KR20170004011A - 신규 특이적 결합 폴리펩타이드 및 이의 용도 - Google Patents
신규 특이적 결합 폴리펩타이드 및 이의 용도 Download PDFInfo
- Publication number
- KR20170004011A KR20170004011A KR1020167035964A KR20167035964A KR20170004011A KR 20170004011 A KR20170004011 A KR 20170004011A KR 1020167035964 A KR1020167035964 A KR 1020167035964A KR 20167035964 A KR20167035964 A KR 20167035964A KR 20170004011 A KR20170004011 A KR 20170004011A
- Authority
- KR
- South Korea
- Prior art keywords
- polypeptide
- binding
- glu
- leu
- lys
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 253
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 216
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 208
- 230000009870 specific binding Effects 0.000 title abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 72
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 48
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 45
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 45
- 238000003745 diagnosis Methods 0.000 claims abstract description 7
- 108050006654 Lipocalin Proteins 0.000 claims description 470
- 102000019298 Lipocalin Human genes 0.000 claims description 467
- 108050003558 Interleukin-17 Proteins 0.000 claims description 417
- 102000013691 Interleukin-17 Human genes 0.000 claims description 415
- 230000027455 binding Effects 0.000 claims description 268
- 108020001507 fusion proteins Proteins 0.000 claims description 268
- 102000037865 fusion proteins Human genes 0.000 claims description 268
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 127
- 108010065637 Interleukin-23 Proteins 0.000 claims description 111
- 102000013264 Interleukin-23 Human genes 0.000 claims description 111
- 108090000623 proteins and genes Proteins 0.000 claims description 83
- 102000004169 proteins and genes Human genes 0.000 claims description 82
- 238000003556 assay Methods 0.000 claims description 60
- 238000006467 substitution reaction Methods 0.000 claims description 60
- 238000002965 ELISA Methods 0.000 claims description 45
- 102000009027 Albumins Human genes 0.000 claims description 44
- 108010088751 Albumins Proteins 0.000 claims description 44
- 102000005962 receptors Human genes 0.000 claims description 42
- 108020003175 receptors Proteins 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 34
- 125000000539 amino acid group Chemical group 0.000 claims description 28
- 230000002860 competitive effect Effects 0.000 claims description 28
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 24
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 24
- 239000012634 fragment Substances 0.000 claims description 23
- 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 claims description 22
- 239000002773 nucleotide Substances 0.000 claims description 22
- 125000003729 nucleotide group Chemical group 0.000 claims description 22
- 210000002966 serum Anatomy 0.000 claims description 20
- 108060003951 Immunoglobulin Proteins 0.000 claims description 19
- 102000018358 immunoglobulin Human genes 0.000 claims description 19
- 102000014914 Carrier Proteins Human genes 0.000 claims description 18
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 18
- 230000014509 gene expression Effects 0.000 claims description 18
- 108091008324 binding proteins Proteins 0.000 claims description 17
- 238000001514 detection method Methods 0.000 claims description 17
- 101001023833 Homo sapiens Neutrophil gelatinase-associated lipocalin Proteins 0.000 claims description 15
- 102000047202 human LCN2 Human genes 0.000 claims description 15
- 238000012217 deletion Methods 0.000 claims description 14
- 230000037430 deletion Effects 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 241000282693 Cercopithecidae Species 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 102000053162 human IL17A Human genes 0.000 claims description 13
- 229960002685 biotin Drugs 0.000 claims description 12
- 235000020958 biotin Nutrition 0.000 claims description 12
- 239000011616 biotin Substances 0.000 claims description 12
- 238000012360 testing method Methods 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 230000001105 regulatory effect Effects 0.000 claims description 10
- 230000001580 bacterial effect Effects 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 238000002955 isolation Methods 0.000 claims description 8
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 241001515942 marmosets Species 0.000 claims description 7
- 229920001515 polyalkylene glycol Polymers 0.000 claims description 7
- 239000013598 vector Substances 0.000 claims description 7
- 102100036672 Interleukin-23 receptor Human genes 0.000 claims description 6
- 230000000536 complexating effect Effects 0.000 claims description 6
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 6
- 108020001580 protein domains Proteins 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 5
- 108040001844 interleukin-23 receptor activity proteins Proteins 0.000 claims description 5
- -1 polyethylene Polymers 0.000 claims description 5
- 238000009007 Diagnostic Kit Methods 0.000 claims description 4
- 238000003149 assay kit Methods 0.000 claims description 4
- 239000003053 toxin Substances 0.000 claims description 4
- 231100000765 toxin Toxicity 0.000 claims description 4
- 108700012359 toxins Proteins 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 238000010353 genetic engineering Methods 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 230000002285 radioactive effect Effects 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 2
- 108091033319 polynucleotide Proteins 0.000 claims description 2
- 102000040430 polynucleotide Human genes 0.000 claims description 2
- 239000002157 polynucleotide Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 108010076561 Interleukin-23 Subunit p19 Proteins 0.000 claims 32
- 102100036705 Interleukin-23 subunit alpha Human genes 0.000 claims 32
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 claims 2
- 102100035018 Interleukin-17 receptor A Human genes 0.000 claims 2
- 101710186083 Interleukin-17 receptor A Proteins 0.000 claims 2
- 150000004696 coordination complex Chemical class 0.000 claims 2
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 claims 2
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 claims 2
- 239000007850 fluorescent dye Substances 0.000 claims 2
- 102000006395 Globulins Human genes 0.000 claims 1
- 108010044091 Globulins Proteins 0.000 claims 1
- 239000004698 Polyethylene Substances 0.000 claims 1
- 239000000824 cytostatic agent Substances 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 229920000573 polyethylene Polymers 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract description 10
- 238000011282 treatment Methods 0.000 abstract description 5
- 229940124829 interleukin-23 Drugs 0.000 description 97
- 235000001014 amino acid Nutrition 0.000 description 90
- 235000018102 proteins Nutrition 0.000 description 74
- 210000004027 cell Anatomy 0.000 description 72
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 69
- 229940024606 amino acid Drugs 0.000 description 65
- 150000001413 amino acids Chemical class 0.000 description 61
- 108010057281 Lipocalin 1 Proteins 0.000 description 60
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 49
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 45
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical class SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 42
- 102100034724 Lipocalin-1 Human genes 0.000 description 42
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 39
- 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 description 37
- 238000002474 experimental method Methods 0.000 description 37
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 36
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 35
- 239000003446 ligand Substances 0.000 description 35
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 32
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 31
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 31
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 31
- 238000010494 dissociation reaction Methods 0.000 description 29
- 230000005593 dissociations Effects 0.000 description 29
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 28
- 230000035772 mutation Effects 0.000 description 28
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 27
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 27
