TWI710637B - 具抗原專一性的t細胞及其用途 - Google Patents
具抗原專一性的t細胞及其用途 Download PDFInfo
- Publication number
- TWI710637B TWI710637B TW108129663A TW108129663A TWI710637B TW I710637 B TWI710637 B TW I710637B TW 108129663 A TW108129663 A TW 108129663A TW 108129663 A TW108129663 A TW 108129663A TW I710637 B TWI710637 B TW I710637B
- Authority
- TW
- Taiwan
- Prior art keywords
- ser
- gly
- thr
- val
- leu
- Prior art date
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 302
- 239000000427 antigen Substances 0.000 title claims abstract description 92
- 102000036639 antigens Human genes 0.000 title claims abstract description 86
- 108091007433 antigens Proteins 0.000 title claims abstract description 86
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 113
- 230000000259 anti-tumor effect Effects 0.000 claims abstract description 52
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 35
- 239000001963 growth medium Substances 0.000 claims abstract description 22
- 230000004069 differentiation Effects 0.000 claims abstract description 17
- 230000035755 proliferation Effects 0.000 claims abstract description 8
- 230000001939 inductive effect Effects 0.000 claims abstract description 7
- 241001529936 Murinae Species 0.000 claims description 131
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 76
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 76
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims description 75
- 201000011510 cancer Diseases 0.000 claims description 56
- 102000004127 Cytokines Human genes 0.000 claims description 31
- 108090000695 Cytokines Proteins 0.000 claims description 31
- 230000004048 modification Effects 0.000 claims description 26
- 238000012986 modification Methods 0.000 claims description 26
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 23
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 23
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 22
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 22
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 22
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 21
- 108010002350 Interleukin-2 Proteins 0.000 claims description 21
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 15
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 15
- 201000002528 pancreatic cancer Diseases 0.000 claims description 15
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 15
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 11
- 210000003289 regulatory T cell Anatomy 0.000 claims description 11
- 230000001588 bifunctional effect Effects 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 206010009944 Colon cancer Diseases 0.000 claims description 8
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 8
- 206010060862 Prostate cancer Diseases 0.000 claims description 8
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 8
- 238000012258 culturing Methods 0.000 claims description 7
- 108010002586 Interleukin-7 Proteins 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 4
- 208000018084 Bone neoplasm Diseases 0.000 claims description 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 208000000277 Splenic Neoplasms Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 239000002609 medium Substances 0.000 claims description 4
- 201000002471 spleen cancer Diseases 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- 206010016935 Follicular thyroid cancer Diseases 0.000 claims description 3
- 208000032612 Glial tumor Diseases 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 3
- 201000000582 Retinoblastoma Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 210000000941 bile Anatomy 0.000 claims description 3
- 201000004101 esophageal cancer Diseases 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 208000025113 myeloid leukemia Diseases 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims description 3
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 claims description 2
- 230000003394 haemopoietic effect Effects 0.000 claims description 2
- 201000002313 intestinal cancer Diseases 0.000 claims description 2
- 210000001519 tissue Anatomy 0.000 claims description 2
- 102000008096 B7-H1 Antigen Human genes 0.000 claims 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical group FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 131
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 71
- 108020004414 DNA Proteins 0.000 description 67
- 241000880493 Leptailurus serval Species 0.000 description 64
- 239000000203 mixture Substances 0.000 description 44
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 42
- 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 35
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 35
- ARHJJAAWNWOACN-FXQIFTODSA-N Ala-Ser-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O ARHJJAAWNWOACN-FXQIFTODSA-N 0.000 description 34
- FEHQLKKBVJHSEC-SZMVWBNQSA-N Leu-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 FEHQLKKBVJHSEC-SZMVWBNQSA-N 0.000 description 34
- 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 32
- OWFGFHQMSBTKLX-UFYCRDLUSA-N Val-Tyr-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N OWFGFHQMSBTKLX-UFYCRDLUSA-N 0.000 description 31
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 30
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 30
- PDIDTSZKKFEDMB-UWVGGRQHSA-N Lys-Pro-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O PDIDTSZKKFEDMB-UWVGGRQHSA-N 0.000 description 29
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 29
- 108010092854 aspartyllysine Proteins 0.000 description 29
- 108010044292 tryptophyltyrosine Proteins 0.000 description 29
- MNQMTYSEKZHIDF-GCJQMDKQSA-N Asp-Thr-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O MNQMTYSEKZHIDF-GCJQMDKQSA-N 0.000 description 28
- 238000004458 analytical method Methods 0.000 description 28
- 108010031719 prolyl-serine Proteins 0.000 description 28
- JXFLPKSDLDEOQK-JHEQGTHGSA-N Gln-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O JXFLPKSDLDEOQK-JHEQGTHGSA-N 0.000 description 27
- SPSSJSICDYYTQN-HJGDQZAQSA-N Met-Thr-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(N)=O SPSSJSICDYYTQN-HJGDQZAQSA-N 0.000 description 27
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 27
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 27
- 108010079364 N-glycylalanine Proteins 0.000 description 26
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 26
- 108010089804 glycyl-threonine Proteins 0.000 description 26
- 108010050848 glycylleucine Proteins 0.000 description 26
- CQGSYZCULZMEDE-UHFFFAOYSA-N Leu-Gln-Pro Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)N1CCCC1C(O)=O CQGSYZCULZMEDE-UHFFFAOYSA-N 0.000 description 25
- 108010087924 alanylproline Proteins 0.000 description 25
- 230000003013 cytotoxicity Effects 0.000 description 25
- 231100000135 cytotoxicity Toxicity 0.000 description 25
- 108010010147 glycylglutamine Proteins 0.000 description 25
- BYYNJRSNDARRBX-YFKPBYRVSA-N Gly-Gln-Gly Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O BYYNJRSNDARRBX-YFKPBYRVSA-N 0.000 description 24
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 24
- KLYYKKGCPOGDPE-OEAJRASXSA-N Phe-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O KLYYKKGCPOGDPE-OEAJRASXSA-N 0.000 description 24
- AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 24
- BIBYEFRASCNLAA-CDMKHQONSA-N Thr-Phe-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 BIBYEFRASCNLAA-CDMKHQONSA-N 0.000 description 24
- 108010017391 lysylvaline Proteins 0.000 description 24
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 23
- IHCXPSYCHXFXKT-DCAQKATOSA-N Pro-Arg-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O IHCXPSYCHXFXKT-DCAQKATOSA-N 0.000 description 23
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 23
- XYBJLTKSGFBLCS-QXEWZRGKSA-N Asp-Arg-Val Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC(O)=O XYBJLTKSGFBLCS-QXEWZRGKSA-N 0.000 description 22
- NVTPVQLIZCOJFK-FOHZUACHSA-N Gly-Thr-Asp Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O NVTPVQLIZCOJFK-FOHZUACHSA-N 0.000 description 22
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 22
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 22
- GXUWHVZYDAHFSV-FLBSBUHZSA-N Thr-Ile-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GXUWHVZYDAHFSV-FLBSBUHZSA-N 0.000 description 22
- 108010037850 glycylvaline Proteins 0.000 description 22
- 108010003137 tyrosyltyrosine Proteins 0.000 description 22
- 108010073969 valyllysine Proteins 0.000 description 22
- IXHKPDJKKCUKHS-GARJFASQSA-N Lys-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IXHKPDJKKCUKHS-GARJFASQSA-N 0.000 description 21
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 21
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 20
- HTONZBWRYUKUKC-RCWTZXSCSA-N Val-Thr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HTONZBWRYUKUKC-RCWTZXSCSA-N 0.000 description 20
- 108010009111 arginyl-glycyl-glutamic acid Proteins 0.000 description 20
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 20
- 201000006107 Familial adenomatous polyposis Diseases 0.000 description 19
- VUBIPAHVHMZHCM-KKUMJFAQSA-N Leu-Tyr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CC=C(O)C=C1 VUBIPAHVHMZHCM-KKUMJFAQSA-N 0.000 description 19
- GJFYFGOEWLDQGW-GUBZILKMSA-N Ser-Leu-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GJFYFGOEWLDQGW-GUBZILKMSA-N 0.000 description 19
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 19
- 108010078144 glutaminyl-glycine Proteins 0.000 description 19
- VKKYFICVTYKFIO-CIUDSAMLSA-N Arg-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N VKKYFICVTYKFIO-CIUDSAMLSA-N 0.000 description 18
- 102000000588 Interleukin-2 Human genes 0.000 description 18
- BRTVHXHCUSXYRI-CIUDSAMLSA-N Leu-Ser-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O BRTVHXHCUSXYRI-CIUDSAMLSA-N 0.000 description 18
- HNDMFDBQXYZSRM-IHRRRGAJSA-N Ser-Val-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HNDMFDBQXYZSRM-IHRRRGAJSA-N 0.000 description 18
- MNYNCKZAEIAONY-XGEHTFHBSA-N Thr-Val-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O MNYNCKZAEIAONY-XGEHTFHBSA-N 0.000 description 18
- 108010051242 phenylalanylserine Proteins 0.000 description 18
- 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 17
- FQCILXROGNOZON-YUMQZZPRSA-N Gln-Pro-Gly Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O FQCILXROGNOZON-YUMQZZPRSA-N 0.000 description 17
- PXKACEXYLPBMAD-JBDRJPRFSA-N Ile-Ser-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PXKACEXYLPBMAD-JBDRJPRFSA-N 0.000 description 17
- 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 17
- AIRZWUMAHCDDHR-KKUMJFAQSA-N Lys-Leu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O AIRZWUMAHCDDHR-KKUMJFAQSA-N 0.000 description 17
- FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 description 17
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 17
- 108010015792 glycyllysine Proteins 0.000 description 17
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 17
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 description 16
- 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 16
- MIIVFRCYJABHTQ-ONGXEEELSA-N Gly-Leu-Val Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O MIIVFRCYJABHTQ-ONGXEEELSA-N 0.000 description 16
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 description 16
- UGCIQUYEJIEHKX-GVXVVHGQSA-N Lys-Val-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O UGCIQUYEJIEHKX-GVXVVHGQSA-N 0.000 description 16
- PRKWBYCXBBSLSK-GUBZILKMSA-N Pro-Ser-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O PRKWBYCXBBSLSK-GUBZILKMSA-N 0.000 description 16
- 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 16
- QOIKZODVIPOPDD-AVGNSLFASA-N Tyr-Cys-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O QOIKZODVIPOPDD-AVGNSLFASA-N 0.000 description 16
- QUILOGWWLXMSAT-IHRRRGAJSA-N Tyr-Gln-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O QUILOGWWLXMSAT-IHRRRGAJSA-N 0.000 description 16
- SSYBNWFXCFNRFN-GUBZILKMSA-N Val-Pro-Ser Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O SSYBNWFXCFNRFN-GUBZILKMSA-N 0.000 description 16
- 238000000684 flow cytometry Methods 0.000 description 16
- 108010050475 glycyl-leucyl-tyrosine Proteins 0.000 description 16
- 108010071635 tyrosyl-prolyl-arginine Proteins 0.000 description 16
- 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 15
- OHLLDUNVMPPUMD-DCAQKATOSA-N Cys-Leu-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N OHLLDUNVMPPUMD-DCAQKATOSA-N 0.000 description 15
- 108010065920 Insulin Lispro Proteins 0.000 description 15
- GPICTNQYKHHHTH-GUBZILKMSA-N Leu-Gln-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GPICTNQYKHHHTH-GUBZILKMSA-N 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 15
- UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-N 0.000 description 15
- XJDMUQCLVSCRSJ-VZFHVOOUSA-N Ser-Thr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O XJDMUQCLVSCRSJ-VZFHVOOUSA-N 0.000 description 15
- YOPQYBJJNSIQGZ-JNPHEJMOSA-N Thr-Tyr-Tyr Chemical compound C([C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 YOPQYBJJNSIQGZ-JNPHEJMOSA-N 0.000 description 15
- SVGAWGVHFIYAEE-JSGCOSHPSA-N Trp-Gly-Gln Chemical compound C1=CC=C2C(C[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)=CNC2=C1 SVGAWGVHFIYAEE-JSGCOSHPSA-N 0.000 description 15
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 15
- 230000003211 malignant effect Effects 0.000 description 15
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 14
- CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 description 14
- QNFRBNZGVVKBNJ-PEFMBERDSA-N Asp-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N QNFRBNZGVVKBNJ-PEFMBERDSA-N 0.000 description 14
- SZQCDCKIGWQAQN-FXQIFTODSA-N Cys-Arg-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O SZQCDCKIGWQAQN-FXQIFTODSA-N 0.000 description 14
- VCHVSKNMTXWIIP-SRVKXCTJSA-N Leu-Lys-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O VCHVSKNMTXWIIP-SRVKXCTJSA-N 0.000 description 14
- ILDSIMPXNFWKLH-KATARQTJSA-N Leu-Thr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ILDSIMPXNFWKLH-KATARQTJSA-N 0.000 description 14
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 14
- MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 14
- FMDHKPRACUXATF-ACZMJKKPSA-N Ser-Gln-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O FMDHKPRACUXATF-ACZMJKKPSA-N 0.000 description 14
- BMGOFDMKDVVGJG-NHCYSSNCSA-N Val-Asp-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N BMGOFDMKDVVGJG-NHCYSSNCSA-N 0.000 description 14
- 108010068265 aspartyltyrosine Proteins 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 14
- 108010034529 leucyl-lysine Proteins 0.000 description 14
- 108010038745 tryptophylglycine Proteins 0.000 description 14
