211511 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 60 "222" (6)..(6) "223" Rep

"221" MY VE5 "222" (7)..(7) "223" May 2 "2205 "221" MY VE5 "222" (8)..(8) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (9)..(9) "223" Tuv(As) "4005 571

Haa bip TPg Tkgr bi1ip Haa Haa yuv uv ABp 1U 1 5 10 "2105 572 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1) ..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" РПпе(3,4-С12) "2205 "2215 МОР БЕ5 "222" (8)..(8) "223" 2-May "2205 "2215 МОР БЕ5 "222" (9)..(9) "223 "airpa-MeoOgp" 4005 572

Haa sip TBg Tgr beep Haa Rope Haa Haa siy ABp 1U 1 5 10 "2105 573 "2115 12 60 "2125 RET "2135 Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СМ) "2205 "221" MY VE5 "222" (8)..(8) " 223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp "4005 573

Haa bip TPg Ter bip Haa Rpe Haa Haa bij Ap 1U 1 5 10 "2105 574 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(3,5-Е2) "2205 "221" MY VE5 "222" (8)..(8) (516) "223" 2-May

"221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp "4005 574

Haa bip TPg Ter bip Haa Rpe Haa Haa siy AvBp 01U 1 5 10 "2105 575 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-СН2СО2Н) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-MeoOgp "4005 575

Haa beep TPg Ter beep Haa Rpe Haa Haa bij Ap 1U 1 5 10 "2105 576 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 » (1)..(1) "223" Rap (516) "220" "221" MY VE5

222 (6). (8)..(8) "223" 2-May "2205 "2215 MOR VEB "222" (9)..(9) "223" airpa-MeoOgp "4005 576

Haa sip TBg Tgr bip Haa Rope Haa Haa siy ABp 1U 1 5 10 "2105 577 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(repsa-E) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-MeoOgp "4005 577

Haa beep TPg Ter beep Haa Rpe Haa Haa bij Ap 1U 1 5 10 60 «2105 578 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-SEZ) "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9)

From "223" Airpa-Meguvs "4005 578

Haa bip TPg Ter bip Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 579 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223 » Rpe|4-(2-aminoethoxy) "2205 60 "2215 MO ВЕ5 "222" (8)..(8)

"223" 2-May "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 579

Haa beep TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 580 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep

From "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8 ) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 580

Haa beep TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 581 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) 60 "223" Rep

"221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 " 221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuvyuraye) "4005 581

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 582 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 60 "222" (9). .(9) "223" airpa-Meguv

"221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 582

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 583 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223 » РПе(4-ОМе) "2205 "2215 МОР БЕ5 "222" (8)..(8) "223" 2-May "2205 "2215 МОР БЕ5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 583

Haa sip TBg Tgr bip Haa Rpe Haa Puv yuv ABp 1U 1 5 10 "2105 584 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7) VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 584

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 585 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rukobits "2205 "221" MY VE5 "222" (2)..2) "223" Rap "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) 60 "223" РПе(4-ОМе)

"221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (11)..(11) "223" Puv(As) "4005 585 bi Haa sbip TPg Ter bip Haa Rpe Haa Gpuv pub AvBp b1U 1 5 10 "2105 586 "2115 12 "2125 RVT " 2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6). .(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8).. (8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) ) "223" Puv(As) "4005 586

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 60 1 v; 10

"2105 587 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (1)..(1) "223" Rep "2205 "2215 MOR VEB "222" (6)..(6) "223" Rep "2205 "2215 МОР БЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 МОР БЕ5 "222 " (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10) ..(10) "223" Puv(As) "4005 587

Haa sip TBg Tgr bip Haa Rpe Haa Puv yuv ABp 1U 1 5 10 "2105 588 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep 60 "2205

"221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "220" "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) " 4005 588

Haa bip TPg Ter bip Haa Rpe Haa Guz Ppuv AvBp b01U 1 5 10 "2105 589 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) 10) "223" Ppuv(As) to

"4005 589

Haa bip TPg Ter bip Haa Rpe Haa Gpuv pub AvBp b1U 1 5 10 "2105 590 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 590

Haa bip TPg Ter bip Haa Rpe Haa puv puv ABp 1U 1 5 10 "2105 591 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 » (1)..(1) "223" Rap (516) "220" "221" MY VE5

"222" (6)..(6) "223" Rep. "4005 591

Haa Aza Avr Tgr Mai Haa Tug Ter Niv TPg Rpoe o1U 1 5 10 "2105 592 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguv "4005 592

Haa siu TPg Ter bip Haa Rpe Haa uv biy Ap 1U 1 5 10 "2105 593 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 60 "222" (6)..(6) "223" Rep

"221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223" 2 - Mai "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 593

Haa TPg TP Ter bip Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 594 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223 » Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 594

Haa bek TPg Tgr beep Haa Rpe Haa Guz bij ABp 1U 1 5 10 "2105 595 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (2)..2) " 223" Rar "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4- (2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May

From "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 595

Haa Haa TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 596 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (2)..2) "223" airpa-MeoOgp "2205 "221" MY VE5 "222" (6)..( 6) 60 "223" Rep

"221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223" 2 - Mai "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 596

Haa Haa TPg Ter beep Haa Rpe Haa uv biy Ap 1U 1 5 10 "2105 597 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguv "4005 597

Haa Avp o TPg Ter bip Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 598 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Rep "2205 "2215 MOR VEB "222" (6)..(6) "223" Rep "2205 "2215 MOR VEB "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" May 2 "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 598

Haa sip TBg Tgr bip Haa Rpe Haa Puv yuv ABp 1U 1 5 10 "2105 599 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) 60 "2205

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 " 221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 599

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105 600 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguvs "4005 600

Haa beep TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 601 "2115 12 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Artificial sequence description: Synthetic peptide "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) " 223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 601

Haa bip TPg Tkr bi1ip Haa Rpe Haa Guv bij ABp Aia 1 5 10 "2105 602 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7).. (7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8) "223" 2-May (516) "220" "221" MY VE5

"222" (9)..(9) "223" airpa-Megetsy "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 602

Haa sip TBPg Tgr bip Haa Robbe Haa Gay Guv ABp o Avp 1 5 10 "2105 603 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9 )..(9) "223" airpa-Megetsy "4005 603

Haa bip TPg Tkgr bi1ip Haa Rpe Haa yeetsy bi1ip Avp Avp 1 5 10 "2105" 604 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 " 222" (1)..(1) "223" Rep

"221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes "4005" 604

Haa bip TPg Tkgr bi1ip Haa Rpe Haa Haa b1y Avp Avp 1 5 10 "2105" 605 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) " 223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR БЕ5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR БЕ5 "222" (9)..(9 ) "223" hole "2205 60 "2215 MO VE5 "222" (10)..(10)

"223" Puv(As) "4005 605

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 606 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy)

From "220" "221" MY VE5 "222" (8)..(8) "223" 2-May "220" "221" MY VE5 "222" (9)..(9) "223" holes " 2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 606

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv ABp sip 1 5 10 "2105 607 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) 60 "223" Rep

"221" MY VE5 "2225 (2)..12) "223" Rar(Ac) "2205 "221" MY VE5 "222" (6)..(6) "223" Rap "2205 "221" MY VE5 "2225 (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221 » MY VE5 "222" (9)..9) "223" airpa-Meguv (As) "4005 607

Haa Haa TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 608 "2115 12 "2125 RET "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (2)..2) "223" ainirpa-MeoOgp(As) "2205 "221" MY VE5 "222" (6 )..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 60 "222 » (8)..(8) "223" May 2

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguvzv (As) "4005" 6О08

Haa Haa TPg Ter beep Haa Rpe Haa uv biy Ap 1U 1 5 10 "2105" 609 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) " 223" Rpe|4-(2-acetylaminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9 ) "223" airpa-Meguv (As) "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005" 609

Haa sip TBg Tgr bip Haa Rpe Haa Puv iuv ABp 1U 1 5 10 "2105 610 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "2225 (1)..11) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "2225 (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..9) "223" airpa-Meguv (As) "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 610

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105 611 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "2225 (1 )..11) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "2225 (7)..(7) "223 » Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) (516) "223" 2-May

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguv (As) "4005 611

Haa beep TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 612 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguv (As) "4005 612

Haa bip TPg Tkr bi1ip Haa Rpe Haa Guv bij ABp Aia 1 5 10 "2105 613 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 » (1)..(1) "223" Rap (516) "220" "221" MY VE5

222 (6). "222" (8)..(8) "223" 2-May "2205 "2215 MOR VEB "222" (9)..(9) "223" airpa-Megetsy "2205 "2215 MOR VE5 "222" ( 10)..(10) "223" Puv(As) "4005 613

Haa sip TBPg Tgr beep Haa Robbe Haa Gay Guv ABp o Avp 1 5 10 «2105 614 «2115 12

From "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222 " (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy 60 "4005 614

Haa bip TPg Tkgr bi1ip Haa Rpe Haa yeetsy bi1ip Avp Avp 1 5 10 "2105 615 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8)

From "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Air "4005 615

Haa bip TPg Tkgr bi1ip Haa Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 616 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" Rpe|4-(2-acetylaminoethoxy) "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 616

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 617 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 " 221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2- My "220" "221" MY VE5 "222" (9)..(9) "223" holes "220" "221" MY VE5 "222" (10)..(10) "223" Puv(Ac) 60 "4005 617

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv ABp sip

1 5 10 "2105" 618 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) " 2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" holes "4005 618

Haa bip TPg Tkgr bi1ip Haa Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 619 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 60 "222" (7)..( 7) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Petz "4005 619

Haa bip TPg Tkgr bi1ip Haa Rpe Haa yeetsy bij ABp Aia 1 5 10 "2105 620 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223 » Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" hole "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 620

Haa TPg TPg Ter beep Haa Ribe Haa Haa Guz ABp Avp 1 5 10 "2105 621 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) " 223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes

From "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 621

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv ABp Aia 1 5 10 "2105 622 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) 10) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 622

Haa TPg TPg Ter bi1ip Haa Rpe Haa Haa Guv ABp sip 1 5 10 "2105 623 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 623

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv ABp sip 60 1 in; 10

"2105 624 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (1)..(1) "223" Rep "2205 "2215 MOR VEB "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" holes "2205 "2215 MOR VE5 "222" (10 )..(10) "223" Puv(As) "4005 624

Haa sip TBg Tgr bip Haa Ribe Haa Haa Guz ABp Aia 1 5 10 "2105 625 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep 60 "2205

"221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "220" "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" hole "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 625

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 626 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" Petz "2205 "221" MY VE5 "222" (10)..(10) 10) "223" Ppuv(Ac)

"221" MY VE5 "222" (12)..(12) "223" Vega-Ai1a "4005 626

Haa bip TPg Tkr bi1ip Haa Rpe Haa Iyetsy Guv ABp Aia 1 5 10 "2105 627 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" pPTey "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "2205 "221" MY VE5 "222" (12)..(12) " 223" Vega-Ai1a "4005 627

Haa bip TPg Tkr bi1ip Haa Rpe Haa Iyetsy Guv ABp Aia 1 5 10 "2105 628 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Rep "2205 "2215 MOR VEB "222" (6)..(6) "223" Rep "2205 "2215 MOR VEB "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" May 2 "2205 "2215 MOR VE5 "222" (9)..(9) "223" hole "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "2205 "2215 MOR VE5 "222" (12)..(12) "223" Vega-Ai1a "4005 628

Haa sip TBg Tgr bip Haa Ribe Haa Haa Guz ABp Aia 1 5 10 "2105 629 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep 60 "2205

"221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "220" "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "2205 " 221" MY VE5 "222" (12)..(12) "223" Vega-Ai1a "4005 629

Haa bip TPg Tkr bi1ip Haa Rpe Haa Haa Guv Avp Ai1a 1 5 10 "2105 630

From "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY ВЕ5 "222" (6)..(6) "223" Rep "2205 "221" MY ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY ВЕ5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) (516) "223" Air

"4005 630

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 631 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9 )..(9) "223" pPTey "4005 631

Haa Avp o TPg Ter bi1ip Haa Rpe Haa yeetsy bij ABp Aia 1 5 10 "2105 632 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 » (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep (516) "220" "221" MY VE5

222 (7). MOR WEB "222" (9)..(9) "223" hole "2205 "2215 MOR WEB "222" (10)..(10) "223" Puv(As) "4005 632

Haa Avp TPg Tgr bip Haa Ripe Haa Haa Guz ABp Avp 1 5 10 "2105 633 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "2205

"221" MY VE5 "222" (12)..(12) "223" Vega-Ai1a "4005 633

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa uv Avp Aa 1 5 10 "2105" 634 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7).. (7) 0) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222 " (9)..(9) "223" hole "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 634

Haa Avp o TPg Ter beep Haa Rpe Haa Haa pub Avp o beep 1 5 10 "2105 635 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222 » (1)..(1)

"223" Rep "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе ) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 " 221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 635

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv ABp Aia 1 5 10 "2105 636 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7). .(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8) "223" 2-May (516) "220" "221" MY VE5

"222" (9)..(9) "223" hole "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 636

Haa Avp TPg Tgr bip Haa Ribe Haa Haa Guz ABp Aia 1 5 10 "2105 637 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" hole "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 637

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 638 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 " 222 (7). "222" (9)..(9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) 0) "223" Ppuv(As) "4005" 638

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv ABp sip 1 5 10 "2105" 639 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 60 "2215 MO ВЕ5 "222" (8)..(8)

"223" 2-May "221" MY VE5 "222" (9)..(9) "223" hole "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As ) "2205 "221" MY VE5 "222" (12)..(12) "223" Vega-Ai1a "4005" 639

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv ABp Aia 1 5 10 "2105" 640 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 " 221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "220 » "221" MY VE5 "222" (9)..(9) "223" pPTey "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) (516) "220" "221" MY VE5

"222" (12)..(12) "223" Vega-Ai1a "4005" 640

Haa Avp TPg Tgr bip Haa Ribe Haa Iiep Guv ABp Aia 1 5 10 "2105" 641 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9 )..(9) "223" pPTey "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "2205 "221" MY VE5 "222" (12).. (12) "223" Vega-Ai1a "4005" 641

Haa Avp o TPg Ter bip Haa Rpe Haa Gay Gpuv Avp Aia 1 5 10 "2105 642 "2115 13 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222 " (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" hole "2205 "221" MY VE5 "222" (11)..(11) 0) "223" Ppuv(As) "4005 642 bi Haa beep TPpg Ter beep Haa Rbe Haa Haa Gpuv Avp Avp 1 5 10

"2105 643 "2115 13 "2125 RVT "2135 Artificial sequence

"2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOP BE5 "222" (1)..(1) "223" 0-Avr "2205 "2215 MOP BE5 "222" (2)..2) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rep "2205 60 "2215 MO VE5 "222" (8)..(8)

"223" Rpe|4-(2-aminoethoxy) "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..( 10) "223" holes "2205 "221" MY VE5 "222" (11)..(11) "223" Puv(As) "4005 643

Avr Haa sip TBPg Tgr bip Haa Ribe Haa Haa Guv Avp Avp 1 5 10 "2105" 644 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (2)..2) "223" Rep "220" "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221 » MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "220" "221" MY VE5 "222" (10)..(10) "223" hole "220" "221" MY VE5 "222" (11)..(11) "223" Puv(Ac) 60 "4005" 644

Akud Haa sip TBPg Tesr beep Haa Ribe Haa Haa Guv Avp Avp

1 5 10 "2105" 645 "2115 13 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0 -Agd "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May " 2205 "221" MY VE5 "222" (10)..(10) "223" holes "2205 "221" MY VE5 "222" (11)..(11) "223" Puv(As) "4005" 645

Akud Haa sip TBPg Tesr bip Haa Ribe Haa Haa Guv Avp Avp 1 5 10 "2105" 646 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (2)..2) "223" Rep

"221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" holes "2205 "221 » MY VE5 "222" (11)..(11) "223" Tuv(As) "4005" 646

Rpe Haa bip TPg Tgr b1ip Haa Robe Haa Haa Guv Avp Avp 1 5 10 "2105 647 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" 0-RIe "2205 "2215 MOR VE5 "222" (2)..2) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rep "2205 "2215 MOR BE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 60 "2215 MO BE5 "222" (9)..(9 )

"223" 2-May "221" MY VE5 "222" (10)..(10) "223" hole "2205 "221" MY VE5 "222" (11)..(11) "223" Puv(As ) "4005 647

Rpe Haa bip TPg Tgr b1ip Haa Robe Haa Haa Guv Avp Avp 1 5 10 "2105" 648 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (1)..(1) "223" May 2

From "220" "221" MY VE5 "222" (2)..2) "223" Rep "220" "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221 » MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "220" "221" MY VE5 "222" (10)..(10) "223" hole "220" "221" MY VE5 "222" (11)..(11) "223" Puv(Ac) 60 "4005" 648

Haa Haa beep TPg Ter sip Haa Rpe Haa Haa Guv Avp Avp

1 5 10 "2105" 649 "2115 13 "2125 RET "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Rep " 2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) ) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" holes "2205 " 221" MY VE5 "222" (11)..(11) "223" Puv(As) "4005" 649

TPgE Haa sip TBPg Tesr bip Haa Ribe Haa Haa Guv Avp Avp 1 5 10 "2105 650 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (2)..2) "223" Rep. "2205 "221" MY VE5 60 "222" (7)..(7) "223" Rep.

"221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2 -Mai "2205 "221" MY VE5 "222" (10)..(10) "223" hole "2205 "221" MY VE5 "222" (11)..(11) "223" Tuv(As) " 4005 650

Tecp Haa bip TPpg Ter bip Haa Rpe Haa Haa Gpuv Avp Avp 1 5 10 "2105 651 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" r-s1p "2205 "2215 MOR VE5 "222" (2)..2) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rep "2205 "2215 MOR BE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR BE5 "222" (9)..(9) "223" May 2 "2205 60 "2215 MO VE5 "222" (10)..(10)

"223" hole "221" MY VE5 "222" (11)..(11) "223" Puv(As) "4005 651 beep Haa sbip TPg Ter beep Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 652 " 2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-Avp "2205 "221" MY VE5 "222" (2)..2) "223" Rep

From "220" "221" MY VE5 "222" (7)..(7) "223" Rep "220" "221" MY VE5 "222" (8)..(8) "223" Rpe|4- (2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" holes "220" "221" MY VE5 "222" (11)..(11) "223" Puv(As) "4005 652

Ap oHaa sip TBPg Tgr bip Haa Ribe Haa Haa Guv Avp Avp 1 5 10 "2105 653 (516) "2115 13 "2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6).. (6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..( 8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 653

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Gpuv Avp Avp Guv 1 5 10 "2105 654 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Rep "2205 "221" MY VE5 60 "222" (6)..(6) "223" Rep

"221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2 -May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "4005 654

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Guv Avp Avp 1 5 10 "2105 655 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" (1 )..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223 » Rpe|4-(2-acetylaminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 655

Haa sip TBPg Tgr beep Haa Robpe Haa Puv Guv ABp o Avp 1 5 10 "2105 656 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-(acetyl-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" ( 9)..(9) "223" airpa-Meguv (As) "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 656

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 657 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-(acetyl-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) 10) "223" airpa-Meguvzv (As)

"4005 657

Haa beep TPg Ter beep Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 658 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" 4-amino-4-carboxy-tetrahydropyran "4005 658

Haa beep TPg Ter beep Suv Rpe Haa Haa sbits Avp Avp 1 5 10 "2105 659 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8) "223" May 2 (516) "220" "221" MY VE5

"222" (9)..(9) "223" airpa-Meguv "4005 659

Haa sip TBPg Tgr bip Suv Ribe Haa Puv bij ABp sip 1 5 10 "2105" 660 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 660

Haa bip TPg Ter bip Suv Rpe Haa Uai Gguv ABp sh1U 1 5 10 "2105" 661 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (1).

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Petz "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "2205 "221" MY VE5 "222" (12)..(12) "223" Vega-A1a "4005" 661

Haa bip TP Ter bi1ip Suv Rpe Haa Iietsy Guv ABp Aia 1 5 10 "2105 662 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-(acetyl-aminoethoxy) "2205 "2215 MOR ВЕ5 "222 " (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv (As) "4005 662

Haa sip TBPg Tgr beep Suv Ribe Haa Puv bij ABp sip 1 5 10 "2105 663 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-(acetyl-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" ( 9)..(9) "223" airpa-Meguv (As) "4005 663

Haa bip TPg Ter bi1ip Suv Rpe Haa Guv b1y Avp Avp 1 5 10 "2105" 664

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Airpa-Metiyei "4005" 664

Haa beep TPg Ter beep Suv Rpe Haa Gay sb1its Avp Avp 1 5 10 60 "2105" 665

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "2205 "221" MY VE5 "222" (10)..(10) "223" sie "4005" 665

Haa beep TPg Ter beep Suv Rpe Haa Gay Haa Ap Avp 1 5 10 "2105" 666 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7). .(7) "223" РПе(4-ОМе) (516) "220" "221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR WEB "222" ( 10)..(10) "223" Puv(As) "4005" 666

Haa sip TBg Tgr bip Haa Rpe Haa Guz pub Avp Avp 1 5 10 "2105 667 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" 0-Guv "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (9)..(9 ) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-MeUai "2205 "221" MY VE5 "222" (11)..(11) " 223" Puv(As) 60 "4005 667

Tpuv Haa bip TPpg Ter bip Haa Rpe Haa Ua1i Gpuv Avp Avp 1 5 10 "2105" 668 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7).. (7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8)

From "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) " 223" Tuv(As) "4005" 668

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105" 669 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" ( 1)..(1) "223" Rep "2205 60 "2215 MO VE5 "222" (6)..(6)

"223" Rep. "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "2205 "221" MY VE5 "222" (10)..(10) "223" Puv( Ac) "4005" 669

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Guv Avp Avp 1 5 10 "2105 670 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 " (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7).. (7) "223" РПе(4-СОМН2) "220" "221" MY ВЕ5 "222" (8)..(8) "223" РПе(3,4-ОМе2) "220" "221" MY ВЕ5 "222" (9)..(9) "223" airpa-MeUai (516) "220" "221" MY VE5

"222" (10)..(10) "223" Puv(As) "4005 670

Haa sip TBPg Tgr beep Haa Ribpe Rpe Ua1i! Guv ABp Avp 1 5 10 "2105 671 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223 » 0-RIe "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 " 221" MY BE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (9)..(9) "223" 2- Mai "2205 "221" MY VE5 "222" (10)..(10) "223" hole "2205 "221" MY VE5 "222" (11)..(11) "223" Puv(As) "4005 671

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa Guv Avp Avp 1 5 10 "2105 672 "2115 13 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" V-Rre "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10)

From "223" 4-amino-4-carboxy-tetrahydropyran "2205 "221" MY VE5 "222" (11)..(11) "223" Ppuv(Ac) "4005 672

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa Guv Avp Avp 1 5 10 "2105 673 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" 0-RIe "2205 "2215 MOR VE5 "222" (2)..2) "223" Rep "2205 60 "2215 MO VE5 "222" (7)..(7 )

"223" Rep "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" Aspes "2205 "221" MY VE5 "222" (11)..(11) "223" Puv (Ac) "4005 673

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa Guv Avp Avp 1 5 10 "2105 674 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (1)..(1) "223" 0-RIe "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7) ..(7) "223" Rep "220" "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222 » (9)..(9) «223» May 2 (516) «220» «221» MY VE5

222 (10).

Rpe Haa Avp TPg Tgr bip Haa Rpe Haa Haa Haa ABp Avp 1 5 10 "2105 675 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-RIe "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7).. (7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9) ..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" Asps "2205 "221" MY VE5 "222" (11)..(11) ) "223" reads "4005 675

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa Haa Avp Avp 1 5 10 60 «2105 676 «2115 13

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-RIe "2205 "221" MY VE5 " 222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8).. (8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9)

From "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" Air "2205 "221" MY VE5 "222" (11)..(11) "223" Tuv(As) "2205 "221" MY VE5 "222" (13)..(13) "223" Vega-A1a "4005 676

Rpe Haa Avp TPg Tgr bi1p Haa Robe Haa Haa Guv ABp Aia 1 5 10 "2105 677 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" (1)..(1)

"223" 0-RIe "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 " 221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" 4-amino-4-carboxy-tetrahydropyran "2205 "221" MY VE5 "222" (11)..(11) "223" Puv (Ac) "4005 677

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa Guv Avp Avp 1 in; 10 "2105 678 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-RIe " 220" "221" MY VE5 "222" (2)..2) "223" Rep "220" "221" MY VE5 "222" (7)..(7) "223" Rep 60 "220" "221 » MY VE5

222 (8). 222 (10).