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 27
- 230000004927 fusion Effects 0.000 description 27
- 239000000523 sample Substances 0.000 description 26
- 238000005406 washing Methods 0.000 description 24
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 23
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 23
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 21
- 102000003752 Lipocalin 1 Human genes 0.000 description 21
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 108091006905 Human Serum Albumin Proteins 0.000 description 19
- 102000008100 Human Serum Albumin Human genes 0.000 description 19
- 238000011534 incubation Methods 0.000 description 19
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 18
- 239000013642 negative control Substances 0.000 description 16
- 102000004127 Cytokines Human genes 0.000 description 14
- 108090000695 Cytokines Proteins 0.000 description 14
- 102000013519 Lipocalin-2 Human genes 0.000 description 14
- 108010051335 Lipocalin-2 Proteins 0.000 description 14
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000005259 measurement Methods 0.000 description 13
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000003993 interaction Effects 0.000 description 11
- 231100000350 mutagenesis Toxicity 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 10
- HVHRPWQEQHIQJF-AVGNSLFASA-N Leu-Lys-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HVHRPWQEQHIQJF-AVGNSLFASA-N 0.000 description 10
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 10
- 235000018417 cysteine Nutrition 0.000 description 10
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 238000003780 insertion Methods 0.000 description 10
- 230000037431 insertion Effects 0.000 description 10
- 201000006417 multiple sclerosis Diseases 0.000 description 10
- 238000002703 mutagenesis Methods 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 10
- 108010029020 prolylglycine Proteins 0.000 description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 description 10
- DZQMXBALGUHGJT-GUBZILKMSA-N Leu-Glu-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O DZQMXBALGUHGJT-GUBZILKMSA-N 0.000 description 9
- 108010047857 aspartylglycine Proteins 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 230000028327 secretion Effects 0.000 description 9
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
- 210000004899 c-terminal region Anatomy 0.000 description 8
- 230000009260 cross reactivity Effects 0.000 description 8
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 7
- RMAWDDRDTRSZIR-ZLUOBGJFSA-N Ala-Ser-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RMAWDDRDTRSZIR-ZLUOBGJFSA-N 0.000 description 7
- 239000004471 Glycine Substances 0.000 description 7
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 7
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 7
- 201000004681 Psoriasis Diseases 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 108010038633 aspartylglutamate Proteins 0.000 description 7
- 238000002820 assay format Methods 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 108010087904 neutravidin Proteins 0.000 description 7
- 210000000440 neutrophil Anatomy 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- GFEDXKNBZMPEDM-KZVJFYERSA-N Ala-Met-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GFEDXKNBZMPEDM-KZVJFYERSA-N 0.000 description 6
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 6
- MTYLORHAQXVQOW-AVGNSLFASA-N Arg-Lys-Met Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(O)=O MTYLORHAQXVQOW-AVGNSLFASA-N 0.000 description 6
- GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- PONUFVLSGMQFAI-AVGNSLFASA-N Gln-Asn-Phe Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PONUFVLSGMQFAI-AVGNSLFASA-N 0.000 description 6
- QYTKAVBFRUGYAU-ACZMJKKPSA-N Gln-Asp-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O QYTKAVBFRUGYAU-ACZMJKKPSA-N 0.000 description 6
- UTKUTMJSWKKHEM-WDSKDSINSA-N Glu-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O UTKUTMJSWKKHEM-WDSKDSINSA-N 0.000 description 6
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 6
- RMJWFINHACYKJI-SIUGBPQLSA-N Ile-Tyr-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N RMJWFINHACYKJI-SIUGBPQLSA-N 0.000 description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 6
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- GURGCNUWVSDYTP-SRVKXCTJSA-N Pro-Leu-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GURGCNUWVSDYTP-SRVKXCTJSA-N 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- YRBGKVIWMNEVCZ-WDSKDSINSA-N Ser-Glu-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O YRBGKVIWMNEVCZ-WDSKDSINSA-N 0.000 description 6
- GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 6
- 108700011201 Streptococcus IgG Fc-binding Proteins 0.000 description 6
- CAJFZCICSVBOJK-SHGPDSBTSA-N Thr-Ala-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAJFZCICSVBOJK-SHGPDSBTSA-N 0.000 description 6
- BDENGIGFTNYZSJ-RCWTZXSCSA-N Thr-Pro-Met Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(O)=O BDENGIGFTNYZSJ-RCWTZXSCSA-N 0.000 description 6
- 102000004338 Transferrin Human genes 0.000 description 6
- 108090000901 Transferrin Proteins 0.000 description 6
- LABUITCFCAABSV-BPNCWPANSA-N Val-Ala-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 LABUITCFCAABSV-BPNCWPANSA-N 0.000 description 6
- LABUITCFCAABSV-UHFFFAOYSA-N Val-Ala-Tyr Natural products CC(C)C(N)C(=O)NC(C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LABUITCFCAABSV-UHFFFAOYSA-N 0.000 description 6
- USXYVSTVPHELAF-RCWTZXSCSA-N Val-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](C(C)C)N)O USXYVSTVPHELAF-RCWTZXSCSA-N 0.000 description 6
- AEFJNECXZCODJM-UWVGGRQHSA-N Val-Val-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)NCC([O-])=O AEFJNECXZCODJM-UWVGGRQHSA-N 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 238000000423 cell based assay Methods 0.000 description 6
- 230000004663 cell proliferation Effects 0.000 description 6
- 230000009918 complex formation Effects 0.000 description 6
- 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 6
- 229940050526 hydroxyethylstarch Drugs 0.000 description 6
- 229930182817 methionine Natural products 0.000 description 6
- 235000006109 methionine Nutrition 0.000 description 6
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 239000012581 transferrin Substances 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 108010014563 tryptophyl-cysteinyl-serine Proteins 0.000 description 6
- 108010051110 tyrosyl-lysine Proteins 0.000 description 6
- ZVFVBBGVOILKPO-WHFBIAKZSA-N Ala-Gly-Ala Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O ZVFVBBGVOILKPO-WHFBIAKZSA-N 0.000 description 5
- OLVCTPPSXNRGKV-GUBZILKMSA-N Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OLVCTPPSXNRGKV-GUBZILKMSA-N 0.000 description 5
- ULBHWNVWSCJLCO-NHCYSSNCSA-N Arg-Val-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N ULBHWNVWSCJLCO-NHCYSSNCSA-N 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 5
- BDMIFVIWCNLDCT-CIUDSAMLSA-N Asn-Arg-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O BDMIFVIWCNLDCT-CIUDSAMLSA-N 0.000 description 5
- YGHCVNQOZZMHRZ-DJFWLOJKSA-N Asn-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)N)N YGHCVNQOZZMHRZ-DJFWLOJKSA-N 0.000 description 5
- MVXJBVVLACEGCG-PCBIJLKTSA-N Asn-Phe-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MVXJBVVLACEGCG-PCBIJLKTSA-N 0.000 description 5
- KVPHTGVUMJGMCX-BIIVOSGPSA-N Asp-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CC(=O)O)N)C(=O)O KVPHTGVUMJGMCX-BIIVOSGPSA-N 0.000 description 5
- KQBVNNAPIURMPD-PEFMBERDSA-N Asp-Ile-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KQBVNNAPIURMPD-PEFMBERDSA-N 0.000 description 5
- RKXVTTIQNKPCHU-KKHAAJSZSA-N Asp-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O RKXVTTIQNKPCHU-KKHAAJSZSA-N 0.000 description 5
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- LKUWAWGNJYJODH-KBIXCLLPSA-N Gln-Ala-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LKUWAWGNJYJODH-KBIXCLLPSA-N 0.000 description 5
- WLODHVXYKYHLJD-ACZMJKKPSA-N Gln-Asp-Ser Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N WLODHVXYKYHLJD-ACZMJKKPSA-N 0.000 description 5
- IXFVOPOHSRKJNG-LAEOZQHASA-N Gln-Asp-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O IXFVOPOHSRKJNG-LAEOZQHASA-N 0.000 description 5