- KUDREHRZRIVKHS-UWJYBYFXSA-N Ala-Asp-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KUDREHRZRIVKHS-UWJYBYFXSA-N 0.000 description 13
- RFTVTKBHDXCEEX-WDSKDSINSA-N Glu-Ser-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RFTVTKBHDXCEEX-WDSKDSINSA-N 0.000 description 13
- YQPFCZVKMUVZIN-AUTRQRHGSA-N Glu-Val-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O YQPFCZVKMUVZIN-AUTRQRHGSA-N 0.000 description 13
- UQJNXZSSGQIPIQ-FBCQKBJTSA-N Gly-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)CN UQJNXZSSGQIPIQ-FBCQKBJTSA-N 0.000 description 13
- GBYYQVBXFVDJPJ-WLTAIBSBSA-N Gly-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)CN)O GBYYQVBXFVDJPJ-WLTAIBSBSA-N 0.000 description 13
- NZGTYCMLUGYMCV-XUXIUFHCSA-N Ile-Lys-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N NZGTYCMLUGYMCV-XUXIUFHCSA-N 0.000 description 13
- NTBFKPBULZGXQL-KKUMJFAQSA-N Lys-Asp-Tyr Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NTBFKPBULZGXQL-KKUMJFAQSA-N 0.000 description 13
- 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 13
- UIMCLYYSUCIUJM-UWVGGRQHSA-N Pro-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 UIMCLYYSUCIUJM-UWVGGRQHSA-N 0.000 description 13
- YDTUEBLEAVANFH-RCWTZXSCSA-N Pro-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 YDTUEBLEAVANFH-RCWTZXSCSA-N 0.000 description 13
- 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 13
- MBLJBGZWLHTJBH-SZMVWBNQSA-N Trp-Val-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 MBLJBGZWLHTJBH-SZMVWBNQSA-N 0.000 description 13
- MQGGXGKQSVEQHR-KKUMJFAQSA-N Tyr-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MQGGXGKQSVEQHR-KKUMJFAQSA-N 0.000 description 13
- 108010049041 glutamylalanine Proteins 0.000 description 13
- 108010064235 lysylglycine Proteins 0.000 description 13
- 108010070643 prolylglutamic acid Proteins 0.000 description 13
- BUDNAJYVCUHLSV-ZLUOBGJFSA-N Ala-Asp-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O BUDNAJYVCUHLSV-ZLUOBGJFSA-N 0.000 description 12
- MNZHHDPWDWQJCQ-YUMQZZPRSA-N Ala-Leu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O MNZHHDPWDWQJCQ-YUMQZZPRSA-N 0.000 description 12
- HSWYMWGDMPLTTH-FXQIFTODSA-N Asp-Glu-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HSWYMWGDMPLTTH-FXQIFTODSA-N 0.000 description 12
- OSCLNNWLKKIQJM-WDSKDSINSA-N Gln-Ser-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O OSCLNNWLKKIQJM-WDSKDSINSA-N 0.000 description 12
- ZYRXTRTUCAVNBQ-GVXVVHGQSA-N Glu-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZYRXTRTUCAVNBQ-GVXVVHGQSA-N 0.000 description 12
- GQZMPWBZQALKJO-UWVGGRQHSA-N Lys-Gly-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O GQZMPWBZQALKJO-UWVGGRQHSA-N 0.000 description 12
- SKRGVGLIRUGANF-AVGNSLFASA-N Lys-Leu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SKRGVGLIRUGANF-AVGNSLFASA-N 0.000 description 12
- QLFAPXUXEBAWEK-NHCYSSNCSA-N Lys-Val-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QLFAPXUXEBAWEK-NHCYSSNCSA-N 0.000 description 12
- XXXAXOWMBOKTRN-XPUUQOCRSA-N Ser-Gly-Val Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O XXXAXOWMBOKTRN-XPUUQOCRSA-N 0.000 description 12
- OZPDGESCTGGNAD-CIUDSAMLSA-N Ser-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CO OZPDGESCTGGNAD-CIUDSAMLSA-N 0.000 description 12
- LGIMRDKGABDMBN-DCAQKATOSA-N Ser-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N LGIMRDKGABDMBN-DCAQKATOSA-N 0.000 description 12
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 12
- ANHVRCNNGJMJNG-BZSNNMDCSA-N Tyr-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CS)C(=O)O)N)O ANHVRCNNGJMJNG-BZSNNMDCSA-N 0.000 description 12
- 230000002494 anti-cea effect Effects 0.000 description 12
- 231100000433 cytotoxic Toxicity 0.000 description 12
- 230000001472 cytotoxic effect Effects 0.000 description 12
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 12
- 210000004881 tumor cell Anatomy 0.000 description 12
- WQKAQKZRDIZYNV-VZFHVOOUSA-N Ala-Ser-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WQKAQKZRDIZYNV-VZFHVOOUSA-N 0.000 description 11
- 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 11
- VNXQRBXEQXLERQ-CIUDSAMLSA-N Asp-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N VNXQRBXEQXLERQ-CIUDSAMLSA-N 0.000 description 11
- FGYPOQPQTUNESW-IUCAKERBSA-N Gln-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N FGYPOQPQTUNESW-IUCAKERBSA-N 0.000 description 11
- 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 11
- XHVONGZZVUUORG-WEDXCCLWSA-N Gly-Thr-Lys Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN XHVONGZZVUUORG-WEDXCCLWSA-N 0.000 description 11
- AIQWYVFNBNNOLU-RHYQMDGZSA-N Leu-Thr-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O AIQWYVFNBNNOLU-RHYQMDGZSA-N 0.000 description 11
- QARPMYDMYVLFMW-KKUMJFAQSA-N Phe-Pro-Glu Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C1=CC=CC=C1 QARPMYDMYVLFMW-KKUMJFAQSA-N 0.000 description 11
- ZKOKTQPHFMRSJP-YJRXYDGGSA-N Ser-Thr-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZKOKTQPHFMRSJP-YJRXYDGGSA-N 0.000 description 11
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 11
- XSEPSRUDSPHMPX-KATARQTJSA-N Thr-Lys-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O XSEPSRUDSPHMPX-KATARQTJSA-N 0.000 description 11
- HGJRMXOWUWVUOA-GVXVVHGQSA-N Val-Leu-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N HGJRMXOWUWVUOA-GVXVVHGQSA-N 0.000 description 11
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 108010087823 glycyltyrosine Proteins 0.000 description 11
- 230000002147 killing effect Effects 0.000 description 11
- 108010024654 phenylalanyl-prolyl-alanine Proteins 0.000 description 11
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 11
- WCBVQNZTOKJWJS-ACZMJKKPSA-N Ala-Cys-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O WCBVQNZTOKJWJS-ACZMJKKPSA-N 0.000 description 10
- MEFILNJXAVSUTO-JXUBOQSCSA-N Ala-Leu-Thr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MEFILNJXAVSUTO-JXUBOQSCSA-N 0.000 description 10
- PRLPSDIHSRITSF-UNQGMJICSA-N Arg-Phe-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PRLPSDIHSRITSF-UNQGMJICSA-N 0.000 description 10
- PUUPMDXIHCOPJU-HJGDQZAQSA-N Asn-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O PUUPMDXIHCOPJU-HJGDQZAQSA-N 0.000 description 10
- YNQIDCRRTWGHJD-ZLUOBGJFSA-N Asp-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(O)=O YNQIDCRRTWGHJD-ZLUOBGJFSA-N 0.000 description 10
- 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 10
- AMRLSQGGERHDHJ-FXQIFTODSA-N Cys-Ala-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMRLSQGGERHDHJ-FXQIFTODSA-N 0.000 description 10
- OYTPNWYZORARHL-XHNCKOQMSA-N Gln-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N OYTPNWYZORARHL-XHNCKOQMSA-N 0.000 description 10
- 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 10
- XCLCVBYNGXEVDU-WHFBIAKZSA-N Gly-Asn-Ser Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O XCLCVBYNGXEVDU-WHFBIAKZSA-N 0.000 description 10
- BIRKKBCSAIHDDF-WDSKDSINSA-N Gly-Glu-Cys Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(O)=O BIRKKBCSAIHDDF-WDSKDSINSA-N 0.000 description 10
- FFJQHWKSGAWSTJ-BFHQHQDPSA-N Gly-Thr-Ala Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O FFJQHWKSGAWSTJ-BFHQHQDPSA-N 0.000 description 10
- ZZWUYQXMIFTIIY-WEDXCCLWSA-N Gly-Thr-Leu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O ZZWUYQXMIFTIIY-WEDXCCLWSA-N 0.000 description 10
- UXSATKFPUVZVDK-KKUMJFAQSA-N His-Lys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CN=CN1)N UXSATKFPUVZVDK-KKUMJFAQSA-N 0.000 description 10
- 108060003951 Immunoglobulin Proteins 0.000 description 10
- MPGHETGWWWUHPY-CIUDSAMLSA-N Lys-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN MPGHETGWWWUHPY-CIUDSAMLSA-N 0.000 description 10
- XABXVVSWUVCZST-GVXVVHGQSA-N Lys-Val-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN XABXVVSWUVCZST-GVXVVHGQSA-N 0.000 description 10
- HXSUFWQYLPKEHF-IHRRRGAJSA-N Phe-Asn-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N HXSUFWQYLPKEHF-IHRRRGAJSA-N 0.000 description 10
- XNQMZHLAYFWSGJ-HTUGSXCWSA-N Phe-Thr-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XNQMZHLAYFWSGJ-HTUGSXCWSA-N 0.000 description 10
- SJRQWEDYTKYHHL-SLFFLAALSA-N Phe-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O SJRQWEDYTKYHHL-SLFFLAALSA-N 0.000 description 10
- ULVMNZOKDBHKKI-ACZMJKKPSA-N Ser-Gln-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ULVMNZOKDBHKKI-ACZMJKKPSA-N 0.000 description 10
- QYSFWUIXDFJUDW-DCAQKATOSA-N Ser-Leu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYSFWUIXDFJUDW-DCAQKATOSA-N 0.000 description 10
- 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 10
- NADLKBTYNKUJEP-KATARQTJSA-N Ser-Thr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NADLKBTYNKUJEP-KATARQTJSA-N 0.000 description 10
- SNXUIBACCONSOH-BWBBJGPYSA-N Ser-Thr-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CO)C(O)=O SNXUIBACCONSOH-BWBBJGPYSA-N 0.000 description 10
- HSWXBJCBYSWBPT-GUBZILKMSA-N Ser-Val-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)C(O)=O HSWXBJCBYSWBPT-GUBZILKMSA-N 0.000 description 10
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 10
- KGKWKSSSQGGYAU-SUSMZKCASA-N Thr-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KGKWKSSSQGGYAU-SUSMZKCASA-N 0.000 description 10
- GKWNLDNXMMLRMC-GLLZPBPUSA-N Thr-Glu-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O GKWNLDNXMMLRMC-GLLZPBPUSA-N 0.000 description 10
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 10
- OGOYMQWIWHGTGH-KZVJFYERSA-N Thr-Val-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O OGOYMQWIWHGTGH-KZVJFYERSA-N 0.000 description 10
- NLWCSMOXNKBRLC-WDSOQIARSA-N Trp-Lys-Val Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NLWCSMOXNKBRLC-WDSOQIARSA-N 0.000 description 10
- SLCSPPCQWUHPPO-JYJNAYRXSA-N Tyr-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SLCSPPCQWUHPPO-JYJNAYRXSA-N 0.000 description 10
- JJNXZIPLIXIGBX-HJPIBITLSA-N Tyr-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N JJNXZIPLIXIGBX-HJPIBITLSA-N 0.000 description 10
- VJOWWOGRNXRQMF-UVBJJODRSA-N Val-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 VJOWWOGRNXRQMF-UVBJJODRSA-N 0.000 description 10
- TVGWMCTYUFBXAP-QTKMDUPCSA-N Val-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N)O TVGWMCTYUFBXAP-QTKMDUPCSA-N 0.000 description 10
- GVNLOVJNNDZUHS-RHYQMDGZSA-N Val-Thr-Lys Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O GVNLOVJNNDZUHS-RHYQMDGZSA-N 0.000 description 10
- ZHWZDZFWBXWPDW-GUBZILKMSA-N Val-Val-Cys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(O)=O ZHWZDZFWBXWPDW-GUBZILKMSA-N 0.000 description 10
- 108010081404 acein-2 Proteins 0.000 description 10
- 108010047857 aspartylglycine Proteins 0.000 description 10
- 238000010276 construction Methods 0.000 description 10
- 108010060199 cysteinylproline Proteins 0.000 description 10
- 102000018358 immunoglobulin Human genes 0.000 description 10
- 108010077112 prolyl-proline Proteins 0.000 description 10
- 108010026333 seryl-proline Proteins 0.000 description 10
- 108010035534 tyrosyl-leucyl-alanine Proteins 0.000 description 10
- FEZJJKXNPSEYEV-CIUDSAMLSA-N Arg-Gln-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O FEZJJKXNPSEYEV-CIUDSAMLSA-N 0.000 description 9
- COXMUHNBYCVVRG-DCAQKATOSA-N Arg-Leu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O COXMUHNBYCVVRG-DCAQKATOSA-N 0.000 description 9
- QNJIRRVTOXNGMH-GUBZILKMSA-N Asn-Gln-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(N)=O QNJIRRVTOXNGMH-GUBZILKMSA-N 0.000 description 9
- RBOBTTLFPRSXKZ-BZSNNMDCSA-N Asn-Phe-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RBOBTTLFPRSXKZ-BZSNNMDCSA-N 0.000 description 9
- HPBNLFLSSQDFQW-WHFBIAKZSA-N Asn-Ser-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O HPBNLFLSSQDFQW-WHFBIAKZSA-N 0.000 description 9
- TVYMKYUSZSVOAG-ZLUOBGJFSA-N Cys-Ala-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O TVYMKYUSZSVOAG-ZLUOBGJFSA-N 0.000 description 9
- MADFVRSKEIEZHZ-DCAQKATOSA-N Gln-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N MADFVRSKEIEZHZ-DCAQKATOSA-N 0.000 description 9
- HAOUOFNNJJLVNS-BQBZGAKWSA-N Gly-Pro-Ser Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O HAOUOFNNJJLVNS-BQBZGAKWSA-N 0.000 description 9
- ZNTSGDNUITWTRA-WDSOQIARSA-N His-Trp-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C(C)C)C(O)=O ZNTSGDNUITWTRA-WDSOQIARSA-N 0.000 description 9
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 9
- RCFDOSNHHZGBOY-UHFFFAOYSA-N L-isoleucyl-L-alanine Natural products CCC(C)C(N)C(=O)NC(C)C(O)=O RCFDOSNHHZGBOY-UHFFFAOYSA-N 0.000 description 9
- MVJRBCJCRYGCKV-GVXVVHGQSA-N Leu-Val-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O MVJRBCJCRYGCKV-GVXVVHGQSA-N 0.000 description 9
- BPCLGWHVPVTTFM-QWRGUYRKSA-N Phe-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O BPCLGWHVPVTTFM-QWRGUYRKSA-N 0.000 description 9
- CGBYDGAJHSOGFQ-LPEHRKFASA-N Pro-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 CGBYDGAJHSOGFQ-LPEHRKFASA-N 0.000 description 9
- RMODQFBNDDENCP-IHRRRGAJSA-N Pro-Lys-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O RMODQFBNDDENCP-IHRRRGAJSA-N 0.000 description 9
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 9
- RXUOAOOZIWABBW-XGEHTFHBSA-N Ser-Thr-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RXUOAOOZIWABBW-XGEHTFHBSA-N 0.000 description 9
- 125000000539 amino acid group Chemical group 0.000 description 9
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 9
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 9
- 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 8
- CXRCVCURMBFFOL-FXQIFTODSA-N Ala-Ala-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O CXRCVCURMBFFOL-FXQIFTODSA-N 0.000 description 8
- 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 8
- MJIJBEYEHBKTIM-BYULHYEWSA-N Asn-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N MJIJBEYEHBKTIM-BYULHYEWSA-N 0.000 description 8
- OZHXXYOHPLLLMI-CIUDSAMLSA-N Cys-Lys-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OZHXXYOHPLLLMI-CIUDSAMLSA-N 0.000 description 8
- HMIXCETWRYDVMO-GUBZILKMSA-N Gln-Pro-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O HMIXCETWRYDVMO-GUBZILKMSA-N 0.000 description 8
- CQMFNTVQVLQRLT-JHEQGTHGSA-N Gly-Thr-Gln Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O CQMFNTVQVLQRLT-JHEQGTHGSA-N 0.000 description 8
- 102000001398 Granzyme Human genes 0.000 description 8
- 108060005986 Granzyme Proteins 0.000 description 8
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 8
- 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 8
- WSGXUIQTEZDVHJ-GARJFASQSA-N Leu-Ala-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(O)=O WSGXUIQTEZDVHJ-GARJFASQSA-N 0.000 description 8
- KIZIOFNVSOSKJI-CIUDSAMLSA-N Leu-Ser-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N KIZIOFNVSOSKJI-CIUDSAMLSA-N 0.000 description 8