Rpe Haa Avp TPg Tgr bip Haa Rpe Haa Haa Guz ABp Avp 1 5 10 "2105 679 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-RIe "2205 "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7).. (7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9)..( 9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" 4-amino-4-carboxy-tetrahydropyran 60 "2205

"221" MY VE5 "222" (11)..(11) "223" sows "4005 679

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa Haa Avp Avp 1 5 10 "2105" 680 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (1)..(1) «223» 0-RIe «2205 «221» MY VE5 «222» (2). .(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9).. (9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" Aspes "2205 "221" MY VE5 "222" (11)..(11) " 223" reads "4005" 680

Rpe Haa Avp TPg Tgr bi1ip Haa Ribe Haa Haa Haa Avp Avp 1 5 10 "2105" 681 "2115 13 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of the artificial sequence: Synthetic peptide "221" MY VE5 "222" (1)..(1) "223" 0-RIe "2205 "221" MY VE5 "222" (2)..2) "223 » Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе ) "2205 "221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" Asps "4005 681

Rpe Haa Avp TPg Tgr bi1ip Haa Rpe Haa Haa b11p Avp Avp 1 5 10 "2105 682 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7). .(7) "223" РПе(4-СОМН2) (516) "220" "221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" A156 "2205 "2215 MOR VEB "222" (10) ..(510) "223" Puv(As) "4005 682

Haa Avp TPg Tgr beep Haa Ripe Haa Haa Guz ABp Avp 1 5 10 "2105 683 "2115 12 "212" RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep

From "2205 "221" MY VE5 "222" (6)..(6) "223" Rep

З5 "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2 - May "2205 "221" MY VE5 "222" (9)..(9) "223" 4-amino-4-carboxy-tetrahydropyran "2205 "221" MY VE5 "222" (10)..(510) "223" Puv(As) "4005 683

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 60 "2105" 684 "2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Asps "2205 "221" MY VE5 "222" (10).. (10) "223" Ppuv(As) "4005" 684

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 685 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 60 "2215 MO VE5 "222" (7)..(7 )

"223" РПе(4-СОМН2) "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) " 223" Asre "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 685

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 686 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Rep

З5 "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2 ) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "4005" 686

Haa Avp o TPg Ter bip Haa Rpe Haa Tetsy Guv Avp Avp

1 5 10 "2105 687 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep " 2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 687

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 688 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (1)..(1) "223" Rep "2205 "221" MY VE5 60 "222" (6)..(6) "223" Rep

"221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May " 2205 "221" MY BE5 "222" (9)..(9) "223" 4-amino-4-carboxy-tetrahydropyran "2205 "221" MY BE5 "222" (10)..(10) "223" Tuv(As) "4005" 688

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 689 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 МОР БЕ5 "222" (8)..(8) "223" 2-May "2205 "2215 МОР БЕ5 "222" (9)..(9) " 223" Asps "2205 60 "2215 MO VE5 "222" (10)..(10)

"223" Puv(As) "4005" 689

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 690 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (12). Suv Tuk Ter Agd bij Avp s1iu Haa Guv 1 5 10 "2105" 691

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (5)..(5) "223" pSuv "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 691 beeps Avr Ter sip Suv Suv Tukg Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 692 "2115 14 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Artificial sequence description: Synthetic peptide "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 692

Haa Akd TPg Ter bip Suv Tug Ter Agd Ppuv Rpe siu Haa Guv 1 5 10 "2105 693 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (6)..(6) "223" Ar "220" "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy )acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 693

Suv Akud TPg Ter bip Haa Tukg Tgr Agud puv Rpe s1iu Haa Guv 1 5 10 "2105" 694 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (1)..(1) (516) "223" Ar

"221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005" 694

Haa beep TPg Ter beep Suv Tug Tgr Agd bij Avp s1iu Haa Guv 1 5 10 "2105" 695 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (6)..(6) "223" Rap "2205 "221" MY VE5 "222" (13). .(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005" 695

Haa Akd TPg Ter bip Haa Tug Ter Agd Ppuv Rpe siu Haa Guv 1 5 10 "2105 696 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Rep (516) "220" "221" MY VE5

222 (6). » (14)..(14) «223» 0-Guv «4005 696

Haa Akud TPg Tgr bip Haa Tug Ter Agud Ppuv Rpe s1u Haa Guz 1 5 10 "2105 697 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (1). ..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 697

Suv Akud TPg Ter bip Haa Tukg Tgr Agud puv Rpe s1iu Haa Guv 1 5 10 "2105" 698 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (1)..(1) "223" Ar

"221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "2205 "221" MY VE5 " 222 (13).

Haa bip TPg Ter bip Suv Tug Tgr Haa Haa Avp s1iu Haa Guv 1 5 10 "2105" 699 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222 (1).

Haa sip TBg Tgr bip Suv Tug Ter Gay bij ABp 1U 1 5 10 "2105 700 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars 60 "2205

"221" MY VE5 "222" (6)..(6) "223" 0-Suv "220" "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 700

Haa beep TPg Ter beep Suv Tug Ter Gay bij Ap 1U 1 5 10 "2105 701 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9 ) "223" Petz "4005 701

Haa bip TPg Ter bip Haa Tug Ter gay sb1its AvBp 01Uu 1 5 10 "2105 702 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ar "2205 "2215 MOB БЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 60 "2215 MO БЕ5 "222" (8). .(8)

"223" 2-May "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 702

Haa beep TPg Ter beep Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 703 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "4005 703

Haa beep TPg Ter beep Suv Tug Ter gay sbits AvBp 01Uu 1 5 10 «2105 704

C5 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "4005 704

Haa beep TPg Ter beep Suv Tugk Haa guv bij ABp 1U 1 5 10 60 «2105 705

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 705

Haa beep TPg Ter beep Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 706 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "220" "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp 60 "4005 706

Haa beep TPg Ter beep Suv Rpe Haa Haa bij Ap 1U

1 5 10 "2105 707 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari " 2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp "4005 707

Haa bip TPg Ter bip Suv Rpe Tgr Haa bij Ap 1U 1 5 10 "2105 708 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" ( 8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 708

Haa bip TPg Ter bip Suv Rpe Haa puv siy AvBp b01U 60 1 v; 10

"2105 709 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR ВЕ5 "222" (10)..(10) "223" Puv(As) "4005 709

Zo Haa sip TBg Tgr bip Suv Rbe Ter Guv yuv ABp 1U 1 5 10 "2105 710 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" ( 9)..(9) "223" airpa-Meguv "4005 710

Haa beep TPg Ter beep Suv Rpe Ter Guv bij ABp 1U 1 5 10 60 «2105 711 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 1-May "2205 "221" MY VE5 "222 " (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) 0) "223" Ppuv(As) "4005 711

Haa bip TPg Ter bip Suv Rpe Haa puv pub AvBp b1U 1 5 10 "2105 712 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" (1 )..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8).. (8) "223" May 2 "2205 60 "2215 MO VE5 "222" (9)..(9)

"223" airpa-Meguv "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 712

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 713 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp

From "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 713

Haa bip TPg Ter bip Suv Tug Ter Haa guv ABp 1U 1 5 10 "2105 714 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) (516) "223" May 2

"221" MY VE5 "222" (9)..(9) "223" 0-Avp "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 714

Haa bip Ts Ter bip Suv Rpe Haa Avp Gguv Ap 1U 1 5 10 "2105 715 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПпе(4-Riepohu) "2205 "221" MY VE5 "222" (8 )..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10). .(10) "223" Puv(As) "4005 715

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 716 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

222 (1). "222" (8)..(8) "223" 2-May "2205 "2215 MOR VEB "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" ( 10)..(10) "223" Puv(As) "4005 716

Haa sip TBg Tgr bip Suv Rpe Haa Guz pub ABp s1U 1 5 10 "2105 717 "2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222 (7). ..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "4005 717

Haa beep TPg Ter beep Suv Haa Haa Gpuv puv ABp 1U 1 5 10 "2105 718 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8 )..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9)

From "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 718

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 719 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ary "2205 "2215 МОР БЕ5 "222" (7)..(7) "223" РПпе(3,4-С12) "2205 60 "2215 МО БЕ5 "222" (8 )..(8)

"223" May 2 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv (Ac) "4005 719

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 720 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar

From "220" "221" MY VE5 "222" (6)..(6) "223" Rep "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4- OMe) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 720

Haa beep TPg Ter beep Haa Rpe Haa uv bij Ap 1U 1 5 10 "2105 721 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (6)..(6) "223" Rap "2205 "221" MY VE5 " 222 (7). "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 721

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 722 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rap "2205 "221" MY VE5 "222" (6)..(6) "223" Ari "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 60 "222" (8)..(8) "223" 2-May

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 722

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 723 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MORPHE5 "222" (1 )..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8).. (8) "223" TeEr(2,5,7-tri-tert-butyl) "2205 "2215 МОР ВЕ5 "222" (9)..(9) "223" airpa-Meguv "4005 723

Haa sip TBg Tgr bip Suv Rbe Ter uv bij ABp 1U 1 5 10 "2105 724 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars 60 "2205

"221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "220" "221" MY ВЕ5 "222" (8)..(8) "223" РПе(4 -Oa11u1) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 724

Haa beep Ts Ter beep Suv Rpe Rpe Gpuv bij Ap 1U 1 5 10 "2105 725 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1)

From "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" Tuk(3-EVy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 725

Haa beep TPg Ter beep Suv Rpe Tug Gpuv bij ABp 1U 1 5 10 "2105 726 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" ( 1)..(1)

"223" Ari "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-EVy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 726

Haa beep Ts Ter beep Suv Rpe Rpe Gpuv bij Ap 1U 1 5 10 "2105 727 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4- ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe(4-dsccapidipo) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 727

Haa beep Ts Ter beep Suv Rpe Rpe Gpuv bij Ap 1U 1 5 10 "2105 728 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 " 221" MY VE5 "222" (8)..(8) "223" РПе(В2х1) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 728

Haa beep Ts Ter beep Suv Rpe Rpe Gpuv bij Ap 1U 1 5 10 "2105 729 "2115 12 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7).. (7) "223" Tuk(3-EVYy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 729

Haa beep TPg Ter beep Suv Tug Ter guv bij ABp 1U 1 5 10 "2105 730 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

222 (1). (7) "223" РПе(4-ОМе) "2205 "2215 MOR VEB "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..( 9) "223" Asre "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 730

Zo Haa Avp TPg Tgr beep Haa Ripe Haa Haa Guz ABp Avp 1 5 10 "2105 731 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..( 7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May 60 "2205

"221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 731

Haa Avp o TPg Ter bip Haa Rpe Haa Tetsy Guv Avp Avp 1 5 10 "2105 732 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" M-MeA1a "2205 "221" MY VE5 "222" (12)..(12) 0) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" V-Puv "4005 732

Aza Avr Tgr Uai Suv Tuk Ter Niv TPg Rpe si1u Haa Guv 1 5 10 "2105 733 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" M-MeAtTa "2205 "2215 MOR VE5 "222" (5)..(5) "223" Rep "2205 60 "2215 MO VE5 "222" (12)..( 12)

"223" (2-aminoethoxy)acetic acid "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 733

Aza Avr Tgr Ua! Haa Tug Ter Ni TPg Rpe s1u Haa Guv 1 5 10 "2105 734 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1). .(1) "223" M-MeAtTa "2205 "221" MY VE5 "222" (5)..(5) "223" P-Rep

From "220" "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "220" "221" MY VE5 "222" (13)..(13) " 223" 0-Guv "4005 734

Aza Avr Tgr Ua! Haa Tug Ter Ni TPg Rpe s1u Haa Guv 1 5 10 "2105 735 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1). .(1) "223" M-MeA1a "2205 "221" MY VE5 "222" (5)..(5) (516) "223" pSuv

"221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 735

Aza Avr Tgr Uai Suv Tuk Ter Ni TPg Rpe s1u Haa Guv 1 5 10 "2105 736 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 736

Aza Avr Tgr Uai Suv Tuk Ter Ni TPg Rpe s1u Haa Guv 1 5 10 "2105 737 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (5)..(5) "223" Rep "220" "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "220" "221" MY VE5 " 222" (13)..(13) "223" 0-Guv 60 "4005 737

Aza Avr Tgr Ua! Haa Tug Ter Ni TPg Rpe s1u Haa Guv

1 5 10 "2105 738 "2115 13 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (5)..(5) "223" P- Rep "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 738

Aza Avr Tgr Ua! Haa Tugk Ter Ni TPg Rpe s1u Haa Guv 1 5 10 "2105 739 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (5) ..(5) "223" pSuv "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13) ..(13) "223" 0-Guv "4005 739

Aza Avr Tgr Uai Suv Tuk Ter Ni TPg Rpe s1u Haa Guv 1 5 10 «2105 740 «2115 13 «2125 RVT

Gs10) "213" Artificial sequence

"223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VEB "222" (13).. (13) "223" 0-Guv "4005 740 sbip Avr Tgr bip Suv Tug Tgr Akud bij AvBp sb1iu Haa Guz 1 5 10 "2105 741 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

"2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid

"2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv

"4005 741 beep Avr Ter sbip Suv Tuk Ter Agud bij Avp s1iu Haa Guv 1 5 10 "2105 742 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 742 bip Avr Ter sbip Suv Tuk Ter Agud bij Avp s1iu Haa Guv 60 1 5 10

"2105 743 "2115 13 "2125 RVT "2135 Artificial sequence

"2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VEB "222" (13) ..(13) "223" 0-Guv "4005 743 sip Avr Tgr beep Suv Tug Tgr Akud bij ABp siu Haa Tuv 1 5 10 "2105 744 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

"2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid

"2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv

"4005 744 bip Avr Ter sbip Suv Tuk Ter Agud bij Avp s1iu Haa Guv 1 5 10 "2105 745 "2115 13 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 60 "222" (13)..(13) "223" 0-Guv

"4005 745 bip Avr Ter sbip Suv Tuk Ter Agd bij Avp s1iu Haa Guv 1 5 10 "2105 746 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB " (5). (13)..(13) "223" 0-Guv "4005 746

Zo sip Avr Tgr bip Suv Tug Tgr Akud bij ABp siu Haa Tuv 1 5 10 "2105 747 "2115 13 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (5)..(5) "223" pSuv "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 (13).

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (5)..(5) "223" pSuv "2205 "221" MY VE5 "222" (12)..(12) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (13)..(13) "223" r-Guv "4005" 748 beep Avr Ter sbip Suv Tuk Ter Agud biy Avp s1iu Haa Guv 1 5 10

"2105" 749 "2115 13 "2125 RVT "2135 Artificial sequence

"2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOP BE5 "222" (5)..(5) "223" pSuv "2205 "2215 MOP BE5 "222" (12)..(12) " 223" (2-aminoethoxy)acetic acid "2205 "2215 МОР ВЕ5 "222" (13)..(13) "223" 0-Guv "4005 749 sip Avr Tgr bip Suv Tug Tgr Akud bij ABp siu Haa Tuv 1 5 10 "2105 750 "4005 750 oo "2105 751 60 "4005 751 oo

"2105 752 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221 » MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy

From "220" "221" MY VE5 "222" (12)..(12) "223" Vega-Ai1a "4005 752

Haa bip TP Ter bi1ip Suv Rpe Haa Iyetsy bip ABp Aia 1 5 10 "2105 753 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 » (8)..(8) (516) "223" May 2

"221" MY VE5 "222" (9)..(9) "223" Ass's "4005 753

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 754 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Asps "4005 754

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 755 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Ary "220" "221" MY VE5 "222" (7)..(7) "223" РПпе|4-(2-aminoethoxy) (516) "220" " 221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" Asus "4005 755

Haa sip TBPg Tgr bip Suv Ribe Haa Haa bij ABp Avp 1 5 10 "2105 756 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-MeUai "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "2205 "221" MY VE5 "222" (13)..(13 ) "223" 0-Guv "4005 756

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Gpuv Avp Avp Guv 1 5 10 60 «2105 757 «2115 13

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9)

From "223" airpa-MeuUa1i "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "2205 "221" MY VE5 "222" (13)..(13) "223" r-Guv "4005 757

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Gpuv Avp Avp Guv 1 5 10 "2105 758 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Rep "2205 60 "2215 MO VE5 "222" (6)..(6)

"223" Rep "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeUai "4005 758

Haa bip TPg Ter bi1ip Haa Rpe Haa Uaii Guv Avp Avp 1 5 10 "2105 759 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep "2205 " 221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-acetylaminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2- My "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 759

Haa bip TPg Ter bi1ip Haa Rpe Haa Gpuv Guv Avp Avp 1 5 10 "2105 760 60 "2115 629 "2125 RVT

"213" Nosho zariyeep "4005 7b6o

Mee Avp o sbip Uai1i TPg Iie bip Ter Ar Aia Uaii I1e Aza iey Tu She 1 c) 10 15

Tecp Rpe bek Tgr Suv Niv siu s1u Iie TPg Up I1e Up Suv beg 01Uu 20 25 30

Niv Iie Ter Uai! bij Rgo Aza TPg Iie Rpe Puv Meyes s1u Mee Ap I1e 35 40 45 zek Iie Tuk Sub bip Asia1a Aza I1e gub AvBp o Suv bip Rgo Agd Puv Iets 50 55 bo

Niv Rpe Tuk Ppuv Avp biu I1e puv sit Agd Rbe bip I1e TPg Agd She 65 70 75 80

Avpopuv TBg TBg Aza Agd Tetsy Ter Tug Guv Avp Rpe Tey siy Rgo Niv 85 90 95

Aza bek Meisje Tuk Sub TPg Asia bets Sub Rgo Gpuv Niv Rpe sbip bij TEG 100 105 110

Tem I1ie Suv s1u Ppuv Avr I1e bek bek sb1u Tuk Rgo Rgo AvBr I1e Rgo 115 120 125

Avr siy Uai TPg Suv Uai I1e Tuk bis Tuk bek b1u Avp Mee TPg Suv 130 135 140

Zo

TPgE Ter Avp Aia siu pub Tecyp TPg Tuk I1e Avr TPg Guv Tuk Ua1i Uai 145 150 155 160

Niv Uai1 Ppuv bek Gets bitz TE siy bij bi bip bip Tuk Gay TPg 5eg

Z5 165 170 175 zek Tuk I1ie AvBp I1e bek TPg Avr bek ITecp bip siu s1u Ppuv Ppuv Tug 180 185 190

Tem Mai Tgr Uai sip Aia Asia Avp Aza Getsp siu Mee bij siy Bek Guv 195 200 205 bip Gay bip I1ie Niv Gay Avr Avr I1ie Uai Iie Rgo bBeg Aza A1a Uai 210 215 220

I1e Bek Agud Aia bicp TPg I1ie ABp Aia TPg o Uai Rgo Gpuv TPg Ie Pe 225 230 235 240

Tuk Ter puv Bek bip TPg TPg Iie siy pub Uaii bek Suv bij Mee Agd 245 250 255

Tuk puv Aia TPg TBg Avp obip TBg Ter Avp o Uaii uv bij Rpe Avr TEG 260 265 270

Avp o Rpe TPg Tuk Uaii sbip sip bek siy Ribe Tug Gay bij Rgo Ap I1e 275 280 285

Tpuv Tuk Uaiii Rpe sip Uai Agud Suv bip bij TPkg s1u puv Agd Tug Tgr 290 295 300 60 bip Rkgo Ter bek Bek Hey Rpe Rpe Niv Ppuv TPg Rgo bis TiPg Uai Rgo

305 310 315 320 bip Mai TPg bek puv Aia Rpe sbip Niv Avr TPg Ter Avp bek s1Uu Ietsy 325 330 335

TPg Uai1 Aia bek I1i1e bek TPg siu Niv Iets TPg bek Avr ABp Agd 1U 340 345 350

Avr I1e s1u Pec Iets Iets bi1u Mesye I1e Uai Rpe Aza Ua1 Meyes Iets 5eg 355 3Z6o 365

I1e Gets bek Iiets I1e sb1u I1e Robe AvBp Agud bek Rpe Agu TPg s1u Te 370 375 380 tsuv Agud Agud I1ie Hey Gay tey I1ie Rgo Ppuv Tkgr Tey Tug bij Ar I1e 385 390 395 400

Rgo Avp o Mee Guv Avp bek Avp Ua! Uaiyi Guz Mee Hey beep bij Avp beg 405 410 415 bis Hey Mee Avp Avp Avp back back beat beep Uai Iets Tuk Uai Avr Rgo 420 425 430

My I1ie TPg siy Iie puv sbits Iie Rbe Ii1e Rgo bits Niv Guv Rgo TPg 435 440 445

Avr Tuk puv puv bis AvBp o Tpg b1iu Rgo Gay bij Tbg Agud Avr Tug Rgo 450 455 460

Zo sbip Avp o bek geish Rpe Avr AvBp o TPg TBPg oUai Uai Tuk I1ie Rgo Avr Gay 465 470 475 480

AvpoTpkE s1u Tuk puv Rkgo bip I1ie Bek Avp Rpe Hey Rgo bit siu b5eg 485 490 495

C5

Niv Hey back Avp Avp AvBp obits I1e TBPg back Tec TPg Ietsy Guv Rgo Rgo 500 505 510

Uai Avr bek Gay Avr bek b1iu Avp AvBp Rgo Agd Tec bip Guv Niv Rgo 515 520 525

Avp o Rpe Aza Rie bBeg Ua! back back Uai Avp back Gay back Up TPg I1e 530 535 540

Rpe Gay siu bii Getsy bek Gay I1i1e Gay AvBp bip siu siy Suv bek beg 545 550 555 560

Rgo Avr I1e bip AvBp back Uai bis bis bis TPg Tps Mee Gay Gay s1its 565 570 575

Avp o Avr object Rgo bek b1itsp TPg I1ie Rgo bij bip TP Gay Gay Rgo Avr 580 585 590 bi Rpe Uai bek Suv Ggesh s1iu Iie Uai AvBp bij siy Gets Rgo bek I1e 595 (51048) 605

AvpoTPg Tuk Rbe Rgo bip AvBp I1e Iets bij bek Niv Rpe A5p Agd I1e 610 615 620 (516) zek Gech Ge bij Guv 625

"2105 7bv1 "2115" 659 "212" RET "213" Myv shtivsy1y5 "4005 7bv1

Mee guv Agud bi Akud biy Mesye Agud b1u Rpe Tug Tug Iie Ter Avr Mee 1 5 10 15 zek Niv Gecp TPg Iets bip Gay Ni Uaiyi Mai I1і1e Aia Gay Tuk Uai1i Iets 20 25 30

Rpe Agud Tgr Sat Niv b1u sb1u Iie TPg bek I1i1e Avp Suv Bek s1u Avr 35 40 45

Mee Ter Uai bij Rkgo siu bits Iie Rbe sip Mes sSiu Mee Avp Uai 5eg 50 55 bo

Iie Tuk Suv bip bish Aza Gay Ppuv Niv Suv Agud Rgo Agud Avp o Tech Tug 65 70 75 80

Rpe Tuk Mpuv Avp obiu Rpe Gpuv bis bis Rpe AvBr I1e TPg Agud I1e Avp 85 90 95

Akud TE TBg Aza Agud I1e Ter Tuk Guz b1u Rpe back fight Rgo Niv Aia 100 105 110

Tuk Mee Niv Suv TPg Aza bitz Suv Rgo biu Niv Rore beep bij TPg Gay

From 115 120 125

ITIe Suv bi1u Gpuv Avr I1e bek bek biu Tuk Rgo Rgo Avr Aia Rgo 5eg 130 135 140

Avp oGecp TPg Suv Uaii Iie Tuk bij Tuk back b1i1u AvBp Mee TPg Suv TPg 145 150 155 160

Ter Avp o TpPg s1u Ppuv Rgo TPg Tukg Iie Avr TPg Guv Tug I1e Uai1i Niv 165 170 175