- LFIVHGMKWFGUGK-IHRRRGAJSA-N Gln-Glu-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N LFIVHGMKWFGUGK-IHRRRGAJSA-N 0.000 description 5
- KFHASAPTUOASQN-JYJNAYRXSA-N Gln-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCC(=O)N)N KFHASAPTUOASQN-JYJNAYRXSA-N 0.000 description 5
- AUTNXSQEVVHSJK-YVNDNENWSA-N Glu-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O AUTNXSQEVVHSJK-YVNDNENWSA-N 0.000 description 5
- KMSGYZQRXPUKGI-BYPYZUCNSA-N Gly-Gly-Asn Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(N)=O KMSGYZQRXPUKGI-BYPYZUCNSA-N 0.000 description 5
- DENRBIYENOKSEX-PEXQALLHSA-N Gly-Ile-His Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 DENRBIYENOKSEX-PEXQALLHSA-N 0.000 description 5
- JPVGHHQGKPQYIL-KBPBESRZSA-N Gly-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 JPVGHHQGKPQYIL-KBPBESRZSA-N 0.000 description 5
- BMWFDYIYBAFROD-WPRPVWTQSA-N Gly-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN BMWFDYIYBAFROD-WPRPVWTQSA-N 0.000 description 5
- LLWQVJNHMYBLLK-CDMKHQONSA-N Gly-Thr-Phe Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LLWQVJNHMYBLLK-CDMKHQONSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- SPQWWEZBHXHUJN-KBIXCLLPSA-N Ile-Glu-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O SPQWWEZBHXHUJN-KBIXCLLPSA-N 0.000 description 5
- KYLIZSDYWQQTFM-PEDHHIEDSA-N Ile-Ile-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CCCN=C(N)N KYLIZSDYWQQTFM-PEDHHIEDSA-N 0.000 description 5
- KBDIBHQICWDGDL-PPCPHDFISA-N Ile-Thr-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N KBDIBHQICWDGDL-PPCPHDFISA-N 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 5
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
- LZDNBBYBDGBADK-UHFFFAOYSA-N L-valyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-UHFFFAOYSA-N 0.000 description 5
- 241000880493 Leptailurus serval Species 0.000 description 5
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 5
- HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-N 0.000 description 5
- OMHLATXVNQSALM-FQUUOJAGSA-N Leu-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(C)C)N OMHLATXVNQSALM-FQUUOJAGSA-N 0.000 description 5
- VULJUQZPSOASBZ-SRVKXCTJSA-N Leu-Pro-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O VULJUQZPSOASBZ-SRVKXCTJSA-N 0.000 description 5
- FBNPMTNBFFAMMH-UHFFFAOYSA-N Leu-Val-Arg Natural products CC(C)CC(N)C(=O)NC(C(C)C)C(=O)NC(C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-UHFFFAOYSA-N 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- ABHIXYDMILIUKV-CIUDSAMLSA-N Lys-Asn-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ABHIXYDMILIUKV-CIUDSAMLSA-N 0.000 description 5
- YFQSSOAGMZGXFT-MEYUZBJRSA-N Lys-Thr-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YFQSSOAGMZGXFT-MEYUZBJRSA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- VSJAPSMRFYUOKS-IUCAKERBSA-N Met-Pro-Gly Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O VSJAPSMRFYUOKS-IUCAKERBSA-N 0.000 description 5
- GWADARYJIJDYRC-XGEHTFHBSA-N Met-Thr-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GWADARYJIJDYRC-XGEHTFHBSA-N 0.000 description 5
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 5
- PSKRILMFHNIUAO-JYJNAYRXSA-N Phe-Glu-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N PSKRILMFHNIUAO-JYJNAYRXSA-N 0.000 description 5
- JJHVFCUWLSKADD-ONGXEEELSA-N Phe-Gly-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](C)C(O)=O JJHVFCUWLSKADD-ONGXEEELSA-N 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- BQWCDDAISCPDQV-XHNCKOQMSA-N Ser-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N)C(=O)O BQWCDDAISCPDQV-XHNCKOQMSA-N 0.000 description 5
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 5
- CUXJENOFJXOSOZ-BIIVOSGPSA-N Ser-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CO)N)C(=O)O CUXJENOFJXOSOZ-BIIVOSGPSA-N 0.000 description 5
- VGQVAVQWKJLIRM-FXQIFTODSA-N Ser-Ser-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O VGQVAVQWKJLIRM-FXQIFTODSA-N 0.000 description 5
- VTVVYQOXJCZVEB-WDCWCFNPSA-N Thr-Leu-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VTVVYQOXJCZVEB-WDCWCFNPSA-N 0.000 description 5
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 5
- IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 5
- XHWCDRUPDNSDAZ-XKBZYTNZSA-N Thr-Ser-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N)O XHWCDRUPDNSDAZ-XKBZYTNZSA-N 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- JZHJLBPBQKPTNX-UBHSHLNASA-N Trp-Cys-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 JZHJLBPBQKPTNX-UBHSHLNASA-N 0.000 description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
- LRHBBGDMBLFYGL-FHWLQOOXSA-N Tyr-Phe-Glu Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C1=CC=C(O)C=C1 LRHBBGDMBLFYGL-FHWLQOOXSA-N 0.000 description 5
- HHSILIQTHXABKM-YDHLFZDLSA-N Val-Asp-Phe Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](Cc1ccccc1)C(O)=O HHSILIQTHXABKM-YDHLFZDLSA-N 0.000 description 5
- KTEZUXISLQTDDQ-NHCYSSNCSA-N Val-Lys-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KTEZUXISLQTDDQ-NHCYSSNCSA-N 0.000 description 5
- VCIYTVOBLZHFSC-XHSDSOJGSA-N Val-Phe-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N VCIYTVOBLZHFSC-XHSDSOJGSA-N 0.000 description 5
- SJRUJQFQVLMZFW-WPRPVWTQSA-N Val-Pro-Gly Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O SJRUJQFQVLMZFW-WPRPVWTQSA-N 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000012491 analyte Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
- 235000009582 asparagine Nutrition 0.000 description 5
- 229960001230 asparagine Drugs 0.000 description 5
- 235000003704 aspartic acid Nutrition 0.000 description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 5
- 238000001516 cell proliferation assay Methods 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 235000013922 glutamic acid Nutrition 0.000 description 5
- 239000004220 glutamic acid Substances 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 239000000710 homodimer Substances 0.000 description 5
- 235000014705 isoleucine Nutrition 0.000 description 5
- 229960000310 isoleucine Drugs 0.000 description 5
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 5
- 108010078274 isoleucylvaline Proteins 0.000 description 5
- 235000005772 leucine Nutrition 0.000 description 5
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 5
- 108010034529 leucyl-lysine Proteins 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
- 230000004962 physiological condition Effects 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 108010090894 prolylleucine Proteins 0.000 description 5
- 108010053725 prolylvaline Proteins 0.000 description 5
- 108010071207 serylmethionine Proteins 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 239000004474 valine Substances 0.000 description 5
- 235000014393 valine Nutrition 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 4
- AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 description 4
- ZEDBMCPXPIYJLW-XHNCKOQMSA-N Asp-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)N)C(=O)O ZEDBMCPXPIYJLW-XHNCKOQMSA-N 0.000 description 4
- 102100037362 Fibronectin Human genes 0.000 description 4
- 108010067306 Fibronectins Proteins 0.000 description 4
- 108010026132 Gelatinases Proteins 0.000 description 4
- 102000013382 Gelatinases Human genes 0.000 description 4
- JJKKWYQVHRUSDG-GUBZILKMSA-N Glu-Ala-Lys Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O JJKKWYQVHRUSDG-GUBZILKMSA-N 0.000 description 4
- IQACOVZVOMVILH-FXQIFTODSA-N Glu-Glu-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O IQACOVZVOMVILH-FXQIFTODSA-N 0.000 description 4
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 4
- LHRXAHLCRMQBGJ-RYUDHWBXSA-N Gly-Glu-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CN LHRXAHLCRMQBGJ-RYUDHWBXSA-N 0.000 description 4
- QITBQGJOXQYMOA-ZETCQYMHSA-N Gly-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CN QITBQGJOXQYMOA-ZETCQYMHSA-N 0.000 description 4
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 4
- CVFOYJJOZYYEPE-KBPBESRZSA-N Gly-Lys-Tyr Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CVFOYJJOZYYEPE-KBPBESRZSA-N 0.000 description 4
- OHUKZZYSJBKFRR-WHFBIAKZSA-N Gly-Ser-Asp Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O OHUKZZYSJBKFRR-WHFBIAKZSA-N 0.000 description 4
- UWNUQPZUSRFIIN-JUKXBJQTSA-N His-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC2=CN=CN2)N UWNUQPZUSRFIIN-JUKXBJQTSA-N 0.000 description 4
- 101000852980 Homo sapiens Interleukin-23 subunit alpha Proteins 0.000 description 4