- SBANPBVRHYIMRR-UHFFFAOYSA-N Leu-Ser-Pro Natural products CC(C)CC(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O SBANPBVRHYIMRR-UHFFFAOYSA-N 0.000 description 8
- LCNASHSOFMRYFO-WDCWCFNPSA-N Leu-Thr-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(N)=O LCNASHSOFMRYFO-WDCWCFNPSA-N 0.000 description 8
- RFQATBGBLDAKGI-VHSXEESVSA-N Lys-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCCCN)N)C(=O)O RFQATBGBLDAKGI-VHSXEESVSA-N 0.000 description 8
- MIFFFXHMAHFACR-KATARQTJSA-N Lys-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCCCN MIFFFXHMAHFACR-KATARQTJSA-N 0.000 description 8
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 8
- 102000004503 Perforin Human genes 0.000 description 8
- 108010056995 Perforin Proteins 0.000 description 8
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 8
- BWTKUQPNOMMKMA-FIRPJDEBSA-N Phe-Ile-Phe Chemical compound C([C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 BWTKUQPNOMMKMA-FIRPJDEBSA-N 0.000 description 8
- JDMKQHSHKJHAHR-UHFFFAOYSA-N Phe-Phe-Leu-Tyr Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)CC1=CC=CC=C1 JDMKQHSHKJHAHR-UHFFFAOYSA-N 0.000 description 8
- FGWUALWGCZJQDJ-URLPEUOOSA-N Phe-Thr-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FGWUALWGCZJQDJ-URLPEUOOSA-N 0.000 description 8
- FMLRRBDLBJLJIK-DCAQKATOSA-N Pro-Leu-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 FMLRRBDLBJLJIK-DCAQKATOSA-N 0.000 description 8
- MHHQQZIFLWFZGR-DCAQKATOSA-N Pro-Lys-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O MHHQQZIFLWFZGR-DCAQKATOSA-N 0.000 description 8
- UGJRQLURDVGULT-LKXGYXEUSA-N Ser-Asn-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UGJRQLURDVGULT-LKXGYXEUSA-N 0.000 description 8
- FTVRVZNYIYWJGB-ACZMJKKPSA-N Ser-Asp-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FTVRVZNYIYWJGB-ACZMJKKPSA-N 0.000 description 8
- CKDXFSPMIDSMGV-GUBZILKMSA-N Ser-Pro-Val Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O CKDXFSPMIDSMGV-GUBZILKMSA-N 0.000 description 8
- XQJCEKXQUJQNNK-ZLUOBGJFSA-N Ser-Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O XQJCEKXQUJQNNK-ZLUOBGJFSA-N 0.000 description 8
- KZSYAEWQMJEGRZ-RHYQMDGZSA-N Thr-Leu-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O KZSYAEWQMJEGRZ-RHYQMDGZSA-N 0.000 description 8
- FWTFAZKJORVTIR-VZFHVOOUSA-N Thr-Ser-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O FWTFAZKJORVTIR-VZFHVOOUSA-N 0.000 description 8
- FYBFTPLPAXZBOY-KKHAAJSZSA-N Thr-Val-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O FYBFTPLPAXZBOY-KKHAAJSZSA-N 0.000 description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 8
- NKUGCYDFQKFVOJ-JYJNAYRXSA-N Tyr-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NKUGCYDFQKFVOJ-JYJNAYRXSA-N 0.000 description 8
- VFOHXOLPLACADK-GVXVVHGQSA-N Val-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N VFOHXOLPLACADK-GVXVVHGQSA-N 0.000 description 8
- ZXYPHBKIZLAQTL-QXEWZRGKSA-N Val-Pro-Asp Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)O)N ZXYPHBKIZLAQTL-QXEWZRGKSA-N 0.000 description 8
- HWNYVQMOLCYHEA-IHRRRGAJSA-N Val-Ser-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N HWNYVQMOLCYHEA-IHRRRGAJSA-N 0.000 description 8
- JVGDAEKKZKKZFO-RCWTZXSCSA-N Val-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N)O JVGDAEKKZKKZFO-RCWTZXSCSA-N 0.000 description 8
- 108010070783 alanyltyrosine Proteins 0.000 description 8
- 125000003275 alpha amino acid group Chemical group 0.000 description 8
- 108010008355 arginyl-glutamine Proteins 0.000 description 8
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 8
- 108010003700 lysyl aspartic acid Proteins 0.000 description 8
- 229930192851 perforin Natural products 0.000 description 8
- 108010005652 splenotritin Proteins 0.000 description 8
- YJHKTAMKPGFJCT-NRPADANISA-N Ala-Val-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O YJHKTAMKPGFJCT-NRPADANISA-N 0.000 description 7
- GYWQGGUCMDCUJE-DLOVCJGASA-N Asp-Phe-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O GYWQGGUCMDCUJE-DLOVCJGASA-N 0.000 description 7
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 7
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 7
- BPHKULHWEIUDOB-FXQIFTODSA-N Cys-Gln-Gln Chemical compound SC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BPHKULHWEIUDOB-FXQIFTODSA-N 0.000 description 7
- IOFDDSNZJDIGPB-GVXVVHGQSA-N Gln-Leu-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IOFDDSNZJDIGPB-GVXVVHGQSA-N 0.000 description 7
- ZFBBMCKQSNJZSN-AUTRQRHGSA-N Gln-Val-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZFBBMCKQSNJZSN-AUTRQRHGSA-N 0.000 description 7
- HUFCEIHAFNVSNR-IHRRRGAJSA-N Glu-Gln-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HUFCEIHAFNVSNR-IHRRRGAJSA-N 0.000 description 7
- WGYHAAXZWPEBDQ-IFFSRLJSSA-N Glu-Val-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGYHAAXZWPEBDQ-IFFSRLJSSA-N 0.000 description 7
- WNZOCXUOGVYYBJ-CDMKHQONSA-N Gly-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CN)O WNZOCXUOGVYYBJ-CDMKHQONSA-N 0.000 description 7
- FULZDMOZUZKGQU-ONGXEEELSA-N Gly-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN FULZDMOZUZKGQU-ONGXEEELSA-N 0.000 description 7
- QQFSKBMCAKWHLG-UHFFFAOYSA-N Ile-Phe-Pro-Pro Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(NC(=O)C(N)C(C)CC)CC1=CC=CC=C1 QQFSKBMCAKWHLG-UHFFFAOYSA-N 0.000 description 7
- AXZGZMGRBDQTEY-SRVKXCTJSA-N Leu-Gln-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O AXZGZMGRBDQTEY-SRVKXCTJSA-N 0.000 description 7
- RMOKGALPSPOYKE-KATARQTJSA-N Lys-Thr-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O RMOKGALPSPOYKE-KATARQTJSA-N 0.000 description 7
- ZJPGOXWRFNKIQL-JYJNAYRXSA-N Phe-Pro-Pro Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=CC=C1 ZJPGOXWRFNKIQL-JYJNAYRXSA-N 0.000 description 7
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 7
- QGMLKFGTGXWAHF-IHRRRGAJSA-N Ser-Arg-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QGMLKFGTGXWAHF-IHRRRGAJSA-N 0.000 description 7
- QPFJSHSJFIYDJZ-GHCJXIJMSA-N Ser-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO QPFJSHSJFIYDJZ-GHCJXIJMSA-N 0.000 description 7
- JFWDJFULOLKQFY-QWRGUYRKSA-N Ser-Gly-Phe Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JFWDJFULOLKQFY-QWRGUYRKSA-N 0.000 description 7
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 7
- KRPKYGOFYUNIGM-XVSYOHENSA-N Thr-Asp-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N)O KRPKYGOFYUNIGM-XVSYOHENSA-N 0.000 description 7
- SGAOHNPSEPVAFP-ZDLURKLDSA-N Thr-Ser-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SGAOHNPSEPVAFP-ZDLURKLDSA-N 0.000 description 7
- NGALWFGCOMHUSN-AVGNSLFASA-N Tyr-Gln-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NGALWFGCOMHUSN-AVGNSLFASA-N 0.000 description 7
- VYQQQIRHIFALGE-UWJYBYFXSA-N Tyr-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VYQQQIRHIFALGE-UWJYBYFXSA-N 0.000 description 7
- NUQZCPSZHGIYTA-HKUYNNGSSA-N Tyr-Trp-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N NUQZCPSZHGIYTA-HKUYNNGSSA-N 0.000 description 7
- KRAHMIJVUPUOTQ-DCAQKATOSA-N Val-Ser-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N KRAHMIJVUPUOTQ-DCAQKATOSA-N 0.000 description 7
- SDHZOOIGIUEPDY-JYJNAYRXSA-N Val-Ser-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 SDHZOOIGIUEPDY-JYJNAYRXSA-N 0.000 description 7
- 108010062796 arginyllysine Proteins 0.000 description 7
- 230000024245 cell differentiation Effects 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 7
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 7
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 7
- 108010061238 threonyl-glycine Proteins 0.000 description 7
- 108010052774 valyl-lysyl-glycyl-phenylalanyl-tyrosine Proteins 0.000 description 7
- 108010027345 wheylin-1 peptide Proteins 0.000 description 7
- SUHLZMHFRALVSY-YUMQZZPRSA-N Ala-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)NCC(O)=O SUHLZMHFRALVSY-YUMQZZPRSA-N 0.000 description 6
- XWFWAXPOLRTDFZ-FXQIFTODSA-N Ala-Pro-Ser Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O XWFWAXPOLRTDFZ-FXQIFTODSA-N 0.000 description 6
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 6
- ISJWBVIYRBAXEB-CIUDSAMLSA-N Arg-Ser-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O ISJWBVIYRBAXEB-CIUDSAMLSA-N 0.000 description 6
- XYOVHPDDWCEUDY-CIUDSAMLSA-N Asn-Ala-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O XYOVHPDDWCEUDY-CIUDSAMLSA-N 0.000 description 6
- GXMSVVBIAMWMKO-BQBZGAKWSA-N Asn-Arg-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCN=C(N)N GXMSVVBIAMWMKO-BQBZGAKWSA-N 0.000 description 6
- PBSQFBAJKPLRJY-BYULHYEWSA-N Asn-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N PBSQFBAJKPLRJY-BYULHYEWSA-N 0.000 description 6
- JWQWPRCDYWNVNM-ACZMJKKPSA-N Asn-Ser-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N JWQWPRCDYWNVNM-ACZMJKKPSA-N 0.000 description 6
- HNXWVVHIGTZTBO-LKXGYXEUSA-N Asn-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O HNXWVVHIGTZTBO-LKXGYXEUSA-N 0.000 description 6
- WLVLIYYBPPONRJ-GCJQMDKQSA-N Asn-Thr-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O WLVLIYYBPPONRJ-GCJQMDKQSA-N 0.000 description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 6
- NDUSUIGBMZCOIL-ZKWXMUAHSA-N Cys-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N NDUSUIGBMZCOIL-ZKWXMUAHSA-N 0.000 description 6
- YMBAVNPKBWHDAW-CIUDSAMLSA-N Cys-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N YMBAVNPKBWHDAW-CIUDSAMLSA-N 0.000 description 6
- VIRYODQIWJNWNU-NRPADANISA-N Cys-Glu-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)N VIRYODQIWJNWNU-NRPADANISA-N 0.000 description 6
- -1 EGFR Proteins 0.000 description 6
- IULKWYSYZSURJK-AVGNSLFASA-N Gln-Leu-Lys Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O IULKWYSYZSURJK-AVGNSLFASA-N 0.000 description 6
- CKOFNWCLWRYUHK-XHNCKOQMSA-N Glu-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O CKOFNWCLWRYUHK-XHNCKOQMSA-N 0.000 description 6
- CLROYXHHUZELFX-FXQIFTODSA-N Glu-Gln-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O CLROYXHHUZELFX-FXQIFTODSA-N 0.000 description 6
- XTZDZAXYPDISRR-MNXVOIDGSA-N Glu-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N XTZDZAXYPDISRR-MNXVOIDGSA-N 0.000 description 6
- JSNNHGHYGYMVCK-XVKPBYJWSA-N Gly-Glu-Val Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O JSNNHGHYGYMVCK-XVKPBYJWSA-N 0.000 description 6
- 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 6
- AFWYPMDMDYCKMD-KBPBESRZSA-N Gly-Leu-Tyr Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AFWYPMDMDYCKMD-KBPBESRZSA-N 0.000 description 6
- GGAPHLIUUTVYMX-QWRGUYRKSA-N Gly-Phe-Ser Chemical compound OC[C@@H](C([O-])=O)NC(=O)[C@@H](NC(=O)C[NH3+])CC1=CC=CC=C1 GGAPHLIUUTVYMX-QWRGUYRKSA-N 0.000 description 6
- TTYKEFZRLKQTHH-MELADBBJSA-N His-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O TTYKEFZRLKQTHH-MELADBBJSA-N 0.000 description 6
- GTSAALPQZASLPW-KJYZGMDISA-N Ile-His-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N GTSAALPQZASLPW-KJYZGMDISA-N 0.000 description 6
- DBVWMYGBVFCRBE-CIUDSAMLSA-N Leu-Asn-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O DBVWMYGBVFCRBE-CIUDSAMLSA-N 0.000 description 6
- FAELBUXXFQLUAX-AJNGGQMLSA-N Leu-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C FAELBUXXFQLUAX-AJNGGQMLSA-N 0.000 description 6
- 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 6
- AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 description 6
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 6
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 6
- VUTWYNQUSJWBHO-BZSNNMDCSA-N Lys-Leu-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VUTWYNQUSJWBHO-BZSNNMDCSA-N 0.000 description 6
- YTJFXEDRUOQGSP-DCAQKATOSA-N Lys-Pro-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O YTJFXEDRUOQGSP-DCAQKATOSA-N 0.000 description 6
- CTJUSALVKAWFFU-CIUDSAMLSA-N Lys-Ser-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N CTJUSALVKAWFFU-CIUDSAMLSA-N 0.000 description 6
- SJDQOYTYNGZZJX-SRVKXCTJSA-N Met-Glu-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O SJDQOYTYNGZZJX-SRVKXCTJSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- JOXIIFVCSATTDH-IHPCNDPISA-N Phe-Asn-Trp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N JOXIIFVCSATTDH-IHPCNDPISA-N 0.000 description 6
- YYKZDTVQHTUKDW-RYUDHWBXSA-N Phe-Gly-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)O)N YYKZDTVQHTUKDW-RYUDHWBXSA-N 0.000 description 6
- JLLJTMHNXQTMCK-UBHSHLNASA-N Phe-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 JLLJTMHNXQTMCK-UBHSHLNASA-N 0.000 description 6
- UAYHMOIGIQZLFR-NHCYSSNCSA-N Pro-Gln-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O UAYHMOIGIQZLFR-NHCYSSNCSA-N 0.000 description 6
- HWLKHNDRXWTFTN-GUBZILKMSA-N Pro-Pro-Cys Chemical compound C1C[C@H](NC1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CS)C(=O)O HWLKHNDRXWTFTN-GUBZILKMSA-N 0.000 description 6
- 238000011579 SCID mouse model Methods 0.000 description 6
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 6
- LQESNKGTTNHZPZ-GHCJXIJMSA-N Ser-Ile-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O LQESNKGTTNHZPZ-GHCJXIJMSA-N 0.000 description 6
- 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 6
- PPNPDKGQRFSCAC-CIUDSAMLSA-N Ser-Lys-Asp Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(O)=O)C(O)=O PPNPDKGQRFSCAC-CIUDSAMLSA-N 0.000 description 6
- UPLYXVPQLJVWMM-KKUMJFAQSA-N Ser-Phe-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O UPLYXVPQLJVWMM-KKUMJFAQSA-N 0.000 description 6
- 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 6
- AXKJPUBALUNJEO-UBHSHLNASA-N Ser-Trp-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(O)=O AXKJPUBALUNJEO-UBHSHLNASA-N 0.000 description 6
- KIEIJCFVGZCUAS-MELADBBJSA-N Ser-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CO)N)C(=O)O KIEIJCFVGZCUAS-MELADBBJSA-N 0.000 description 6
- SIEBDTCABMZCLF-XGEHTFHBSA-N Ser-Val-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SIEBDTCABMZCLF-XGEHTFHBSA-N 0.000 description 6
- IGROJMCBGRFRGI-YTLHQDLWSA-N Thr-Ala-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O IGROJMCBGRFRGI-YTLHQDLWSA-N 0.000 description 6
- CYVQBKQYQGEELV-NKIYYHGXSA-N Thr-His-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O CYVQBKQYQGEELV-NKIYYHGXSA-N 0.000 description 6
- JLNMFGCJODTXDH-WEDXCCLWSA-N Thr-Lys-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O JLNMFGCJODTXDH-WEDXCCLWSA-N 0.000 description 6
- IQPWNQRRAJHOKV-KATARQTJSA-N Thr-Ser-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN IQPWNQRRAJHOKV-KATARQTJSA-N 0.000 description 6
- ZESGVALRVJIVLZ-VFCFLDTKSA-N Thr-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O ZESGVALRVJIVLZ-VFCFLDTKSA-N 0.000 description 6
- RPECVQBNONKZAT-WZLNRYEVSA-N Thr-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]([C@@H](C)O)N RPECVQBNONKZAT-WZLNRYEVSA-N 0.000 description 6