Uai Ppuv Bek geish bij TbPg bis bi bij bip bip Tuye ITec A1a bek 5eg 180 185 190

Tuk Ua1 Ppuv Iie bek TPg Avr bek Gay beep siu b1u Ppuv Guv Tuk Ietsy 195 200 205

Uai Ter Uai sbip Aza Ua1i Avp Bek Gay siu Mesye bitz AvBp bek bip sip 210 215 220 em Niv Uai Ni Gay Avr Avr I1e Uai I1e Rgo bek Aia bek I1e Pe 225 230 235 240 zek Agud Aia bitz TP TPg ABp Avr o Ts Uai Rgo Ppuv TPg Iie I1e Tug 245 250 255

TER Ppuv Bek Ppuv TPg Meyese I1e siy puv Uaii Rre Suv bij Mee Agd Tug 260 265 270

Tpuv TPg TpPg TpPg Avp o bip TBg Ter bek Uai Ppuv siy Ribe Avr Aia Avp 60 275 280 285

Rpe TPg Tuk Uai beep bi1ip bek bitsh Rpe Tuk Gay bij Rgo Avr bek Guv 290 295 300

Tuk Uai1 Rpe sip Uai Agkd Suv bip bij TBg b1u Guv Agd ABp Tgr sip 305 310 315 320

Rkgo Ter bek bek Rgo Rpe Uai Niv beep TPg bek beep bi TPkg s1u Buv 325 330 335

Agud Avp Ter bip Rgo Ter bek bek Rgo Ribe Uai Niv sbip TPg bek sip 340 345 350

TPg Ua1 Back sip Uaii TBPg Aza Ppuv back back Niv bis Rgo bip Ppuv Mee 355 3Z6o 365 bis Mee Hey bek Aza TPg Iie Rpe Agud siu Niv Rgo Aza bek S1u Avp 370 375 380

Niv beep Avr I1ie siu Gets Iets bek siu Mesye Ua! Rpe ieyp Ai1a iI1e Mee 385 390 395 400

Tecp Rkgo I1ie Rpe bek Gay Iie siu Iie Rpe Avzp Agud bek Gay Agd I1e 405 410 415 s1u Iie Ppuv Agud Ppuv Ua1i Iiei Gay Mees I1e Rgo Ppuv Tkgr ITey Tuk s1ts 420 425 430

Avr I1e Rgo AvBp Mesye bis AvBp o beg AvBp Ua! Aia Gpuv Gay Gay sbip social 435 440 445

Zo

Tpuv bek Uaiyi Rpe bij Avp Avr Avp Aza bek bij sip Aia Gets Tuk Uai 450 455 460

Avr Rkgo Uaii Gecp TPg bis I1i1e bek bis I1e bek Rgo Gay soi Niv Guv 465 470 475 480

Rkgo TPg Avr Tuk Gpuv bij bij Agd ITecyp TPg s1u Gay Gay bi TPg Agd 485 490 495

Avr Suv Rgo ITey biu MeeEee Hey bek TPg bek bek bek Wow! Wai Tuk Pe 500 505 510

Rgo Avr Gets AvBp o TPg o biu Tuk pub Rgo bip Uaii Bek Avp Uai1i Rgo Rgo 515 520 525 sbi1u b1u Avp Hey Rpe Iie Avp Agd Avr bij Agud Avr Rgo TBPg bek Ietsy 530 535 540 bis Ts Tpg Avr o Avr o Niv Rpe Aza Agud Gay Ppuv TPg Tuk Rgo AvBp Rie 545 550 555 560 bip Rpe bek Aia bek bek Mee Aza Gay Gay AvBp o Guv TPg Iep Iie Ietsy 565 570 575

Avr bij Hey Suv Gets Maii Hey Avp o sip sbiu bij Rre Avp bek Ietsy Avr 580 585 590

I1e puv Avp bBeg Agud bib bij bis TB o bBeg Iie Uai1i! Ggets bip 5eg Avr 595 bo 605 60 zek Rgo bek bis TPg I1e Rgo Aia bip TPg Gay Gay bBeg Avr bij Re

610 615 620

Uai bek Suv Ggesh Aza I1ie s1iu AvBp bis Avr Gay Rgo Bek Iie Avp b5eg 625 630 635 640

Tuk Rpe Rgo sip Avp Uaii Iets sii bek Niv Rie beg Agud I1e bek Ieeets 645 650 655

Rpe sip Guv "2105 762 "2115" 639 "212" RET "213" Vayessiv poguedisyv "4005 762

Mee Agud Agud fight Agud fight Mesie Agud s1iu Rbe Tug Tug I1e Tgr Avr Mee 1 5 10 15 zek Niv Uaiyi Aia Iets beep Hey No Uai! Mai I1i1e Aza Gay Tug Aia Iey 20 25 30

Rpe Agud Tgr siu Niv b1u c1u I1e Asia TPg I1e ABp Suv Bek c01u Avp

Mee Ter Uai bij Rgo siu sbits Iie Rpe sip Mes siu Mee Avp Ua1i! 5eg because

Zo Uai Tuk Suv bip siy Aia Gay Guv Avp Suv Agud Rgo Agud ABp Gay Niv 65 70 75 80

Rpe Tuk Mpuv Avp obiu Rpe uv bis Agd Rpe Niv Iie TBPg Agud I1e Avp 85 90 95

C5

Akud TE TBg Aza Agud Uai Ter Ts Guz b1u Rpe bek bij Rgo Niv Aia 100 105 110 zek Mee Tuk Sub TPg Asia bij Suv Rgo b1u Agud Rpe sip bis TPgE Iey 40 115 120 125

ITIe Suv bi1u Gpuv Avr I1e back back biu Tuk Rgo Rgo Avr Aia Rgo 5eg 130 135 140 45 Avp oMee TPg Suv Uaii Iie Tuk bis Tuk bek b1u Avp Mee TPg Suv TiPg 145 150 155 160

Ter Avp o TpPg s1u Ppuv Rgo TPg Tuk I1ie Avr TPg Guv Tuk TPg Ua1i Niv 165 170 175 50

Uai Ppuv Bek Gay bij TbPg sbits bits bip bi1ip bi1ip Tu Gay Aia Bek Avp 180 185 190

Tuk Uai1 Avp I1ie bek TPg Avr bek Gay bip siu b1u Ppuv Guv Tuk Ietsy 55 195 200 205

Uai Ter Ua1i sbip Aza Ua1i Avp Aza Iets bi1u Mee bij Avp Bek bip sip 210 215 220 (516) em beep Uai No Hey Avr Avr I1e Uai I1e Rgo bek Rgo bek I1e Pe 225 230 235 240 zek Agud Aia bit TPg Tpg Avp Aza Avp o Uaii Rgo Ppuv TPg Iie I1e Tug 245 250 255

Ter pub bek Puv I1e Mesye TPg s1u Ppuv Uai Rbe Suv bis Mee Agd Tug 260 265 270 puv Aza TPg o TpPg Avp obip TBg Ter Avp o Ua1i puv siy Rbe Avr TPg Avp 275 280 285

Rpe TPg Tuk Uai beep bi1ip bek bitsh Rpe Tuk Gay bij Rgo Avp bek Guv 290 295 300

Tuk Uai1 Rpe sip Uaii Agkd Suv bip siu TBPg s1i1u Guv Agd Tugye Tgr sip 305 310 315 320

Rkgo Ter bek bek Rgo Rpe Ua! Niv beep TPg Rgo sip TPg Aia back sip 325 330 335

Uai Tpg Bek Ppuv Rgo Rgo Niv bij Rgo sip Puv I1ie sbits Mee Gay TAG 340 345 350

Aa TPg I1ie Re Guz b1u Niv bek TPg bek Avr Avp Bek bip Avr I1e 355 3Z6o 365 sb1u Getsshp Hey bek siu Mee Uai1 Rpe geish Aia Iie Mee Getsy Rgo I1e RBPe 370 375 380 zek Gets I1e siu I1e Rpe AvBets Agd I bek s1u Iie Gpuv Agd

Zo 385 390 395 400 yipuv Mai Iiep Gay Mee Iie Rgo Ppuv Tgr Gay Tug bij Avr I1e Rgo AvBp 405 410 415

Mee bi Avp bek Avp I1ie Aia Gpuv Getsp Gay sip bij Ppuv bek Uai Rie 420 425 430 bi AvBp bij Avp Aza bek bij sbip Aza Gay Tuk Ua1 Avr Rgo I1e Iey 435 440 445

TPgE bi Iie Bek sats I1e bek Rgo Gay bets Niv Guv Rgo TPg ABr Tug 450 455 460

Ace Guv Avr Agud Gay TpPg s1iu Rpe Gay bij TPg Agud Avr Suv Rgo Iey 465 470 475 480

TPg TpPkg Gay back TPg back back back Uai Uai Tug I1e Rgo Avr Gay Aup 485 490 495

TE b1u Tuk Puv Rgo beep Uai Bek Aup Uai Rgo Rgo bitz bij Aup Niv 500 505 510

Rpe I1e AvBp Agd Avr bij Agud Avr Rgo Mee bek ep si Aia TP sh1U 515 520 525

Avr Niv Ripe Aza Agd Tetsy Gpuv TPg Tuk Rgo Avp Rpe TPg Rrpe beg Aia 530 535 540 zek bek Mees TPg bek Tetsyp bek pub TPg Ietsp I1e Gay Avr bij Gay 5eg (516) 545 550 555 560

Tets Mai Hey Avp beep sbiu bij Rpe Avp bek Hey Avr I1e beep Avp b5eg 565 570 575

Akud bip bi bts Ts bek Mee I1e Iiets bip Avp Avr Bek Rgo bek sitc 580 585 590

TPE Iie Rkgo Ua1! sip TBPg Iets Gay Rgo Avr bit Rore Ua! bek Suv Ietsi 595 or 605

A1i1a I1e siu bek bitz Avr Gay Rgo bek I1ie AvBp bek Tuk Rope Rgo sip 610 615 620

Ap oUai1! Gay bis bek No Rpe bek biu I1e Rgo Iieetsp Gay sip Guv 625 630 635 "2105 763 "2115" 629 "212" RET "213" Rap vr. "4005 763

May Avp o sbip Uai1! TPg Iie sbip Tgr ABr Ai1a Uai I1i1e Aia Gay Tug Ie 1 5 10 15

Pes Ribe bek Tgr Suv Niv siu s1u I1e TPg AvBp I1e Avp Suv bek 1U 20 25 30

Niv Iie Ter Uai sitz Rgo Aia TPg I1ie Rbe Guz Mee b1u Mee ABp She

Zo zek Iie Tuk Sub bip Asia1a Aza I1e gub AvBp o Suv bip Rgo Agd Puv Iets bo

Niv Rpe Tuk Ppuv Avp biu I1e Guv sit Agd Rbe bip I1e TPg Agd She 35 65 70 75 80

Avpopuv TBg TBg Aza Agd Tetsy Ter Tug Guv Avp Rpe Tei siy Rgo Niv 85 90 95 40 A1ia bek Mee Tuk Suv TPg Aia sitzsh Suv Rko Puv Niv Rpe sip bij TPg 100 105 110

Tecp I1i1e Suv s1u Ppuv Avr Iie Bek Bek s1iu Tuk Rgo Rgo Avr I1e Rgo 115 120 125 45

Avr siy Uai TPg Suv Uai I1e Tuk bis Tuk bek b1u Avp Mee TPg Suv 130 135 140

TPgE Ter Avp Aia siu pub Tecyp TPg Tuk Mes Avr TPg Guv Tuk Ua1i Uai 50 145 150 155 160

Niv Uai1 Ppuv bek Gets bec TE siy bij bi bip bip Tuk Gay TPg 5eg 165 170 175 55 Zzek Tuk Iie AvBp I1e bek TPg Avr bek Te bip siu s1u Ppuv Tuv Tug 180 185 190

Tets Mai Ter Uai sbip Aia Aza Awp Aia Gay siu Mee bec bi bek Guv 195 200 205 60 bip Gay bip I1ie Tuk geish Avr Avr Iie Uai Iie Rgo bBeg Aza bek Uai

210 215 220

I1e Bek Agud Aia bicp TPg I1ie ABp Aia TPg o Uai Rgo Gpuv TPg Ie Pe 225 230 235 240

Tuk Ter Avr bek bip TPg TBg Iie siy pub Uaii bek Suv bij Mee Agd 245 250 255

Tuk puv Aia TPg TBg Avp obip TBg Ter Avp o Uai Guz bij Rpe AvBr TPg 260 265 270

Ap oRpe TPg Tuk Uai beep bi1ip bek bitsh Rpe Tuk Gay bij Rgo Ap I1e 275 280 285 puv Tuk Maii Rpe sip Uai Agud Suv beep bish TPk s1u Guv Agud Tuk Ter 290 295 300 bip Rkgo Ter Bek Bek Rgo Rpe Rpe Niv Ppuv TPg Rgo bis TPg Uai Rgo 305 310 315 320 bip Mai TPg bek puv Aia Rpe sip Niv Avr TPg Ter Avp bek S1Uu Iey 325 330 335

TPg Uai1 Aia bek I1i1e bek TPg siu Niv Iets TPg bek Avr ABp Agd 1U 340 345 350

Avr I1e s1u Gets Iets Iets bi1u Mesye I1e Uai Rpe Aza Ua1i Mee Gay 5eg 355 3Z6o 365

Zo I1ie Gay back Tape I1e s1iu Iie Rpe Azp Akud bBeg Gay Agud TPg s1u I1e 370 375 380 pub Agud Agud chI1e Gay Gay Gay Iie Rgo Ppuv Ter Gay Tug bitz ABr I1e 385 390 395 400

C5

Rgo Avp o Mee Guv Avp bek Avp Ua! Uaii Guz Mee Hey beep bij Avp beg 405 410 415 bis Hey Mee Avp Avp Avp back back bi beep Ua1i1 Hey Tuk Uai ABr Rgo 420 425 430

My I1ie TPg siy Iie puv sbits Iie Rbe Ii1e Rgo bits Niv Guv Rgo TPg 435 440 445

Avr Tuk puv yuv Hey ABp o TpPK s1iu Rgo Hey bij TPg Agud Avr TEG TIetsy 450 455 460 bip Avp obek Hey Rpe Avr Avp TPg TpPg o Ua1i Ua1 Tug I1ie Rgo Avr Ietsy 465 470 475 480

AvpoTpkE s1u Tuk pub Rgo bip I1e bek AvBp Rpe Gay Rgo bi siu b5eg 485 490 495

Niv Gay back Avp Avp Avp o bis I1ie TBbg bek Gets TPg Ietsy Guv Rgo Rgo 500 505 510

Uai Avr bek Hey Avr bek b1iu Avp Avp Rgo Agd Tets bip Guv Niv Rgo 515 520 525 (516) Avp o Rpe Aia Rie bBeg Uai! back back Uai Avp back Gay back ABp TPgE Te 530 535 540

Rpe Gets siu bets Iets bek Gay I1e Ietsshc ABp bip si1u bij Suv bek b5eg 545 550 555 560

Rgo Avr I1e bip ABp bek Uai bij siy bij Ts Ts TBg Tetsy Gay si1ts 565 570 575

Avp o Avr object Rgo bek b1itsp TPg I1e Rgo bij bip TP Gay Gay Rgo Avr 580 585 590 bi Rpe Uai bek Suv Gesh s1i1u Iie Uai AvBp bis bis Tetsy Rgo Bek She 595 bo 605

AvpoTPg Tuk Rbe Rgo bip AvBp I1e Iets bij bek Niv Rpe A5p Agd I1e 610 615 620 zek Gets Gets bit Guv 625 "2105" 764 "2115 631 "212" RET "213" Sapiv Tashti1iiagiv "4005 764

Mee ABp o sbip Iie TPg Iie bip Ter Avr Uai Uai I1e Aza iey Tu She 1 5 10 15

Rpe Rbe Avp o Tgr Sat Niv bi1u bi1u I1e TPg ABp o I1e Up Suv beg 01Uu

From 20 25 30

Niv Iie Ter Uai sitz Rgo Aia TPg Iie Rbe Guz Mee b1u Mee ABp She 35 zek Iie Tuk Suv bip Aia Aia chI1e Puv Avp Suv bip Rkgo Agud Puv Gay bo

Tuk Rpe Tuk Ppuv Avp biu I1e puv sit Agd Rbe bip I1e TPg Agd She 65 70 75 80 40

Avpopuv TBPg TBg Aza Agud Tetsy Ter Tug bek Avp Robe Gets bit Rgo Niv 85 90 95

Aza bek Meisje Tug Sub TPg Asia1a bis Sub Rgo b1u Tuk Rgo bip bij TEG 45 100 105 110

Tecp I1i1e Suv s1u Ppuv Avr Iie Bek bek biu Tuk Rgo Rgo Avr Ua1i Rgo 115 120 125 50 Avr Ppuv Uai TPg Suv Mai Iie Tuk siy Tuk bek b1u AvBp Mee TPg Suv 130 135 140

TPE Ter Avp bek siu Ppuv Rgo TPg Tuk I1ie Avr TPg puv Tuk Ua1! Uai 145 150 155 160 55

Tuk Ua1 Ppuv Bek Gets bts uv bii bii bts beep beep Tuk Getsp bek 5beg 165 170 175 zek Tuk I1e AvBp I1e bek TPg Avr bek Gay beep siu s1iu Ppuv Puv Tug 60 180 185 190

Tets Mai Ter Uai sbip Aia Aza Avp Aia Gay siu Meye bis Gpuv bek Guv 195 200 205 bip Gay bip I1ie Avp Gay Avr Avr I1e Uai Iie Rgo bBeg Aza Aza I1e 210 215 220

I1e bek Agd Aia bitsshc ABr I1e ABp TPg TPg I1e Rgo Gpuv TPg I1e Pe 225 230 235 240

Niv Ter Avp bek bip TPg Ts o I1e bis Ap Ua1i bek Suv bi Mee Agd 245 250 255

Niv Ppuv TPg TBbg TBEg Avp obip TBg Ter pub Uai Guz b1p Rpe AvBr TPg 260 265 270

Avp oRpe Rgo Tug bitz beep bi1ip bek bitzsh Rpe Tuk Gay bij Rgo Avp o TPg 275 280 285

Tpuv Tuk I1i1e Rpe sbip Uai Agkud Suv bip bij TPg s1iu MPuv Agd Tug Tgr 290 295 300 bip Rkgo Ter Bek Bek Rgo Rpe Rpe Niv Ppuv TPg Aza sbits TiPg Uai Rgo 305 310 315 320 sip Maii TPE Umai Ppuv bek Robe TP Niv Avr sbip Avp bek sei Gay 325 330 335

Tets I1i1e Aza bek Iie Rpe Ppuv siu Niv Gay TPg bek Avr Ap Agd bip 340 345 350

Zo bip Avr I1e si1u Hey Hey Ggesh siu Mee Iie Rpe Robe Aza Aia Mee Iey 355 3Z6o 365 zek Iie Hec bek Iets I1e s1u I1e Rore ABp Agud bBeg Iie Agd TP sh1U 370 375 380

I1e puv Agud Agud I1e Ietsy Gay Iiets I1e Rgo Gpuv Tgr Gay Niv bij Avr 385 390 395 400

I1ie Rgo Avp Mes si Avp bek Ppuv Uaii Ua1i! siy Mee Gay sip Tuv si1ip 405 410 415 zek bis Rbe Mesb Avp AvBp Avp beg bek bij bip Uai Gay Tug Aia Avr 420 425 430

Rgo Uai Iie TPg bitzsh I1e siy I1e Rrbe Iiecy Rgo siy bi Niv Ppuv Rgo 435 440 445

TPE Avr Tuk puv Aia bis Guv Avp o TBPg biu bek ITec 611 TPg Agd Avr 450 455 460

Suv Hey beep Avp back Hey Hey TPg Avp TPg Tpg Ua1i Uai Tug I1e Rgo 465 470 475 480 s1u Gay back TPKg s1u Tuk Puv Rkgo beep I1e Back Avp Ribe Tey TE 1U 485 490 495 b1u Avp Niv Gay back Ppuv puv Avr bij TpPg back back back TPg Iets Gu 500 505 510 60

Rgo Gets Aza Avr bek bek Avr ITec bi1u b1u ABp Aza Agud Rpe Ppuv Guv

515 520 525

Tuk Rgo Avp Rpe Aza Rie bek Ua1 bek bek Mes Avp bek Ietsy bek Avp 530 535 540

TPE geish Rpe Gay sitz bic ITec bek Ggets I1e Gets ABp bip b1u siy Ag4d 545 550 555 560 zek Rgo Gets Avr Mee bip Avp bek Uai bi sb1u siy TPg TPg Mee Gay 565 570 575

Ten bij ABp Aza bek Rgo ABp obi TBPg I1e Rgo siy bip TBg Gay Gay 580 585 590

Rgo Avr bij Robe Uaii bek Suv Hep s1u I1ie Mes ABp siy si Ietsy Rgo 595 bo 605 zek Iie Avp bek Tuk Rpe Rgo bip ABp I1e ieyp siy AvBp Niv Rope Avp 610 615 620

TPg Iie bek Ggets Gets b1its Guv 625 630 "2105 765 "2115" 630 "212" RET "213" Vov5 vr. "4005 765

Zo Mee ABp obip Uai TBbg Iie Niv Tgr Avr Uai Uaii Iie A1a Gay Tuk Te 1 5 10 15

Rpe RibPe bek Tgr Sat Niv si1u bi1u I1e TPg ABp I1e Avp Suv Beh schu 20 25 30

C5

Niv Iie Ter Uai sitz Rgo Aia TPg Iie Rbe Guz Mee b1u Mee ABp She zek Iie Tuk Sub bip Asia1a Aza I1e gub AvBp o Suv bip Rgo Bek Puv Iets 40 50 55 bo

Tuk Rpe Tuk Ppuv Avp biu I1e puv sit Agkd Robe Ni5 I1e TPg Agd She 65 70 75 80 45 Avpopuv Tpg TBg Aza Agud Gay Ter Tuk Avp Avp Rpe Uai siy Rgo sip 85 90 95

Aza Rpe Mee Tuk Suv TPg Asia1a bis Sub Bek Agud Tuk Rpe Rgo bij TEPg 100 105 110

Tecp I1і1e Suv s1u Ppuv Avr Iie Bek Bek s1u Tuk Rgo Rgo Avr Uai1i! Rgo 115 120 125

Avr puv Uaii Aza Suv Maiii I1i1e Tuk b1itsp Tuk bek s1u Avp Mee TPg Suv 130 135 140

TPE Ter Avp o Rgo b1iu Agd Rgo TPg Tug I1e Avr TPg Guv Tuk Ua1i Uai 145 150 155 160 (516) Tuk UMai Ppuv bek Te sbits TPkg si siy bij bip bi Tuk TPg 5eg 165 170 175 zek Tuk I1ie AvBp I1e bek TPg Avr bek ITetsyp bip Ppuv s1u Ppuv Puv Tug 180 185 190 em Ma1i Tegr Uaii sip Aia bek Avp Uai Gecp siu Mesye sitsch Ppuv bek Tuz 195 200 205 beep Gay beep I1ie Niv Gay Avr Avr I1ie Uai Iie Rgo bBeg Aza 52 10 bek 12 1e

I1e bek Agud Aia bitshshc AvBr I1e ABp TPg TPg oUa1 bek pub TPg Uai I1e 225 230 235 240

Niv Ter Avr bek bip TPg bek Iie siy pub Uaii bek Suv bij Mee Agd 245 250 255

Tuk puv Aia TPg TBg Avp obip TbPg Ter Avp o Ua1i puv siy Robe Avr TEG 260 265 270

Avp o Rpe TPg Tug bis bip sip bek si Rbe Tug Gay bip Rgo AvBp A1a 275 280 285

Mee Tuk Uai Rpe sip Ua1i Agkd Suv bip b1p TPpg s1u Ppuv Ppuv Tuk Tgr 290 295 300 bip Rkgo Ter Bek Bek Rgo Rpe Rpe Niv Puv TPg Rgo sitc I1e Uai1i Rgo 305 310 315 320 bip Mai TPpg Mee Ppuv bek Rpe sip TP Niv Avr beep AvBp bek s1Uu Ietsy

From 325 330 335

Tets I1ie Aza bek Iie Rpe Ppuv Ppuv Niv Gay TPg bek Avr AvBp Agd Gu 340 345 350 sip Avr I1e s1u Hey Hey Tey si1u Mister Uai! Rre Rpe Aia Uai Mee Geyi 355 3Z6o 365 zek Uaiyi Gets bek Iets I1e s1u I1e Rore ABp Agud bek Gay Agd TP sh1U 370 375 380