- SVZFKLBRCYCIIY-CYDGBPFRSA-N Ile-Pro-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SVZFKLBRCYCIIY-CYDGBPFRSA-N 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 4
- IRNSXVOWSXSULE-DCAQKATOSA-N Lys-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN IRNSXVOWSXSULE-DCAQKATOSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- 102100035405 Neutrophil gelatinase-associated lipocalin Human genes 0.000 description 4
- 101710147507 Neutrophil gelatinase-associated lipocalin Proteins 0.000 description 4
- INHMISZWLJZQGH-ULQDDVLXSA-N Phe-Leu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 INHMISZWLJZQGH-ULQDDVLXSA-N 0.000 description 4
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 description 4
- RIAKPZVSNBBNRE-BJDJZHNGSA-N Ser-Ile-Leu Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O RIAKPZVSNBBNRE-BJDJZHNGSA-N 0.000 description 4
- KKKVOZNCLALMPV-XKBZYTNZSA-N Ser-Thr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KKKVOZNCLALMPV-XKBZYTNZSA-N 0.000 description 4
- NJEMRSFGDNECGF-GCJQMDKQSA-N Thr-Ala-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O NJEMRSFGDNECGF-GCJQMDKQSA-N 0.000 description 4
- WMBFONUKQXGLMU-WDSOQIARSA-N Trp-Leu-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N WMBFONUKQXGLMU-WDSOQIARSA-N 0.000 description 4
- DVLHKUWLNKDINO-PMVMPFDFSA-N Trp-Tyr-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O DVLHKUWLNKDINO-PMVMPFDFSA-N 0.000 description 4
- PMDWYLVWHRTJIW-STQMWFEESA-N Tyr-Gly-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PMDWYLVWHRTJIW-STQMWFEESA-N 0.000 description 4
- LKUDRJSNRWVGMS-QSFUFRPTSA-N Val-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LKUDRJSNRWVGMS-QSFUFRPTSA-N 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 230000009137 competitive binding Effects 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 108010078326 glycyl-glycyl-valine Proteins 0.000 description 4
- 239000000833 heterodimer Substances 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 229940100601 interleukin-6 Drugs 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 108010064486 phenylalanyl-leucyl-valine Proteins 0.000 description 4
- 230000000704 physical effect Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 238000011069 regeneration method Methods 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 108010044292 tryptophyltyrosine Proteins 0.000 description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
- LNNSWWRRYJLGNI-NAKRPEOUSA-N Ala-Ile-Val Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O LNNSWWRRYJLGNI-NAKRPEOUSA-N 0.000 description 3
- MDNAVFBZPROEHO-UHFFFAOYSA-N Ala-Lys-Val Natural products CC(C)C(C(O)=O)NC(=O)C(NC(=O)C(C)N)CCCCN MDNAVFBZPROEHO-UHFFFAOYSA-N 0.000 description 3
- SJPZTWAYTJPPBI-GUBZILKMSA-N Asn-Gln-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)N SJPZTWAYTJPPBI-GUBZILKMSA-N 0.000 description 3
- SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 3
- CTWCFPWFIGRAEP-CIUDSAMLSA-N Asp-Lys-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O CTWCFPWFIGRAEP-CIUDSAMLSA-N 0.000 description 3
- DPNWSMBUYCLEDG-CIUDSAMLSA-N Asp-Lys-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O DPNWSMBUYCLEDG-CIUDSAMLSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 238000012286 ELISA Assay Methods 0.000 description 3
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 3
- YKJUITHASJAGHO-HOTGVXAUSA-N Gly-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CN YKJUITHASJAGHO-HOTGVXAUSA-N 0.000 description 3
- 101000853012 Homo sapiens Interleukin-23 receptor Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 3
- VWHGTYCRDRBSFI-ZETCQYMHSA-N Leu-Gly-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)NCC(O)=O VWHGTYCRDRBSFI-ZETCQYMHSA-N 0.000 description 3
- AMSSKPUHBUQBOQ-SRVKXCTJSA-N Leu-Ser-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N AMSSKPUHBUQBOQ-SRVKXCTJSA-N 0.000 description 3
- YEIYAQQKADPIBJ-GARJFASQSA-N Lys-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)N)C(=O)O YEIYAQQKADPIBJ-GARJFASQSA-N 0.000 description 3
- DCRWPTBMWMGADO-AVGNSLFASA-N Lys-Glu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DCRWPTBMWMGADO-AVGNSLFASA-N 0.000 description 3
- NROQVSYLPRLJIP-PMVMPFDFSA-N Lys-Trp-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NROQVSYLPRLJIP-PMVMPFDFSA-N 0.000 description 3
- 241000282567 Macaca fascicularis Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 241000219061 Rheum Species 0.000 description 3
- XNCUYZKGQOCOQH-YUMQZZPRSA-N Ser-Leu-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O XNCUYZKGQOCOQH-YUMQZZPRSA-N 0.000 description 3
- PMCMLDNPAZUYGI-DCAQKATOSA-N Ser-Lys-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PMCMLDNPAZUYGI-DCAQKATOSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 210000000068 Th17 cell Anatomy 0.000 description 3
- JVTHIXKSVYEWNI-JRQIVUDYSA-N Thr-Asn-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JVTHIXKSVYEWNI-JRQIVUDYSA-N 0.000 description 3
- UXUFNBVCPAWACG-SIUGBPQLSA-N Tyr-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N UXUFNBVCPAWACG-SIUGBPQLSA-N 0.000 description 3
- DOBHJKVVACOQTN-DZKIICNBSA-N Val-Tyr-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=C(O)C=C1 DOBHJKVVACOQTN-DZKIICNBSA-N 0.000 description 3
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 239000012911 assay medium Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 3
- 229960002986 dinoprostone Drugs 0.000 description 3
- 201000002491 encephalomyelitis Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 238000002825 functional assay Methods 0.000 description 3
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 3
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 3
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 3
- 108010050848 glycylleucine Proteins 0.000 description 3
- 230000007085 granulocyte colony-stimulating factor production Effects 0.000 description 3
- 108010040030 histidinoalanine Proteins 0.000 description 3
- 102000057111 human IL23R Human genes 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 229940096397 interleukin-8 Drugs 0.000 description 3
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 108010017391 lysylvaline Proteins 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 210000003071 memory t lymphocyte Anatomy 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- MXHCPCSDRGLRER-UHFFFAOYSA-N pentaglycine Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(O)=O MXHCPCSDRGLRER-UHFFFAOYSA-N 0.000 description 3
- 210000001322 periplasm Anatomy 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 102000029752 retinol binding Human genes 0.000 description 3
- 108091000053 retinol binding Proteins 0.000 description 3
- 239000012146 running buffer Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 150000003573 thiols Chemical group 0.000 description 3
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GJLXVWOMRRWCIB-MERZOTPQSA-N (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanamide Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=C(O)C=C1 GJLXVWOMRRWCIB-MERZOTPQSA-N 0.000 description 2
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 2
- OYJCVIGKMXUVKB-GARJFASQSA-N Ala-Leu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N OYJCVIGKMXUVKB-GARJFASQSA-N 0.000 description 2
- OINVDEKBKBCPLX-JXUBOQSCSA-N Ala-Lys-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OINVDEKBKBCPLX-JXUBOQSCSA-N 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 102000008102 Ankyrins Human genes 0.000 description 2
- 108010049777 Ankyrins Proteins 0.000 description 2
- 102000009333 Apolipoprotein D Human genes 0.000 description 2
- 108010025614 Apolipoproteins D Proteins 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 2
- CGXQUULXFWRJOI-SRVKXCTJSA-N Arg-Val-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O CGXQUULXFWRJOI-SRVKXCTJSA-N 0.000 description 2
- 206010051728 Bone erosion Diseases 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102000012545 EGF-like domains Human genes 0.000 description 2
- 108050002150 EGF-like domains Proteins 0.000 description 2
- ITYRYNUZHPNCIK-GUBZILKMSA-N Glu-Ala-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O ITYRYNUZHPNCIK-GUBZILKMSA-N 0.000 description 2
- OQXDUSZKISQQSS-GUBZILKMSA-N Glu-Lys-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OQXDUSZKISQQSS-GUBZILKMSA-N 0.000 description 2
- CQAHWYDHKUWYIX-YUMQZZPRSA-N Glu-Pro-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O CQAHWYDHKUWYIX-YUMQZZPRSA-N 0.000 description 2