- QNXZCKMXHPULME-ZNSHCXBVSA-N Thr-Val-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O QNXZCKMXHPULME-ZNSHCXBVSA-N 0.000 description 6
- KZTLZZQTJMCGIP-ZJDVBMNYSA-N Thr-Val-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KZTLZZQTJMCGIP-ZJDVBMNYSA-N 0.000 description 6
- UOXPLPBMEPLZBW-WDSOQIARSA-N Trp-Val-Lys Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(O)=O)=CNC2=C1 UOXPLPBMEPLZBW-WDSOQIARSA-N 0.000 description 6
- OLWFDNLLBWQWCP-STQMWFEESA-N Tyr-Gly-Met Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O OLWFDNLLBWQWCP-STQMWFEESA-N 0.000 description 6
- ZPFLBLFITJCBTP-QWRGUYRKSA-N Tyr-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O ZPFLBLFITJCBTP-QWRGUYRKSA-N 0.000 description 6
- ZYVAAYAOTVJBSS-GMVOTWDCSA-N Tyr-Trp-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O ZYVAAYAOTVJBSS-GMVOTWDCSA-N 0.000 description 6
- SQUMHUZLJDUROQ-YDHLFZDLSA-N Tyr-Val-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O SQUMHUZLJDUROQ-YDHLFZDLSA-N 0.000 description 6
- GNWUWQAVVJQREM-NHCYSSNCSA-N Val-Asn-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N GNWUWQAVVJQREM-NHCYSSNCSA-N 0.000 description 6
- OXVPMZVGCAPFIG-BQFCYCMXSA-N Val-Gln-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N OXVPMZVGCAPFIG-BQFCYCMXSA-N 0.000 description 6
- 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 6
- KSFXWENSJABBFI-ZKWXMUAHSA-N Val-Ser-Asn Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KSFXWENSJABBFI-ZKWXMUAHSA-N 0.000 description 6
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 6
- BZDGLJPROOOUOZ-XGEHTFHBSA-N Val-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N)O BZDGLJPROOOUOZ-XGEHTFHBSA-N 0.000 description 6
- WUFHZIRMAZZWRS-OSUNSFLBSA-N Val-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)N WUFHZIRMAZZWRS-OSUNSFLBSA-N 0.000 description 6
- ZLNYBMWGPOKSLW-LSJOCFKGSA-N Val-Val-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLNYBMWGPOKSLW-LSJOCFKGSA-N 0.000 description 6
- 108010013835 arginine glutamate Proteins 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 108010090894 prolylleucine Proteins 0.000 description 6
- 108010063779 seryl-tyrosyl-prolyl-tyrosyl-aspartic acid Proteins 0.000 description 6
- 108010071097 threonyl-lysyl-proline Proteins 0.000 description 6
- YQGZIRIYGHNSQO-ZPFDUUQYSA-N Arg-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N YQGZIRIYGHNSQO-ZPFDUUQYSA-N 0.000 description 5
- CVXXSWQORBZAAA-SRVKXCTJSA-N Arg-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N CVXXSWQORBZAAA-SRVKXCTJSA-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
- QUAWOKPCAKCHQL-SRVKXCTJSA-N Asn-His-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N QUAWOKPCAKCHQL-SRVKXCTJSA-N 0.000 description 5
- JTXVXGXTRXMOFJ-FXQIFTODSA-N Asn-Pro-Asn Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O JTXVXGXTRXMOFJ-FXQIFTODSA-N 0.000 description 5
- UGXYFDQFLVCDFC-CIUDSAMLSA-N Asn-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O UGXYFDQFLVCDFC-CIUDSAMLSA-N 0.000 description 5
- JBDLMLZNDRLDIX-HJGDQZAQSA-N Asn-Thr-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O JBDLMLZNDRLDIX-HJGDQZAQSA-N 0.000 description 5
- LGCVSPFCFXWUEY-IHPCNDPISA-N Asn-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N LGCVSPFCFXWUEY-IHPCNDPISA-N 0.000 description 5
- KYQNAIMCTRZLNP-QSFUFRPTSA-N Asp-Ile-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O KYQNAIMCTRZLNP-QSFUFRPTSA-N 0.000 description 5
- 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 5
- USNJAPJZSGTTPX-XVSYOHENSA-N Asp-Phe-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O USNJAPJZSGTTPX-XVSYOHENSA-N 0.000 description 5
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 description 5
- GCACQYDBDHRVGE-LKXGYXEUSA-N Asp-Thr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC(O)=O GCACQYDBDHRVGE-LKXGYXEUSA-N 0.000 description 5
- PLNJUJGNLDSFOP-UWJYBYFXSA-N Asp-Tyr-Ala 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](C)C(O)=O PLNJUJGNLDSFOP-UWJYBYFXSA-N 0.000 description 5
- HTSSXFASOUSJQG-IHPCNDPISA-N Asp-Tyr-Trp 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=CNC2=C1C=CC=C2)C(O)=O HTSSXFASOUSJQG-IHPCNDPISA-N 0.000 description 5
- MXZYQNJCBVJHSR-KATARQTJSA-N Cys-Lys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N)O MXZYQNJCBVJHSR-KATARQTJSA-N 0.000 description 5
- XKBASPWPBXNVLQ-WDSKDSINSA-N Gln-Gly-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O XKBASPWPBXNVLQ-WDSKDSINSA-N 0.000 description 5
- WPJDPEOQUIXXOY-AVGNSLFASA-N Gln-Tyr-Asn Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O WPJDPEOQUIXXOY-AVGNSLFASA-N 0.000 description 5
- BFEZQZKEPRKKHV-SRVKXCTJSA-N Glu-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCCCN)C(=O)O BFEZQZKEPRKKHV-SRVKXCTJSA-N 0.000 description 5
- NNQDRRUXFJYCCJ-NHCYSSNCSA-N Glu-Pro-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O NNQDRRUXFJYCCJ-NHCYSSNCSA-N 0.000 description 5
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 5
- ICUTTWWCDIIIEE-BQBZGAKWSA-N Gly-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN ICUTTWWCDIIIEE-BQBZGAKWSA-N 0.000 description 5
- WTUSRDZLLWGYAT-KCTSRDHCSA-N Gly-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)CN WTUSRDZLLWGYAT-KCTSRDHCSA-N 0.000 description 5
- GWCJMBNBFYBQCV-XPUUQOCRSA-N Gly-Val-Ala Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O GWCJMBNBFYBQCV-XPUUQOCRSA-N 0.000 description 5
- YGHSQRJSHKYUJY-SCZZXKLOSA-N Gly-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN YGHSQRJSHKYUJY-SCZZXKLOSA-N 0.000 description 5
- CSTDQOOBZBAJKE-BWAGICSOSA-N His-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC2=CN=CN2)N)O CSTDQOOBZBAJKE-BWAGICSOSA-N 0.000 description 5
- RKQAYOWLSFLJEE-SVSWQMSJSA-N Ile-Thr-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)O)N RKQAYOWLSFLJEE-SVSWQMSJSA-N 0.000 description 5
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 5
- RSFGIMMPWAXNML-MNXVOIDGSA-N Leu-Gln-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RSFGIMMPWAXNML-MNXVOIDGSA-N 0.000 description 5
- NRFGTHFONZYFNY-MGHWNKPDSA-N Leu-Ile-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NRFGTHFONZYFNY-MGHWNKPDSA-N 0.000 description 5
- IAJFFZORSWOZPQ-SRVKXCTJSA-N Leu-Leu-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IAJFFZORSWOZPQ-SRVKXCTJSA-N 0.000 description 5
- LJBVRCDPWOJOEK-PPCPHDFISA-N Leu-Thr-Ile 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)CC)C(O)=O LJBVRCDPWOJOEK-PPCPHDFISA-N 0.000 description 5
- 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 5
- LUTDBHBIHHREDC-IHRRRGAJSA-N Lys-Pro-Lys Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(O)=O LUTDBHBIHHREDC-IHRRRGAJSA-N 0.000 description 5
- GILLQRYAWOMHED-DCAQKATOSA-N Lys-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN GILLQRYAWOMHED-DCAQKATOSA-N 0.000 description 5
- CAODKDAPYGUMLK-FXQIFTODSA-N Met-Asn-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O CAODKDAPYGUMLK-FXQIFTODSA-N 0.000 description 5
- MHQXIBRPDKXDGZ-ZFWWWQNUSA-N Met-Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CNC(=O)[C@@H](N)CCSC)C(O)=O)=CNC2=C1 MHQXIBRPDKXDGZ-ZFWWWQNUSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 5
- BKWJQWJPZMUWEG-LFSVMHDDSA-N Phe-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 BKWJQWJPZMUWEG-LFSVMHDDSA-N 0.000 description 5
- MCIXMYKSPQUMJG-SRVKXCTJSA-N Phe-Ser-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MCIXMYKSPQUMJG-SRVKXCTJSA-N 0.000 description 5
- BPIMVBKDLSBKIJ-FCLVOEFKSA-N Phe-Thr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 BPIMVBKDLSBKIJ-FCLVOEFKSA-N 0.000 description 5
- KIPIKSXPPLABPN-CIUDSAMLSA-N Pro-Glu-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1 KIPIKSXPPLABPN-CIUDSAMLSA-N 0.000 description 5
- MGDFPGCFVJFITQ-CIUDSAMLSA-N Pro-Glu-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O MGDFPGCFVJFITQ-CIUDSAMLSA-N 0.000 description 5
- HZWAHWQZPSXNCB-BPUTZDHNSA-N Ser-Arg-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HZWAHWQZPSXNCB-BPUTZDHNSA-N 0.000 description 5
- KNCJWSPMTFFJII-ZLUOBGJFSA-N Ser-Cys-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(O)=O KNCJWSPMTFFJII-ZLUOBGJFSA-N 0.000 description 5
- VQBCMLMPEWPUTB-ACZMJKKPSA-N Ser-Glu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O VQBCMLMPEWPUTB-ACZMJKKPSA-N 0.000 description 5
- KDGARKCAKHBEDB-NKWVEPMBSA-N Ser-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CO)N)C(=O)O KDGARKCAKHBEDB-NKWVEPMBSA-N 0.000 description 5
- NLOAIFSWUUFQFR-CIUDSAMLSA-N Ser-Leu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O NLOAIFSWUUFQFR-CIUDSAMLSA-N 0.000 description 5
- GZSZPKSBVAOGIE-CIUDSAMLSA-N Ser-Lys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O GZSZPKSBVAOGIE-CIUDSAMLSA-N 0.000 description 5
- FPCGZYMRFFIYIH-CIUDSAMLSA-N Ser-Lys-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O FPCGZYMRFFIYIH-CIUDSAMLSA-N 0.000 description 5
- RRVFEDGUXSYWOW-BZSNNMDCSA-N Ser-Phe-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RRVFEDGUXSYWOW-BZSNNMDCSA-N 0.000 description 5
- XSLXHSYIVPGEER-KZVJFYERSA-N Thr-Ala-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O XSLXHSYIVPGEER-KZVJFYERSA-N 0.000 description 5
- JRAUIKJSEAKTGD-TUBUOCAGSA-N Thr-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N JRAUIKJSEAKTGD-TUBUOCAGSA-N 0.000 description 5
- DXPURPNJDFCKKO-RHYQMDGZSA-N Thr-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O DXPURPNJDFCKKO-RHYQMDGZSA-N 0.000 description 5
- PKZIWSHDJYIPRH-JBACZVJFSA-N Trp-Tyr-Gln 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](CCC(N)=O)C(O)=O PKZIWSHDJYIPRH-JBACZVJFSA-N 0.000 description 5
- QYSBJAUCUKHSLU-JYJNAYRXSA-N Tyr-Arg-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O QYSBJAUCUKHSLU-JYJNAYRXSA-N 0.000 description 5
- 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 5
- MVFQLSPDMMFCMW-KKUMJFAQSA-N Tyr-Leu-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O MVFQLSPDMMFCMW-KKUMJFAQSA-N 0.000 description 5
- WURLIFOWSMBUAR-SLFFLAALSA-N Tyr-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O WURLIFOWSMBUAR-SLFFLAALSA-N 0.000 description 5
- AUZADXNWQMBZOO-JYJNAYRXSA-N Tyr-Pro-Arg Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=C(O)C=C1 AUZADXNWQMBZOO-JYJNAYRXSA-N 0.000 description 5
- PWKMJDQXKCENMF-MEYUZBJRSA-N Tyr-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O PWKMJDQXKCENMF-MEYUZBJRSA-N 0.000 description 5
- OJCISMMNNUNNJA-BZSNNMDCSA-N Tyr-Tyr-Asp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(O)=O)C(O)=O)C1=CC=C(O)C=C1 OJCISMMNNUNNJA-BZSNNMDCSA-N 0.000 description 5
- ZIGZPYJXIWLQFC-QTKMDUPCSA-N Val-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C(C)C)N)O ZIGZPYJXIWLQFC-QTKMDUPCSA-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
- KISFXYYRKKNLOP-IHRRRGAJSA-N Val-Phe-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)O)N KISFXYYRKKNLOP-IHRRRGAJSA-N 0.000 description 5
- DEGUERSKQBRZMZ-FXQIFTODSA-N Val-Ser-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O DEGUERSKQBRZMZ-FXQIFTODSA-N 0.000 description 5
- JQTYTBPCSOAZHI-FXQIFTODSA-N Val-Ser-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N JQTYTBPCSOAZHI-FXQIFTODSA-N 0.000 description 5
- 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 5
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 5
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 108010016616 cysteinylglycine Proteins 0.000 description 5
- 108010069495 cysteinyltyrosine Proteins 0.000 description 5
- 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 5
- 108010027338 isoleucylcysteine Proteins 0.000 description 5
- 108010057821 leucylproline Proteins 0.000 description 5
- 108010012058 leucyltyrosine Proteins 0.000 description 5
- 108010038320 lysylphenylalanine Proteins 0.000 description 5
- 108010070409 phenylalanyl-glycyl-glycine Proteins 0.000 description 5
- 108010058119 tryptophyl-glycyl-glycine Proteins 0.000 description 5
- 108010051110 tyrosyl-lysine Proteins 0.000 description 5
- 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 4
- KXEVYGKATAMXJJ-ACZMJKKPSA-N Ala-Glu-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O KXEVYGKATAMXJJ-ACZMJKKPSA-N 0.000 description 4
- OBVSBEYOMDWLRJ-BFHQHQDPSA-N Ala-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N OBVSBEYOMDWLRJ-BFHQHQDPSA-N 0.000 description 4
- SUMYEVXWCAYLLJ-GUBZILKMSA-N Ala-Leu-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O SUMYEVXWCAYLLJ-GUBZILKMSA-N 0.000 description 4
- 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 4
- MDNAVFBZPROEHO-DCAQKATOSA-N Ala-Lys-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O MDNAVFBZPROEHO-DCAQKATOSA-N 0.000 description 4
- NZGRHTKZFSVPAN-BIIVOSGPSA-N Ala-Ser-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N NZGRHTKZFSVPAN-BIIVOSGPSA-N 0.000 description 4
- IOFVWPYSRSCWHI-JXUBOQSCSA-N Ala-Thr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)N IOFVWPYSRSCWHI-JXUBOQSCSA-N 0.000 description 4
- PGNNQOJOEGFAOR-KWQFWETISA-N Ala-Tyr-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 PGNNQOJOEGFAOR-KWQFWETISA-N 0.000 description 4
- ZDILXFDENZVOTL-BPNCWPANSA-N Ala-Val-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDILXFDENZVOTL-BPNCWPANSA-N 0.000 description 4
- BHSYMWWMVRPCPA-CYDGBPFRSA-N Arg-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CCCN=C(N)N BHSYMWWMVRPCPA-CYDGBPFRSA-N 0.000 description 4
- AUFHLLPVPSMEOG-YUMQZZPRSA-N Arg-Gly-Glu Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AUFHLLPVPSMEOG-YUMQZZPRSA-N 0.000 description 4
- HGKHPCFTRQDHCU-IUCAKERBSA-N Arg-Pro-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HGKHPCFTRQDHCU-IUCAKERBSA-N 0.000 description 4
- SYFHFLGAROUHNT-VEVYYDQMSA-N Arg-Thr-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O SYFHFLGAROUHNT-VEVYYDQMSA-N 0.000 description 4
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-N 0.000 description 4
- ZUVMUOOHJYNJPP-XIRDDKMYSA-N Arg-Trp-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZUVMUOOHJYNJPP-XIRDDKMYSA-N 0.000 description 4
- POZKLUIXMHIULG-FDARSICLSA-N Arg-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCCN=C(N)N)N POZKLUIXMHIULG-FDARSICLSA-N 0.000 description 4
- IZSMEUDYADKZTJ-KJEVXHAQSA-N Arg-Tyr-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IZSMEUDYADKZTJ-KJEVXHAQSA-N 0.000 description 4
- QLSRIZIDQXDQHK-RCWTZXSCSA-N Arg-Val-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QLSRIZIDQXDQHK-RCWTZXSCSA-N 0.000 description 4
- NVGWESORMHFISY-SRVKXCTJSA-N Asn-Asn-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NVGWESORMHFISY-SRVKXCTJSA-N 0.000 description 4
- WONGRTVAMHFGBE-WDSKDSINSA-N Asn-Gly-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N WONGRTVAMHFGBE-WDSKDSINSA-N 0.000 description 4
- PNHQRQTVBRDIEF-CIUDSAMLSA-N Asn-Leu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)N)N PNHQRQTVBRDIEF-CIUDSAMLSA-N 0.000 description 4