I1e puv Agud Agud I1e Ietsy Gay Iiets I1e Rgo Gpuv Tgr Gay Tug bij Avr 385 390 395 400

IT1e Rgo Avp Mesye bits AvBp bek yuv Uaiyi Uai uv Iie Gay bip bij Agd 405 410 415

Ap obits Robe Mes Avp AvBp Avp o beg back bitz bip Uai Gay Tuk Ua1 Avr 420 425 430

Rgo Uai I1ie TPg sats I1e siy chI1e Iie Tey Rgo bis siy Puv Rgo Mes 435 440 445 sbi1u Tuk Gpuv Ppuv bij Avp Avp TpPg s1iu Suv Gay bij Agd puv bis beg 450 455 460

Tets bish Ppuv Bek Gay Gay TPg Avr TPg TpPg Ua1! Ua1i Tug I1e Rgo Avr 465 470 475 480

Tets ABp o TPg s1iu Tuk Ppuv Rgo bip Iie Bek bek Rpe Gay Rgo s1iu 01Uu 60 485 490 495

AvpoNiv Hey bBeg Avp Avr Avr bis TPg Aza bek bek Iiee Hey soi Rgo 500 505 510

Rgo Aia Avr bek Iets ABp Gay b1i1u AvBp ABp Aza Agud Rpe Ppuv Ppuv Tug 515 520 525

Rgo Avr Ripe Aza RPe bek Uai! back back TPg Avp back Gay Back Avp OTG 530 535 540

Pes Robe Gets bis sii Gay AvBp Gay I1e Gay AvBp sip siu bii Suv 5bBekg 545 550 555 560

Rkgo Rgo Avr Mayes bip AvBp bek I1e bic b1u bij TpPg Aza Mee Gay Gay 565 570 575 bi Avr Avr Gay Gay Up bij TpPgs chI1e Rgo bij sbip TBg Gets Ietsy Rgo 580 585 590

Avr siy Rbe Uai bek Suv Gay biu bek Mee AvBp o Guv bij Gay Rgo 5eg 595 (21019) 605

IT1e Avp bek Tuk Rope Rgo bip AvBp I1e Iiietsy bij Bek Niv Rope Avp Agd 610 615 620

I1ie bek Iey Iets siy Guv 625 630 "210" 766 "2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

C5 "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2 -aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa- Megetsy "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "4005" 766

Haa bip TPg Ter bi1ip Suv Rpe Haa ITecy Guv Avp Avp 1 5 10 "2105 767 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9)

From "223" Air "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 767

Haa beep TPg Ter beep Suv Rpe Haa Haa uv Ap 1U 1 5 10 "2105 768 "4005 768 oo "2105 769 "4005 769 oo "2105 770 "4005 770 oo "2105 771 "4005 771 oo 60 "2105 772

"4005 772 o.o. "2105 773 "4005 773 o.o. "2105 774 "4005 774 o.o. "2105 775 "4005 775 o.o. "2105 776 "4005 776 o.o. "2105 777 "4005 777 o.o. "2105 778 "4005 778 "4005 777 4005 779 oo "2105 780 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari " 2205 "221" MY VE5 "222" (7)..(7) "223" RPe(4-EVy) "2205 "221" MY VE5 60 "222" (9)..(9) "223" airpa- I could

"4005 780

Haa bip TPg Ter bip Suv Rpe Ter Guv bij ABp 1U 1 5 10 "2105 781 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПпе(4-guanidino) "2205 "2215 MOR ВЕ5 "222" (9).. (9) "223" airpa-Meguv "4005 781

Zo Haa sip TBg Tgr bip Suv Rbe Ter uv bij ABp 1U 1 5 10 "2105 782 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (9)..(9) "223" airpa-Meguv "4005 782

Haa beep TPg Ter beep Suv Rpe Ter Guv bij ABp 1U 1 5 10 60 «2105 783 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-СО2Н) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 783

Haa bip TPg Ter bip Suv Rpe Ter Guv bij ABp 1U 1 5 10 "2105 784 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR БЕ5 "222" (7)..(7) "223" РПе(4-phenoxy) "2205 "2215 MOR БЕ5 "222" (9).. (9) "223" airpa-Meguv "4005 784

Haa sip TBg Tgr bip Suv Rbe Ter uv bij ABp 1U 1 5 10 "2105 785 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (1)..(1) "223" Ari "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4-СМ) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 785

Haa beep TPg Ter beep Suv Rpe Ter Guv bij ABp 1U 1 5 10 "2105 786 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1)

From "223" Arya "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-Вге) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 786

Haa beep TPg Ter beep Suv Rpe Ter Guv bij ABp 1U 1 5 10 "2105 787 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ars "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" РПе(4-МН2) "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 787

Haa beep TPg Ter beep Suv Rpe Ter Guv bij ABp 1U 1 5 10 "2105 788 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе)

From "220" "221" MY VE5 "222" (8)..(8) "223" RIP(4-Me) "220" "221" MY VE5 "222" (9)..(9) "223 "airpa-Meguv" 4005 788

Haa beep Ts Ter beep Suv Rpe Rpe Gpuv bij Ap 1U 1 5 10 "2105 789 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) 60 "223" РПе(4-ОМе)

"221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 789

Haa bip TPg Ter bip Suv Rpe Haa puv siy AvBp b01Uu 1 5 10 "2105 790 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-MeoOgp "2205 "221" MY VE5 "222" (10). .(10) "223" Puv(As) "4005 790

Haa beep TPg Ter beep Suv Rpe Haa Haa uv Ap 1U 1 v; 10 "2105 791 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

"222" (1)..(1) "223" Arya "2205 "2215 MOR VE5 "222" (7)..(7) "223" 2-May "2205 "2215 MOR WEB "222" (8) ..(8) "223" 2-May "2205 "2215 MOR VEB "222" (9)..(9) "223" airpa-MeoOgp "2205 "2215 MOR VE5 "222" (10)..(10 ) "223" Puv(As) "4005 791

Haa sip TBg Tgr beep Suv Haa Haa Haa yuv ABp 1U 1 5 10 "2105 792 "2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222 " (7)..(7) "223" Vir "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "4005 792

Haa beep TPg Ter beep Suv Haa Haa Gpuv puv ABp 1U 1 5 10 "2105 793 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Spa "2205 "221" MY VE5 "222" (8)..(8 ) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9)

From "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 793

Haa bip TPg Ter bip Suv Haa Haa Gpuv puv ABp 1U 1 5 10 "2105 794 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Arya "2205 "2215 MOR VE5 "222" (7)..(7) "223" 2-May "2205 60 "2215 MO VE5 "222" (8)..(8 )

"223" May 2 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv (Ac) "4005 794

Haa beep TPg Ter beep Suv Haa Haa Gpuv puv ABp 1U 1 5 10 "2105 795 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar

From "220" "221" MY VE5 "222" (7)..(7) "223" 4A4-Rukiau1iaiiapipe

З5 "220" "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 795

Haa beep TPg Ter beep Suv Aia Haa Gpuv puv ABp 1U 1 5 10 "2105 796 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Weba-PpotshotTug "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 " 222" (10)..(10) "223" Puv(As) "4005 796

Haa beep TPg Ter beep Suv Tuk Haa Gpuv puv ABp 1U 1 5 10 "2105 797 "2115 12 "2125 RVT "2135 Artificial sequence

C5 "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7).. (7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9). .(9) "223" airpa-Meguv "2205 "221" MY VE5 60 "222" (10)..(10) "223" Puv(As)

"4005 797

Haa bip TPg Ter bip Suv Rpe Haa Gpuv pub Avp b1U 1 5 10 "2105 798 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" (1 )..(1) "223" Arya "2205 "2215 MOR VE5 "222" (7)..(7) "223" 2-May "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 798

Haa sip TBg Tgr beep Suv Haa Haa uv biy ABp 1U 1 5 10 "2105 799 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" May 2 "2205 "221" MY VE5 "222" (7).. (7) "223" РПе(4-ОМе) 60 "2205

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 " 221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 799

Haa bip Ts Haa sbip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 800 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1)

From "223" Ari "2205 "221" MY VE5 "222" (4)..(4)

З5 "223" 1-May "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..( 8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 800

Haa bip Ts Haa sbip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 60 «2105 801

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 801

Haa bip Ts Tuk bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 802 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "220" "221" MY VE5 "222" (8)..(8) "223" May 2 (516) "220" "221" MY VE5

"222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 802

Haa sip TBg Tgr bip Suv Rbe Haa Puv yuv ABp 1U 1 5 10 "2105 803 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10). .(10) "223" Puv(As) "4005 803

Haa bip TP Ter bip Suv Rpe Haa Guv Gpuv Avp sbiu s1u sats 1 5 10 "2105" 804 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (1)..(1) "223" Ar

"221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May " 2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 » 804

Haa bip TP Ter bip Suv Rpe Haa Guv Gpuv Avp sb1u Aia s1its 1 5 10 "2105 805 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1)..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8) ..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10 ) "223" Puv(As) "4005 805 (516) Haa bek TPg Tgr bip Suv Rbe Haa Puv iuv ABp o1u s1u Jan 1 5 10

"2105 806 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221 » MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 " 221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 806

Haa beep TP Ter beep Suv Rpe Tkgr uv Ppuv Avp biu s1i1u bij 1 5 10 "2105 807 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (1). ..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) 10) "223" Ppuv(As)

"4005 807

Haa bip TPg Ter bip Suv Tuk Haa Guv Gpuv Avp sb1iu s1u sic 1 5 10 "2105 808 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10 )..(10) "223" Puv(As) "4005 808

Haa bip TPg Ter bi1ip Suv Rpe Haa Guv Guv Avp beg 1 5 10 "2105 809 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) (516) "220" "221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR WEB "222" ( 10)..(10) "223" Puv(As) "4005 809

Haa sip TBg Tgr bip Suv Ribe Haa Puv Guv ABp Aia 1 5 10 "2105 810 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 "221" MY VE5 "222" (10)..( 10) "223" Puv(As) "4005 810

Haa bip TPg Ter bip Suv Rpe Haa Haa uv Ap 1U 1 5 10 "2105 811 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПе-4-М3 "2205 "221 » MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 811

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 812 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8).. (8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 60 "2215 MO VE5 "222" (10)..(10)

"223" Puv(As) "4005 812

Haa beep TPg Ter beep Suv Rpe Haa Gpuv Ppuv beep Sh1U 1 5 10 "2105 813 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) "223" May 2

From "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "220" "221" MY VE5 "222" (10)..(10) "223" Puv( Ac) "2205 "221" MY VE5 "222" (11)..(11) "223" seeds "4005 813

Haa beep TPg Ter beep Suv Rpe Haa Gpuv Ppuv Haa Sh1U 1 5 10 "2105" 814 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) (516) "223" Ar

"221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May " 2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 814

Haa bip TPg Ter bip Suv Rpe Haa puv Uai ABp sh1U 1 5 10 "2105 815 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10)..( 10) "223" Puv(As) "4005 815

Haa beep TPg Ter beep Suv Rpe Haa Haa uv Ap 1U 1 v; 10 "2105 816 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR WEB "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" Ogp "2205 "2215 MOR VE5 "222" (10)..(10) "223" Rar "4005 816

Zo Haa sip TBg Tgr bip Suv Ribe Haa Haa Haa ABp 1U 1 5 10 "2105 817 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv 60 "2205

"221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 817

Haa Avp o TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 818 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" Vir "2205 "221" MY VE5 "222" (7)..( 7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9).. (9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 818

Haa bip Ts Haa sbip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 819 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO ВЕ5 "222" ( 1)..(1)

"223" Ari "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Spa "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(Ac) "4005 819

Haa bip TPg Ter bip Suv Rpe Haa Haa uv Ap 1U 1 5 10 "2105 820 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

C5 "220" "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе ) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" Seed "220 » "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "4005 820

Haa beep TPg Ter beep Suv Rpe Haa Haa uv Ap 1U

1 5 10 "2105 821 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari " 2205 "221" MY VE5 "222" (4)..(4) "223" Osta1uU "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 821

Haa beep Ts b1u beep Suv Rpe Haa Ppuv Ppuv ABp 1U 1 5 10 "2105 822 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 60 "222" (7)..(7) "223" Osta1uU

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 822

Haa bip TPg Ter bip Suv s1u Haa puv Ppuv ABp 1U 1 5 10 "2105 823 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8).. (8) "223" Osta1uU "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 823

Haa sip TBg Tgr beep Suv Rpe s1u Puv uv ABp 1U 1 5 10 "2105" 824 "2115 13 60 "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9 ) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 824

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv AvBp s1iu sitc 1 5 10 "2105 825 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" ( 8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) (516) "223" airpa-Meguvs

"221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 825

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv AvBp Aia s1its 1 5 10 "2105 826 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10) ..(10) "223" Puv(As) "4005 826

Haa bek TPg Ter bip Suv Rpe Haa Gpuv Ppuv AvBp s1iu sitc 1 5 10 "2105 827 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (1)..(1) "223" Ari (516) "220" "221" MY VE5

222 (7). 222" (10)..(10) "223" Puv(As) "4005 827

Haa sip TBPg Tgr bip Suv Ribe Ter Tuz Guv ABp s1u Jan 1 5 10 "2105 828 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9). .(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 828

Haa beep TP Ter beep Suv Tuk Haa puv Puv Avp biu biu 1 5 10 "2105" 829 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (1)..(1) "223" Ar

"221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223" 2 - Mai "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 829

Haa bip TPg Ter bip Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 830 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (8 )..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 830

Haa sip TBPg beep sbip Suv Rbe Haa Puv bij ABp 1U 1 5 10 "2105 831 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (1)..(1) "223" Ar "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy ) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv " 4005 831

Haa bip Ts Niv bip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 832 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (4)..(4) "223" PRIE "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguvs "4005 832

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 60 «2105 833

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" c1its(Bv-x1) "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy ) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv " 4005 833

Haa beep Ts bii beep Suv Rpe Haa guv bii Ap 1U 1 5 10 "2105 834 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "220" "221" MY VE5 "222" (4)..(4) "223" Vir "220" "221" MY VE5 "222" (7).. (7) "223" Rpe|4-(2-aminoethoxy) (516) "220" "221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 834

Haa sip TBg Haa sip Suv Rpe Haa Guz bij ABp 1U 1 5 10 "2105 835 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" Yew "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguv "4005 835

Haa beep TPg Haa sbip Suv Rpe Haa uv bij Ap 01Uu 1 5 10 "2105 836 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222 » (1)..(1) "223" Ar

"221" MY BE5 "222" (4)..(4) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (7)..(7) "223" Rpe |4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 836

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 837 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (4)..(4) "223" РПпе(3,4-С12) "2205 "2215 MOR ВЕ5 "222" (7) ..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-Mai "2205 "2215 MOR VE5 "222" ( 9)..(9) "223" airpa-Meguv "4005 837 (516) Haa sip TPg Rpre sbip Suv Rbe Haa Puv bij ABp 1U 1 5 10

"2105 838 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221 » MY VE5 "222" (4)..(4) "223" РПе(4-ОМе) "2205 "221" MY ВЕ5 "222" (7)..(7) "223" Рпе|4-(2 -aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2

From "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 838

Haa beep Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105" 839 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" Ogp(Vepghu1) "2205 "221" MY VE5 "222" (7) ..(7) 10) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 839

Haa beep TPg Haa sbip Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105" 840 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" Ogp(Vepla1adepuae) "2205 "221" MY VE5 "222" (7) ..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222 » (9)..(9) "223" airpa-Meguv "4005" 840

Haa bip TPg Haa sbip Suv Rpe Haa uv biy Ap 1U 1 5 10 "2105 841 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

"222" (1)..(1) "223" Ars "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rpe-ОСН2СН2МНАсС "2205 "2215 MOR VEB "222" (8) ..(8) "223" 2-May "2205 "2215 MOR WEB "222" (9)..(9) "223" airpa-Meguv "4005 841

Haa sip TBg Tgr beep Suv Rbe Haa Puv bij ABp 1U 1 5 10 "2105" 842 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222 (8).

Haa bip TPg Ter bip Suv Rpe Haa Gay bij Ap 1U 1 5 10 "2105 843 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (4)..(4) "223" 5-hydroxyTgr "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 843

Haa bip TPg Ter bip Suv Rpe Haa uv biy Ap 1U 1 5 10 "2105" 844 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR VE5 "222" (4)..(4) "223" 6-sp1ogoTgr "2205 "2215 MOR VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOB БЕ5 "222" (8)..(8) "223" 2-Mai "2205 60 "2215 MO БЕ5 "222" (9). .(9)

"223" airpa-Meguv "4005" 844

Haa beep TPg Ter beep Suv Rpe Haa puv bij Ap 1U 1 5 10 "2105" 845 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" M-MetTgr "2205 "221" MY VE5 "222" (7). .(7) "223" Rpe|4-(2-aminoethoxy)

From "220" "221" MY VE5 "222" (8)..(8) "223" May 2

Z5 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005" 845

Haa bip TPg Ter bip Suv Rpe Haa puv siy AvBp b01U 1 5 10 "2105" 846 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ars "2205 "221" MY VE5 "222" (4)..(4) (516) "223" 1,2,3,4-tetrahydro-norharmane

"221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223" 2 - Mai "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005" 846

Haa bip TPg Haa sbip Suv Rpe Haa puv siy AvBp b01U 1 5 10 "2105" 847 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (4)..(4) "223" РПе(4-СО2Н) "2205 "221" MY VE5 "222" ( 7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvi "4005" 847

Haa beep Ts Rpe sbip Suv Rpe Haa uv bij Ap 01U 1 5 10 "2105" 848 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (4)..(4) "223" РПе(4-СОМН2) "2205 "2215 MOR VEB "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR БЕ5 "222" (8)..( 8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005" 848

Zo Haa sip TPg Rpre sbip Suv Rbe Haa Puv bij ABp 1U 1 5 10 "2105" 849 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May 60 "2205

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005" 849

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 850 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (4)..(4) "223" РПе(3,4-ОМе) "2205 "221" MY VE5 "222" (7)..(7) 0) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221 » MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 850

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 851 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ars "2205 60 "2215 MO VE5 "222" (4)..(4)

"223" airpa-MeRre "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..( 8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 851

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 852 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (4)..(4) "223" РПе(4- SEZ) "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 852

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 853 (516) "2115 12 "2125 RVT

"2135 Artificial sequence "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4).. (4) "223" РПе(4-ЕВы) "2205 "221" MY ВЕ5 "222" (7)..(7) "223" Рпе|4-(2-aminoethoxy) "2205 "221" MY ВЕ5 " 222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvi "4005 853

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 854 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (4)..(4) "223" РПе(2,4-Me2) "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 60 "222" (8)..(8) "223" 2-May

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "4005 854

Haa bip Ts Rpe sbip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 855 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (8 )..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 855

Haa sip TBg Tgr bip Suv Rbe Haa Puv Avr ABp 1U 1 5 10 "2105 856 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) 60 "2205

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 856

Haa beep TPg Ter beep Suv Rpe Haa Guz sbip AvBp 01Uu 1 5 10 "2105 857 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) 0) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8) » (10)..(10) «223» puvi (Benzoic acid) «4005 857

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv Avp b1U 1 5 10 "2105 858 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" ( 1)..(1)

"223" Ar "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223 » Gguvi (succinic acid) «4005 858

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv AvBp b1Uu 1 5 10 "2105 859 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 (1). "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "220" "221" MY VE5 "222" (10)..(10) "223" Gpuv (glutaric acid) 60 "4005 859

Haa beep TPg Ter beep Suv Rpe Haa Gpuv Ppuv ABp 1U

1 5 10 "2105" 860 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223 » May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Kuv (ipyroglutamic acid) conjugated through the side chain "4005" 860

Haa beep TPg Ter beep Suv Rpe Haa puv puv ABp 1U 1 5 10 "2105 861 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 60 " 222" (8)..(8) "223" May 2

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" pKuvi(isovaleric acid) "4005 861

Haa bip TPg Ter bip Suv Rpe Haa puv puv ABp 1U 1 5 10 "2105" 862 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10).. (10) "223" Ppuv(Rait) "4005 862

Haa sip TBg Tgr bip Suv Rpe Haa Puv pub ABp s1U 1 5 10 "2105 863 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (1)..(1) "223" Ar "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy ) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv " 2205 "221" MY VE5 "222" (10)..(10) "223" puv(RESI1) "4005 863

Haa beep TPg Ter beep Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 864

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) 60 "223" puv(RES2)

"4005" 864

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 865 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Rar (Benzoic acid) "4005" 865

Haa beep TPg Ter beep Suv Rpe Haa Guz Haa Ap 1U 1 5 10 "2105" 866 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 (1). "221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR WEB "222" ( 10)..(10) "223" Rar (succinic acid) "4005" 866

Haa sip TBg Tgr bip Suv Rbe Haa Puv Haa ABp 1U 1 5 10 "2105 867 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" ( 10)..(10) "223" Rar (glutaric acid) "4005 867

Haa bip TPg Ter bip Suv Rpe Haa Guz Haa Ap 1U 1 5 10 "2105" 868 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(510) "223" Rar (pyroglutamic acid) conjugated through the side chain "4005 868

Haa beep TPg Ter beep Suv Rpe Haa Guz Haa Ap 1U 1 5 10

From "2105" 869 "2115 12 "212" RET "2135 Artificial sequence

C5 "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR БЕ5 "222" (1)..(1) "223" Ari "2205 "2215 MOR БЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (8)..(8) "223" 2-Mai "2205 "2215 MOR ВЕ5 "222" (9)..( 9) "223" airpa-Meguv "2205 60 "2215 МО ВЕ5 "222" (10)..(510) 5В8ВО

"223" RBar(IMA) "4005" 869

Haa bip TPg Ter bip Suv Rpe Haa Guz Haa Ap 1U 1 5 10 "2105 870 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 » (8)..(8) "223" May 2

From "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "220" "221" MY VE5 "222" (10)..(10) "223" Rar( RESI1) "4005 870

Haa bip TPg Ter bip Suv Rpe Haa Guz Haa Ap 1U 1 5 10 "2105 871 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) 10) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Rar(RES2) "4005 871

Haa bip TPg Ter bip Suv Rpe Haa Guz Haa Ap 1U 1 5 10 "2105 872 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" ( 10)..(10) "223" Bar(RES2-Ac) "4005 872

Haa beep TPg Ter beep Suv Rpe Haa Guz Haa Ap 1U 1 in; 10 "2105 873 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VEB "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) " 223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "2205 "2215 MOR VE5 "222" (13)..(13) "223" ( 2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14)..(14) "223" 0-Guv "4005 873

Haa sip TBg Tgr bip Suv Ribe Haa Ppuv pub Avp s1u Haa Guz 1 5 10 "2105 874 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (1).