- DMYACXMQUABZIQ-NRPADANISA-N Glu-Ser-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O DMYACXMQUABZIQ-NRPADANISA-N 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- IUKIDFVOUHZRAK-QWRGUYRKSA-N Gly-Lys-His Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IUKIDFVOUHZRAK-QWRGUYRKSA-N 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- XINDHUAGVGCNSF-QSFUFRPTSA-N His-Ala-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XINDHUAGVGCNSF-QSFUFRPTSA-N 0.000 description 2
- 102100022103 Histone-lysine N-methyltransferase 2A Human genes 0.000 description 2
- 108050002855 Histone-lysine N-methyltransferase 2A Proteins 0.000 description 2
- 101001019598 Homo sapiens Interleukin-17 receptor A Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- KLBVGHCGHUNHEA-BJDJZHNGSA-N Ile-Leu-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)O)N KLBVGHCGHUNHEA-BJDJZHNGSA-N 0.000 description 2
- VZSDQFZFTCVEGF-ZEWNOJEFSA-N Ile-Phe-Tyr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O VZSDQFZFTCVEGF-ZEWNOJEFSA-N 0.000 description 2
- 102100033461 Interleukin-17A Human genes 0.000 description 2
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 2
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 101150055061 LCN2 gene Proteins 0.000 description 2
- AAKRWBIIGKPOKQ-ONGXEEELSA-N Leu-Val-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AAKRWBIIGKPOKQ-ONGXEEELSA-N 0.000 description 2
- IOQWIOPSKJOEKI-SRVKXCTJSA-N Lys-Ser-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IOQWIOPSKJOEKI-SRVKXCTJSA-N 0.000 description 2
- YRNRVKTYDSLKMD-KKUMJFAQSA-N Lys-Ser-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YRNRVKTYDSLKMD-KKUMJFAQSA-N 0.000 description 2
- GIKFNMZSGYAPEJ-HJGDQZAQSA-N Lys-Thr-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O GIKFNMZSGYAPEJ-HJGDQZAQSA-N 0.000 description 2
- XATKLFSXFINPSB-JYJNAYRXSA-N Lys-Tyr-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O XATKLFSXFINPSB-JYJNAYRXSA-N 0.000 description 2
- PPNCMJARTHYNEC-MEYUZBJRSA-N Lys-Tyr-Thr Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@H](O)C)C(O)=O)CC1=CC=C(O)C=C1 PPNCMJARTHYNEC-MEYUZBJRSA-N 0.000 description 2
- VVURYEVJJTXWNE-ULQDDVLXSA-N Lys-Tyr-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O VVURYEVJJTXWNE-ULQDDVLXSA-N 0.000 description 2
- 101710196975 Major allergen Can f 1 Proteins 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 2
- 102100023302 Myelin-oligodendrocyte glycoprotein Human genes 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- RBRNEFJTEHPDSL-ACRUOGEOSA-N Phe-Phe-Lys Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 RBRNEFJTEHPDSL-ACRUOGEOSA-N 0.000 description 2
- HPXVFFIIGOAQRV-DCAQKATOSA-N Pro-Arg-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O HPXVFFIIGOAQRV-DCAQKATOSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- IDCKUIWEIZYVSO-WFBYXXMGSA-N Ser-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C)C(O)=O)=CNC2=C1 IDCKUIWEIZYVSO-WFBYXXMGSA-N 0.000 description 2
- VBKBDLMWICBSCY-IMJSIDKUSA-N Ser-Asp Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O VBKBDLMWICBSCY-IMJSIDKUSA-N 0.000 description 2
- JHBHMCMKSPXRHV-NUMRIWBASA-N Thr-Asn-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O JHBHMCMKSPXRHV-NUMRIWBASA-N 0.000 description 2
- RFKVQLIXNVEOMB-WEDXCCLWSA-N Thr-Leu-Gly Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)O)N)O RFKVQLIXNVEOMB-WEDXCCLWSA-N 0.000 description 2
- SCSVNSNWUTYSFO-WDCWCFNPSA-N Thr-Lys-Glu Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O SCSVNSNWUTYSFO-WDCWCFNPSA-N 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 108010028230 Trp-Ser- His-Pro-Gln-Phe-Glu-Lys Proteins 0.000 description 2
- PRONOHBTMLNXCZ-BZSNNMDCSA-N Tyr-Leu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PRONOHBTMLNXCZ-BZSNNMDCSA-N 0.000 description 2
- 101710153009 Uterocalin Proteins 0.000 description 2
- VVZDBPBZHLQPPB-XVKPBYJWSA-N Val-Glu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VVZDBPBZHLQPPB-XVKPBYJWSA-N 0.000 description 2
- LYERIXUFCYVFFX-GVXVVHGQSA-N Val-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LYERIXUFCYVFFX-GVXVVHGQSA-N 0.000 description 2
- BCBFMJYTNKDALA-UFYCRDLUSA-N Val-Phe-Phe Chemical compound N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O BCBFMJYTNKDALA-UFYCRDLUSA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 230000001174 ascending effect Effects 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011157 data evaluation Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 108010037850 glycylvaline Proteins 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 102000043448 human IL17RA Human genes 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000000111 isothermal titration calorimetry Methods 0.000 description 2
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 108010004914 prolylarginine Proteins 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000000700 radioactive tracer Substances 0.000 description 2
- 238000002708 random mutagenesis Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- 102100036537 von Willebrand factor Human genes 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- DTLVBHCSSNJCMJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoate Chemical compound S1CC2NC(=O)NC2C1CCCCC(=O)NCCOCCOCCOCCOCCC(=O)ON1C(=O)CCC1=O DTLVBHCSSNJCMJ-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- QMOQBVOBWVNSNO-UHFFFAOYSA-N 2-[[2-[[2-[(2-azaniumylacetyl)amino]acetyl]amino]acetyl]amino]acetate Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(O)=O QMOQBVOBWVNSNO-UHFFFAOYSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 1
- ISCMYZGMRHODRP-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCN=C=N ISCMYZGMRHODRP-UHFFFAOYSA-N 0.000 description 1
- FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical group NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 1
- JBGSZRYCXBPWGX-BQBZGAKWSA-N Ala-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CCCN=C(N)N JBGSZRYCXBPWGX-BQBZGAKWSA-N 0.000 description 1
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
- TVUFMYKTYXTRPY-HERUPUMHSA-N Ala-Trp-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O TVUFMYKTYXTRPY-HERUPUMHSA-N 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- XLWSGICNBZGYTA-CIUDSAMLSA-N Arg-Glu-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XLWSGICNBZGYTA-CIUDSAMLSA-N 0.000 description 1
- NKBQZKVMKJJDLX-SRVKXCTJSA-N Arg-Glu-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NKBQZKVMKJJDLX-SRVKXCTJSA-N 0.000 description 1
- LEFKSBYHUGUWLP-ACZMJKKPSA-N Asn-Ala-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LEFKSBYHUGUWLP-ACZMJKKPSA-N 0.000 description 1
- DAPLJWATMAXPPZ-CIUDSAMLSA-N Asn-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(N)=O DAPLJWATMAXPPZ-CIUDSAMLSA-N 0.000 description 1
- MKJBPDLENBUHQU-CIUDSAMLSA-N Asn-Ser-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O MKJBPDLENBUHQU-CIUDSAMLSA-N 0.000 description 1
- JHFNSBBHKSZXKB-VKHMYHEASA-N Asp-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(O)=O JHFNSBBHKSZXKB-VKHMYHEASA-N 0.000 description 1
- OMMIEVATLAGRCK-BYPYZUCNSA-N Asp-Gly-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)NCC(O)=O OMMIEVATLAGRCK-BYPYZUCNSA-N 0.000 description 1
- SWTQDYFZVOJVLL-KKUMJFAQSA-N Asp-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)O)N)O SWTQDYFZVOJVLL-KKUMJFAQSA-N 0.000 description 1
- RXBGWGRSWXOBGK-KKUMJFAQSA-N Asp-Lys-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RXBGWGRSWXOBGK-KKUMJFAQSA-N 0.000 description 1
- KOWYNSKRPUWSFG-IHPCNDPISA-N Asp-Phe-Trp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)NC(=O)[C@H](CC(=O)O)N KOWYNSKRPUWSFG-IHPCNDPISA-N 0.000 description 1
- NONWUQAWAANERO-BZSNNMDCSA-N Asp-Phe-Tyr Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 NONWUQAWAANERO-BZSNNMDCSA-N 0.000 description 1
- YIDFBWRHIYOYAA-LKXGYXEUSA-N Asp-Ser-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O YIDFBWRHIYOYAA-LKXGYXEUSA-N 0.000 description 1
- ALMIMUZAWTUNIO-BZSNNMDCSA-N Asp-Tyr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ALMIMUZAWTUNIO-BZSNNMDCSA-N 0.000 description 1
- QOJJMJKTMKNFEF-ZKWXMUAHSA-N Asp-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O QOJJMJKTMKNFEF-ZKWXMUAHSA-N 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 102000000119 Beta-lactoglobulin Human genes 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 206010058822 Bone marrow necrosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000003930 C-Type Lectins Human genes 0.000 description 1