- BYLSYQASFJJBCL-DCAQKATOSA-N Asn-Pro-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O BYLSYQASFJJBCL-DCAQKATOSA-N 0.000 description 4
- YQPSDMUGFKJZHR-QRTARXTBSA-N Asn-Trp-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)N)N YQPSDMUGFKJZHR-QRTARXTBSA-N 0.000 description 4
- QNNBHTFDFFFHGC-KKUMJFAQSA-N Asn-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QNNBHTFDFFFHGC-KKUMJFAQSA-N 0.000 description 4
- WMLFFCRUSPNENW-ZLUOBGJFSA-N Asp-Ser-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O WMLFFCRUSPNENW-ZLUOBGJFSA-N 0.000 description 4
- KNDCWFXCFKSEBM-AVGNSLFASA-N Asp-Tyr-Glu 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](CCC(O)=O)C(O)=O KNDCWFXCFKSEBM-AVGNSLFASA-N 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- XMTDCXXLDZKAGI-ACZMJKKPSA-N Cys-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N XMTDCXXLDZKAGI-ACZMJKKPSA-N 0.000 description 4
- GEEXORWTBTUOHC-FXQIFTODSA-N Cys-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N GEEXORWTBTUOHC-FXQIFTODSA-N 0.000 description 4
- SOBBAYVQSNXYPQ-ACZMJKKPSA-N Gln-Asn-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O SOBBAYVQSNXYPQ-ACZMJKKPSA-N 0.000 description 4
- 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 4
- ZNZPKVQURDQFFS-FXQIFTODSA-N Gln-Glu-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O ZNZPKVQURDQFFS-FXQIFTODSA-N 0.000 description 4
- XZLLTYBONVKGLO-SDDRHHMPSA-N Gln-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XZLLTYBONVKGLO-SDDRHHMPSA-N 0.000 description 4
- ZEEPYMXTJWIMSN-GUBZILKMSA-N Gln-Lys-Ser Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ZEEPYMXTJWIMSN-GUBZILKMSA-N 0.000 description 4
- MSHXWFKYXJTLEZ-CIUDSAMLSA-N Gln-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N MSHXWFKYXJTLEZ-CIUDSAMLSA-N 0.000 description 4
- LHMWTCWZARHLPV-CIUDSAMLSA-N Gln-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N LHMWTCWZARHLPV-CIUDSAMLSA-N 0.000 description 4
- JILRMFFFCHUUTJ-ACZMJKKPSA-N Gln-Ser-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O JILRMFFFCHUUTJ-ACZMJKKPSA-N 0.000 description 4
- BETSEXMYBWCDAE-SZMVWBNQSA-N Gln-Trp-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N BETSEXMYBWCDAE-SZMVWBNQSA-N 0.000 description 4
- JRCUFCXYZLPSDZ-ACZMJKKPSA-N Glu-Asp-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O JRCUFCXYZLPSDZ-ACZMJKKPSA-N 0.000 description 4
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 4
- YGLCLCMAYUYZSG-AVGNSLFASA-N Glu-Lys-His Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 YGLCLCMAYUYZSG-AVGNSLFASA-N 0.000 description 4
- FZQLXNIMCPJVJE-YUMQZZPRSA-N Gly-Asp-Leu Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O FZQLXNIMCPJVJE-YUMQZZPRSA-N 0.000 description 4
- IXKRSKPKSLXIHN-YUMQZZPRSA-N Gly-Cys-Leu Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O IXKRSKPKSLXIHN-YUMQZZPRSA-N 0.000 description 4
- DTRUBYPMMVPQPD-YUMQZZPRSA-N Gly-Gln-Arg Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DTRUBYPMMVPQPD-YUMQZZPRSA-N 0.000 description 4
- VBOBNHSVQKKTOT-YUMQZZPRSA-N Gly-Lys-Ala Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O VBOBNHSVQKKTOT-YUMQZZPRSA-N 0.000 description 4
- FGPLUIQCSKGLTI-WDSKDSINSA-N Gly-Ser-Glu Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O FGPLUIQCSKGLTI-WDSKDSINSA-N 0.000 description 4
- ABPRMMYHROQBLY-NKWVEPMBSA-N Gly-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)CN)C(=O)O ABPRMMYHROQBLY-NKWVEPMBSA-N 0.000 description 4
- TVTZEOHWHUVYCG-KYNKHSRBSA-N Gly-Thr-Thr Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O TVTZEOHWHUVYCG-KYNKHSRBSA-N 0.000 description 4
- SYOJVRNQCXYEOV-XVKPBYJWSA-N Gly-Val-Glu Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SYOJVRNQCXYEOV-XVKPBYJWSA-N 0.000 description 4
- KSOBNUBCYHGUKH-UWVGGRQHSA-N Gly-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN KSOBNUBCYHGUKH-UWVGGRQHSA-N 0.000 description 4
- FYVHHKMHFPMBBG-GUBZILKMSA-N His-Gln-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N FYVHHKMHFPMBBG-GUBZILKMSA-N 0.000 description 4
- HVCRQRQPIIRNLY-IUCAKERBSA-N His-Gln-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)NCC(=O)O)N HVCRQRQPIIRNLY-IUCAKERBSA-N 0.000 description 4
- HZWWOGWOBQBETJ-CUJWVEQBSA-N His-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N)O HZWWOGWOBQBETJ-CUJWVEQBSA-N 0.000 description 4
- MDOBWSFNSNPENN-PMVVWTBXSA-N His-Thr-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O MDOBWSFNSNPENN-PMVVWTBXSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000622304 Homo sapiens Vascular cell adhesion protein 1 Proteins 0.000 description 4
- UKTUOMWSJPXODT-GUDRVLHUSA-N Ile-Asn-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N UKTUOMWSJPXODT-GUDRVLHUSA-N 0.000 description 4
- FADXGVVLSPPEQY-GHCJXIJMSA-N Ile-Cys-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N FADXGVVLSPPEQY-GHCJXIJMSA-N 0.000 description 4
- DFFTXLCCDFYRKD-MBLNEYKQSA-N Ile-Gly-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N DFFTXLCCDFYRKD-MBLNEYKQSA-N 0.000 description 4
- GVKKVHNRTUFCCE-BJDJZHNGSA-N Ile-Leu-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)O)N GVKKVHNRTUFCCE-BJDJZHNGSA-N 0.000 description 4
- NPAYJTAXWXJKLO-NAKRPEOUSA-N Ile-Met-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)O)N NPAYJTAXWXJKLO-NAKRPEOUSA-N 0.000 description 4
- CAHCWMVNBZJVAW-NAKRPEOUSA-N Ile-Pro-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)O)N CAHCWMVNBZJVAW-NAKRPEOUSA-N 0.000 description 4
- YKZAMJXNJUWFIK-JBDRJPRFSA-N Ile-Ser-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)O)N YKZAMJXNJUWFIK-JBDRJPRFSA-N 0.000 description 4
- JHNJNTMTZHEDLJ-NAKRPEOUSA-N Ile-Ser-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O JHNJNTMTZHEDLJ-NAKRPEOUSA-N 0.000 description 4
- FBGXMKUWQFPHFB-JBDRJPRFSA-N Ile-Ser-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N FBGXMKUWQFPHFB-JBDRJPRFSA-N 0.000 description 4
- ZLFNNVATRMCAKN-ZKWXMUAHSA-N Ile-Ser-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N ZLFNNVATRMCAKN-ZKWXMUAHSA-N 0.000 description 4
- VGSPNSSCMOHRRR-BJDJZHNGSA-N Ile-Ser-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N VGSPNSSCMOHRRR-BJDJZHNGSA-N 0.000 description 4
- DTPGSUQHUMELQB-GVARAGBVSA-N Ile-Tyr-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=C(O)C=C1 DTPGSUQHUMELQB-GVARAGBVSA-N 0.000 description 4
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 4
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 4
- 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 4
- HPBCTWSUJOGJSH-MNXVOIDGSA-N Leu-Glu-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HPBCTWSUJOGJSH-MNXVOIDGSA-N 0.000 description 4
- QVFGXCVIXXBFHO-AVGNSLFASA-N Leu-Glu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O QVFGXCVIXXBFHO-AVGNSLFASA-N 0.000 description 4
- QJUWBDPGGYVRHY-YUMQZZPRSA-N Leu-Gly-Cys Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N QJUWBDPGGYVRHY-YUMQZZPRSA-N 0.000 description 4
- BTNXKBVLWJBTNR-SRVKXCTJSA-N Leu-His-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(O)=O BTNXKBVLWJBTNR-SRVKXCTJSA-N 0.000 description 4
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 description 4
- JLWZLIQRYCTYBD-IHRRRGAJSA-N Leu-Lys-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JLWZLIQRYCTYBD-IHRRRGAJSA-N 0.000 description 4
- QWWPYKKLXWOITQ-VOAKCMCISA-N Leu-Thr-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QWWPYKKLXWOITQ-VOAKCMCISA-N 0.000 description 4
- DAYQSYGBCUKVKT-VOAKCMCISA-N Leu-Thr-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O DAYQSYGBCUKVKT-VOAKCMCISA-N 0.000 description 4
- UWKNTTJNVSYXPC-CIUDSAMLSA-N Lys-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN UWKNTTJNVSYXPC-CIUDSAMLSA-N 0.000 description 4
- BRSGXFITDXFMFF-IHRRRGAJSA-N Lys-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)N BRSGXFITDXFMFF-IHRRRGAJSA-N 0.000 description 4
- NRQRKMYZONPCTM-CIUDSAMLSA-N Lys-Asp-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O NRQRKMYZONPCTM-CIUDSAMLSA-N 0.000 description 4
- MWVUEPNEPWMFBD-SRVKXCTJSA-N Lys-Cys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCCCN MWVUEPNEPWMFBD-SRVKXCTJSA-N 0.000 description 4
- FGMHXLULNHTPID-KKUMJFAQSA-N Lys-His-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CN=CN1 FGMHXLULNHTPID-KKUMJFAQSA-N 0.000 description 4
- DIBZLYZXTSVGLN-CIUDSAMLSA-N Lys-Ser-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O DIBZLYZXTSVGLN-CIUDSAMLSA-N 0.000 description 4
- YKBSXQFZWFXFIB-VOAKCMCISA-N Lys-Thr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O YKBSXQFZWFXFIB-VOAKCMCISA-N 0.000 description 4
- VWPJQIHBBOJWDN-DCAQKATOSA-N Lys-Val-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O VWPJQIHBBOJWDN-DCAQKATOSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- FSPGBMWPNMRWDB-AVGNSLFASA-N Phe-Cys-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N FSPGBMWPNMRWDB-AVGNSLFASA-N 0.000 description 4
- AUJWXNGCAQWLEI-KBPBESRZSA-N Phe-Lys-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O AUJWXNGCAQWLEI-KBPBESRZSA-N 0.000 description 4
- WWPAHTZOWURIMR-ULQDDVLXSA-N Phe-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 WWPAHTZOWURIMR-ULQDDVLXSA-N 0.000 description 4
- LTAWNJXSRUCFAN-UNQGMJICSA-N Phe-Thr-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LTAWNJXSRUCFAN-UNQGMJICSA-N 0.000 description 4
- JHSRGEODDALISP-XVSYOHENSA-N Phe-Thr-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O JHSRGEODDALISP-XVSYOHENSA-N 0.000 description 4
- MLQVJYMFASXBGZ-IHRRRGAJSA-N Pro-Asn-Tyr Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O MLQVJYMFASXBGZ-IHRRRGAJSA-N 0.000 description 4
- LGSANCBHSMDFDY-GARJFASQSA-N Pro-Glu-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O LGSANCBHSMDFDY-GARJFASQSA-N 0.000 description 4
- PCWLNNZTBJTZRN-AVGNSLFASA-N Pro-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 PCWLNNZTBJTZRN-AVGNSLFASA-N 0.000 description 4
- GOMUXSCOIWIJFP-GUBZILKMSA-N Pro-Ser-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GOMUXSCOIWIJFP-GUBZILKMSA-N 0.000 description 4
- OWQXAJQZLWHPBH-FXQIFTODSA-N Pro-Ser-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O OWQXAJQZLWHPBH-FXQIFTODSA-N 0.000 description 4
- ZYJMLBCDFPIGNL-JYJNAYRXSA-N Pro-Tyr-Arg Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1)C(O)=O ZYJMLBCDFPIGNL-JYJNAYRXSA-N 0.000 description 4
- ZUGXSSFMTXKHJS-ZLUOBGJFSA-N Ser-Ala-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O ZUGXSSFMTXKHJS-ZLUOBGJFSA-N 0.000 description 4
- LVVBAKCGXXUHFO-ZLUOBGJFSA-N Ser-Ala-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O LVVBAKCGXXUHFO-ZLUOBGJFSA-N 0.000 description 4
- VAUMZJHYZQXZBQ-WHFBIAKZSA-N Ser-Asn-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O VAUMZJHYZQXZBQ-WHFBIAKZSA-N 0.000 description 4
- BNFVPSRLHHPQKS-WHFBIAKZSA-N Ser-Asp-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O BNFVPSRLHHPQKS-WHFBIAKZSA-N 0.000 description 4
- BPMRXBZYPGYPJN-WHFBIAKZSA-N Ser-Gly-Asn Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O BPMRXBZYPGYPJN-WHFBIAKZSA-N 0.000 description 4
- GDUZTEQRAOXYJS-SRVKXCTJSA-N Ser-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GDUZTEQRAOXYJS-SRVKXCTJSA-N 0.000 description 4
- MQUZANJDFOQOBX-SRVKXCTJSA-N Ser-Phe-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O MQUZANJDFOQOBX-SRVKXCTJSA-N 0.000 description 4
- ADJDNJCSPNFFPI-FXQIFTODSA-N Ser-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO ADJDNJCSPNFFPI-FXQIFTODSA-N 0.000 description 4
- NMZXJDSKEGFDLJ-DCAQKATOSA-N Ser-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CCCCN)C(=O)O NMZXJDSKEGFDLJ-DCAQKATOSA-N 0.000 description 4
- JURQXQBJKUHGJS-UHFFFAOYSA-N Ser-Ser-Ser-Ser Chemical compound OCC(N)C(=O)NC(CO)C(=O)NC(CO)C(=O)NC(CO)C(O)=O JURQXQBJKUHGJS-UHFFFAOYSA-N 0.000 description 4
- PCJLFYBAQZQOFE-KATARQTJSA-N Ser-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N)O PCJLFYBAQZQOFE-KATARQTJSA-N 0.000 description 4
- BEBVVQPDSHHWQL-NRPADANISA-N Ser-Val-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O BEBVVQPDSHHWQL-NRPADANISA-N 0.000 description 4
- 230000006052 T cell proliferation Effects 0.000 description 4
- LIXBDERDAGNVAV-XKBZYTNZSA-N Thr-Gln-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O LIXBDERDAGNVAV-XKBZYTNZSA-N 0.000 description 4
- MSIYNSBKKVMGFO-BHNWBGBOSA-N Thr-Gly-Pro Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N1CCC[C@@H]1C(=O)O)N)O MSIYNSBKKVMGFO-BHNWBGBOSA-N 0.000 description 4
- SXAGUVRFGJSFKC-ZEILLAHLSA-N Thr-His-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SXAGUVRFGJSFKC-ZEILLAHLSA-N 0.000 description 4
- KPNSNVTUVKSBFL-ZJDVBMNYSA-N Thr-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KPNSNVTUVKSBFL-ZJDVBMNYSA-N 0.000 description 4
- JMBRNXUOLJFURW-BEAPCOKYSA-N Thr-Phe-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N)O JMBRNXUOLJFURW-BEAPCOKYSA-N 0.000 description 4
- XKWABWFMQXMUMT-HJGDQZAQSA-N Thr-Pro-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XKWABWFMQXMUMT-HJGDQZAQSA-N 0.000 description 4
- HUPLKEHTTQBXSC-YJRXYDGGSA-N Thr-Ser-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HUPLKEHTTQBXSC-YJRXYDGGSA-N 0.000 description 4
- LECUEEHKUFYOOV-ZJDVBMNYSA-N Thr-Thr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](N)[C@@H](C)O LECUEEHKUFYOOV-ZJDVBMNYSA-N 0.000 description 4
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 4
- BKVICMPZWRNWOC-RHYQMDGZSA-N Thr-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O BKVICMPZWRNWOC-RHYQMDGZSA-N 0.000 description 4
- VIWQOOBRKCGSDK-RYQLBKOJSA-N Trp-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)O VIWQOOBRKCGSDK-RYQLBKOJSA-N 0.000 description 4
- UKINEYBQXPMOJO-UBHSHLNASA-N Trp-Asn-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N UKINEYBQXPMOJO-UBHSHLNASA-N 0.000 description 4
- UDCHKDYNMRJYMI-QEJZJMRPSA-N Trp-Glu-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O UDCHKDYNMRJYMI-QEJZJMRPSA-N 0.000 description 4
- XGFGVFMXDXALEV-XIRDDKMYSA-N Trp-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N XGFGVFMXDXALEV-XIRDDKMYSA-N 0.000 description 4
- ARKBYVBCEOWRNR-UBHSHLNASA-N Trp-Ser-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O ARKBYVBCEOWRNR-UBHSHLNASA-N 0.000 description 4
- QJBWZNTWJSZUOY-UWJYBYFXSA-N Tyr-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N QJBWZNTWJSZUOY-UWJYBYFXSA-N 0.000 description 4
- NSGZILIDHCIZAM-KKUMJFAQSA-N Tyr-Leu-Ser Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N NSGZILIDHCIZAM-KKUMJFAQSA-N 0.000 description 4
- GZUIDWDVMWZSMI-KKUMJFAQSA-N Tyr-Lys-Cys Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CS)C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GZUIDWDVMWZSMI-KKUMJFAQSA-N 0.000 description 4
- BIWVVOHTKDLRMP-ULQDDVLXSA-N Tyr-Pro-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O BIWVVOHTKDLRMP-ULQDDVLXSA-N 0.000 description 4
- RZAGEHHVNYESNR-RNXOBYDBSA-N Tyr-Trp-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RZAGEHHVNYESNR-RNXOBYDBSA-N 0.000 description 4