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 " 221" MY VE5 "222" (10)..(10) "223" Puv(As) "2205 "221" MY VE5 "222" (13)..(13) "223" 0-Guv "4005 874

Haa bip TP Ter bi1ip Suv Rpe Haa Guv Gpuv Avp so1Uu Guv 1 5 10 "2105 875 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(Ac) "2205 "221" MY VE5 "222" (13)..(13) 10) "223" (2-aminoethoxy)acetic acid

"4005 875

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv Avp s1iu Haa 1 5 10 "2105 876 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 "221" MY VE5 "222" (10 )..(10) "223" Puv(As) "4005 876

Haa bip TPg Ter bip Suv Rpe Haa Haa Gguv sbip Sh1U 1 5 10 "2105 877 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Ary "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) (516) "220" " 221" MY VE5

"222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" hole "4005 877

Haa sip TBg Tgr bip Suv Ribe Haa Haa sbip ABp 1U 1 5 10 "2105 878 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" hole "4005 878

Haa beep TPg Ter beep Suv Rpe Haa Haa bij Ap 1U 1 5 10 "2105 879 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 60 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" May 1 "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 879

Haa bip TPg Ter bip Suv Rpe Haa Haa uv Ap 1U 1 5 10 "2105" 880 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" hole "2205 "2215 MOR VE5 "222" (10)..(10 ) "223" Puv(As) "4005" 880

Haa sip TBg Tgr beep Suv Ribe Haa Haa Guz ABp Aia 1 5 10 "2105 881 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9). .(9) "223" holes "4005 881

Haa beep TPg Ter beep Suv Rpe Haa Haa uv Ap 1U 1 5 10 "2105" 882

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY БЕ5 "222" (7)..(7) "223" Рпе|4-(2-aminoethoxy) "2205 "221" MY БЕ5 "222" (8)..(8) "223" Рпе(4-СО2Н ) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) 10) "223" Ppuv( Ac)

"4005" 882

Haa beep Ts Ter beep Suv Rpe Rpe Ppuv Ppuv ABp 1U 1 5 10 "2105 883 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (2)..2) "223" Rar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" RPe(4-Phenoxy) "2205 "221" MY VE5 "222" ( 9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 883

Haa Haa TPg Ter beep Suv Rpe Rpe Ppuv Ppuv Ap 1U 1 5 10 "2105" 884 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (1)..(1) "223" Ari (516) "220" "221" MY VE5

"222" (2)..2) "223" Rar "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VEB " 222 (8). VE5 "222" (10)..(10) "223" Puv(As) "4005" 884

Haa Haa TPg Tgr beep Suv Rbe Rpe Puv iuv ABp 1UuU 1 5 10 "2105" 885 "211511

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222 " (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" airpa-Meguv "2205 "221" MY VE5 "222" (9)..(9) "223" Puv(As) "4005" 885

Haa bip TP Ter bi1ip Suv Rpe Guv Guv ABp 1U 1 5 10 60 «2105 886 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (2)..2) "223" Rar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" ACCEPTS "2205 "221" MY VE5 "222" (9)..(9)

From "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 886

Haa Haa TPg Ter bip Suv Rpe Rpe Ppuv Ppuv Ap 1U 1 5 10 "2105 887 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" (1 )..(1) "223" Ars "2205 "2215 MOR VE5 "222" (2)..2) "223" Rar "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" Rpe|4-(2-aminoethoxy) "221" MY VE5 "222" (8)..(8) "223" c1its(Bv-x1) "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 887

Haa Haa TPg Ter beep Suv Rpe bij Ppuv Ppuv ABp 1U 1 5 10 "2105" 888 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4- (2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Me-Ogp "4005" 888

Haa bip TPg Ter bip Suv Rpe Tgr Haa siy AvBp 01U 1 5 10 "2105" 889 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) (516) "223" Ar

"221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa - Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 889

Haa beep Ts Ter beep Suv Rpe Ter Ppuv Ppuv ABp 1U 1 5 10 "2105 890 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (9)..(9) "223" airpa-Me-Ogp "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 890

Haa bip TPg Ter bip Suv Rpe Tgr Haa Gguv ABp 1U 1 5 10 "2105 891 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

222 (1). "222" (8)..(8) "223" May 2 "2205 "2215 MOR VEB "222" (9)..(9) "223" airpa-Me-Ogp "2205 "2215 MOR VE5 "222 " (10)..(10) "223" Puv(As) "4005 891

Haa sip TBg Tgr bip Suv Ribe Haa Haa yuv ABp 1U 1 5 10 "2105 892 "2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222 " (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) 60 "4005 892

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 893 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10) ..(10) "223" Ppuv(As) "4005 893

Haa bip TPg Ter bip Suv Rpe Haa Haa uv Ap 1U 1 5 10 "2105" 894 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" ( 1)..(1) "223" Ar "2205 "2215 MOR БЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 60 "2215 MO БЕ5 "222" (9)..(9)

"223" OGP "4005" 894

Haa bip TPg Ter bip Suv Rpe Tgr Haa bij Ap 1U 1 5 10 "2105" 895 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (9)..(9) "223" Ogp

From "220" "221" MY VE5 "222" (10)..(10) "223" Rar "4005 895

Haa bip TPg Ter bip Suv Rpe Tgr Haa Haa Ap 1U 1 5 10 "2105 896 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 » (9)..(9) 60 "223" Ogp

"221" MY VE5 "222" (10)..(10) "223" Rar(Ac) "4005 896

Haa bip TPg Ter bip Suv Rpe Ter Haa Haa Ap 1U 1 5 10 "2105 897 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Ogp "2205 "221" MY VE5 "222" (10) ..(10) "223" Rar "4005 897

Haa bip TPg Ter bip Suv Rpe Haa Haa Haa AvBp s1U 1 5 10 "2105 898 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 » (1)..(1) "223" Ari (516) "220" "221" MY VE5

222 (7). MOR WEB "222" (9)..(9) "223" OGP "2205 "2215 MOR WEB "222" (10)..(10) "223" Rar(As) "4005 898

Haa sip TBg Tgr beep Suv Ribe Haa Haa Haa ABp 1U 1 5 10 "2105" 899 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (9)..(9) "223" pPTey "4005" 899

Haa beep TPg Ter beep Suv Rpe Ter Gay bij Ap 1U 1 5 10 "2105 900 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222 » (1)..(1) "223" Ar

"221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-(acetyl-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) " 223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguz (As) "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 900

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 901 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (9 )..(9) "223" airpa-Me-Ieiy "4005 901

Haa sip TBg Tgr bip Suv Robe Ter Gay bij ABp 1U 1 5 10 "2105 902 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (1)..(1) "223" Ar "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy ) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv " 2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 902

Haa beep TPg Ter beep Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 «2105 903

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "2205 "221" MY VE5 "222" (11)..(11) (516) "223" Rar 6oo0

"4005 903

Haa beep TPg Ter beep Suv Rpe Ter Ppuv Ppuv Haa C1U 1 5 10 "2105 904 "2115 10 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 904

Haa bip Ts Tkr bi1ip Suv Rpe Tgr Guv Guv 1 5 10 "2105 905 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1) ..(1) "223" Ar "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222 » (9)..(9) "223" Seed (516) "220" "221" MY VE5 because

"222" (10)..(10) "223" Puv(As) "4005 905

Haa sip TBg Tgr bip Suv Rbe Ter Haa Guz ABp 1U 1 5 10 "2105 906 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-(acetyl-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv (As) "4005 906

Haa beep TPg Ter beep Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 907 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 60 " 222" (8)..(8) "223" РПе(4-СОМН2) b6vo2

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 907

Haa bip Ts Ter bip Suv Rpe Rpe Ppuv Ppuv ABp 1U 1 5 10 "2105 908 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (8 )..(8) "223" РПе(3,4-ОМе2) "2205 "2215 MOR ВЕ5 "222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR ВЕ5 "222" ( 10)..(10) "223" Puv(As) "4005 908

Haa sip TBg Tgr bip Suv Rbe Rpe Puv yuv ABp 1UuU 1 5 10 "2105 909 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205 6oZ

"221" MY VE5 "222" (1)..(1) "223" Ari "220" "221" MY VE5 "222" (2)..2) "223" Rar "2205 "221" MY VE5 " 222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" Thys "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 909

Haa Haa TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 910 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (2)..2) "223" Rar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) 60 "223" Rpe(3,4-C12)

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 910

Haa Haa TPg Ter bip Suv Rpe Rpe Guz Puv AvBp b1U 1 5 10 "2105 911 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 911

Haa bip TPg Ter bi1ip Suv Rpe Haa Gguv b1p ABp sip 1 5 10 "2105 912 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222 » (1)..(1) "223" Ari (516) "220" "221" MY VE5

222 (7). MOR WEB "222" (9)..(9) "223" airpa-Meguv "4005 912

Haa sip TBPg Tgr bip Suv Ribe Haa Puv bij ABp Avp 1 5 10 "2105 913 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 913

Haa TPg TP Ter bip Suv Rpe Haa uv biy Ap 1U 1 5 10 "2105 914 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222 » (1)..(1) "223" Ari 6 vol

"221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223" 2 -Mai "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Me-s1u (EEBPU1) "2205 "221" MY VE5 "222" (10)..(10) " 223" Tuv(As) "4005 914

Haa bip TPg Ter bip Suv Rpe Haa c1u puv ABp 1U 1 5 10 "2105 915 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (8 )..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-MeUai "2205 "2215 MOR VE5 "222" (10)..( 10) "223" Puv(As) "4005 915 (516) Haa sip TBg Tgr bip Suv Rbpe Haa Uaii puv ABp 1U 1 5 10

"2105 916 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221 » MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Mebeg

From "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 916

Haa bip TPg Ter bip Suv Rpe Haa bek Ppuv AvBp 01Uu 1 5 10 "2105 917 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" Rar "2205 "221" MY VE5 "222" (7)..(7 ) 10) "223" Rpe|4-(2-aminoethoxy)6o8

"221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221 » MY VE5 "222" (10)..(10) "223" Puv(As) "4005 917

Haa beep Ts Haa sbip Suv Rpe Haa puv pub AvBp b1U 1 5 10 "2105 918 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" Rar "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10) ..(10) "223" Puv(As) "4005 918

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv Avp b1U 1 v; 10 "2105 919 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VEB "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) " 223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 919

Zo Haa sip TBg Agud bip Suv Rbe Haa Puv yuv ABp 1U 1 5 10 "2105 920 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222 (9).

Haa beep Ts Ter beep Suv Rpe Agd Ppuv Ppuv ABp 1U 1 5 10 "2105 921 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (4)..(4) "223" Rar "2205 "221" MY VE5 "222" (7)..(7 ) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8)

From "223" Rar "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 921

Haa bip Ts Haa sbip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 922 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ars "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" Rpe|4-(2-aminoethoxy) "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 922

Haa bip TPg Avr o bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 923 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4- (2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 923

Haa beep Ts Ter beep Suv Rpe Avr Gpuv puv ABp 1U 1 5 10 "2105 924 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) " 4005 924

Haa beep TPg Avr o beep Suv Rpe Avr Gpuv puv ABp 1U 1 5 10 "2105 925 "2115 13 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-Guv "2205 "221" MY VE5 "222" (2) ..2) "223" Ars "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9).. (9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-Megetsy "4005 925

Tpuv Haa beep TPg Ter beep Suv Rpe Haa gay sb1tsp ABp sh1U 60 1 v; 10

"2105 926 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (1)..(1) "223" Ari "2205 "2215 MOR "222" (7). 2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 926

Zo Haa sip TBg Tgr bip Suv Rbe Haa tsuv Agud ABp 1U 1 5 10 "2105 927 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222 (8).

"221" MY VE5 "222" (10)..(10) "223" OGP "4005 927

Haa bip TPg Ter bip Suv Rpe Haa Guz Haa Ap 1U 1 5 10 "2105 928 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 » (8)..(8)

From "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "4005 928

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 929 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 60 "2215 MO BE5 "222" ( 8)..(8)

"223" 2-May "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" PAgd "4005 929

Haa bip TPg Ter bip Suv Rpe Haa uv Agd ABp 1U 1 5 10 "2105 930 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar

From "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8 ) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" pPTeiy "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "220" "221" MY VE5 "222" (12)..(12) "223" Vega-Ai1a "4005 930

Haa bip TP Ter bi1ip Suv Rpe Haa Iietsy Guv ABp Aia 1 5 10 "2105 931 (516) "2115 12 "2125 RVT

"2135 Artificial sequence "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7).. (7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" ( 9)..(9) "223" sows "2205 "221" MY VE5 "222" (10)..(10) "223" Rar "4005 931

Haa beep TPg Ter beep Suv Rpe Haa Haa Haa Ap 1U 1 5 10 "2105 932 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (2)..2) "223" airpa-Me-Ogp "2205 "221" MY VE5 "222" (7). .(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 60 "222" (8)..(8) "223" 2-May

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguvs "4005 932

Haa Haa TPg Ter bip Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 933 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (8 )..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 933

Haa sip TBg Tgr bip Suv Rbpe Haa Puv Avp ABp s1U 1 5 10 "2105 934 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) 60 "2205

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 934

Haa bek TPg Tkgr bip Suv Rpe Haa Guv Gpuv Avp sbiu si1u sic 1 5 10 "2105 935 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Ary "2205 "221" MY VE5 "222" (7)..(7) 0) "223" Rpe|4-(2-(acetyl-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguz (As) " 4005 935

Haa bip TPg Ter bi1ip Suv Rpe Haa Gguv b1p ABp sip 1 5 10 "2105 936 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(1) "223" Ars "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" Rpe|4-(2-(acetyl-aminoethoxy) "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9) ..(9) "223" airpa-Meguv (As) "4005 936

Haa bip TPg Ter bi1ip Suv Rpe Haa Guv b1y Avp Avp 1 5 10 "2105 937 "211511 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1 )..(1) "223" Ar

From "220" "221" MY VE5 "222" (6)..(6) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (7)..(7 ) "223" 2-May "2205 "221" MY VE5 "222" (8)..(8) "223" airpa-Meguv "4005 937

Haa TPg Tgr bi1ip Suv Rpe Haa Gguv bij Ap 1U 1 5 10 "2105 938 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1 )..(1) (516) "223" Ar

"221" MY VE5 "222" (7)..(7) "223" RIP(4-Me) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May " 2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 938

Haa beep TPg Ter beep Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 939 "2115 12 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7).. (7) "223" RIe(3-Me) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9). .(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 939

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv ABp 1U 60 1 v; 10 b21

"2105 940 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" (1)..(1) "223" Ari "2205 "2215 MOR "222" (7). )..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 940

Haa sip TBg Tgr bip Suv Tuk Haa Puv uv ABp 1U 1 5 10 "2105 941 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 » (8)..(8) «223» airpa-MetTgr 60 «2205

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "220" "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 941

Haa beep Ts Ter beep Suv Rpe Ter Ppuv Ppuv ABp 1U 1 5 10 "2105 942 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (2)..2)

From "223" airpa-Mebeg "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8) ..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10).. (10) "223" Ppuv(As) "4005 942

Haa bek TPg Ter beep Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105 943 "2115 12 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Description of artificial sequence: Synthetic peptide "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (3)..(3) "223" airpa-Mebeg "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8 ) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) " 223" Puv(As) "4005 943

Haa beep back Ter beep Suv Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 944 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8) "223" airpa-MeRre (516) "220" "221" MY VE5

"222" (9)..(9) "223" airpa-Meguv "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005" 944

Haa sip TBg Tgr bip Suv Rbe Rpe Puv yuv ABp 1UuU 1 5 10 "2105" 945 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (9)..(9) "223" holes "4005 945

Haa bip TPg Ter bip Suv Rpe Tgr Haa bij Ap 1U 1 5 10 "2105" 946 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 60 "222" (8)..(8) "223" May 2

"221" MY VE5 "222" (9)..(9) "223" Air "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 946

Haa bip TPg Ter bip Suv Rpe Haa Haa uv Ap 1U 1 5 10 "2105" 947 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOP VE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" hole "2205 "2215 MOR VE5 "222" (11)..(11 ) "223" Rar(As) "4005 947

Haa sip TBg Tgr bip Suv Rbpe Haa Haa siy Haa 1U 1 5 10 "2105" 948 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "2205

"221" MY VE5 "222" (1)..(1) "223" Ar "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy ) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes "2205 " 221" MY VE5 "222" (11)..(11) "223" slave(As) "4005 948

Haa beep TPg Ter beep Suv Rpe Haa Haa siy Haa Sh1U 1 5 10 "2105" 949

Zo "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Air "2205 "221" MY VE5 "222" (11)..(11) 10) "223" Ppuv(As)

"4005 949

Haa bip TPg Ter bip Suv Rpe Haa Haa siy guv Sh1U 1 5 10 "2105 950 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (9)..(9) "223" holes "4005 950

Haa bip TPg Ter bi1ip Suv Rpe Tgr Haa b1y Avp Avp 1 5 10 "2105 951 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy 60 "4005 951

Haa beep TPg Ter beep Suv Rpe Haa Gay b1its Avp Avp

1 5 10 "2105 952 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari " 2205 "221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY BE5 "222" (8)..(8) "223" РПе(3,4-ОМе2) "2205 "221" MY VE5 "222" (9)..(9) "223" hole "4005 952

Haa bip TPg Ter bip Suv Rpe Rpe Haa bij Ap 1U 1 5 10 "2105 953 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" РПпе(3,4-С12) "2205 "221" MY VE5 60 "222" (9)..(9) "223" holes

"4005 953

Haa bip TPg Ter bi1ip Suv Rpe Robe Haa b1y Avp Avp 1 5 10 "2105 954 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" (1 )..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" (8 )..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Megetsy "2205 "2215 MOR VE5 "222" (10)..( 10) "223" becomes "4005 954

Haa sip TBPg Tgr bip Suv Ribe Haa Gay Haa ABp Avp 1 5 10 "2105 955 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) 60 "2205

"221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "2205 " 221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005 955

Haa bip TPg Ter bi1ip Suv Rpe Haa ITecy Guv Avp Avp 1 5 10 "2105 956 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1)

From "223" Arya "2205 "221" MY VE5 "222" (7)..(7) "223" RIP(4-Me) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes "4005 956

Haa bip TPg Ter bip Suv Rpe Haa Haa siy Ap 01U 1 5 10 "2105 957 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" ( 1)..(1)

"223" Ari "221" MY VE5 "222" (7)..(7) "223" РПе(3,4-Е2) "2205 "221" MY VE5 "222" (8)..(8) " 223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" holes "4005 957

Haa bip TPg Ter bip Suv Rpe Haa Haa bij Ap 1U 1 5 10 "2105 958 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" РПе(3- SOMN2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" hole "4005 958

Haa beep TPg Ter beep Suv Rpe Haa Haa bij Ap 1U 1 5 10 "2105 959 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" РПпе(2,4-С12) " 2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" holes "4005 959

Haa beep TPg Ter beep Suv Rpe Haa Haa bij Ap 1U 1 5 10 "2105 960 "2115 12 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7).. (7) "223" RIe(3-Me) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9). .(9) "223" holes "4005 960

Haa beep TPg Ter beep Suv Rpe Haa Haa bij Ap 1U 1 in; 10 "2105 961 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (7)..(7) "223" РПе(4-С1) "2205 "2215 MOR VEB "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" holes "4005 961

Haa sip TBg Tgr beep Suv Rbe Haa Haa bij ABp 1U 1 5 10 "2105 962 "2115 12

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222 " (7)..(7) "223" РПе(4-Е) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 " 222" (9)..(9) "223" holes "4005 962

Haa beep TPg Ter beep Suv Rpe Haa Haa bij Ap 1U 1 5 10 60 «2105 963 «2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe(2,4-С12, 4-ОВ7) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 " 221" MY VE5 "222" (9)..(9) "223" holes "4005 963

Haa bip TPg Ter bip Suv Rpe Haa Haa bij Ap 1U 1 5 10 "2105 964 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (1 )..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8).. (8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Megetsy "2205 60 "2215 MO VE5 "222" (13)..(13)

"223" 0-Guv "4005 964

Haa bip TP Ter bi1ip Suv Rpe Haa Iiietsp bii AvBp o1Uu Guv 1 5 10 "2105 965 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Ar "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 » (9)..(9) "223" May 2

From "220" "221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "4005 965 bi Haa beep TPpg Ter beep Suv Rpe Haa Gguv bij Avp Avp 1 5 10 "2105 966 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" p-s1y "2205 "221" MY VE5 "222" (2)..2) "223" Ary "2205 "221" MY VE5 "222" (8)..(8) 10) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "4005 966 bi Haa bip TPpg Ter bip Suv Rpe Haa Gguv bij Avp Avp 1 5 10 "2105 967 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 2)..2) "223" Ars "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "4005 967

Akud Haa sip TBPg Tesr bip Suv Robe Haa yuv b1cp AvBp Avp 1 5 10 "2105 968 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (1)..(1) "223" 0-Agd (516) "220" "221" MY VE5

«222» (2). 222 (9).

Agud Haa sip TBg Ter bip Suv Rpe Haa Puv bij ABp Avp 1 5 10 "2105" 969 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (2). 222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "4005 969

Rpe Haa bip TPg Tkr b1ip Suv Robe Haa Guv 611 Avp Avp 1 5 10 "2105 970 "2115 13 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" B-Rre "2205 "221" MY VE5 "222" (2)..2) "223" Ari "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 " 221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "4005 970

Rpe Haa bip TPg Tkr b1ip Suv Robe Haa Guv 611 Avp Avp 1 5 10 "2105 971 "2115 13 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (1). ..(8) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (9)..(9) "223" 2-May (516) "220" "221 » MY VE5

"222" (10)..(10) "223" airpa-Meguv "4005 971

Haa Haa beep TPg Ter sip Suv Rpe Haa Guz bij Avp Avp 1 5 10 "2105 972 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Ar "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "4005 972

TPgE Haa sip TBg Tesr bip Suv Robe Haa yuv 611 Avp Avp 1 5 10 "2105 973 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" Ar "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 60 " 222" (9)..(9) "223" May 2

"221" MY VE5 "222" (10)..(10) "223" airpa-Meguvs "4005 973

Tecp Haa bip TPpg Ter bip Suv Rpe Haa Gguv bij Avp Avp 1 5 10 "2105 974 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" r-s1p "2205 "2215 MOR VE5 "222" (2)..2) "223" Ar "2205 "2215 MOR VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR БЕ5 "222" (9)..(9) "223" 2-May "2205 "2215 MOR БЕ5 "222" (10)..( 10) "223" airpa-Meguv "4005 974 sip Haa bip TPg Ter sbip Suv Rre Haa Gpuv bij Avp Avp 1 5 10 "2105 975 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari 60 "2205

"221" MY BE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY BE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Asre "4005 975

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 976 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1)

From "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8).. (8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Asyrs "4005 976

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 977 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO VE5 "222" ( 1)..(1)

"223" Ar "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Asps "4005 977

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 978 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Ars "220" "221" MY VE5 "222" (7)..(7) "223" Rpe|4- (2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Asus "4005 978

Haa beep TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 979 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" 4-amino-4 -carboxy-piperidine "4005 979

Haa beep TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105 980 "2115 12 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7).. (7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" ( 9)..(9) "223" 4-amino-4-carboxy-tetrahydropyran "4005 980

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 v; 10 "2105 981 "2115 12 "2125 RVT

Gs10) "213" Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ari "2205 "2215 MOR VEB "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR VEB "222" (8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) " 223" airpa-Megetsy "2205 "2215 MOR VE5 "222" (10)..(10) "223" Puv(As) "4005 981

Zo Haa sip TBg Tgr bip Suv Ribe Haa Gay yuv ABp 1U 1 5 10 "2105 982 "2115 12 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222 (8).

Haa beep TPg Ter beep Suv Rpe Haa Gay bij Ap 1U 1 5 10 "2105 983 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9)

From "223" Airpa-Metiei "4005 983

Haa bip TPg Ter bip Suv Rpe Haa Gay sbip Ap 1U 1 5 10 "2105" 984 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MORPHE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 8)..(8) "223" May 2 "2205 60 "2215 MO VE5 "222" (9)..(9)

"223" airpa-Megetsy "221" MY VE5 "222" (12)..(12) "223" Vega-Ai1a "4005" 984

Haa bip TP Ter bi1ip Suv Rpe Haa Iiietsy bip ABp Aia 1 5 10 "2105 985 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ars "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy)

From "220" "221" MY VE5 "222" (8)..(8) "223" May 2 "220" "221" MY VE5 "222" (9)..(9) "223" airpa- Megetsy "4005 985

Haa beep TPg Ter beep Suv Rpe Haa Gay sbip Ar 01U 1 5 10 "2105 986 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) 10) "223" Rpe|4-(2-aminoethoxy)

"221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "4005 986

Haa beep TPg Ter beep Suv Rpe Haa Gay sbip Ar 01U 1 5 10 "2105 987 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222 " (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" hole "2205 "221" MY VE5 "222" (12) ..(12) "223" Vega-Ai1a "4005 987

Haa bip TP Ter bi1ip Suv Rpe Haa Haa sip ABp Aia 1 5 10 "2105 988 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide (516) "220" "221" MY VE5

222 (1). 222 (8).