- 108090000342 C-Type Lectins Proteins 0.000 description 1
- 102000002110 C2 domains Human genes 0.000 description 1
- 108050009459 C2 domains Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 101100330289 Caenorhabditis elegans cysl-3 gene Proteins 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 238000003734 CellTiter-Glo Luminescent Cell Viability Assay Methods 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- NITLUESFANGEIW-BQBZGAKWSA-N Cys-Pro-Gly Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O NITLUESFANGEIW-BQBZGAKWSA-N 0.000 description 1
- NXQCSPVUPLUTJH-WHFBIAKZSA-N Cys-Ser-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O NXQCSPVUPLUTJH-WHFBIAKZSA-N 0.000 description 1
- 108010025905 Cystine-Knot Miniproteins Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 102100034789 Epididymal-specific lipocalin-6 Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000002090 Fibronectin type III Human genes 0.000 description 1
- 108050009401 Fibronectin type III Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 1
- PAQUJCSYVIBPLC-AVGNSLFASA-N Glu-Asp-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PAQUJCSYVIBPLC-AVGNSLFASA-N 0.000 description 1
- WVYJNPCWJYBHJG-YVNDNENWSA-N Glu-Ile-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O WVYJNPCWJYBHJG-YVNDNENWSA-N 0.000 description 1
- YRMZCZIRHYCNHX-RYUDHWBXSA-N Glu-Phe-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O YRMZCZIRHYCNHX-RYUDHWBXSA-N 0.000 description 1
- ZIYGTCDTJJCDDP-JYJNAYRXSA-N Glu-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZIYGTCDTJJCDDP-JYJNAYRXSA-N 0.000 description 1
- ITVBKCZZLJUUHI-HTUGSXCWSA-N Glu-Phe-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ITVBKCZZLJUUHI-HTUGSXCWSA-N 0.000 description 1
- SYAYROHMAIHWFB-KBIXCLLPSA-N Glu-Ser-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O SYAYROHMAIHWFB-KBIXCLLPSA-N 0.000 description 1
- PUUYVMYCMIWHFE-BQBZGAKWSA-N Gly-Ala-Arg Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PUUYVMYCMIWHFE-BQBZGAKWSA-N 0.000 description 1
- DTPOVRRYXPJJAZ-FJXKBIBVSA-N Gly-Arg-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N DTPOVRRYXPJJAZ-FJXKBIBVSA-N 0.000 description 1
- JVWPPCWUDRJGAE-YUMQZZPRSA-N Gly-Asn-Leu Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JVWPPCWUDRJGAE-YUMQZZPRSA-N 0.000 description 1
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 1
- CSMYMGFCEJWALV-WDSKDSINSA-N Gly-Ser-Gln Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O CSMYMGFCEJWALV-WDSKDSINSA-N 0.000 description 1
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 1
- WSWWTQYHFCBKBT-DVJZZOLTSA-N Gly-Thr-Trp Chemical compound C[C@@H](O)[C@H](NC(=O)CN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O WSWWTQYHFCBKBT-DVJZZOLTSA-N 0.000 description 1
- SBVMXEZQJVUARN-XPUUQOCRSA-N Gly-Val-Ser Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O SBVMXEZQJVUARN-XPUUQOCRSA-N 0.000 description 1
- COZMNNJEGNPDED-HOCLYGCPSA-N Gly-Val-Trp Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O COZMNNJEGNPDED-HOCLYGCPSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 1
- 102000013271 Hemopexin Human genes 0.000 description 1
- 108010026027 Hemopexin Proteins 0.000 description 1
- XJFITURPHAKKAI-SRVKXCTJSA-N His-Pro-Gln Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C1=CN=CN1 XJFITURPHAKKAI-SRVKXCTJSA-N 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000757556 Homo sapiens Apolipoprotein D Proteins 0.000 description 1
- 101000945886 Homo sapiens Epididymal-specific lipocalin-6 Proteins 0.000 description 1
- 101000605055 Homo sapiens Epididymal-specific lipocalin-8 Proteins 0.000 description 1
- 101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- NULSANWBUWLTKN-NAKRPEOUSA-N Ile-Arg-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N NULSANWBUWLTKN-NAKRPEOUSA-N 0.000 description 1
- QYZYJFXHXYUZMZ-UGYAYLCHSA-N Ile-Asn-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N QYZYJFXHXYUZMZ-UGYAYLCHSA-N 0.000 description 1
- IDAHFEPYTJJZFD-PEFMBERDSA-N Ile-Asp-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N IDAHFEPYTJJZFD-PEFMBERDSA-N 0.000 description 1
- QSPLUJGYOPZINY-ZPFDUUQYSA-N Ile-Asp-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N QSPLUJGYOPZINY-ZPFDUUQYSA-N 0.000 description 1
- MTFVYKQRLXYAQN-LAEOZQHASA-N Ile-Glu-Gly Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O MTFVYKQRLXYAQN-LAEOZQHASA-N 0.000 description 1
- YKLOMBNBQUTJDT-HVTMNAMFSA-N Ile-His-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N YKLOMBNBQUTJDT-HVTMNAMFSA-N 0.000 description 1
- GAZGFPOZOLEYAJ-YTFOTSKYSA-N Ile-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N GAZGFPOZOLEYAJ-YTFOTSKYSA-N 0.000 description 1
- IITVUURPOYGCTD-NAKRPEOUSA-N Ile-Pro-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IITVUURPOYGCTD-NAKRPEOUSA-N 0.000 description 1
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 108091029795 Intergenic region Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000004560 Interleukin-12 Receptors Human genes 0.000 description 1
- 108010017515 Interleukin-12 Receptors Proteins 0.000 description 1
- 102100033096 Interleukin-17D Human genes 0.000 description 1
- 101710195550 Interleukin-23 receptor Proteins 0.000 description 1
- 108010066979 Interleukin-27 Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000003456 Juvenile Arthritis Diseases 0.000 description 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 108010060630 Lactoglobulins Proteins 0.000 description 1
- CZCSUZMIRKFFFA-CIUDSAMLSA-N Leu-Ala-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O CZCSUZMIRKFFFA-CIUDSAMLSA-N 0.000 description 1
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 1
- NEEOBPIXKWSBRF-IUCAKERBSA-N Leu-Glu-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O NEEOBPIXKWSBRF-IUCAKERBSA-N 0.000 description 1
- PPGBXYKMUMHFBF-KATARQTJSA-N Leu-Ser-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PPGBXYKMUMHFBF-KATARQTJSA-N 0.000 description 1
- GZRABTMNWJXFMH-UVOCVTCTSA-N Leu-Thr-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZRABTMNWJXFMH-UVOCVTCTSA-N 0.000 description 1
- FBNPMTNBFFAMMH-AVGNSLFASA-N Leu-Val-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-AVGNSLFASA-N 0.000 description 1
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 102000010954 Link domains Human genes 0.000 description 1
- 108050001157 Link domains Proteins 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- KCXUCYYZNZFGLL-SRVKXCTJSA-N Lys-Ala-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O KCXUCYYZNZFGLL-SRVKXCTJSA-N 0.000 description 1
- YNNPKXBBRZVIRX-IHRRRGAJSA-N Lys-Arg-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O YNNPKXBBRZVIRX-IHRRRGAJSA-N 0.000 description 1
- FACUGMGEFUEBTI-SRVKXCTJSA-N Lys-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCCCN FACUGMGEFUEBTI-SRVKXCTJSA-N 0.000 description 1
- HKCCVDWHHTVVPN-CIUDSAMLSA-N Lys-Asp-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O HKCCVDWHHTVVPN-CIUDSAMLSA-N 0.000 description 1
- LLSUNJYOSCOOEB-GUBZILKMSA-N Lys-Glu-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O LLSUNJYOSCOOEB-GUBZILKMSA-N 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010029379 Neutrophilia Diseases 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- SFKOEHXABNPLRT-KBPBESRZSA-N Phe-His-Gly Chemical compound N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)NCC(O)=O SFKOEHXABNPLRT-KBPBESRZSA-N 0.000 description 1
- KDYPMIZMXDECSU-JYJNAYRXSA-N Phe-Leu-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 KDYPMIZMXDECSU-JYJNAYRXSA-N 0.000 description 1
- BSHMIVKDJQGLNT-ACRUOGEOSA-N Phe-Lys-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 BSHMIVKDJQGLNT-ACRUOGEOSA-N 0.000 description 1
- IPFXYNKCXYGSSV-KKUMJFAQSA-N Phe-Ser-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N IPFXYNKCXYGSSV-KKUMJFAQSA-N 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 241000255972 Pieris <butterfly> Species 0.000 description 1
- 241000255969 Pieris brassicae Species 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 102000007584 Prealbumin Human genes 0.000 description 1
- AQGUSRZKDZYGGV-GMOBBJLQSA-N Pro-Ile-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O AQGUSRZKDZYGGV-GMOBBJLQSA-N 0.000 description 1
- CGSOWZUPLOKYOR-AVGNSLFASA-N Pro-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 CGSOWZUPLOKYOR-AVGNSLFASA-N 0.000 description 1