- RMRFSFXLFWWAJZ-HJOGWXRNSA-N Tyr-Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 RMRFSFXLFWWAJZ-HJOGWXRNSA-N 0.000 description 4
- 108010064997 VPY tripeptide Proteins 0.000 description 4
- CGGVNFJRZJUVAE-BYULHYEWSA-N Val-Asp-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N CGGVNFJRZJUVAE-BYULHYEWSA-N 0.000 description 4
- XKVXSCHXGJOQND-ZOBUZTSGSA-N Val-Asp-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N XKVXSCHXGJOQND-ZOBUZTSGSA-N 0.000 description 4
- LHADRQBREKTRLR-DCAQKATOSA-N Val-Cys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)N LHADRQBREKTRLR-DCAQKATOSA-N 0.000 description 4
- AGKDVLSDNSTLFA-UMNHJUIQSA-N Val-Gln-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N AGKDVLSDNSTLFA-UMNHJUIQSA-N 0.000 description 4
- ROLGIBMFNMZANA-GVXVVHGQSA-N Val-Glu-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)N ROLGIBMFNMZANA-GVXVVHGQSA-N 0.000 description 4
- WDIGUPHXPBMODF-UMNHJUIQSA-N Val-Glu-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N WDIGUPHXPBMODF-UMNHJUIQSA-N 0.000 description 4
- KZKMBGXCNLPYKD-YEPSODPASA-N Val-Gly-Thr Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O KZKMBGXCNLPYKD-YEPSODPASA-N 0.000 description 4
- OVBMCNDKCWAXMZ-NAKRPEOUSA-N Val-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](C(C)C)N OVBMCNDKCWAXMZ-NAKRPEOUSA-N 0.000 description 4
- DIOSYUIWOQCXNR-ONGXEEELSA-N Val-Lys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O DIOSYUIWOQCXNR-ONGXEEELSA-N 0.000 description 4
- FMQGYTMERWBMSI-HJWJTTGWSA-N Val-Phe-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C(C)C)N FMQGYTMERWBMSI-HJWJTTGWSA-N 0.000 description 4
- HJSLDXZAZGFPDK-ULQDDVLXSA-N Val-Phe-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C(C)C)N HJSLDXZAZGFPDK-ULQDDVLXSA-N 0.000 description 4
- GBIUHAYJGWVNLN-AEJSXWLSSA-N Val-Ser-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N GBIUHAYJGWVNLN-AEJSXWLSSA-N 0.000 description 4
- GBIUHAYJGWVNLN-UHFFFAOYSA-N Val-Ser-Pro Natural products CC(C)C(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O GBIUHAYJGWVNLN-UHFFFAOYSA-N 0.000 description 4
- NZYNRRGJJVSSTJ-GUBZILKMSA-N Val-Ser-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NZYNRRGJJVSSTJ-GUBZILKMSA-N 0.000 description 4
- UVHFONIHVHLDDQ-IFFSRLJSSA-N Val-Thr-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O UVHFONIHVHLDDQ-IFFSRLJSSA-N 0.000 description 4
- 108010041407 alanylaspartic acid Proteins 0.000 description 4
- 108010047495 alanylglycine Proteins 0.000 description 4
- 108010038850 arginyl-isoleucyl-tyrosine Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000022534 cell killing Effects 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 108010077435 glycyl-phenylalanyl-glycine Proteins 0.000 description 4
- 108010084389 glycyltryptophan Proteins 0.000 description 4
- 108010018006 histidylserine Proteins 0.000 description 4
- 108010024607 phenylalanylalanine Proteins 0.000 description 4
- 239000008055 phosphate buffer solution Substances 0.000 description 4
- 108010025488 pinealon Proteins 0.000 description 4
- 108010053725 prolylvaline Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 108010017949 tyrosyl-glycyl-glycine Proteins 0.000 description 4
- 108010020532 tyrosyl-proline Proteins 0.000 description 4
- 108010009962 valyltyrosine Proteins 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- DWINFPQUSSHSFS-UVBJJODRSA-N Ala-Arg-Trp Chemical compound N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)O DWINFPQUSSHSFS-UVBJJODRSA-N 0.000 description 3
- DPNZTBKGAUAZQU-DLOVCJGASA-N Ala-Leu-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N DPNZTBKGAUAZQU-DLOVCJGASA-N 0.000 description 3
- REAQAWSENITKJL-DDWPSWQVSA-N Ala-Met-Asp-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O REAQAWSENITKJL-DDWPSWQVSA-N 0.000 description 3
- WQLDNOCHHRISMS-NAKRPEOUSA-N Ala-Pro-Ile Chemical compound [H]N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WQLDNOCHHRISMS-NAKRPEOUSA-N 0.000 description 3
- BTRULDJUUVGRNE-DCAQKATOSA-N Ala-Pro-Lys Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(O)=O BTRULDJUUVGRNE-DCAQKATOSA-N 0.000 description 3
- QDGMZAOSMNGBLP-MRFFXTKBSA-N Ala-Trp-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)N QDGMZAOSMNGBLP-MRFFXTKBSA-N 0.000 description 3
- OTOXOKCIIQLMFH-KZVJFYERSA-N Arg-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N OTOXOKCIIQLMFH-KZVJFYERSA-N 0.000 description 3
- CPSHGRGUPZBMOK-CIUDSAMLSA-N Arg-Asn-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O CPSHGRGUPZBMOK-CIUDSAMLSA-N 0.000 description 3
- UVTGNSWSRSCPLP-UHFFFAOYSA-N Arg-Tyr Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccc(O)cc1)C(=O)O UVTGNSWSRSCPLP-UHFFFAOYSA-N 0.000 description 3
- PCKRJVZAQZWNKM-WHFBIAKZSA-N Asn-Asn-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O PCKRJVZAQZWNKM-WHFBIAKZSA-N 0.000 description 3
- BVLIJXXSXBUGEC-SRVKXCTJSA-N Asn-Asn-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BVLIJXXSXBUGEC-SRVKXCTJSA-N 0.000 description 3
- SRUUBQBAVNQZGJ-LAEOZQHASA-N Asn-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)N SRUUBQBAVNQZGJ-LAEOZQHASA-N 0.000 description 3
- OLVIPTLKNSAYRJ-YUMQZZPRSA-N Asn-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N OLVIPTLKNSAYRJ-YUMQZZPRSA-N 0.000 description 3
- WQLJRNRLHWJIRW-KKUMJFAQSA-N Asn-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)N)N)O WQLJRNRLHWJIRW-KKUMJFAQSA-N 0.000 description 3
- RCFGLXMZDYNRSC-CIUDSAMLSA-N Asn-Lys-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O RCFGLXMZDYNRSC-CIUDSAMLSA-N 0.000 description 3
- ANRZCQXIXGDXLR-CWRNSKLLSA-N Asn-Trp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CC(=O)N)N)C(=O)O ANRZCQXIXGDXLR-CWRNSKLLSA-N 0.000 description 3
- KBQOUDLMWYWXNP-YDHLFZDLSA-N Asn-Val-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KBQOUDLMWYWXNP-YDHLFZDLSA-N 0.000 description 3
- KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 3
- VAWNQIGQPUOPQW-ACZMJKKPSA-N Asp-Glu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VAWNQIGQPUOPQW-ACZMJKKPSA-N 0.000 description 3
- WSGVTKZFVJSJOG-RCOVLWMOSA-N Asp-Gly-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O WSGVTKZFVJSJOG-RCOVLWMOSA-N 0.000 description 3
- HOBNTSHITVVNBN-ZPFDUUQYSA-N Asp-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N HOBNTSHITVVNBN-ZPFDUUQYSA-N 0.000 description 3
- SPKCGKRUYKMDHP-GUDRVLHUSA-N Asp-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N SPKCGKRUYKMDHP-GUDRVLHUSA-N 0.000 description 3
- DONWIPDSZZJHHK-HJGDQZAQSA-N Asp-Lys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N)O DONWIPDSZZJHHK-HJGDQZAQSA-N 0.000 description 3
- YUELDQUPTAYEGM-XIRDDKMYSA-N Asp-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)O)N YUELDQUPTAYEGM-XIRDDKMYSA-N 0.000 description 3
- NJLLRXWFPQQPHV-SRVKXCTJSA-N Asp-Tyr-Asn 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](CC(N)=O)C(O)=O NJLLRXWFPQQPHV-SRVKXCTJSA-N 0.000 description 3
- 108010062580 Concanavalin A Proteins 0.000 description 3
- BYALSSDCQYHKMY-XGEHTFHBSA-N Cys-Arg-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N)O BYALSSDCQYHKMY-XGEHTFHBSA-N 0.000 description 3
- BVFQOPGFOQVZTE-ACZMJKKPSA-N Cys-Gln-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O BVFQOPGFOQVZTE-ACZMJKKPSA-N 0.000 description 3
- NIXHTNJAGGFBAW-CIUDSAMLSA-N Cys-Lys-Ser Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CS)N NIXHTNJAGGFBAW-CIUDSAMLSA-N 0.000 description 3
- SMEYEQDCCBHTEF-FXQIFTODSA-N Cys-Pro-Ala Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O SMEYEQDCCBHTEF-FXQIFTODSA-N 0.000 description 3
- KSMSFCBQBQPFAD-GUBZILKMSA-N Cys-Pro-Pro Chemical compound SC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 KSMSFCBQBQPFAD-GUBZILKMSA-N 0.000 description 3
- NDNZRWUDUMTITL-FXQIFTODSA-N Cys-Ser-Val Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NDNZRWUDUMTITL-FXQIFTODSA-N 0.000 description 3
- ALTQTAKGRFLRLR-GUBZILKMSA-N Cys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N ALTQTAKGRFLRLR-GUBZILKMSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- DHNWZLGBTPUTQQ-QEJZJMRPSA-N Gln-Asp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N DHNWZLGBTPUTQQ-QEJZJMRPSA-N 0.000 description 3
- NVEASDQHBRZPSU-BQBZGAKWSA-N Gln-Gln-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O NVEASDQHBRZPSU-BQBZGAKWSA-N 0.000 description 3
- OOLCSQQPSLIETN-JYJNAYRXSA-N Gln-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CCC(=O)N)N)O OOLCSQQPSLIETN-JYJNAYRXSA-N 0.000 description 3
- WLRYGVYQFXRJDA-DCAQKATOSA-N Gln-Pro-Pro Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 WLRYGVYQFXRJDA-DCAQKATOSA-N 0.000 description 3
- VNTGPISAOMAXRK-CIUDSAMLSA-N Gln-Pro-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O VNTGPISAOMAXRK-CIUDSAMLSA-N 0.000 description 3
- GHAXJVNBAKGWEJ-AVGNSLFASA-N Gln-Ser-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GHAXJVNBAKGWEJ-AVGNSLFASA-N 0.000 description 3
- HPBKQFJXDUVNQV-FHWLQOOXSA-N Gln-Tyr-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O HPBKQFJXDUVNQV-FHWLQOOXSA-N 0.000 description 3
- ZMXZGYLINVNTKH-DZKIICNBSA-N Gln-Val-Phe Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZMXZGYLINVNTKH-DZKIICNBSA-N 0.000 description 3
- FITIQFSXXBKFFM-NRPADANISA-N Gln-Val-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O FITIQFSXXBKFFM-NRPADANISA-N 0.000 description 3
- AVZHGSCDKIQZPQ-CIUDSAMLSA-N Glu-Arg-Ala Chemical compound C[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CCC(O)=O)C(O)=O AVZHGSCDKIQZPQ-CIUDSAMLSA-N 0.000 description 3
- DYFJZDDQPNIPAB-NHCYSSNCSA-N Glu-Arg-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O DYFJZDDQPNIPAB-NHCYSSNCSA-N 0.000 description 3
- IESFZVCAVACGPH-PEFMBERDSA-N Glu-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O IESFZVCAVACGPH-PEFMBERDSA-N 0.000 description 3
- WATXSTJXNBOHKD-LAEOZQHASA-N Glu-Asp-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O WATXSTJXNBOHKD-LAEOZQHASA-N 0.000 description 3
- ZZIFPJZQHRJERU-WDSKDSINSA-N Glu-Cys-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O ZZIFPJZQHRJERU-WDSKDSINSA-N 0.000 description 3
- HVYWQYLBVXMXSV-GUBZILKMSA-N Glu-Leu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HVYWQYLBVXMXSV-GUBZILKMSA-N 0.000 description 3
- DNPCBMNFQVTHMA-DCAQKATOSA-N Glu-Leu-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O DNPCBMNFQVTHMA-DCAQKATOSA-N 0.000 description 3
- IVGJYOOGJLFKQE-AVGNSLFASA-N Glu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N IVGJYOOGJLFKQE-AVGNSLFASA-N 0.000 description 3
- NJCALAAIGREHDR-WDCWCFNPSA-N Glu-Leu-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NJCALAAIGREHDR-WDCWCFNPSA-N 0.000 description 3
- 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 3
- SUIAHERNFYRBDZ-GVXVVHGQSA-N Glu-Lys-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O SUIAHERNFYRBDZ-GVXVVHGQSA-N 0.000 description 3
- AAJHGGDRKHYSDH-GUBZILKMSA-N Glu-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O AAJHGGDRKHYSDH-GUBZILKMSA-N 0.000 description 3
- ZALGPUWUVHOGAE-GVXVVHGQSA-N Glu-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZALGPUWUVHOGAE-GVXVVHGQSA-N 0.000 description 3
- KRRMJKMGWWXWDW-STQMWFEESA-N Gly-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KRRMJKMGWWXWDW-STQMWFEESA-N 0.000 description 3
- QGZSAHIZRQHCEQ-QWRGUYRKSA-N Gly-Asp-Tyr Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QGZSAHIZRQHCEQ-QWRGUYRKSA-N 0.000 description 3
- UFPXDFOYHVEIPI-BYPYZUCNSA-N Gly-Gly-Asp Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O UFPXDFOYHVEIPI-BYPYZUCNSA-N 0.000 description 3
- QPTNELDXWKRIFX-YFKPBYRVSA-N Gly-Gly-Gln Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O QPTNELDXWKRIFX-YFKPBYRVSA-N 0.000 description 3
- XMPXVJIDADUOQB-RCOVLWMOSA-N Gly-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C([O-])=O)NC(=O)CNC(=O)C[NH3+] XMPXVJIDADUOQB-RCOVLWMOSA-N 0.000 description 3
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 3
- BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 3
- FQKKPCWTZZEDIC-XPUUQOCRSA-N Gly-His-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 FQKKPCWTZZEDIC-XPUUQOCRSA-N 0.000 description 3
- GMTXWRIDLGTVFC-IUCAKERBSA-N Gly-Lys-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GMTXWRIDLGTVFC-IUCAKERBSA-N 0.000 description 3
- MTBIKIMYHUWBRX-QWRGUYRKSA-N Gly-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN MTBIKIMYHUWBRX-QWRGUYRKSA-N 0.000 description 3
- QAMMIGULQSIRCD-IRXDYDNUSA-N Gly-Phe-Tyr Chemical compound C([C@H](NC(=O)C[NH3+])C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C([O-])=O)C1=CC=CC=C1 QAMMIGULQSIRCD-IRXDYDNUSA-N 0.000 description 3
- GGLIDLCEPDHEJO-BQBZGAKWSA-N Gly-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)CN GGLIDLCEPDHEJO-BQBZGAKWSA-N 0.000 description 3
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 3
- JSLVAHYTAJJEQH-QWRGUYRKSA-N Gly-Ser-Phe Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JSLVAHYTAJJEQH-QWRGUYRKSA-N 0.000 description 3
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 3
- MAABHGXCIBEYQR-XVYDVKMFSA-N His-Asn-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CN=CN1)N MAABHGXCIBEYQR-XVYDVKMFSA-N 0.000 description 3
- HIAHVKLTHNOENC-HGNGGELXSA-N His-Glu-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HIAHVKLTHNOENC-HGNGGELXSA-N 0.000 description 3
- STOOMQFEJUVAKR-KKUMJFAQSA-N His-His-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)C1=CNC=N1 STOOMQFEJUVAKR-KKUMJFAQSA-N 0.000 description 3
- NCSIQAFSIPHVAN-IUKAMOBKSA-N Ile-Asn-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N NCSIQAFSIPHVAN-IUKAMOBKSA-N 0.000 description 3
- WNQKUUQIVDDAFA-ZPFDUUQYSA-N Ile-Gln-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCSC)C(=O)O)N WNQKUUQIVDDAFA-ZPFDUUQYSA-N 0.000 description 3
- RMNMUUCYTMLWNA-ZPFDUUQYSA-N Ile-Lys-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RMNMUUCYTMLWNA-ZPFDUUQYSA-N 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 3
- HXWALXSAVBLTPK-NUTKFTJISA-N Leu-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(C)C)N HXWALXSAVBLTPK-NUTKFTJISA-N 0.000 description 3
- OIARJGNVARWKFP-YUMQZZPRSA-N Leu-Asn-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O OIARJGNVARWKFP-YUMQZZPRSA-N 0.000 description 3
- USTCFDAQCLDPBD-XIRDDKMYSA-N Leu-Asn-Trp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N USTCFDAQCLDPBD-XIRDDKMYSA-N 0.000 description 3
- QLQHWWCSCLZUMA-KKUMJFAQSA-N Leu-Asp-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QLQHWWCSCLZUMA-KKUMJFAQSA-N 0.000 description 3
- VQPPIMUZCZCOIL-GUBZILKMSA-N Leu-Gln-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O VQPPIMUZCZCOIL-GUBZILKMSA-N 0.000 description 3
- CQGSYZCULZMEDE-SRVKXCTJSA-N Leu-Gln-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O CQGSYZCULZMEDE-SRVKXCTJSA-N 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
- BKTXKJMNTSMJDQ-AVGNSLFASA-N Leu-His-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N BKTXKJMNTSMJDQ-AVGNSLFASA-N 0.000 description 3