Haa sip TBg Tgr bip Suv Robe Haa Haa sbip ABp s1U 1 5 10 "2105" 989 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 " 222" (8)..(8) "223" 5-puaygohutTgr "2205 "221" MY VE5 "222" (9)..(9) "223" holes "4005 989

Haa bip TPg Ter bip Suv Rpe Tgr Haa sbip A5Bp 1U 1 5 10 "2105 990 "2115 13 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(Ac) "2205 "221" MY VE5 "222" (11)..(11) 0) "223" Avp(isobutyl) "4005 990

Haa bip TPg Ter bip Suv Rpe Haa Gpuv Ppuv Avp b1u Avp 1 5 10 "2105 991 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 8)..(8) "223" May 2 "2205 60 "2215 MO VE5 "222" (9)..(9)

"223" airpa-Meguv "221" MY VE5 "222" (10)..(10) "223" Puv(As) "2205 "221" MY VE5 "222" (11)..(11) "223" Avr(1,4-Z3iatipoeepase) "4005 991

Haa bip TPg Ter bip Suv Rpe Haa Ppuv Ppuv ABvr 01U 1 5 10 "2105 992 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" 0-RIe

From "220" "221" MY VE5 "222" (2). 2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" 4 -amino-4-carboxy-tetrahydropyran "4005 992

Rpe Haa bip TPg Tgr b1ip Sub Rore Haa Haa b11p Avp Avp 1 5 10 "2105 993 "2115 13 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" 0-Agd "2205 "221" MY VE5 "222" (2)..2) "223" Ari "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 " 221" MY VE5 "222" (10)..(10) "223" 4-amino-4-carboxy-tetrahydropyran "4005 993

Akud Haa sip TBPg Tesr beep Suv Rre Haa Haa b1tsy AvBp Avp 1 5 10 "2105 994 "2115 13 "2125 RVT "2135 Artificial sequence

C5 "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-Guv "2205 "221" MY VE5 "222" (2) ..2) "223" Ars "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9).. (9) "223" 2-May "2205 "221" MY VE5 60 "222" (10)..(10) "223" airpa-Megetsy

"4005 994

Tpuv Haa sbip TPg Ter bip Suv Ribe Haa gay siy AvBp 01U 1 5 10 "2105 995 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VEB "222" ( 1)..(1) "223" Ary "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "2215 MOR ВЕ5 "222" ( 8)..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" hole "4005 995

Haa sip TBg Tgr bip Suv Ribe Haa Haa sbip ABp 1U 1 5 10 "2105 996 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (8 )..(8) "223" 2-May 60 "2205

"221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 996

Haa beep TPg Ter beep Suv Rpe Haa uv bij Ap 1U 1 5 10 "2105 997 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" r-Guv "2205 "221" MY VE5 "222" (2)..2) "223" Ar "2205 "221" MY VE5 "222" (8)..( 8) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9)..(9)

З5 "223" 2-May "2205 "221" MY VE5 "222" (10)..(10) "223" airpa-Meguv "4005 997

Tpuv Haa sbip TPg Ter bip Suv Rpe Haa puv siy AvBp s01U 1 5 10 "2105 998 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" ( 1)..(1) "223" Ars "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" РПе(4-0о871) "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 998

Haa beep TPg Ter beep Suv Rpe Ter Guv bij ABp 1U 1 5 10 "2105 999 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Ari "2205 "221" MY VE5 "222" (7)..(7) "223" Tuk(vg1)

From "220" "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "4005 999

Haa beep TPg Ter beep Suv Tug Ter guv bij ABp 1U 1 5 10 "2105 1000 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" aii1u101U "2205 "221" MY VE5 "222" (6)..(6) "223" aii1u101U "4005 1000 sb1u A1i1a Avr Tgr Uai1i s1u Tuk Ter Niv TP RpPe S1U 1 5 10 60 "2105 1001

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" aiii1u101U "2205 "221" MY VE5 "222" (6)..(6) "223" aiii1u101U "4005 1001 sb1u A1a Avr Tgr Ua1i s1u Tuk Ter Niv TPg Roe 01Uu 1 5 10 "2105 1002 "2115 14 "2125 RVT "2135 Artificial sequence "2205 " 223» Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" 2-(3'-butenyl)b1u "220" "221" MY VE5 "222" (6)..(6 ) "223" 2-(4'-pentenyl)c1u "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 " (14)..(14) "223" 0-Guv "4005 1002 b1u Akd TPpg Ter bip b1u Tuk Ter Agud puv Rpe s1iu Haa Guv 1 5 10 "2105 1003 "2115 14 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" 2-(4'-pentenyl)c1u "2205 "221" MY VE5 "222" (6)..(6) "223" 2 -(3'-butenyl)b1u "2205 "221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY BE5 "222" (14). .(14) "223" 0-Guv "4005 1003 b1u Akd TPpg Ter bip b1u Tuk Ter Agud puv Rpe s1iu Haa Guv 1 5 10 "2105" 1004 "2115 14 "2125 RVT "2135 Artificial sequence

From "220" "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" aiii1u101U "2205 "221" MY VE5 "222" (6).. (6) "223" 2-(4'-pentenyl)c1u "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 222 (14).

Gs10) "213" Artificial sequence

"223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" 2-(4'-pentenyl)c1u "2205 "2215 MOR VEB "222" (6) ..(6) "223" aiii1u101U "2205 "2215 MOR VEB "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR VE5 "222" (14).. (14) "223" 0-Guv "4005 1005 s1u Agkud TPE Ter sip sb1iu Tug Ter Agud Ppuv Rpe s1u Haa Guz 1 5 10 "2105" 1006 "2115 14

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 2-(3'-butenyl)b1u " 2205 "221" MY VE5 "222" (6)..(6) "223" 2-(3'-butenyl)b1u "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005" 1006 b1u Akd TPpg Ter bip b1u Tuk Ter Agud puv Rpe s1iu Haa Guv 1 5 10 60 "2105 1007 "2115 14

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 2-(3'-butenyl)c1Uu "2205 "221" MY VE5 "222" (6)..(6) "223" ai1iu191u "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" r-Guv "4005 1007 b1u Akd TPpg Ter bip b1u Tuk Ter Agud puv Rpe s1iu Haa Guv 1 5 10

"2105" 1008 "2115 14 "2125 RVT "2135 Artificial sequence

"2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOP BE5 "222" (1)..(1) "223" aiii1u101U "2205 "2215 MOP BE5 "222" (6)..(6) " 223" 2-(3'-butenyl)b1u "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 MOR ВЕ5 "222" (14) ..(14) "223" 0-Guv "4005 1008 (516) s1u Agkud TPE Ter sip sb1iu Tug Ter Agud Ppuv Rpe s1u Haa Guz 1 5 10

"2105 1009 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rar "2205 "221 » MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 1009

Haa bip TPg Ter bip si Tugye Ter Agd bij Avp s1iu Haa Gu 1 5 10 «2105 1010

From "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (6)..(6) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" B-Puv "4005 1010 bi beep Tps Ter beep Haa Tug Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 1011 "2115 14 "2125 RVT "2135 Artificial sequence 60 "2205 6bo

"223" Description of artificial sequence: Synthetic peptide "221" MY VE5 "222" (6)..(6) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 1011 bi bip Tps Ter bip Haa Tug Tgr Agud bij Avp s1u Haa Guv 1 5 10 "2105 1012 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" Rar "220" "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy )acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 1012

Haa bip TPg Ter bip si Tug Ter Agd bij Avp s1iu Haa Guv 1 5 10 "2105 1013 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 » (1)..(1) (516) "223" Rar

"221" MY BE5 "222" (6)..(6) "223" 0-Aur "2205 "221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 1013

Haa beep TPg Ter beep Avr Tug Ter Agd bij Avp s1u Haa Guv 1 5 10 "2105" 1014 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 " 222" (1)..(1) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 " 222" (14)..(14) "223" 0-Guv "4005" 1014

Haa bip TPg Ter bip Avr Tug Ter Agd bij Avp s1u Haa Guv 1 5 10 "2105 1015 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (6)..(6) "223" Rar (516) "220" "221" MY VE5 6b2

"222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 МОР БЕ5 "222" (14)..(14) "223" 0-Guv "4005 1015

Avr bip TpPg Ter b1ip Haa Tuk Tgr Agd siy Avp sb1u Haa Guv 1 5 10 "2105 1016 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Rar "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 " (14)..(14) "223" 0-Guv "4005 1016

Haa beep TPg Ter beep Avr Tug Ter Agd bij Avp s1u Haa Guv 1 5 10 "2105 1017 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" r-Rar "2205 "221" MY VE5 "222" (6)..(6) "223" 0-Avr "2205 "221" MY VE5 60 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid

"221" MY VE5 "222" (14)..(14) "223" V-Puv "4005 1017

Haa bip TPg Ter bip Avr Tug Ter Agd bij Avp s1u Haa Guv 1 5 10 "2105" 1018 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222 " (1)..(1) "223" 0-Avr "2205 "2215 MOR VE5 "222" (6)..(6) "223" p-Rar "2205 "2215 MOR VE5 "222" (13) ..(13) "223" (2-aminoethoxy)acetic acid "2205 "2215 МОР БЕ5 "222" (14)..(14) "223" 0-Guv "4005 1018

Avr bip TpPg Ter b1ip Haa Tuk Tgr Agd siy Avp sb1u Haa Guv 1 5 10 "2105 1019 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" 0-Avr "2205 "221" MY VE5 "222" (6)..(6) "223" R-Rar 60 "2205

"221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "220" "221" MY BE5 "222" (14)..(14) "223" 0- Guv "4005 1019

Avr beep TBg Ter beep Haa Tug Tgr Agud bij Avp s1iu Haa Guv 1 5 10 "2105 1020 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Rep. "4005 1020

Haa A1i1a Avr Tgr Uaiii Suv Tug Ter Niv TPgs Rpe S1U 1 5 10 "2105 1021 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (6 )..(6) "223" Rep. "4005 1021

Suv Aia Avr Tgr Uai Haa Tug Ter Niv TPg Rpe 1U 1 5 10 "2105 1022 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" P-Rep 60 "2205

"221" MY BE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "220" "221" MY BE5 "222" (14)..(14) "223" 0- Guv "4005 1022

Haa Ai1a Avr Tkgr Uai Suv Tug Ter Niv TPg Rpe siu Haa Guv 1 5 10 "2105 1023 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (6)..(6) "223" P-Rep "2205 "221" MY VE5 "222" (13)..(13) 0) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" V-Puv "4005 1023

Suv A1a Avr Tgr Uai Haa Tukg Ter Niv TPg Rpe s1iu Haa Guv 1 5 10 "2105" 1024 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222 " (1)..(1) "223" Rep "2205 "2215 MOR ВЕ5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 60 "2215 MO ВЕ5 "222" (14)..(14)

"223" 0-Guv "4005" 1024

Haa Akd TPg Ter bip Suv Tug Ter Akud pub Rore s1iu Haa Gu 1 5 10 "2105 1025 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222 " (14)..(14) "223" 0-Guv "4005 1025

A1ia Suv Avr Tgr Uai! Haa Tuk Tgr Agd iuv Rpe s1Uu Haa Guv 1 5 10 "2105" 1026 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2) ..2) "223" Rep "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14). .(14) "223" V-Puv "4005" 1026

A1ia Haa Avr Tkgr Uai Suv Tuk Tgr Agd Guv Rpe s1Uu Haa Guv 1 5 10 60 «2105 1027

"2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (2)..2) "223" pSuv "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005 1027

A1ia Suv Avr Tgr Uai! Haa Tuk Tgr Agd iuv Rpe s1Uu Haa Guv 1 5 10 "2105" 1028 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (6 )..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Megetsy "4005" 1028

Suv beep TPpg Ter beep Haa Tug Tgr Gay bij Ap 1U 1 5 10 "2105 1029 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9) "223" 0-Avp "4005 1029

Suv bip TPpg Ter bip Haa Tug Tgr ABp bij Ap 1U 1 5 10 "2105 1030 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (9)..(9 ) "223" M-Me-Ag4d "4005 1030

Haa bip TPg Ter bip Haa Tug Tgr Agd bij ABp 1U 1 5 10 "2105 1031 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (1)..(1) "223" Rep "220" "221" MY VE5 "222" (6)..(6) "223" Rep (516) "220" "221" MY VE5

"222" (7)..(7) "223" |РБПе (4-ОМе) | (ОМе) "2205 "2215 MOR VE5 "222" (8)..(8) "223" 2-May "2205 "2215 MOR VEB "222" (9)..(9) "223" airpa-MeoOgp " 2205 "2215 MOR WEB "222" (10)..(10) "223" Puv(As) "4005 1031

Haa sip TBg Tgr beep Haa Rope Haa Haa Guz ABp 1U 1 5 10 "2105 1032 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7 ) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9)..(9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..( 10) "223" Puv(As) "4005 1032

Haa beep TPg Ter beep Haa Rpe Ter Gpuv Ppuv ABp 1U 1 5 10 60 "2105 1033 "2115 12

"2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" ( 8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9)

From "223" airpa-Meguvs "2205 "221" MY VE5 "222" (10)..(10) "223" Ppuv(As) "4005 1033

Haa bip TPg Ter bip Haa Rpe Haa Gpuv Ppuv ABp 1U 1 5 10 "2105" 1034 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORPHE5 "222" ( 1)..(1) "223" Rep "2205 "2215 MOR VE5 "222" (6)..(6) "223" Rep "2205 60 "2215 MO VE5 "222" (7)..(7)

"223" Rpe|4-(2-aminoethoxy) "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..( 9) "223" airpa-Meguv "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 1034

Haa bip TPg Ter bi1ip Haa Rpe Haa Guv Guv Avp Avp 1 5 10 "2105" 1035 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (1)..(1) "223" 0-RIe "220" "221" MY VE5 "222" (2)..2) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" Rep "2205 "221" MY VE5 "222" (8)..(8) "223" Rpe|4-(2-aminoethoxy) "220" "221" MY VE5 "222" (9)..(9) "223" May 2 "220" "221" MY VE5 "222" (10)..(10) "223" holes (516 ) "220" "221" MY VE5

"222" (11)..(11) "223" Puv(As) "4005 1035

Rpe Haa Avp TPg Tgr bip Haa Rpe Haa Haa Guz ABp Avp 1 5 10 "2105" 1036 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7).. (7) "223" РПе(4-СОМН2) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9). .(9) "223" Asus "2205 "221" MY VE5 "222" (10)..(10) "223" Puv(As) "4005" 1036

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 1037 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 "222" (1)..(1) "223" Rep

"221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 " 221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Asus "2205 "221" MY VE5 "222" (10)..(10) "223" Tuv(As) "4005 1037

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105" 1038 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(1) "223" Ars "2205 "2215 MOR ВЕ5 "222" (7)..(7) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (8) ..(8) "223" 2-May "2205 "2215 MOR VE5 "222" (9)..(9) "223" airpa-Meguv "4005 1038 (516) Haa sip TBg Tgr bip Suv Rbe Haa Puv biy ABp 1U 1 5 10

"2105 1039 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" 0-Guv "2205 "221" MY VE5 "222" (2)..2) "223" Ar "2205 "221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "221 » MY VE5 "222" (9)..(9) "223" May 2

From "220" "221" MY VE5 "222" (10)..(10) "223" airpa-Megetsy "4005 1039

Tpuv Haa sbip TPg Ter bip Suv Rpe Haa gay siy AvBp 01U 1 5 10 "2105" 1040 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 (1). )..(9) (516) "223" airpa-Meguvs

"4005 1040

Haa beep TPg Ter beep Suv Tug Ter guv bij ABp 1U 1 5 10 "2105 1041 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 1)..(1) "223" 0-Agd "2205 "221" MY VE5 "222" (2)..2) "223" Ars "2205 "221" MY VE5 "222" (8)..( 8) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (9)..(9) "223" 2-May "2205 "221" MY VE5 "222" (10 )..(10) "223" airpa-Meguv "4005 1041

Akud Haa sip TBPg Tesr bip Suv Robe Haa Guv b1cp Avp Avp 1 5 10 "2105" 1042 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (1)..(1) "223" r-s1p "220" "221" MY VE5 "222" (2)..2) "223" Ary (516) "220" "221" MY VE5

222 (8). MOR WEB "222" (10)..(10) "223" airpa-Meguv "4005" 1042 sip Haa bip TPg Ter sbip Suv Rbe Haa Gpuv bij Avp Avp 1 5 10 "2105" 1043 "2115 12 "2125 RVT " 2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "221" MY BE5 "222" (1)..(1) "223" Ari "2205 "221" MY BE5 "222" (7). .(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" 2-May "2205 "221" MY VE5 "222" (9)..(9) "223" Asre "4005" 1043

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105" 1044 "2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 60 " 222" (9)..(9) "223" pPTey

"4005" 1044

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105" 1045 "2115 16 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR WEB "222" ( 15)..(15) "223" Ah "2205 "2215 MOR VE5 "222" (16)..(16) "223" 0-Guv "4005" 1045

Suv Aia Avr Ter Uai Tkgr Suv Tug Ter Ni TPK Rpe siu Aia Haa Guv 1 5 10 15 "2105" 1046 "2115 14

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(1) "223" Ari "2205 "221" MY VE5 "222 " (13)..(13) "223" (2-aminoethoxy)acetic acid "2205 "221" MY VE5 "222" (14)..(14) "223" 0-Guv "4005" 1046

Haa Akd TPg Ter bip Suv Tug Ter Agd Ppuv Rpe siu Haa Guv 1 5 10 "2105" 1047 "2115 12 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Ar "2205 "221" MY VE5 "222" (7)..(7) "223" Rpe|4-(2-aminoethoxy) "2205 "221" MY VE5 "222" (8)..(8) "223" May 2 "2205 "221" MY VE5 "222" (9)..(9) "223" Aspes "4005" 1047

Haa bip TPg Ter bi1ip Suv Rpe Haa Haa b1y Avp Avp 1 5 10 "2105" 1048 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" ( 1)..(1) "223" 0-RIe "2205 "2215 MOR VE5 "222" (2)..2) "223" Rep "2205 "2215 MOR VE5 "222" (7)..(7) "223" Rep "2205 "2215 MOR ВЕ5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "2215 MOR ВЕ5 "222" (9)..(9) "223" May 2 "2205 60 "2215 MO VE5 "222" (10)..(10)

"223" 4-amino-4-carboxy-tetrahydropyran "221" MY VE5 "222" (11)..(11) "223" see "4005" 1048

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa Haa Avp Avp 1 5 10 "2105" 1049 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222 " (1)..(1) "223" 0-RIe "2205 "221" MY VE5 "222" (2)..2) "223" Rep

From "220" "221" MY VE5 "222" (7)..(7) "223" Rep

З5 "220" "221" MY VE5 "222" (8)..(8) "223" РПе(4-ОМе) "2205 "221" MY VE5 "222" (9)..(9) "223" May 2 "2205 "221" MY VE5 "222" (10)..(10) "223" Asps "4005 1049

Rpe Haa Avp TPg Tgr bi1ip Haa Robe Haa Haa b11p Avp Avp 1 5 10 "2105 1050 "2115 12 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"221" MY VE5 "222" (1)..(1) "223" Rep "2205 "221" MY VE5 "222" (6)..(6) "223" Rep "2205 "221" MY VE5 " 222 (7). (9).

Haa Avp o TPg Ter bi1ip Haa Rpe Haa Haa Guv Avp Avp 1 5 10 "2105 1051 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1051

Suv Akud Bek Tgr bip Suv Tuk Tgr Avp puv Rope s1iu Aia AvBr ABr 1 5 10 15 "2105 1052 "2115 15 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1052

Suv Niv TPg Ter beep Suv Tuk Ter Gay Avp Rpe s1u Avr bis siy 1 5 10 15 "2105 1053 60 "2115 15 "2125 RVT

"2135 Artificial sequence "223" Artificial sequence description: Synthetic peptide "4005 1053

Suv Akud TPg Ter bip Suv Tukg Ter Gay Avp Rope s1u Avp bis sip 1 5 10 15 "2105" 1054 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1054

Suv Akud TPg Ter bip Suv Tug Ter Bek bish Rpe siu TPg s1u siy 1 5 10 15 "2105 1055 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1055

Suv Akud TPg Ter bip Suv Tukg Ter Gay Agd Gay sS1u Avr sbits s1Uu 1 5 10 15 "2105" 1056 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 1056

Suv Niv TPg Ter beep Suv Tukg Ter Bek TPg Gay s1iu Rgo bis A1a 1 5 10 15 "2105 1057 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1057

Suv back TPE Ter sip Suv Tug Tgr back Ppuv beep back sbiu s1u 5ekg 1 5 10 15 "2105" 1058 "2115 15 (516) "2125 RET "2135 Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 1058

Suv Niv TPg Ter beep Suv Tuk Ter Gay Up Avp s1iu TPg back beep 1 5 10 15 "2105 1059 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1059

Suv Niv TPg Ter bip Suv Tug Tgr Agd Aia Avp Avr b1u Agd Avr 1 5 10 15 "2105" 1060 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1060

Zo zek b1u Suv Agud TPgE Ter sip Suv Tug Ter Niv sbits Rpe Sh1U 1 5 10 "2105 1061 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1061

Avp opuv Suv Agud TBPg Tegr bip Suv Tug Tgr Ni5 b1cp Tuyekye Sh1U 1 5 10 "2105" 1062 "2115 14 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 1062 zek siu Suv Agd TPg Ter si Suv Tuk Ter Niv bi Tu U 1 5 10 "2105" 1063 "2115 14 "2125 RVT

Gs10) "213" Artificial sequence

"223" Artificial sequence description: Synthetic peptide "4005 1063

Avr Aia Suv Agkud Tk Ter bij Suv Tuk Ter Niv Ppuv Rpe 1U 1 5 10 "2105" 1064 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 1064

Rho bis Suv Agd TPg Ter bij Suv Tuk Ter Niv puv RpPe С1У 1 5 10 "2105" 1065 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1065 beep UMaii Suv beep TPg Ter bii Suv Tu Tgr Akd sic Roe S1U 1 5 10 "2105" 1066 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 1066

Awr Akud Suv Uai! TiPg Tgr b1p Suv Tug Tgr Agd b1p1 Rpe Sh1U 1 5 10 "2105 1067 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1067

Aza Avr sbip Suv Agd TP Ter beep Suv Tug Ter Niv bi Rpe S1U 1 5 10 15 "2105" 1068 "2115 15 "2125 RVT "2135 Artificial sequence 60 "2205

"223" Artificial sequence description: Synthetic peptide "4005" 1068

Tpuv bij Avp Suv Agud TpPg Ter bij Suv Tug Ter Akgd sbits Roe s1Uu 1 5 10 15 "2105" 1069 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1069

Uuai bip bij Suv Bek TPg Ter bip Suv Tug Tgr Agd TPg Rpe SHU 1 5 10 15 "2105 1070 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1070 si1u 611 bij Suv Bek TPg Ter sbip Suv Tug Ter Akgd puv Roe S1Uu 1 5 10 15 "2105 1071 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1071

Avr siu bek Suv Agud TP Ter bip Suv Tug Ter Niv sbip Rpe Sh1U 1 5 10 15 "2105 1072 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1072

Ap Aza Avr Suv Niv bek Tgr bij Suv Tug Tgr Agd bi RpPe S1U 1 5 10 15 "2105 1073 "2115 15 "2125 RVT "2135 Artificial sequence (516) "220" "223" Description of artificial sequence: Synthetic peptide

"4005 1073 bi Agud Avp oSuv Bek TPg Ter siy Suv Tug Ter Agd Aia Roe s1Uu 1 5 10 15 "2105 1074 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1074

Agkud Uai s1u Suv bek TPgE Ter siy Suv Tug Tgr Agd siy Ribe s1Uu 1 5 10 15 "2105 1075 "2115 15 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1075

Ace Az1a AvBp o Suv Agud TPg Ter bip Suv Tug Tgr Agd uv Rpe si1y 1 5 10 15 "2105 1076 "2115 15 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "4005 1076

Tuk bis Avr Suv Agud TBg Tegr bip Suv Tug Tgr bij AvBp Rpe S1U 1 5 10 15 "2105 1077 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1077

Suv bip TPpg Ter bip Suv Tukg Ter Agd AvBp Rpe b1u Avr 5eg 1 5 10 "2105" 1078 "2115 14 "2125 RVT "2135 Artificial sequence "2205

Gs10) "223" Description of artificial sequence: Synthetic peptide

"4005 1078

Suv bip TPpg Ter bip Suv Tukg TEgr Agd Avp Roe biy bek Sh1U 1 5 10 "2105 1079 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1079

Suv bip Avr Tgr bip Suv Tug Tgr Agd bish Rbe cS1u Rgo U 1 5 10 "2105 1080 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1080