- ZMLRZBWCXPQADC-TUAOUCFPSA-N Pro-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 ZMLRZBWCXPQADC-TUAOUCFPSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102100033279 Prostaglandin-H2 D-isomerase Human genes 0.000 description 1
- 101710145576 Prostaglandin-H2 D-isomerase Proteins 0.000 description 1
- 108010010974 Proteolipids Proteins 0.000 description 1
- 102000016202 Proteolipids Human genes 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 101000930457 Rattus norvegicus Albumin Proteins 0.000 description 1
- 101001023831 Rattus norvegicus Neutrophil gelatinase-associated lipocalin Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 102000000395 SH3 domains Human genes 0.000 description 1
- 108050008861 SH3 domains Proteins 0.000 description 1
- 108050008568 SRCR domains Proteins 0.000 description 1
- 102000000185 SRCR domains Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- BGOWRLSWJCVYAQ-CIUDSAMLSA-N Ser-Asp-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O BGOWRLSWJCVYAQ-CIUDSAMLSA-N 0.000 description 1
- RHAPJNVNWDBFQI-BQBZGAKWSA-N Ser-Pro-Gly Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O RHAPJNVNWDBFQI-BQBZGAKWSA-N 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 102000000890 Somatomedin B domains Human genes 0.000 description 1
- 108050007913 Somatomedin B domains Proteins 0.000 description 1
- 101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010042566 Superinfection Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 241000053227 Themus Species 0.000 description 1
- JNQZPAWOPBZGIX-RCWTZXSCSA-N Thr-Arg-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)CCCN=C(N)N JNQZPAWOPBZGIX-RCWTZXSCSA-N 0.000 description 1
- ONNSECRQFSTMCC-XKBZYTNZSA-N Thr-Glu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O ONNSECRQFSTMCC-XKBZYTNZSA-N 0.000 description 1
- CJEHCEOXPLASCK-MEYUZBJRSA-N Thr-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=C(O)C=C1 CJEHCEOXPLASCK-MEYUZBJRSA-N 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- UABYBEBXFFNCIR-YDHLFZDLSA-N Tyr-Asp-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UABYBEBXFFNCIR-YDHLFZDLSA-N 0.000 description 1
- CTDPLKMBVALCGN-JSGCOSHPSA-N Tyr-Gly-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O CTDPLKMBVALCGN-JSGCOSHPSA-N 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- ISERLACIZUGCDX-ZKWXMUAHSA-N Val-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N ISERLACIZUGCDX-ZKWXMUAHSA-N 0.000 description 1
- XXROXFHCMVXETG-UWVGGRQHSA-N Val-Gly-Val Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O XXROXFHCMVXETG-UWVGGRQHSA-N 0.000 description 1
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- 101710185494 Zinc finger protein Proteins 0.000 description 1
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 108010076089 accutase Proteins 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 238000003314 affinity selection Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001337 aliphatic alkines Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108010036533 arginylvaline Proteins 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical class [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 238000002869 basic local alignment search tool Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000013357 binding ELISA Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 125000000707 boryl group Chemical group B* 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000012054 celltiter-glo Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 229960003115 certolizumab pegol Drugs 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000001808 coupling effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 1
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 229960001743 golimumab Drugs 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 102000056778 human APOD Human genes 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 108010044348 lysyl-glutamyl-aspartic acid Proteins 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 210000002500 microbody Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000014925 multi-organism signaling Effects 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 108010012581 phenylalanylglutamate Proteins 0.000 description 1
- 239000003016 pheromone Substances 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 108010094020 polyglycine Proteins 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000007112 pro inflammatory response Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 230000007363 regulatory process Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229950001790 tendamistat Drugs 0.000 description 1
- 108010037401 tendamistate Proteins 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000004846 x-ray emission Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/525—Tumor necrosis factor [TNF]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- General Engineering & Computer Science (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14169488.5 | 2014-05-22 | ||
| EP14169488 | 2014-05-22 | ||
| PCT/EP2015/061034 WO2015177175A2 (en) | 2014-05-22 | 2015-05-20 | Novel specific-binding polypeptides and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20170004011A true KR20170004011A (ko) | 2017-01-10 |
Family
ID=50771150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020167035964A Ceased KR20170004011A (ko) | 2014-05-22 | 2015-05-20 | 신규 특이적 결합 폴리펩타이드 및 이의 용도 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US10774119B2 (enExample) |
| EP (2) | EP3789397B1 (enExample) |
| JP (2) | JP6753784B2 (enExample) |
| KR (1) | KR20170004011A (enExample) |
| CN (2) | CN113621050A (enExample) |
| AU (2) | AU2015261968B2 (enExample) |
| BR (1) | BR112016027024A2 (enExample) |
| CA (2) | CA2949405C (enExample) |
| DK (1) | DK3145945T3 (enExample) |
| ES (1) | ES2823563T3 (enExample) |
| MX (2) | MX384363B (enExample) |
| RU (1) | RU2723034C2 (enExample) |
| SG (2) | SG10201912019WA (enExample) |
| WO (1) | WO2015177175A2 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2891557A1 (en) | 2013-03-26 | 2014-05-22 | Pieris Ag | Novel specific-binding polypeptides and uses thereof |
| CN113621050A (zh) | 2014-05-22 | 2021-11-09 | 皮里斯制药有限公司 | 新型特异性结合多肽及其用途 |
| SG11201803732PA (en) * | 2015-11-30 | 2018-06-28 | Pieris Australia Pty Ltd | Novel anti-angiogenic fusion polypeptides |
| PT3583120T (pt) | 2017-02-17 | 2022-12-15 | Denali Therapeutics Inc | Polipeptídeos de ligação ao recetor de transferrina manipulados |
| US11077199B2 (en) | 2017-08-09 | 2021-08-03 | Massachusetts Institute Of Technology | Albumin binding peptide conjugates and methods thereof |
| JP2020530465A (ja) * | 2017-08-10 | 2020-10-22 | デナリ セラピューティクス インコーポレイテッドＤｅｎａｌｉ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | トランスフェリン受容体結合タンパク質を使用するための、親和性に基づく方法 |
| CA3092551A1 (en) | 2018-03-05 | 2019-09-12 | Janssen Biotech, Inc. | Methods of treating crohn's disease with anti-il23 specific antibody |
| AU2019275733B2 (en) * | 2018-05-31 | 2025-07-31 | The Chinese University Of Hong Kong | Composition and application of arginine-depleting agents for cancer, obesity, metabolic disorders, and related complications and comorbidities |
| EP3599245A1 (en) | 2018-07-27 | 2020-01-29 | Dompé farmaceutici S.p.A. | Il-17a binding polypeptides and medical uses thereof |
| CN109206485B (zh) * | 2018-09-27 | 2022-04-08 | 山东聚胜生物科技有限公司 | 一种防治肺癌转移的寡肽 |
| CN109180789B (zh) * | 2018-09-27 | 2022-08-19 | 上海揽微赛尔生物科技有限公司 | 一种寡肽及制药应用 |
| CN109096374B (zh) * | 2018-09-27 | 2022-11-18 | 深圳乐土沃森精准医疗有限公司 | 一种抑制肺癌转移的合成寡肽 |
| CN109096373B (zh) * | 2018-09-27 | 2022-06-21 | 江苏亨瑞生物医药科技有限公司 | 合成寡肽及其用途 |
| CN113939307A (zh) * | 2019-03-29 | 2022-01-14 | 皮里斯制药有限公司 | 脂质运载蛋白突变蛋白的吸入施用 |
| AU2021269222A1 (en) * | 2020-05-05 | 2023-01-19 | Janssen Biotech, Inc. | Methods of treating Crohn's disease with anti-IL23 specific antibody |
| CN114805546B (zh) * | 2022-06-08 | 2024-05-28 | 宁波市健康口腔医学研究院 | 一种检测口腔癌的t细胞表位多肽及其应用 |
| WO2025226984A1 (en) * | 2024-04-24 | 2025-10-30 | Mopac Biologics, Inc. | Human il-17 binding polypeptides |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3779221D1 (de) | 1986-08-19 | 1992-06-25 | Genentech Inc | Einrichtung und dispersion zum intrapulmonalen eingeben von polypeptidwuchsstoffen und -zytokinen. |