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 3
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 3
- AUNMOHYWTAPQLA-XUXIUFHCSA-N Leu-Met-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AUNMOHYWTAPQLA-XUXIUFHCSA-N 0.000 description 3
- UHNQRAFSEBGZFZ-YESZJQIVSA-N Leu-Phe-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N UHNQRAFSEBGZFZ-YESZJQIVSA-N 0.000 description 3
- WMIOEVKKYIMVKI-DCAQKATOSA-N Leu-Pro-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WMIOEVKKYIMVKI-DCAQKATOSA-N 0.000 description 3
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 3
- IRMLZWSRWSGTOP-CIUDSAMLSA-N Leu-Ser-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O IRMLZWSRWSGTOP-CIUDSAMLSA-N 0.000 description 3
- KZZCOWMDDXDKSS-CIUDSAMLSA-N Leu-Ser-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KZZCOWMDDXDKSS-CIUDSAMLSA-N 0.000 description 3
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 3
- SBANPBVRHYIMRR-GARJFASQSA-N Leu-Ser-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N SBANPBVRHYIMRR-GARJFASQSA-N 0.000 description 3
- AEDWWMMHUGYIFD-HJGDQZAQSA-N Leu-Thr-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O AEDWWMMHUGYIFD-HJGDQZAQSA-N 0.000 description 3
- LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 description 3
- WSXTWLJHTLRFLW-SRVKXCTJSA-N Lys-Ala-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O WSXTWLJHTLRFLW-SRVKXCTJSA-N 0.000 description 3
- YKIRNDPUWONXQN-GUBZILKMSA-N Lys-Asn-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YKIRNDPUWONXQN-GUBZILKMSA-N 0.000 description 3
- PXHCFKXNSBJSTQ-KKUMJFAQSA-N Lys-Asn-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N)O PXHCFKXNSBJSTQ-KKUMJFAQSA-N 0.000 description 3
- KWUKZRFFKPLUPE-HJGDQZAQSA-N Lys-Asp-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KWUKZRFFKPLUPE-HJGDQZAQSA-N 0.000 description 3
- DFXQCCBKGUNYGG-GUBZILKMSA-N Lys-Gln-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCCN DFXQCCBKGUNYGG-GUBZILKMSA-N 0.000 description 3
- ODUQLUADRKMHOZ-JYJNAYRXSA-N Lys-Glu-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N)O ODUQLUADRKMHOZ-JYJNAYRXSA-N 0.000 description 3
- LCMWVZLBCUVDAZ-IUCAKERBSA-N Lys-Gly-Glu Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CCC([O-])=O LCMWVZLBCUVDAZ-IUCAKERBSA-N 0.000 description 3
- OIQSIMFSVLLWBX-VOAKCMCISA-N Lys-Leu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OIQSIMFSVLLWBX-VOAKCMCISA-N 0.000 description 3
- QQPSCXKFDSORFT-IHRRRGAJSA-N Lys-Lys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN QQPSCXKFDSORFT-IHRRRGAJSA-N 0.000 description 3
- ODTZHNZPINULEU-KKUMJFAQSA-N Lys-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N ODTZHNZPINULEU-KKUMJFAQSA-N 0.000 description 3
- SBQDRNOLGSYHQA-YUMQZZPRSA-N Lys-Ser-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SBQDRNOLGSYHQA-YUMQZZPRSA-N 0.000 description 3
- VHTOGMKQXXJOHG-RHYQMDGZSA-N Lys-Thr-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O VHTOGMKQXXJOHG-RHYQMDGZSA-N 0.000 description 3
- SUZVLFWOCKHWET-CQDKDKBSSA-N Lys-Tyr-Ala 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(O)=O SUZVLFWOCKHWET-CQDKDKBSSA-N 0.000 description 3
- UYAKZHGIPRCGPF-CIUDSAMLSA-N Met-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)N UYAKZHGIPRCGPF-CIUDSAMLSA-N 0.000 description 3
- FWAHLGXNBLWIKB-NAKRPEOUSA-N Met-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCSC FWAHLGXNBLWIKB-NAKRPEOUSA-N 0.000 description 3
- RUTZUJXAVNWLQP-BVSLBCMMSA-N Met-Tyr-Trp Chemical compound C([C@H](NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=C(O)C=C1 RUTZUJXAVNWLQP-BVSLBCMMSA-N 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 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 3
- CUMXHKAOHNWRFQ-BZSNNMDCSA-N Phe-Asp-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 CUMXHKAOHNWRFQ-BZSNNMDCSA-N 0.000 description 3
- 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 3
- XDMMOISUAHXXFD-SRVKXCTJSA-N Phe-Ser-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O XDMMOISUAHXXFD-SRVKXCTJSA-N 0.000 description 3
- BPIFSOUEUYDJRM-DCPHZVHLSA-N Phe-Trp-Ala Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(O)=O)C1=CC=CC=C1 BPIFSOUEUYDJRM-DCPHZVHLSA-N 0.000 description 3
- OOLOTUZJUBOMAX-GUBZILKMSA-N Pro-Ala-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O OOLOTUZJUBOMAX-GUBZILKMSA-N 0.000 description 3
- ZSKJPKFTPQCPIH-RCWTZXSCSA-N Pro-Arg-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZSKJPKFTPQCPIH-RCWTZXSCSA-N 0.000 description 3
- JARJPEMLQAWNBR-GUBZILKMSA-N Pro-Asp-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JARJPEMLQAWNBR-GUBZILKMSA-N 0.000 description 3
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 3
- VPEVBAUSTBWQHN-NHCYSSNCSA-N Pro-Glu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O VPEVBAUSTBWQHN-NHCYSSNCSA-N 0.000 description 3
- KWMUAKQOVYCQJQ-ZPFDUUQYSA-N Pro-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@@H]1CCCN1 KWMUAKQOVYCQJQ-ZPFDUUQYSA-N 0.000 description 3
- ULWBBFKQBDNGOY-RWMBFGLXSA-N Pro-Lys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@@H]2C(=O)O ULWBBFKQBDNGOY-RWMBFGLXSA-N 0.000 description 3
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 3
- UEJYSALTSUZXFV-SRVKXCTJSA-N Rigin Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O UEJYSALTSUZXFV-SRVKXCTJSA-N 0.000 description 3
- BTKUIVBNGBFTTP-WHFBIAKZSA-N Ser-Ala-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NCC(O)=O BTKUIVBNGBFTTP-WHFBIAKZSA-N 0.000 description 3
- QVOGDCQNGLBNCR-FXQIFTODSA-N Ser-Arg-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O QVOGDCQNGLBNCR-FXQIFTODSA-N 0.000 description 3
- VGNYHOBZJKWRGI-CIUDSAMLSA-N Ser-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO VGNYHOBZJKWRGI-CIUDSAMLSA-N 0.000 description 3
- MOVJSUIKUNCVMG-ZLUOBGJFSA-N Ser-Cys-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O)N)O MOVJSUIKUNCVMG-ZLUOBGJFSA-N 0.000 description 3
- KJMOINFQVCCSDX-XKBZYTNZSA-N Ser-Gln-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KJMOINFQVCCSDX-XKBZYTNZSA-N 0.000 description 3
- GZFAWAQTEYDKII-YUMQZZPRSA-N Ser-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO GZFAWAQTEYDKII-YUMQZZPRSA-N 0.000 description 3
- OQPNSDWGAMFJNU-QWRGUYRKSA-N Ser-Gly-Tyr Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OQPNSDWGAMFJNU-QWRGUYRKSA-N 0.000 description 3
- HMRAQFJFTOLDKW-GUBZILKMSA-N Ser-His-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O HMRAQFJFTOLDKW-GUBZILKMSA-N 0.000 description 3
- FUMGHWDRRFCKEP-CIUDSAMLSA-N Ser-Leu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O FUMGHWDRRFCKEP-CIUDSAMLSA-N 0.000 description 3
- HDBOEVPDIDDEPC-CIUDSAMLSA-N Ser-Lys-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O HDBOEVPDIDDEPC-CIUDSAMLSA-N 0.000 description 3
- PJIQEIFXZPCWOJ-FXQIFTODSA-N Ser-Pro-Asp Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O PJIQEIFXZPCWOJ-FXQIFTODSA-N 0.000 description 3
- HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 3
- STIAINRLUUKYKM-WFBYXXMGSA-N Ser-Trp-Ala Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CO)=CNC2=C1 STIAINRLUUKYKM-WFBYXXMGSA-N 0.000 description 3
- FGBLCMLXHRPVOF-IHRRRGAJSA-N Ser-Tyr-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FGBLCMLXHRPVOF-IHRRRGAJSA-N 0.000 description 3
- JZRYFUGREMECBH-XPUUQOCRSA-N Ser-Val-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O JZRYFUGREMECBH-XPUUQOCRSA-N 0.000 description 3
- RCOUFINCYASMDN-GUBZILKMSA-N Ser-Val-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O RCOUFINCYASMDN-GUBZILKMSA-N 0.000 description 3
- PXQUBKWZENPDGE-CIQUZCHMSA-N Thr-Ala-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)N PXQUBKWZENPDGE-CIQUZCHMSA-N 0.000 description 3
- UNURFMVMXLENAZ-KJEVXHAQSA-N Thr-Arg-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O UNURFMVMXLENAZ-KJEVXHAQSA-N 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
- LAFLAXHTDVNVEL-WDCWCFNPSA-N Thr-Gln-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N)O LAFLAXHTDVNVEL-WDCWCFNPSA-N 0.000 description 3
- AQAMPXBRJJWPNI-JHEQGTHGSA-N Thr-Gly-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AQAMPXBRJJWPNI-JHEQGTHGSA-N 0.000 description 3
- PAXANSWUSVPFNK-IUKAMOBKSA-N Thr-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N PAXANSWUSVPFNK-IUKAMOBKSA-N 0.000 description 3
- FIFDDJFLNVAVMS-RHYQMDGZSA-N Thr-Leu-Met Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O FIFDDJFLNVAVMS-RHYQMDGZSA-N 0.000 description 3
- IJVNLNRVDUTWDD-MEYUZBJRSA-N Thr-Leu-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IJVNLNRVDUTWDD-MEYUZBJRSA-N 0.000 description 3
- SPVHQURZJCUDQC-VOAKCMCISA-N Thr-Lys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O SPVHQURZJCUDQC-VOAKCMCISA-N 0.000 description 3
- MROIJTGJGIDEEJ-RCWTZXSCSA-N Thr-Pro-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 MROIJTGJGIDEEJ-RCWTZXSCSA-N 0.000 description 3
- IEZVHOULSUULHD-XGEHTFHBSA-N Thr-Ser-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O IEZVHOULSUULHD-XGEHTFHBSA-N 0.000 description 3
- JAWUQFCGNVEDRN-MEYUZBJRSA-N Thr-Tyr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O JAWUQFCGNVEDRN-MEYUZBJRSA-N 0.000 description 3
- DIHPMRTXPYMDJZ-KAOXEZKKSA-N Thr-Tyr-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N)O DIHPMRTXPYMDJZ-KAOXEZKKSA-N 0.000 description 3
- JVTHMUDOKPQBOT-NSHDSACASA-N Trp-Gly-Gly Chemical compound C1=CC=C2C(C[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O)=CNC2=C1 JVTHMUDOKPQBOT-NSHDSACASA-N 0.000 description 3
- SSSDKJMQMZTMJP-BVSLBCMMSA-N Trp-Tyr-Val Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CC=C(O)C=C1 SSSDKJMQMZTMJP-BVSLBCMMSA-N 0.000 description 3
- UGFOSENEZHEQKX-PJODQICGSA-N Trp-Val-Ala Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(=O)N[C@@H](C)C(O)=O UGFOSENEZHEQKX-PJODQICGSA-N 0.000 description 3
- AKXBNSZMYAOGLS-STQMWFEESA-N Tyr-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AKXBNSZMYAOGLS-STQMWFEESA-N 0.000 description 3
- DKKHULUSOSWGHS-UWJYBYFXSA-N Tyr-Asn-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N DKKHULUSOSWGHS-UWJYBYFXSA-N 0.000 description 3
- YGKVNUAKYPGORG-AVGNSLFASA-N Tyr-Asp-Glu 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](CCC(O)=O)C(O)=O YGKVNUAKYPGORG-AVGNSLFASA-N 0.000 description 3
- JWHOIHCOHMZSAR-QWRGUYRKSA-N Tyr-Asp-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 JWHOIHCOHMZSAR-QWRGUYRKSA-N 0.000 description 3
- BVOCLAPFOBSJHR-KKUMJFAQSA-N Tyr-Cys-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O BVOCLAPFOBSJHR-KKUMJFAQSA-N 0.000 description 3
- GULIUBBXCYPDJU-CQDKDKBSSA-N Tyr-Leu-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 GULIUBBXCYPDJU-CQDKDKBSSA-N 0.000 description 3
- NVZVJIUDICCMHZ-BZSNNMDCSA-N Tyr-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O NVZVJIUDICCMHZ-BZSNNMDCSA-N 0.000 description 3
- AGDDLOQMXUQPDY-BZSNNMDCSA-N Tyr-Tyr-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O AGDDLOQMXUQPDY-BZSNNMDCSA-N 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- PVPAOIGJYHVWBT-KKHAAJSZSA-N Val-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N)O PVPAOIGJYHVWBT-KKHAAJSZSA-N 0.000 description 3
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 3
- PWRITNSESKQTPW-NRPADANISA-N Val-Gln-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N PWRITNSESKQTPW-NRPADANISA-N 0.000 description 3
- SZTTYWIUCGSURQ-AUTRQRHGSA-N Val-Glu-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SZTTYWIUCGSURQ-AUTRQRHGSA-N 0.000 description 3
- UEHRGZCNLSWGHK-DLOVCJGASA-N Val-Glu-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UEHRGZCNLSWGHK-DLOVCJGASA-N 0.000 description 3
- OACSGBOREVRSME-NHCYSSNCSA-N Val-His-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(O)=O OACSGBOREVRSME-NHCYSSNCSA-N 0.000 description 3
- XTDDIVQWDXMRJL-IHRRRGAJSA-N Val-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N XTDDIVQWDXMRJL-IHRRRGAJSA-N 0.000 description 3
- AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 3
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 3
- SBJCTAZFSZXWSR-AVGNSLFASA-N Val-Met-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N SBJCTAZFSZXWSR-AVGNSLFASA-N 0.000 description 3
- UJMCYJKPDFQLHX-XGEHTFHBSA-N Val-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N)O UJMCYJKPDFQLHX-XGEHTFHBSA-N 0.000 description 3
- BGTDGENDNWGMDQ-KJEVXHAQSA-N Val-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C(C)C)N)O BGTDGENDNWGMDQ-KJEVXHAQSA-N 0.000 description 3
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 108010078326 glycyl-glycyl-valine Proteins 0.000 description 3
- 108010077515 glycylproline Proteins 0.000 description 3
- 108010028295 histidylhistidine Proteins 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 108010053037 kyotorphin Proteins 0.000 description 3
- 108010091871 leucylmethionine Proteins 0.000 description 3
- 108010057952 lysyl-phenylalanyl-lysine Proteins 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 108010073101 phenylalanylleucine Proteins 0.000 description 3
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 3
- 108010079317 prolyl-tyrosine Proteins 0.000 description 3
- 108010071207 serylmethionine Proteins 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 108010033670 threonyl-aspartyl-tyrosine Proteins 0.000 description 3
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 2
- SKHCUBQVZJHOFM-NAKRPEOUSA-N Ala-Arg-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O SKHCUBQVZJHOFM-NAKRPEOUSA-N 0.000 description 2
- YWWATNIVMOCSAV-UBHSHLNASA-N Ala-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YWWATNIVMOCSAV-UBHSHLNASA-N 0.000 description 2
- WYPUMLRSQMKIJU-BPNCWPANSA-N Ala-Arg-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WYPUMLRSQMKIJU-BPNCWPANSA-N 0.000 description 2
- NHLAEBFGWPXFGI-WHFBIAKZSA-N Ala-Gly-Asn Chemical compound C[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)N)C(=O)O)N NHLAEBFGWPXFGI-WHFBIAKZSA-N 0.000 description 2
- CFPQUJZTLUQUTJ-HTFCKZLJSA-N Ala-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)N CFPQUJZTLUQUTJ-HTFCKZLJSA-N 0.000 description 2
- RZZMZYZXNJRPOJ-BJDJZHNGSA-N Ala-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](C)N RZZMZYZXNJRPOJ-BJDJZHNGSA-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
- SDZRIBWEVVRDQI-CIUDSAMLSA-N Ala-Lys-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O SDZRIBWEVVRDQI-CIUDSAMLSA-N 0.000 description 2
- IORKCNUBHNIMKY-CIUDSAMLSA-N Ala-Pro-Glu Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O IORKCNUBHNIMKY-CIUDSAMLSA-N 0.000 description 2
- RTZCUEHYUQZIDE-WHFBIAKZSA-N Ala-Ser-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RTZCUEHYUQZIDE-WHFBIAKZSA-N 0.000 description 2
- WNHNMKOFKCHKKD-BFHQHQDPSA-N Ala-Thr-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O WNHNMKOFKCHKKD-BFHQHQDPSA-N 0.000 description 2
- WZGZDOXCDLLTHE-SYWGBEHUSA-N Ala-Trp-Ile Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)NC(=O)[C@H](C)N)=CNC2=C1 WZGZDOXCDLLTHE-SYWGBEHUSA-N 0.000 description 2