Suv beep Avr Tgr beep Suv Tug Tgr Agud Bek Robe s1u Rgo sip 1 5 10 "2105 1081

Zo "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1081

Suv beep TPpg Ter beep Suv Tug Tgr Agud TPg Gets s1u Rgo 5eg 1 5 10 "2105" 1082 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1082

Suv Akud TPE Ter sip Suv Tug Ter b1p ABp Rpe c1U 1 5 10 "2105 1083 "2115 14 "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "4005 1083

Suv b1u TPg Ter bip Suv Tukg Ter Agud TpPg Robe s1u Rgo 5eg 1 5 10 "2105" 1084 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 1084

Suv back TPg Ter beep Suv Tuk Ter Niv Ppuv Robe s1u AvBp bij 1 5 10 "2105" 1085 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1085

Suv Akud TPE Ter siy Suv Tug Tgr Agud TPg Tuk s1u Rgo 5eg 1 5 10 "2105" 1086 "2115 14

Zo "2125 RET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 1086

Suv Akud TPg Ter beep Suv Tukg Ter Ter bij Avp beg beep Mee 1 5 10 "2105" 1087 "2115 14 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005" 1087

Suv bip TPpg Ter bip Suv Tug Tgr Agd bis Rbe sSiu s1u s1U 1 v; 10 "2105" 1088 "2115 14 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide 60 "4005 1088

Suv beep TPpg Ter beep Suv Tukg Tgr Agud TpPg Niv s1u Avr Agd

1 5 10 "2105 1089 "2115 12 "2125 PET "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "4005 1089

Suv Agkud Avr Tgr bip Suv Tukg Tgr Gay 5Beg Agd Rgo 1 5 10 "2105 1090 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Ppuv(Rait) "4005 1090

Suv beep TPpg Ter beep Suv Tuk Ter guv bij ABp 1U 1 5 10 "2105 1091 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" KTuv(RESV) "4005 1091

Suv beep TPpg Ter beep Suv Tuk Ter guv bij ABp 1U 1 5 10 "2105" 1092 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) 60 "223" Pet

"4005 1092

Suv beep TPpg Ter beep Suv Tuk Ter geish bi beep Sh1U 1 5 10 "2105" 1093 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (7)..(7) "223" 0-Tukg "2205 "221" MY VE5 "222" (9)..(9) "223" pPTeiy "4005 1093

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105" 1094 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (7)..(7) "223" M-Metug "2205 "221" MY VE5 "222" (9)..(9) "223" pPTeiy "4005" 1094

Suv beep TPpg Ter beep Suv Tuk Ter Gay fight Ap 1U 1 5 10 "2105" 1095 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (7)..(7) (516) "223" tis-on

"221" MY VE5 "222" (9)..(9) "223" pPTey "4005 1095

Suv bip TPpg Ter sbip Suv Haa Tgr gay bij Ap 1U 1 5 10 "2105" 1096 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005" 1096

Suv beep TPpg Ter beep Suv bij Ter Gay bij Ap 1U 1 5 10 "2105" 1097 "2115 12 "2125 RVT "213" Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "220" "221" MY VE5 " 222" (9)..(9) "223" pPTey "4005 1097

Suv beep TPpg Ter beep Suv TPg Ter Gay fight Ap 1U 1 5 10 "2105" 1098 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (7)..(7) "223" Spa "2205 "221" MY VE5 "222" (9)..(9) 60 "223" Petz

"4005" 1098

Suv bip TPpg Ter sbip Suv Haa Tgr gay bij Ap 1U 1 5 10 "2105 1099 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" airpa-Megetsy "4005 1099

Suv beep TPpg Ter beep Suv Tuk Ter gay bis AvBp 01Uu 1 5 10 "2105 1100 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide

From "220" "221" MY VE5 "222" (9)..(9) "223" P-Getsy "4005 1100

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Ap 1U 1 5 10 "2105 1101 "2115 13 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "2205 "221" MY VE5 "222" (13)..(13) "223" V-Puv "4005 1101

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Avp s1u Guv 1 5 10 60 «2105 1102

"2115 12 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 1102

Suv beep TPpg Ter beep Suv Tuk Ter Gay fight Ap 1U 1 5 10 "2105 1103 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" pPTey "4005 1103

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Ap s1ts 1 5 10 "2105" 1104 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" Petz "4005 1104

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Avp Agd 1 5 10 "2105 1105 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 60 "2215 MO ВЕ5 "222" ( 9)..(9)

"223" pPTeiy "4005 1105

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Avp Re 1 5 10 "2105" 1106 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 1106

Suv beep TPpg Ter beep Suv Tuk Tgr gay bij Avp Rgo 1 5 10 "2105 1107 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "4005 1107

Suv beep TPpg Ter beep Suv Tuk Ter Gay bij Avp o sip 1 5 10 "2105" 1108 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MORP VE5 "222" (9)..(9) "223" pPTey "4005 1108

Suv bip TPE Ter sip Suv Tuk Ter Gay bij Avp TIetsy 1 5 10 "2105 1109 "2115 12 (516) "2125 RET "2135 Artificial sequence

"223" Description of the artificial sequence: Synthetic peptide "220" "221" MY VE5 "222" (9)..(9) "223" pPTey "4005 1109

Suv beep TPpg Ter sbip Suv Tuk Ter gay sbits s1Uu 1 5 10 "2105 1110 "2115 12 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" ( 9)..(9) "223" Petz "4005 1110

Suv bip TPpg Ter bip Suv Tuk Ter Gay bij Agd Sh1U 1 5 10 "2105 1111 "2115 20 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1 )..(3) "223" Any amino acid or absent "2205 "221" MY VE5 "222" (4)..(4) "223" 2-aliglycine, 2-(3'-butenyl)glycine, 2-(4'-pentenyl)glycine, ok 2-(5'-hexenyl)glycine "2205 "2215 MOP VE5 "222" (5)..(5) "223" A1i1a, Akud, bBax, airpa-MeOgp, airpa-Mebek, Si, Rar, Rab, rRar(As), s1u, Ppuv, Avp, M-Mesip, M-MeAgu, Ogp or sip "220" "221" MY VE5 "222" (6)..(6 ) "223" Avr, TPg og Aup (516) "220" "221" MY VE5

222 (8). ) glycine, 2-(4'-pentenyl) glycine ok 2-(5'-hexenyl) glycine "2205 "221" MY VE5 "222" (11)..(11) "223" Ter, 1-Ma1i, 2 -Ma1i, Rpe(3,4-OMe2) 5-Nudygohu-Tegr, RpPe(3,4-С12) or Tuk(3-E-Vy) "2205 "221" MY VE5 "222" (13)..( 13) "223" TPg, bBax, si, Rre, Agd, Temp, Ppuv, Vega-pPAia, Uai, Ai1B,

Tuv(As), SiE, Avr, Rar, RrRar, sitzsh, BAgd, Ppuv, Avp, Ogp or sip "2205 "221" MY VE5 "222" (15)..(15) "223" sbi1u, bek, TPg , beep, Aia, 5ax, Vega-Aia, b11, Agd or Avp "2205 "221" MY VE5 "222" (16)..(20) "223" Any amino acid or missing "4005 1111

Haa Haa Haa s1u Haa Haa Tgr Haa s1u Tug Haa Niv Haa Rpe Haa Haa 1 5 10 15

Haa Haa Haa Haa 20 "2105 1112 "2115 20 "2125 RVT "2135 Artificial sequence "2205 "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(3) "223" Any amino acid or absent "2205 "221" MY VE5 "222" (5)..(5) "223" A1ia, Akud, sits, РПе, Iецы, ТПг, бек, А1Б, 5закс, airpa-Meogp, airpa - Mebek, SiE, Rar, Rar, rRar(As), b1u, Ppuv, Avp, M-Mesip,

M-MeAgd, OGP or sip (516) "220" "221" MY VE5

"222" (6)..(6) "223" Avr, TPg, Avp or RiPe "2205 "2215 MOR VE5 "222" (8)..(8) "223" Ua1, bip, bitz or Guv "2205 "2215 MOR VEB "222" (11)..(11) "223" Ter, 1-Mai, 2-Mai, Rpe(3,4-OMe2), 5-Hydroxy-Tgr, RpPe(3,4-С12 ) or Tuk(3-E-Vy) "2205 "221" MY VE5 "222" (13)..(13) "223" TPg, bBax, si, Rre, Agud, Petz, Ppuv, Weba-pPAia, Uai , Ai1B,

Tuv(As), SiE, Avr, Rar, RrRar, sitzsh, BAgd, Ppuv, Avp, Ogp, bip or absent "2205 "221" MY VE5 "222" (14)..(14) "223" РПе, Tug , Avp, Akud, beep, Ppuv(As), Niv, Rar(As), rar(As),

Avr or absent "2205 "221" MY VE5 "222" (15)..(15) "223" sbi1u, bek, TPg, bip, Aia, 5aks, rega-Aia, 611, Agd, Avp or absent "2205 " 2215 MOR VE5 "222" (16)..(20) "223" Any amino acid or absent "4005 1112

Haa Haa Haa Suv Haa Haa Tgr Haa Suv Tug Haa Niv Haa Haa Haa Haa 1 5 10 15

Haa Haa Haa Haa 20 "2105 1113 "2115 20 "2125 RVT "2135 Artificial sequence "2205 "223" Description of the artificial sequence: Synthetic peptide "2205 "2215 MOR VE5 "222" (1)..(3) "223" Any - what amino acid is missing or absent "2205 60 "2215 MO ВЕ5 "222" (5)..(5)

"223" A1i1a, Akud, bBaks, airpa-MeOgp, airpa-Mebek, Si, Rar, Rab, rRar(As), s1u, Ppuv, Avp, M-Mesip, M-MeAgu, Ogp or sip "2205 "2215 MOR VE5 "222" (6)..(6) "223" Avr, TPg or Avp "2205 "2215 MOR VEB "222" (8)..(8) "223" Ua1, bi1ip or s1tsy "2205 "2215 MOR VEB "222" (11)..(11) "223" Ter, 1-Mai, 2-Mai, Rpe(3,4-OMe2), 5-Hydroxy-Tgr, RpPe(3,4-С12) or Tuk (3-E-Vy) "2205 "221" MY VE5 "222" (13)..(13) "223" TPg, bBax, si, Rre, Agud, Pets, Ppuv, Beba-pPATia, Uai, Ai1B,

Tuv(As), SiE, Avr, Rar, RrRar, sitzsh, BAgd, Ppubv, Avp, Ogp, bip or missing "2205 "221" MY VE5 "222" (15)..(15) "223" si1u, bBeg .

Haa Haa Haa Sub Haa Haa Tgr Haa Suv Tuk Haa Niv Haa Rpe Haa Haa 1 5 10 15

Haa Haa Haa Haa 20 "2105 1114 "2115 19 "2125 RVT "2135 Artificial sequence "220" "223" Description of artificial sequence: Synthetic peptide "2205 "221" MY VE5 "222" (1)..(3) "223 » Any amino acid or absent "2205 "221" MY VE5 60 "222" (5)..(6) "223" Any amino acid

"221" MY VE5 "222" (8)..(8) "223" Any amino acid "2205 "221" MY VE5 "222" (10)..(10) "223" Tuk, 1-Ma1, 2-Ma1i, Rie(3,4-E2), Rie(3,4-C12), RiePe(3-Me),

Rpe|4-(2-aminoethoxy)|, Rpe|4-(2-(acetyl-aminoethoxy)|,

Rpe(4-Vg), Rpe(4-SOMN2), RiPe(4-C1), RiPe(4-CM),

Rpe(4-guanidino) Rpe(4-Me), Rpe(4-MH2), Rpe(4-M3), "2205 "221" MY VE5 "222" (10)..(10) "223" continued from of the above; RPE(4-OMe) or RPE(4-ov71) "2205 "221" MY VE5 "222" (11)..(11) "223" Ter, 1-Ma1!, Rbe(3,4-OMe2), 5-Nuaigohu-Tgr, Rpe(3,4-C12) or

Tuk(3-E-Vy) "2205 "221" MY VE5 "222" (12)..(12) "223" Akud, Kpuv, Niv, PAgd, Sie, Op, 1-Mai, 0-Aia, 0 -Giechsh, 0-RIe, 0-Avp, 0-Avr, Adr, Iets, Weba-pPGets, Air, Vesa-PA1Ta, Vesa-PUai,

Vesa-PAgud, PPPIetsy, Rar, 4-amino-4-carboxy-tetrahydropyran, Asts,

Asrs, AsBs, Asus, Adr, Air, airpa-dietiloyu, airpa-Meguv, "2205 "2215 MORP VE5 "222" (12)..(12) "223" continuation from the above; airpa-Meguv(As), airpa-Me-Iey, airpa-MeOgp, airpa-Mebzek, airpa-MeUa!i, Spa, Si, Sra, 0-Avp, siy, BAgd or Gu "2205 "221" MY VE5 " 222" (13)..(13) "223" Spa, Odi, AiB, Gets, Ua1i!, Bar, sitzsh, Ppuv, Vega-pPGets, Vega-pPAia,

Webea-pPUai, Vesa-sits, Guv(As), Sis, Avr, Rar, Rar, siy, PAgd,

Tuv, Avp, Ogp, Puv(As) or sip "2205 "221" MY VE5 "222" (14)..(14) "223" Rpe, Tis, Avp, Tug, Avp, Agud, bip, Gpuv(As ), Niv, Rar(Ac), rar(Ac) or Avr "2205 "2215 MOB VE5 "222" (16)..(16) "223" Any amino acid "2205 60 "2215 MO VE5 "222" ( 17)..(17)

"223" 0-Guv "221" MOR VE5 "222" (18)..(19) "223" Any amino acid or absent "400" 1114

Haa Haa Haa Sub Haa Haa Tgr Haa Sub Haa Haa Haa Haa Haa si1u Haa 1 in; 10 15

Huw Haa Haa

Claims (1)