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5728553A (en) | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| WO1995031479A1 (en) | 1994-05-18 | 1995-11-23 | Inhale Therapeutic Systems, Inc. | Methods and compositions for the dry powder formulation of interferons |
| DE4417598A1 (de) | 1994-05-19 | 1995-12-14 | Max Planck Gesellschaft | Verwendung des Tetracyclinpromotors zur stringent regulierten Produktion von rekombinanten Proteinen in prokaryontischen Zellen |
| WO1996023879A1 (en) | 1995-01-30 | 1996-08-08 | Terrapin Technologies, Inc. | Glubodies - multiplicities of proteins capable of binding a variety of small molecules |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| US6620413B1 (en) | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
| DE19641876B4 (de) | 1996-10-10 | 2011-09-29 | Iba Gmbh | Streptavidinmuteine |
| WO1998016873A1 (en) | 1996-10-14 | 1998-04-23 | Firm Forsat Ltd. | Method for preparing dispersions of chromogenic components |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
| CA2233725A1 (en) | 1998-03-31 | 1999-09-30 | Hemosol Inc. | Hemoglobin-hydroxyethyl starch complexes |
| PL192364B1 (pl) | 1998-06-08 | 2006-10-31 | Hoffmann La Roche | Zastosowanie koniugatu PEG-IFN-α 2A w połączeniu z rybawiryną |
| US6403564B1 (en) | 1998-10-16 | 2002-06-11 | Schering Corporation | Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection |
| DE19926068C1 (de) | 1999-06-08 | 2001-01-11 | Arne Skerra | Muteine des Bilin-Bindungsproteins |
| CA2440582A1 (en) | 2001-03-09 | 2002-10-03 | Dyax Corp. | Serum albumin binding moieties |
| EP1430136A1 (en) | 2001-09-27 | 2004-06-23 | Pieris ProteoLab AG | Muteins of apolipoprotein d |
| WO2003029462A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
| US7691970B2 (en) | 2003-08-25 | 2010-04-06 | Pieris Ag | Muteins of a bilin-binding protein with affinity for a given target |
| WO2005019255A1 (en) | 2003-08-25 | 2005-03-03 | Pieris Proteolab Ag | Muteins of tear lipocalin |
| JP2007284351A (ja) | 2004-07-27 | 2007-11-01 | Osaka Bioscience Institute | アミロイド蛋白質の凝集を抑制する物質とその作用 |
| EP2899277A1 (en) * | 2004-11-26 | 2015-07-29 | Pieris AG | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
| US20070212703A1 (en) | 2005-09-27 | 2007-09-13 | Stemmer Willem P | Proteinaceous pharmaceuticals and uses thereof |
| WO2007147019A2 (en) | 2006-06-13 | 2007-12-21 | Zymogenetics, Inc. | Il-17 and il-23 antagonists and methods of using the same |
| TW200815469A (en) * | 2006-06-23 | 2008-04-01 | Astrazeneca Ab | Compounds |
| AU2007280398B2 (en) | 2006-08-01 | 2012-05-10 | Pieris Ag | Muteins of tear lipocalin and methods for obtaining the same |
| CN101516907B (zh) * | 2006-08-01 | 2015-08-26 | 皮里斯股份公司 | 泪液脂质运载蛋白的突变蛋白及其获得方法 |
| MX2009009079A (es) | 2007-02-23 | 2009-08-31 | Schering Corp | Anticuerpos anti-il-23p19 de ingenieria. |
| AR068723A1 (es) | 2007-10-05 | 2009-12-02 | Glaxo Group Ltd | Proteina que se une a antigenos que se une a il-23 humana y sus usos |
| CA2702590A1 (en) | 2007-10-19 | 2009-04-23 | Abbott Laboratories | Glycosylated mammalian ngal and use thereof |
| CA2713557C (en) * | 2008-01-30 | 2016-06-07 | Pieris Ag | Muteins of tear lipocalin having affinity to human c-met receptor tyrosine kinase and methods for obtaining the same |
| EP2313430B1 (en) | 2008-06-24 | 2018-05-02 | Technische Universität München | Muteins of hngal and related proteins with affinity for a given target |
| US20110268818A1 (en) * | 2008-09-18 | 2011-11-03 | Jonathan Barasch | Ngal-binding siderophores and use thereof to treat iron deficiency and iron overload |
| US9549968B2 (en) | 2009-12-07 | 2017-01-24 | Pieris Pharmaceuticals Gmbh | Muteins of human lipocalin 2 (LcnC,hNGAL) with affinity for a given target |
| SMT201900297T1 (it) | 2010-06-08 | 2019-07-11 | Astrazeneca Ab | Muteine di lipocalina lacrimale che si legano a il-4 r alfa |
| CN110437321A (zh) | 2010-07-09 | 2019-11-12 | 阿菲博迪公司 | 多肽 |
| CA2808392C (en) | 2010-08-16 | 2020-03-10 | Pieris Ag | Binding proteins for hepcidin |
| DK2640740T3 (en) | 2010-11-15 | 2017-06-26 | Pieris Pharmaceuticals Gmbh | MUTEINS OF HUMAN LIPOCALIN 2 WITH AFFINITY FOR GLYPICAN-3 (GPC3) |
| GB201100282D0 (en) * | 2011-01-07 | 2011-02-23 | Ucb Pharma Sa | Biological methods |
| UA117218C2 (uk) * | 2011-05-05 | 2018-07-10 | Мерк Патент Гмбх | Поліпептид, спрямований проти il-17a, il-17f та/або il17-a/f |
| SG10201604566QA (en) | 2011-12-13 | 2016-07-28 | Pieris Ag | Methods for preventing or treating certain disorders by inhibiting binding of il-4 and/or il-13 to their respective receptors |
| CA2891557A1 (en) * | 2013-03-26 | 2014-05-22 | Pieris Ag | Novel specific-binding polypeptides and uses thereof |
| AU2015205530B8 (en) * | 2014-01-13 | 2019-09-19 | Pieris Pharmaceuticals Gmbh | Multi-specific polypeptide useful for localized tumor immunomodulation |
| CN113621050A (zh) | 2014-05-22 | 2021-11-09 | 皮里斯制药有限公司 | 新型特异性结合多肽及其用途 |
| SG10201906859PA (en) | 2015-01-28 | 2019-08-27 | Pieris Pharmaceuticals Gmbh | Novel proteins specific for angiogenesis |
| AR103714A1 (es) | 2015-02-18 | 2017-05-31 | Sanofi Sa | Proteínas específicas para pioverdina y pioquelina |
| US11261221B2 (en) | 2015-05-04 | 2022-03-01 | Pieris Pharmaceuticals Gmbh | Proteins specific for CD137 |
| CN107787327B (zh) | 2015-05-18 | 2022-02-08 | 皮里斯制药有限公司 | 对磷脂酰肌醇聚糖-3（gpc3）具有亲和力的人脂质运载蛋白2的突变蛋白 |
| TW201725212A (zh) | 2015-12-10 | 2017-07-16 | 第一三共股份有限公司 | 特異性於降鈣素基因相關胜肽的新穎蛋白 |
-
2015
- 2015-05-20 CN CN202110703906.XA patent/CN113621050A/zh active Pending
- 2015-05-20 ES ES15727573T patent/ES2823563T3/es active Active
- 2015-05-20 MX MX2016015235A patent/MX384363B/es unknown
- 2015-05-20 JP JP2016568907A patent/JP6753784B2/ja not_active Expired - Fee Related
- 2015-05-20 AU AU2015261968A patent/AU2015261968B2/en not_active Ceased
- 2015-05-20 CA CA2949405A patent/CA2949405C/en active Active
- 2015-05-20 SG SG10201912019WA patent/SG10201912019WA/en unknown
- 2015-05-20 US US15/312,094 patent/US10774119B2/en not_active Expired - Fee Related
- 2015-05-20 KR KR1020167035964A patent/KR20170004011A/ko not_active Ceased
- 2015-05-20 BR BR112016027024A patent/BR112016027024A2/pt not_active Application Discontinuation
- 2015-05-20 RU RU2016149596A patent/RU2723034C2/ru active
- 2015-05-20 WO PCT/EP2015/061034 patent/WO2015177175A2/en not_active Ceased
- 2015-05-20 CN CN201580040321.7A patent/CN106573964B/zh not_active Expired - Fee Related
- 2015-05-20 CA CA3170782A patent/CA3170782A1/en active Pending
- 2015-05-20 SG SG11201609274SA patent/SG11201609274SA/en unknown
- 2015-05-20 EP EP20185401.5A patent/EP3789397B1/en active Active
- 2015-05-20 DK DK15727573.6T patent/DK3145945T3/da active
- 2015-05-20 EP EP15727573.6A patent/EP3145945B1/en active Active
-
2016
- 2016-11-18 MX MX2021008318A patent/MX2021008318A/es unknown
-
2019
- 2019-02-13 AU AU2019201007A patent/AU2019201007B2/en not_active Ceased
-
2020
- 2020-08-06 US US16/987,218 patent/US11345728B2/en active Active
- 2020-08-20 JP JP2020139064A patent/JP7084965B2/ja active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7084965B2 (ja) | 特異的結合ポリペプチドおよびその使用 | |
| US20200148733A1 (en) | Novel interleukin-17a-specific and interleukin-23-specific binding polypeptides and uses thereof | |
| US11034738B2 (en) | Nucleic acid molecules encoding human neutrophil gelatinase-associated lipocalin (hNGAL) which bind angiopoietin-2 (Ang-2) | |
| US10703810B2 (en) | Fusion polypeptides which bind vascular endothelial growth factor a (VEGF-A) and angiopoietin-2 (Ang-2) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20161222 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20200520 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20220413 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20221025 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20220413 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |
|
| E601 | Decision to refuse application | ||
| E801 | Decision on dismissal of amendment | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20230424 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20220413 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |
|
| PE0801 | Dismissal of amendment |
Patent event code: PE08012E01D Comment text: Decision on Dismissal of Amendment Patent event date: 20230424 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20230324 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20220613 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20200520 |