FORMULA OF THE INVENTION 1. A peptide inhibitor of the interleukin-23 receptor or a pharmaceutically acceptable salt thereof, and the peptide inhibitor or a pharmaceutically acceptable salt thereof is selected from: 20. As-KO)RPeI-(RepI-MTUUSu(RepiI-(Rpe(4-OMe)|-(2-Ma|-(4-amino-4-carboxytetrahydropyrani|-(ISХ-MM- МНг) (ZEO IO MO) : 679); (RepI- MTM O-(Repi-(Rpe(4-COMNHg)I-(2-MapP-(AiVI-(Suv(AsD-MM-MH)" (5EO 10 MO:682); As--IbSh-OTUMOS- |РНе|4-(2-aminoethoxy)||-(2-MyC-(a-Me-H uvgI-( uz(isovaleric / acid)|-MO- MH)" (BEO IU MO:861); Ac-- KbSh-OTUMOS-|РНе|4-(2-aminoethoxy)||-(2-MaЦ-(АивБИ-ОМа-МН» (ZEO IU MO:877); As--KBSH-OTUMOS-|РНе|4-( 2-aminoethoxy) acetylaminoethoxy)|-(2-MaCC-(a-Me-I uv(Ac)I-(uz(AsL-MOa-MHg (5EO IO MO:900); As-IABSH-OTUMOS-|Rpe(|4-( 2-aminoethoxy) |I-(2-MaC-(a-Me-HGhuz|-EMO-MH)" (5EO 10 MO:911); As--AbSh-OTMOS-|РНе|4-(2-aminoethoxy)| |-(2-MaiC-(a-Me-I uv|I-EMM-MH" (5EO 10 MO:912); As--AbSh-OTUMOS-|РНе|4-(2-aminoethoxy)))-( 2-MaC-(α-Memayl-(Huz(Ac)-Ma-MH)" (5EO 10 MO:915); As--IbSh-OTUMOS-|РНе|4-(2-aminoethoxy)||-(2- Ma-(a-Me-H ets)-(S Sh-AMM-MN" (ZEO 1O MO:954); As-KO)RPpeI--AvSh-OTUOS-|Rpe|4-(2-aminoethoxy)||-(2-MaC-(a-Me-HGuvz|-EMM-MN)" (ZEO 10 MO:970); / As-T-IABSH-OPUMOS-|Rpe|4-(2-aminoethoxy)||-(2-Ma|-(a-Me-H uz|-EMM-MN" (5EO 1O MO:972); As- -AbSh-OTUMOS-|РНе|4-(2-aminoethoxy)||-(2-MaP-(Асбс|-ЕММ-МН» (ZEO 10 MO:976); As--AbSh-OTUMOSI-(Рпе(4 -(2-aminoethoxy)I-(2-MaC-(Asps|-EMM-MH" (ZEO 1О MO:977) As--AbSh-OTMOS-|РНе|4-(2-aminoethoxy)||-(2 -Ma/|-(4-amino-4-carboxytetrahydropyran|-EMM-MH" (ZEO I MO:980); As-IABSH-OTUOS-|Rpe(4-(2-aminoethoxy)||-(2-MaP -(a-Me-esch-OomMa-MH" (5EO 10 MO:983); As--KBSH-OTUMOS-|РНе|4-(2-aminoethoxy)||-(2-MaЦ-(а-Me- Hesh-OM(B-AiIa)-MH" (Z5EO 10 MO:984); As--IBSH-OTUMOS-|РНе|4-(2-aminoethoxy)||-(2-MaPC-(a-Me-Hesh) -O00a-MmH»e (ZEO 10 MO:985); » (ZEO IO MO:987); EMM-MH» (ZEO 10 MO:992); |- EMM-MN" (ZEO 10 MO:993); As--KBSH-OTUMOS-|RHe|4-(2-aminoethoxy)|I-(2-MaC-(Asrs|- EMM-MH" (ZEO IU MO:1043); IRa!ti-(isos111-(PEG4I) -(RepI-MTUUO-(RepiI-IRNpe(4-(2-aminoethoxy)|-(2-MaC-HAiBI-(uz(Ac)|-MM-MH)" (FAILURE MO: 1115); Ac-I(RepI - MTM O-(RepyI-(Ppe(4-(2-aminoethoxy)|-(2-MatC-(AlYVI-(Guv(PEG4-isosti-Rai))|-MM-MHg (5EO IO MO:1116) ; Ac-(RepI-OTUMMO-(Rep|-Rpe(4-SOMHng)-(2-MaC-(a-Me-GG uv(Ac)|-(Huz(Ac)|-MM-MH)" (ZEO 1О MO:1117); MH" (FAILURE MO: 1118); IOctanilI-I(IPEG41-(RepI-MTUMO-|(RepiI-I(Rpe(4-(2-aminoethoxy)|-(2-Ma|-(AIVI-(Huz(Ac )|-MM-MH" (ZEO 10 MO:1119); IRa!tI-IPEG41-(RepI-M TM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MaP|-( AiVI-(Guv(Ac)|-MM-MNa (5EBEO 1 MO: 1120); 60 0/0 As-(RepI-M TM O-|RepiI-(RHe(4-(2-aminoethoxy)|-(2 -MaC-(AiYVI-(Suz(PEG4-octanyl)|-MM-MNa. (5EO 10 MO 1121); As-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AlIVI-(SuUz(PEG4-Ra!t))|-MM-MNa (5EBEO 10 MO 1122); Ac-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)-(PEG4-Rai)|-(2-MaC-HAiIVI-(Huz(Ac)|-MM -MH»g (ZEO 10 MO: 1123); As)-MM-MHg (5EO IO MO: 1124); -(Huz(Ac)-MM-MNa (5EBEO 10 MO:1125); PEG4-lauryl)I-(uz(Ac)|-MM-MHg (ZEO 10 MO 126); Rai!t)|-(2-MaP-(AiBI-(uz(Ac)|I-MM-MN" (ZEO IU MO:1127); As-IRepI-MTUMO-|(Rep|- /I|РНе( 4-(2-aminoethoxy)-(PEG4-Isosyl and -lauryl)I-(2-Map|-(AIVI-(Guv(Ac)|-MM-MH)" (ZEO TO MO:1128); 15. As-I(RepI|-OTUMO-|Rep|-Rpe(4-SOMN?g)-(2-Ma!|-(c-Me-Huz(PEG4-Izosti-Ra/!t)|-( Guv(Ac)-MM-MH" (ZEO IO MO:1129); -I5osty-lauryl)|-(H uv (AsD-MM-MH" (ZEO I MO:1130); a-Me-Guv(IMA)I-(Suv(As)|-MM-MN" (ZEO IO MO 1131); 20. As-I(RepI|-OTUMO-|Rep|-Rpe(4-SOMN?g)-(2-Ma!|-(c-Me-Huz(biotin)|I-(Guv(Ac)|) -MM-MH» (ZEO IO MO: 1132); (Ac)|-MM-MH»g (ZEO IO MO:1133); MaP-(AiVI-(Huz(Ac)|-MM-MNa (FAILED MO1134); AIBI-(Suv(Ac)I-(GUv(IIMA)D-M-MNa (BO 1 MO:1135); As-IRepI-ISuz(biotin)|I- GMO-(Repi-(Rpe|(4-( 2-aminoethoxy)|-(2-MapP-(AiVI-(Huz(Ac)-MM-MHg (5EO 10 MO:1136); Zo As-I(RepI-M GU O-(Repi-IRne(4-( 2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)I-(Huz(biotin)|-M-MHg (5EO 10 MO:1137)); Ac-IRepI-(ICuz(Octanyl)|- GTUMO-(RepiI-(RHe(4-(2-aminoethoxy))-(2-Ma!|-IAiVI-(Suv(Ac)|-MM-MNeg (ZEO 10 MO:1138)); Ac-I(Repi- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AIBI-(Guv(Ac)|-(GuUz(octanyl)|-M-MHg) (5EO 10 MO: 1139) ; MM-MHg. (5EO 1 MO:1140); As-I(RepI- MTM O-(RepiI-(Rpe(4-( 2-aminoethoxy)|-(2-MacC-(AIBI-(Suv(Ac)|-Huz(Rai!t)|-M-MNa (5EO 1 MO:1141); Ac-IRepI-IsuUz(PEG8)I-TUMO-(RepiI-IRNpe(4-(2-aminoethoxy)|-(2-MaC--IAIVI-(Guv(Ac)|-MM-MNa) (5EO 1/0 MO : 1142); M-MNa (5EO 10 MO:1143); As-IRep|-K(IPEG11-Rait) H/O-(RepiI-(RHe(4-(2-aminoethoxy)I-(2-Mali|-IAiIVI) -(Suv(Ac)|-MM-MH" (ZEO 10 MO 1144); As-I(RepI- MTM O-|(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-- GAIBI-(Huz(As)I-(SUz(PEGI11-ra!t)|-M-MN" (ZEO I MO:1145); 4-(2-aminoethoxy)|-(2-Ma|--HAYVI-(uz(Ac)|-MM-MH" (ZEO IO MO:1146); 0 As-IRepI-(Huz(Ac)I- GMU) -ISTSH-(RepI-IRpe(4-(2-aminoethoxy)|-(2-MaC-HAIVI-(Huz(Ac)|-MM-MNa (5EO 10 MO:1147); As-IRep|-MT-IRne) (3,4-OSNZ)21-O-IRepiI-(Rpe(4-(2-aminoethoxy)I-(2-Map|-(AIVI-(Suv(Ac)|-MM-MH)" (ZEO and MO: 1148); Ac-IRep|-MT-IRne(2,4-CHZ)21-O-(RepyI-(Rpe|(4-(2-aminoethoxy)-(2-MaC-(AlivI-(Suv(Ac)) -MM-MHg (5EO 10 МО:1149); -IAIVI-(Huz(Ac)|-MM-MN" (ZEO 10 MO:1150); As-IRep|-MT-IRpe(4- SNZ)|-O-(Repi-(Rpe(4-(2-aminoethoxy)|-(2-Ma|-(AIBI-(Suz(Ac)-MM-MHg) (5EO 10 MO:1151); Ac((B)Ago|-(RepI-MHUUO-(RepiI-I(Pne(4-(2-aminoethoxy)|-(2-MaC--IAIV-( uz(Ac)|-M-IV-AGa| -MH» (ZEO 10 MO:1152); )-M-(B-ATa|-MH" (ZEO I MO:1153); As-IRepI-MTU/O-H(RepiI-IRpe(4-(2-aminoethoxy)I-(2-MaP-(AiVI) -(Huz(As)-OM-MN" (ZEO 1Yu MO:1154); -( uv(Ac)I-(uz(Ac)-M-MN. (5EO (I MO:1155); Ac-I(RepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)| -(2-MatC-(AIVI-(uv(Ac)|-M-(uz(Ac)D-MNa (5BO (1 MO:1156); As-I(RepI-MTUO-(RepiI-IRNe(4- (2-aminoethoxy)I-(2-MaP-(AiYVI-(Suv(Ac)1-FO-MH)" (ZEO IO MO:1157); As-(RepI-M GU O-(Repi-IRne(4- (2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)I-O-(B-ATa|-MH: (ZEO IO MO:1158); Ac-(RepI- MTM O-(RepiI) -(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AiYVI-(Suv(Ac)|-M-(СЩ-АМН)» (ZEO IU MO 1159); Ac-I(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AIVI-(Suv(Ac)-I(SSH-MMN)" (ZEO 10 MO:1160); 15. As-I(RepI-MTUMO-(RepiI-IRNe(4-(2-aminoethoxy)I-(2-Ma|-(AiVI-(Suv(Ac)I-ISISH-O-MH)" (ZEO 10 MO 1161); |-MHg (5EO 10 MO: 1162); Ac-I(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaC-(AivI-( uv(Ac)I- (uz(As)-ISSH-MN: (5EO 1 MO:1163); 20. As-I(RepI-M PU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AivBI-OM-I|V-AIa|-MN)" (ZEO IU MO: 1164); As-IRepI-MTM O-(RepyI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AiYVI-E-ISISH-O-MH)" (ZEO IU MO 1165); As- (Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AiYVI-(СЩ-М-(СЩ-МН)» (ZEO 10 MO:1166); -I(RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AiYVI-(Sisch-O-(SSH-AMN)" (ZEO 10 MO 1167); As- IRepI-(СЩ- GMO-(Repi-IRpe(4-(2-aminoethoxy)|-(2-Mai|-(AIVI-( uz(Ac)-MM-MN)" (ZEO IU MO 1168); 25. As-I(RepI-M PU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-(uv(Ac)|-MM-MN)" (ZEO and MO: 1169); As-I(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaC-(AivB|I-OMM-MH)" (ZEO IU MO:1170); As -I(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaC-(AivI-EMO-MN)" (ZEO 10 MO:1171); As-I(Rep|- SRMO-(RepiI-(Rpe|4-(2-aminoethoxy)|-(2-MaiPC-(AIVI-(uz(AsD-MM-MH)" (Z5EO 10 MO:1172); Ac-I(RepI-REMO- (RepiI-I(Ppe|4-(2-aminoethoxy)|-(2-MaiPC-(AIVI-(uz(AsD-MM-MH)" (Z5EO 10 MO:1173); / As-IRepI-M GPU M- IRepi-(Pne(4-(2-aminoethoxy)|-(2-MaP|-(AIVI-( uz(Ac)-MM-MH)» (ZEO 1 MO:1174); Ac-IRepI-M5UUO-(RepiI- IRNne|(4-(2-aminoethoxy)|-(2-Ma|-(AivI-( uv(Ac)-MM-MH" (ZEO I MO:1175); As-IRep|-M-IAIVI-MO- (RepiI-I(Ppe|4-(2-aminoethoxy)|-(2-MaPC-(AIVI-(uz(AsD-MM-MH)" (ZEO IO MO:1176); As-IRep|-M PM-IAIBI -(Repi-(RHe(4-(2-aminoethoxy)I-(2-MaP|-(AivI-(Suz(Ac)M-(AiYVI|I-MNeg (ZEO IO MO:1177); As-IRepI- OTM/-(Guv(Ac)I-(Repi-IRNe(4-(2-aminoethoxy)|-(2-Ma!|-(AiBI-(Suv(Ac)-MM-MNa) (BO (1 MO:1178 ); As-IRepI-( uz(AsL- GMO-(Repi-I(Rpe(4-(2- minoethoxy)|-(2-Ma!|--IAIV-( uv (Ac3uMMMN) (ZEO IO MO:1179); As-IRepI-OM O-(RepiI-I(Rpe|4-(2-aminoethoxy)|-(2-MaiPC-(AIVI-(uz(AsD-MM-MN)" (Z5EO 10 MO:1180); As- IRep|I-MT-(2-MaC-O-(RepiI-(Pne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)-MM-MH)" (ZEO IO MO : 1181); » (ZEO IO MO: 1182); MM-MH" (ZEO IO MO:1183); As-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)|-(2-Ma-(a-Me-Y ugI -( in (Ac)-MM-MH" (ZEO IO MO:1184); |-(4-amino-4-carboxytetrahydropyran|- (Guv(As)|-MM-MH" (ZEO IO MO 1185); As-I(RepI- MTM O-(RepiI-(Rpe(4-(2- aminoethoxy)|-(2-MacC-(o-Me!echI-(Suv(Ac)|-IM-(B-Aia|i-MNa (5EO 10 MO:1186); Ac-I(RepI- MTM O- (RepiI-(Ppe(4-(2-aminoethoxy)|-(2-MatC-(o-Me-H uvgI-(Guv(Ac)|-M-(B-Aia|-MNa) (5EO 10 MO:1187 ); V-AIa|-MN" (5EO 10 MO 1188); As-I (RepI-M GU O -(Repi-IRne(4-(2-aminoethoxy)|-(2-MaP-(AivI-( uv(Ac)-M-MH)" (Z5EO IU MO:1189); Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AiYVI-(Suv(Ac)|-aM-MH)" (ZEO IO MO:1190 ); Ac-(Rep|I- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)I-(2-MapP-(AIVI-(Suv(Ac)|-54-MH)" (ZEO 10 MO 1191); As-I(RepI-M TU O-|RepI1-IRne(4-(2-aminoethoxy)I-(2-MaP-(AiIVI-(Suz(Ac)I-(AivI-M-MN)" (ZEO IO MO 1192); ); :1194); ?: (5EBEO (I MO:1195); Ac-I (RepI- MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC-(AIBI-(Suv(Ac)|I -(pesh|-IV-Aia|-MNa (5EBEO 10 MO:1196); As-I(RepI-M TU O-|Repi-IRpe(4-(2-aminoethoxy)I-(2-MaP|- (AiYVI-(Suz(Ac)|-a-(B-AIa|-MN»g (ZEO IO MO:1197); As-I(RepI-M TU O-|Repi1-IRpe(4-(2-aminoethoxy )-(2-MaC-IAiVI-(Suz(Ac)I-B-(8-AIa|-MN»g (ZEO IO MO:1198); As-I(RepI-M TU O-|Repi1-IRNe( 4-(2-aminoethoxy)I-(2-Ma|--IaibiI-(Suv(Ac)|1-Zu-|B-Aia|-MN" (ZEO IO MO:1199); 15. Ac-(RepI-MTUMO-|(RepiI-I(Rpe|(4-(2-aminoethoxy)|-(2-MaP|--IAIVI-(Sus(Ac)I-5-(8-ATa| -MH" (ZEO IO MO:1200); Ac-I(RepI-MTUMO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP--IAIBI-(Sus(Ac)I-I- -(B-AIa|-MN»g (ZEO IO MO:1201); As-I(RepI-MTUMO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP--IAIBI-(Suz (Ac)I-IAIV-IV-Ata|-MNa (5EBEO I MO:1202); As-I(RepI-MTUO-|Repi1-IRne(4-(2-aminoethoxy)I-(2-MaP| IAIVI-(Suz(Ac)|-(M-MelA|a)1-(B-AIa|-MNa (5EO IO MO 1203); As-I(RepI-MTUMO-|Repi1-IRne(4-(2- aminoethoxy)I-(2-MaP-(AiIVI-(Guv(Ac)I-(2-MariI-IV-Aia|i-MHg (5EO 10 MO:1204); Ac-(RepI-MPMO-(RepiI-IRpe) (4-(2-aminoethoxy)|-(2-MapC-(AibI-(Sus(Ac)I-E-(B-Alia|-MN»g (ZEO IO MO:1205); Ac-KO)Aga| -(RepI-MTUMO-(RepiI-(Rpe|(4-(2-aminoethoxy)I-(2-MaP-(4-amino-4- carboxytetrahydropyrani-(H uv(Ac)|-MM-MH)" (ZEO I MO:1206); ОО MO 269); M-MN" (ZEO IO MO:1270); As-KO)AgaI-I(AvSh-OHMOSI-(Rpe(4-(2-aminoethoxy)|-(2-MaC-(4-amino-4-carboxytetrahydropyran|- IS uv(Ac)|-MM-MH» (ZEO IU MO:1271); - IS uv(Ac)|-MM-MH" (ZEO IU MO: 1272); As-E-KO)Aga|-(Avsh-OTMMOSI-(P pe(4-(2-aminoethoxy)|-(2- Ma/|-(4-amino-4-carboxytetrahydropyrani|- EMM-MH" (ZEO 10 MO1273); As-KO)А5р1І-KO)Aga|-І(Авш-OTUMOSI-(Рпе(4-(2-aminoethoxy )|-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|I-EMM-MH" (ZEO I MO:1274); As-B-KO)Aga|-(Av-OTUMOSI-(Rpe( 4-(2-aminoethoxy)|-(2-Mac|-(4-amino-4-carboxytetrahydropyran|- EMM-MH" (ZEO 10 MO275); As-MKO)Aga|-KO)Ago|-cyclo(AbBa -OTUOSI-(Rpe(4-(2-aminoethoxy)I-(2-Ma!/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)" (5EO 10 MO: 1276); As-E- KO)Ag9|I--ABSH-OHUMOSI-IRNe(4-(2-aminoethoxy)I-(2-Ma!|-(4-amino-4-carboxytetrahydropyran|- EMM-MNaI2 (ZEO I MO 7277); Ac -KO)RPpeI-KO)Ag91I-AvSH-OTUMOSI-(Rpe|4-(2-aminoethoxy)I-(2-MaC-(4-amino-4- carboxytetrahydropyran|i-EMM-M) N" (5EO 10 MO: 1278); Ac-(2-MaC-KO)Aga|--(АСЧщ-ОТМмОСИ-(Рпе(4-(2-aminoethoxy)|-(2-Ма/|-(4-amino-4- carboxytetrahydropyran|i-EMM- МН» (5EO 10 MO 1279); carboxytetrahydropyrani|- EMM-MH" (ZEO 10 MO: 1280); As-I-KO)AgoI--(Av-OHUMOSI-(Rpe|4-(2-aminoethoxy)|-(2-MaC-(4-amino -4-carboxytetrahydropyrani- EMM-MH" (ZEO 10 MO 1281); As-KO)Sipl-KO)AgoI--ABSH-OTUMmOSI-|(Rpe(4-(2-aminoethoxy) I-(2-Ma!| -(4-amino-4-carboxytetrahydropyran|i-EMM-MH" (5EO 10 MO 1282); As-KO)А5п1-KO)Aga|-I(Авш-OTUMOSI-(Рпе(4-(2-aminoethoxy) |-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|i-EMM-MH" (5EO 10 MO: 1283); As--IASH-OTUMOSI-(Rpe|4-(2-aminoethoxy)- (PEGA-AIekha488)1-(2-Ma!|-(4-amino-4- 60 carboxytetrahydropyran|i-EMM-MN)" (5EO 10 MO 1284); IAIekha4881-(PEG41--( OR HUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)" (5EO 10 MO 1285) ; IAIehab47|-(PEG41--(Av-OTUMOSI-(Rpe(4-(2-aminoethoxy)|-(2-Ma/|-(4-amino-4- carboxytetrahydropyran|i-EMM-MH)" (5EO 10 MO: 1286); IAIekha-6471-IPEG41-KO)AgoI--(AvSh-OTUMOSI-|(Рпе|4-(2-aminoethoxy) |-(2-Ma/|-(4-amino-4- carboxytetrahydropyrani- (H uv(Ac)|-MM-MH" (ZEO 10 MO:1287); IAIehab47|-(PEG121-KO)AgoI-I(ABSH-OGMOSI-(Rpe(4-(2-aminoethoxy) |-(2 -Ma/|-(4-amino-4- carboxytetrahydropyrani-(H uv(Ac)|-MM-MH" (ZEO 10 MO:1288); IAIekha4881-(IPEG41-KO)Aga|-I(Avsh-OTUMOSI- (P pe(4-(2-aminoethoxy)I-(2-Ma/|-(4-amino-4-carboxytetrahydropyrani-(Guv(Ac)|-MM-MH)» (ZEO 10 MO:1289), Ac- (Rep|-OTMMO-(Repi-IRpe(4-(2-aminoethoxy)|-(2-MaC-(o-Me!ecI-(Suv(AsD-MM-MH)» (ZEO IO MO:60g2); -I(RepI-M GU O-(Repi-I(RHe(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)|-MM-MN)" (ZEO IU MO:632 ); (ZEO IO MO:639); As-I (Rep -OTUMO-(Repi-I(Pne(4-OMe)|-(2-Ma!|-(c-Me-I uzI-(Huz(As)-MM-MN)" (ZEO 10 MO:666); Ac-I(RepI-OTUMO-(Repi-I(Pne(4-SOMN2)1-(2-MaP-(a-Me-1 uziI-( uz(Ac)|-MM-MN)" (ZEO IU MO: 668). :669) or a pharmaceutically acceptable salt thereof, where the peptide inhibitor is cyclized by means of a thioether bond between Aby and Su or by means of a disulfide bond between Rep and Rep. 2. The peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt are: -Me-1I uzI-(Huz(isovaleric // acid)|-Ma- MH» (ZEO ІО МО:861); Ас--АВЩ-ОТУМОС-|РНе|4-(2-aminoethoxy))||-( 2-MaC-(AiIVB-OMa-MH" (ZEO IU MO:877) or As--AVSHSH-OPTUMOS-|РНе|4-(2-aminoethoxy)|I-(2-MaPC-(AiIVI-(uz( Ac)-MA-MH" (ZEO I MO:880), or their pharmaceutically acceptable salt, where the peptide inhibitor is cyclized with the help of a thioether bond between Aby and C. Zo 3. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1 , where the peptide inhibitor or its pharmaceutically acceptable salt is: As--АВЩ-OPTUMOS-|РНе|4-(2-(acetylaminoethoxy))|-(2-MaЦ-(α-Me-I uv(Ac)I- (uz(Ac)-MOa-MNg (5EO IO MO:900); Ac--АВЩ-ОТУМОС-|РНе|4-(2-aminoethoxy))|-(2-MaЦ-(o-Me-I uzI- EMO-MH" (ZEO I MO:911); As-IABSH-OPMOS-|РНе|4-(2-aminoethoxy))||-(2-MaЦ-(o-Me-I uz|I-EMM-MH) » (ZEO 10 MO:912); AS--AVSH-OPTUMOS-|РНе |4-(2-aminoethoxy))|I-(2-MaC-(o-MemMaiPC-(Huz(Ac)|-Ma-MH)" (ZEO IU MO:915); As--АВЩ-ОТУМОС-|РНе|4-(2-aminoethoxy))||-(2-MaЦ-(o-Me-yI etssh)-(СЩ-АММ-МН» (ZEO IU MO:954); As-KO)RpeI--(AbSh-O TM OS-|(РНе(4-(2-aminoethoxy))|-(2-MaЦ-(а-Me-Y ug|-EMM-MH)» (ZEO IO MO :970); MO:972) or As-IABSH-OPUMOS-|РНе|4-(2-aminoethoxy))|-(2-MaC-(asrsI-EMM-MH)» (Z5EO IU MO:976), or their pharmaceutically acceptable salt, where the peptide inhibitor is cyclized via a thioether bond between A and C. 4. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is: As-IAB-OTUMOS-|Ppe(|(4-(2-aminoethoxy)|I-(2-MaP| -(asrs|-EMM-MH" (ZEO I MO:1043); As-AVSH-OPTUMOS-|РНе|4-(2-aminoethoxy))||-(2-MaЦ-(asns|I-EMM-MH) » (ZEO IU MO:977) or As--AbSh-OTMOS-|РНе|4-(2-aminoethoxy))I-(2-Ma/|-(4-amino-4-carboxytetrahydropyran|-EMM-MH)» (ZEO I MO:980), or their pharmaceutically acceptable salt, where the peptide inhibitor is cyclized using a thioether bond between Aba and C. 5. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is As-IABSH-OTUOS-|Rpe|4-(2-aminoethoxy)||-(2-MatC-(a- methyl-Y-leucine|-OM-IV-AGa|-MH" (ZEO IU MO:984) or its pharmaceutically acceptable salt, where the peptide inhibitor is cyclized with the help of a thioether bond between Aba and C. 6. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is As-(0)Рпе--АБбЩ-ОТУМОС-|Рпе|4-(2-aminoethoxy))|-(2 -MaC-(4-amino-4-carboxytetrahydropyran|-EMM-MHga) (5ZEO IYUO MO:992) or its pharmaceutically acceptable salt, where the peptide inhibitor is cyclized by means of a thioether bond between Aby and C. 7. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is As-(0)Ag9I|(Absch-OTUMOS-|Rpe(|4-(2-aminoethoxy))|-( 2-MaC-(4-amino-4-carboxytetrahydropyran|-EMM-MNa (ZEO IUO MO:993) or its pharmaceutically acceptable salt, where the peptide inhibitor is cyclized by means of a thioether bond between Ar and C. 8. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is As-IABSH-OTUOS-|Rpe|4-(2-aminoethoxy) ||-(2- MaC-(a- Me-Hesh-OmMa-MH" (ZEO IYUO MO:983); As-AVSH-OTUMOS-|РНе|4-(2-aminoethoxy))|-(2-MaЦ-(o-Me-I esh-OM( B-Aia)-MH»g (Z5EO 10 MO:984); mMH" (ZEO IU MO:985) or As-ABSh-OPTUMOS-|РНе|4-(2-aminoethoxy))||-(2-MaC-(AivBI-OM(B-AiIia)-MN" (ZEO IU MO:987), or a pharmaceutically acceptable salt thereof, where the peptide inhibitor is cyclized by means of a thioether bond between Aby and C. 9. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is: As-IRepI-OTMU-(Huv(Ac)I-IRepy-I(Rpe(4-(2-aminoethoxy )|-(2-Ma!|-(AiBI-( uz(Ac)-MM-MHg (5EO (I MO:1178); As-IRepI- MTM O-(RepiI-(Рпе(4-(2-aminoethoxy )|-(2-MatC-(o-Me!ecI-(Suv(AsD-MM-MH" (ZEO IO MO:1183); As-I(RepI- MTM O-(RepiI-(Rpe(4-( 2-aminoethoxy)|-(2-MacC-(o-Me!echI-(Suv(Ac)|-IM-(B-Aia|i-MNa (5EO 10 MO:1186); Ac-I(RepI- MTM O-(RepyI-(Ppe(4-(2-aminoethoxy)|-(2-MatC-(o-Me-H uvgI-(Guv(Ac)|-M-(B-Aia|-MNa) (5EO 10 MO 1187); |-M-I(B-AIa|-MN" (5EO 10 MO 1188); As-I(RepI-M GU O-(Repi-(Pne(4-(2-aminoethoxy)|-(2-MaPC- (AivI-( uv(Ac)|-54-MN" (ZEO IU MO 1191); As-I(RepI-M GU O-(Repi-I(Pne(4-(2-aminoethoxy)|-(2- MaPC-(AivI-( uv(As)-EM-MN" (ZEO IU MO:1193); As-IRep|I-M HMU-I(СЩ-(Repi-(Рпе(4-(2-aminoethoxy)| -(2-Ma!|-(AIVI-(Huz(As)-MM-MN" (ZEO and MO:1194); Ac-(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac)|-a-(B-AIa|-MH)): ( ZEO IO Zo MO:1197); B-AIa|-MHg (ZEO IO MO:1198); As-I(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AivI-( uv(Ac )I-5-(8-АТа|-МН» (ZEO IO MO 1200); Ac-(RepI-M GPU O-(Repi-IRne(4-(2-aminoethoxy)|-(2-MaPC-(AivI) -( uv(Ac)I-(2-MariI-IV-Aia|-MNg (5EO I MO:1204) or As-I(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)| -(2-MaPC-(AlivI-( uv(Ac)-E-IV-Aliiia|-MN»g (ZEO IO MO:1205), or a pharmaceutically acceptable salt thereof, where the peptide inhibitor is cyclized by means of a disulfide bond) between Rep. 10. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is: Ac-(Rep|-OTMMO-(Repi-IRpe(4-(2-aminoethoxy)|-(2-MaC) -(o-Me! ecI-(Suv(AsD-MM-MN" (ZEO IO MO:60g2); As-IRepI-M PU O-(Repi-IRne(4-(2-aminoethoxy)|-(2- MaPC-(AivI-( uv(Ac)|-MM-MN" (ZEO IU MO:632); As-I(RepI-M GU O-(Repi-IRne(4-(2-aminoethoxy)|-(2 -MaC-(AivI-( uv(Ac)I-M-(8-AIa|-MNg (ZEO IO MO:639); As-I(RepI-OTUMO-(Repi-I(Pne(4-OMe)| -(2-Ma!|-(c-Me-I uzI-(Huz(As)-MM-MN" (ZEO 10 MO:666); As-I(RepI-OTUMO-(Repi-I(Pne(4 -SOMH2)1-(2-Ma|-(a-Me-Y uvzI-(H uv(Ac)|-MM-MH" (5EO IU MO:668) or 0 As-IRepI-OTUMO-(RepiI-I) (Pne(4-СОМН2)1-(2-MaЦ-(α-Memai|-(Guv(Ac)-MM-MH)" (ZEO IU MO:669), or their pharmaceutically acceptable salt, where the peptide inhibitor is cyclized by using a disulfide bond between Rep. 11. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is: As-KO)RPeI-(RepIi-MTUUS(RepiI-(Ppe(4-OMe)|-(2-Ma) |-(4-amino-4-carboxytetrahydropyran|-(ISХ-MM- МН» (ZEO I MO:679) or As-KO)RPpeI-(RepI-MTUO(Repi-IRpe(4-OMe))|-(2 -MaC-(Asps|-EMM-MH" (5EO 1Yu MO:681), or their pharmaceutically acceptable salt, where the peptide inhibitor is cyclized using a disulfide bond between Rep. 12. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is: As-I(RepI-M GU O-(RepiI-(Pne(4-COMH2)I-(2-MaP) |-(AivI-( uv(Ac)-MM-MN" (ZEO OO MO:682) or its pharmaceutically acceptable salt, where the peptide inhibitor is cyclized using a disulfide bond between Rep. 13. Peptide inhibitor or its pharmaceutically acceptable salt according to claim 1, where the peptide inhibitor or its pharmaceutically acceptable salt is: As-IRepI-MTM O-(RepiI-(Rpe(4-(2-aminoethoxy)|-(2-MatC) -(o-Me! ecI-(Suv(AsD-MM-MH)" (ZEO IO MO:1183) or its pharmaceutically acceptable salt, where the peptide inhibitor is cyclized using a disulfide bond between Rep. 14. A pharmaceutical composition containing a peptide inhibitor or its pharmaceutically acceptable salt according to any of claims 1-13. 15. A method of treating inflammatory bowel disease (IBD) in a subject, which includes administering to the subject an effective amount of a peptide inhibitor or a pharmaceutically acceptable salt thereof according to any one of claims 1-13, or a pharmaceutical composition according to claim 14. 16. The method according to claim 15, where the peptide inhibitor or its pharmaceutically acceptable salt or pharmaceutical composition is administered orally. 17. The method according to claim 15, where IVO is ulcerative colitis. 18. The method according to claim 15, where IVO is Crohn's disease. 19. The method according to claim 15, where IVO is a pouchitis that occurs after proctocolectomy and ileoanal anastomosis. with SHI! And more Thebes mi I x X se fon Z M i p sh ok shk sho she X x X he X ra oyi E a g g ne E . M Kai sh - Z zh - shsh - - t sho - - sh h g in everything B Bo v i shi I V in ve 5 KE still what iz 24 sh re: 5 what 5 E k Like ok shcha shcha oi Z OBO Fig. 1 TsO-12 stimulation of IEE XxUu release from human REM 2. 4 And aa for? ay ve She z" za zaoayi Yi s ey i z "Bine yayu mak me com yakome che pnsny ny sny shiny She sheshchau E: r-ya KEYA - 12 u m 7 i ! sh 0.8 zn Compound A sov, and Compound B 0 VV. nny rorirrnnnnnnia ren rr renni rennia: ON p. 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