- ZJLORAAXDAJLDC-CQDKDKBSSA-N Ala-Tyr-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O ZJLORAAXDAJLDC-CQDKDKBSSA-N 0.000 description 2
- DEAGTWNKODHUIY-MRFFXTKBSA-N Ala-Tyr-Trp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O DEAGTWNKODHUIY-MRFFXTKBSA-N 0.000 description 2
- JGDGLDNAQJJGJI-AVGNSLFASA-N Arg-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N JGDGLDNAQJJGJI-AVGNSLFASA-N 0.000 description 2
- NTAZNGWBXRVEDJ-FXQIFTODSA-N Arg-Asp-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NTAZNGWBXRVEDJ-FXQIFTODSA-N 0.000 description 2
- BEXGZLUHRXTZCC-CIUDSAMLSA-N Arg-Gln-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N)CN=C(N)N BEXGZLUHRXTZCC-CIUDSAMLSA-N 0.000 description 2
- VRZDJJWOFXMFRO-ZFWWWQNUSA-N Arg-Gly-Trp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O VRZDJJWOFXMFRO-ZFWWWQNUSA-N 0.000 description 2
- ZZZWQALDSQQBEW-STQMWFEESA-N Arg-Gly-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZZZWQALDSQQBEW-STQMWFEESA-N 0.000 description 2
- PCQXGEUALSFGIA-WDSOQIARSA-N Arg-His-Trp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O PCQXGEUALSFGIA-WDSOQIARSA-N 0.000 description 2
- GXXWTNKNFFKTJB-NAKRPEOUSA-N Arg-Ile-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O GXXWTNKNFFKTJB-NAKRPEOUSA-N 0.000 description 2
- LLUGJARLJCGLAR-CYDGBPFRSA-N Arg-Ile-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N LLUGJARLJCGLAR-CYDGBPFRSA-N 0.000 description 2
- KMFPQTITXUKJOV-DCAQKATOSA-N Arg-Ser-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O KMFPQTITXUKJOV-DCAQKATOSA-N 0.000 description 2
- XRNXPIGJPQHCPC-RCWTZXSCSA-N Arg-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)O)C(O)=O XRNXPIGJPQHCPC-RCWTZXSCSA-N 0.000 description 2
- SLKLLQWZQHXYSV-CIUDSAMLSA-N Asn-Ala-Lys Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O SLKLLQWZQHXYSV-CIUDSAMLSA-N 0.000 description 2
- UDSVWSUXKYXSTR-QWRGUYRKSA-N Asn-Gly-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O UDSVWSUXKYXSTR-QWRGUYRKSA-N 0.000 description 2
- FTSAJSADJCMDHH-CIUDSAMLSA-N Asn-Lys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N FTSAJSADJCMDHH-CIUDSAMLSA-N 0.000 description 2
- GMUOCGCDOYYWPD-FXQIFTODSA-N Asn-Pro-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O GMUOCGCDOYYWPD-FXQIFTODSA-N 0.000 description 2
- KZYSHAMXEBPJBD-JRQIVUDYSA-N Asn-Thr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KZYSHAMXEBPJBD-JRQIVUDYSA-N 0.000 description 2
- MRQQMVZUHXUPEV-IHRRRGAJSA-N Asp-Arg-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O MRQQMVZUHXUPEV-IHRRRGAJSA-N 0.000 description 2
- KHGPWGKPYHPOIK-QWRGUYRKSA-N Asp-Gly-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KHGPWGKPYHPOIK-QWRGUYRKSA-N 0.000 description 2
- 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 2
- YFSLJHLQOALGSY-ZPFDUUQYSA-N Asp-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N YFSLJHLQOALGSY-ZPFDUUQYSA-N 0.000 description 2
- SAKCBXNPWDRWPE-BQBZGAKWSA-N Asp-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(=O)O)N SAKCBXNPWDRWPE-BQBZGAKWSA-N 0.000 description 2
- 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 2
- AHWRSSLYSGLBGD-CIUDSAMLSA-N Asp-Pro-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AHWRSSLYSGLBGD-CIUDSAMLSA-N 0.000 description 2
- JSHWXQIZOCVWIA-ZKWXMUAHSA-N Asp-Ser-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JSHWXQIZOCVWIA-ZKWXMUAHSA-N 0.000 description 2
- SQIARYGNVQWOSB-BZSNNMDCSA-N Asp-Tyr-Phe 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=CC=C1)C(O)=O SQIARYGNVQWOSB-BZSNNMDCSA-N 0.000 description 2
- BYLPQJAWXJWUCJ-YDHLFZDLSA-N Asp-Tyr-Val 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](C(C)C)C(O)=O BYLPQJAWXJWUCJ-YDHLFZDLSA-N 0.000 description 2
- QPDUWAUSSWGJSB-NGZCFLSTSA-N Asp-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N QPDUWAUSSWGJSB-NGZCFLSTSA-N 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 2
- DCJNIJAWIRPPBB-CIUDSAMLSA-N Cys-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CS)N DCJNIJAWIRPPBB-CIUDSAMLSA-N 0.000 description 2
- DZLQXIFVQFTFJY-BYPYZUCNSA-N Cys-Gly-Gly Chemical compound SC[C@H](N)C(=O)NCC(=O)NCC(O)=O DZLQXIFVQFTFJY-BYPYZUCNSA-N 0.000 description 2
- WVLZTXGTNGHPBO-SRVKXCTJSA-N Cys-Leu-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O WVLZTXGTNGHPBO-SRVKXCTJSA-N 0.000 description 2
- BCFXQBXXDSEHRS-FXQIFTODSA-N Cys-Ser-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BCFXQBXXDSEHRS-FXQIFTODSA-N 0.000 description 2
- KFYPRIGJTICABD-XGEHTFHBSA-N Cys-Thr-Val Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N)O KFYPRIGJTICABD-XGEHTFHBSA-N 0.000 description 2
- UGPCUUWZXRMCIJ-KKUMJFAQSA-N Cys-Tyr-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CS)N UGPCUUWZXRMCIJ-KKUMJFAQSA-N 0.000 description 2
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 2
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 2
- SHERTACNJPYHAR-ACZMJKKPSA-N Gln-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O SHERTACNJPYHAR-ACZMJKKPSA-N 0.000 description 2
- OKARHJKJTKFQBM-ACZMJKKPSA-N Gln-Ser-Asn Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N OKARHJKJTKFQBM-ACZMJKKPSA-N 0.000 description 2
- SYZZMPFLOLSMHL-XHNCKOQMSA-N Gln-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)C(=O)O SYZZMPFLOLSMHL-XHNCKOQMSA-N 0.000 description 2
- XKPACHRGOWQHFH-IRIUXVKKSA-N Gln-Thr-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XKPACHRGOWQHFH-IRIUXVKKSA-N 0.000 description 2
- JKDBRTNMYXYLHO-JYJNAYRXSA-N Gln-Tyr-Leu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 JKDBRTNMYXYLHO-JYJNAYRXSA-N 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
- 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 2
- QPRZKNOOOBWXSU-CIUDSAMLSA-N Glu-Asp-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N QPRZKNOOOBWXSU-CIUDSAMLSA-N 0.000 description 2
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 2
- ALMBZBOCGSVSAI-ACZMJKKPSA-N Glu-Ser-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ALMBZBOCGSVSAI-ACZMJKKPSA-N 0.000 description 2
- MFYLRRCYBBJYPI-JYJNAYRXSA-N Glu-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O MFYLRRCYBBJYPI-JYJNAYRXSA-N 0.000 description 2
- VSVZIEVNUYDAFR-YUMQZZPRSA-N Gly-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN VSVZIEVNUYDAFR-YUMQZZPRSA-N 0.000 description 2
- UXJHNZODTMHWRD-WHFBIAKZSA-N Gly-Asn-Ala Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O UXJHNZODTMHWRD-WHFBIAKZSA-N 0.000 description 2
- BGVYNAQWHSTTSP-BYULHYEWSA-N Gly-Asn-Ile Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BGVYNAQWHSTTSP-BYULHYEWSA-N 0.000 description 2
- FMNHBTKMRFVGRO-FOHZUACHSA-N Gly-Asn-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CN FMNHBTKMRFVGRO-FOHZUACHSA-N 0.000 description 2
- IWAXHBCACVWNHT-BQBZGAKWSA-N Gly-Asp-Arg Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IWAXHBCACVWNHT-BQBZGAKWSA-N 0.000 description 2
- PABFFPWEJMEVEC-JGVFFNPUSA-N Gly-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)CN)C(=O)O PABFFPWEJMEVEC-JGVFFNPUSA-N 0.000 description 2
- 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 2
- 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 2
- OJNZVYSGVYLQIN-BQBZGAKWSA-N Gly-Met-Asp Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O OJNZVYSGVYLQIN-BQBZGAKWSA-N 0.000 description 2
- RVGMVLVBDRQVKB-UWVGGRQHSA-N Gly-Met-His Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN RVGMVLVBDRQVKB-UWVGGRQHSA-N 0.000 description 2
- GAFKBWKVXNERFA-QWRGUYRKSA-N Gly-Phe-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 GAFKBWKVXNERFA-QWRGUYRKSA-N 0.000 description 2
- 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 2
- 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 2
- FKYQEVBRZSFAMJ-QWRGUYRKSA-N Gly-Ser-Tyr Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FKYQEVBRZSFAMJ-QWRGUYRKSA-N 0.000 description 2
- ZLCLYFGMKFCDCN-XPUUQOCRSA-N Gly-Ser-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(O)=O ZLCLYFGMKFCDCN-XPUUQOCRSA-N 0.000 description 2
- KOYUSMBPJOVSOO-XEGUGMAKSA-N Gly-Tyr-Ile Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KOYUSMBPJOVSOO-XEGUGMAKSA-N 0.000 description 2
- ZVXMEWXHFBYJPI-LSJOCFKGSA-N Gly-Val-Ile Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZVXMEWXHFBYJPI-LSJOCFKGSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 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 2
- ZVKDCQVQTGYBQT-LSJOCFKGSA-N His-Pro-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O ZVKDCQVQTGYBQT-LSJOCFKGSA-N 0.000 description 2
- YKUAGFAXQRYUQW-KKUMJFAQSA-N His-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O YKUAGFAXQRYUQW-KKUMJFAQSA-N 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- MKWSZEHGHSLNPF-NAKRPEOUSA-N Ile-Ala-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O)N MKWSZEHGHSLNPF-NAKRPEOUSA-N 0.000 description 2
- HDODQNPMSHDXJT-GHCJXIJMSA-N Ile-Asn-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O HDODQNPMSHDXJT-GHCJXIJMSA-N 0.000 description 2
- DFJJAVZIHDFOGQ-MNXVOIDGSA-N Ile-Glu-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N DFJJAVZIHDFOGQ-MNXVOIDGSA-N 0.000 description 2
- UAQSZXGJGLHMNV-XEGUGMAKSA-N Ile-Gly-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N UAQSZXGJGLHMNV-XEGUGMAKSA-N 0.000 description 2
- CKRFDMPBSWYOBT-PPCPHDFISA-N Ile-Lys-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N CKRFDMPBSWYOBT-PPCPHDFISA-N 0.000 description 2
- KTTMFLSBTNBAHL-MXAVVETBSA-N Ile-Phe-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)O)N KTTMFLSBTNBAHL-MXAVVETBSA-N 0.000 description 2
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 2
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- UCOCBWDBHCUPQP-DCAQKATOSA-N Leu-Arg-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O UCOCBWDBHCUPQP-DCAQKATOSA-N 0.000 description 2
- KAFOIVJDVSZUMD-DCAQKATOSA-N Leu-Gln-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-DCAQKATOSA-N 0.000 description 2
- HYMLKESRWLZDBR-WEDXCCLWSA-N Leu-Gly-Thr Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O HYMLKESRWLZDBR-WEDXCCLWSA-N 0.000 description 2
- FOBUGKUBUJOWAD-IHPCNDPISA-N Leu-Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 FOBUGKUBUJOWAD-IHPCNDPISA-N 0.000 description 2
- ZGUMORRUBUCXEH-AVGNSLFASA-N Leu-Lys-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZGUMORRUBUCXEH-AVGNSLFASA-N 0.000 description 2
- MVHXGBZUJLWZOH-BJDJZHNGSA-N Leu-Ser-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MVHXGBZUJLWZOH-BJDJZHNGSA-N 0.000 description 2
- ODRREERHVHMIPT-OEAJRASXSA-N Leu-Thr-Phe Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ODRREERHVHMIPT-OEAJRASXSA-N 0.000 description 2
- 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 2
- RIHIGSWBLHSGLV-CQDKDKBSSA-N Leu-Tyr-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O RIHIGSWBLHSGLV-CQDKDKBSSA-N 0.000 description 2
- XZNJZXJZBMBGGS-NHCYSSNCSA-N Leu-Val-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O XZNJZXJZBMBGGS-NHCYSSNCSA-N 0.000 description 2
- PNPYKQFJGRFYJE-GUBZILKMSA-N Lys-Ala-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNPYKQFJGRFYJE-GUBZILKMSA-N 0.000 description 2
- KNKHAVVBVXKOGX-JXUBOQSCSA-N Lys-Ala-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KNKHAVVBVXKOGX-JXUBOQSCSA-N 0.000 description 2
- SWWCDAGDQHTKIE-RHYQMDGZSA-N Lys-Arg-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWWCDAGDQHTKIE-RHYQMDGZSA-N 0.000 description 2
- NTSPQIONFJUMJV-AVGNSLFASA-N Lys-Arg-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O NTSPQIONFJUMJV-AVGNSLFASA-N 0.000 description 2
- QUCDKEKDPYISNX-HJGDQZAQSA-N Lys-Asn-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QUCDKEKDPYISNX-HJGDQZAQSA-N 0.000 description 2
- KPJJOZUXFOLGMQ-CIUDSAMLSA-N Lys-Asp-Asn Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N KPJJOZUXFOLGMQ-CIUDSAMLSA-N 0.000 description 2
- LMVOVCYVZBBWQB-SRVKXCTJSA-N Lys-Asp-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN LMVOVCYVZBBWQB-SRVKXCTJSA-N 0.000 description 2
- WTZUSCUIVPVCRH-SRVKXCTJSA-N Lys-Gln-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WTZUSCUIVPVCRH-SRVKXCTJSA-N 0.000 description 2
- GPJGFSFYBJGYRX-YUMQZZPRSA-N Lys-Gly-Asp Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O GPJGFSFYBJGYRX-YUMQZZPRSA-N 0.000 description 2
- GOVDTWNJCBRRBJ-DCAQKATOSA-N Lys-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N GOVDTWNJCBRRBJ-DCAQKATOSA-N 0.000 description 2
- JYVCOTWSRGFABJ-DCAQKATOSA-N Lys-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCCN)N JYVCOTWSRGFABJ-DCAQKATOSA-N 0.000 description 2
- WQDKIVRHTQYJSN-DCAQKATOSA-N Lys-Ser-Arg Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N WQDKIVRHTQYJSN-DCAQKATOSA-N 0.000 description 2
- MGKFCQFVPKOWOL-CIUDSAMLSA-N Lys-Ser-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N MGKFCQFVPKOWOL-CIUDSAMLSA-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
- SQXZLVXQXWILKW-KKUMJFAQSA-N Lys-Ser-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SQXZLVXQXWILKW-KKUMJFAQSA-N 0.000 description 2
- IEVXCWPVBYCJRZ-IXOXFDKPSA-N Lys-Thr-His Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IEVXCWPVBYCJRZ-IXOXFDKPSA-N 0.000 description 2
- DLCAXBGXGOVUCD-PPCPHDFISA-N Lys-Thr-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DLCAXBGXGOVUCD-PPCPHDFISA-N 0.000 description 2
- CAVRAQIDHUPECU-UVOCVTCTSA-N Lys-Thr-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAVRAQIDHUPECU-UVOCVTCTSA-N 0.000 description 2
- FPQMQEOVSKMVMA-ACRUOGEOSA-N Lys-Tyr-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)NC(=O)[C@H](CCCCN)N)O FPQMQEOVSKMVMA-ACRUOGEOSA-N 0.000 description 2
- VOOINLQYUZOREH-SRVKXCTJSA-N Met-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCSC)N VOOINLQYUZOREH-SRVKXCTJSA-N 0.000 description 2
- RKIIYGUHIQJCBW-SRVKXCTJSA-N Met-His-Glu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O RKIIYGUHIQJCBW-SRVKXCTJSA-N 0.000 description 2
- WRXOPYNEKGZWAZ-FXQIFTODSA-N Met-Ser-Cys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(O)=O WRXOPYNEKGZWAZ-FXQIFTODSA-N 0.000 description 2
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 2
- 101100068676 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) gln-1 gene Proteins 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- DFEVBOYEUQJGER-JURCDPSOSA-N Phe-Ala-Ile Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O DFEVBOYEUQJGER-JURCDPSOSA-N 0.000 description 2
- UEHNWRNADDPYNK-DLOVCJGASA-N Phe-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=CC=C1)N UEHNWRNADDPYNK-DLOVCJGASA-N 0.000 description 2
- OQTDZEJJWWAGJT-KKUMJFAQSA-N Phe-Lys-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O OQTDZEJJWWAGJT-KKUMJFAQSA-N 0.000 description 2
- IIEOLPMQYRBZCN-SRVKXCTJSA-N Phe-Ser-Cys Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O IIEOLPMQYRBZCN-SRVKXCTJSA-N 0.000 description 2
- UNBFGVQVQGXXCK-KKUMJFAQSA-N Phe-Ser-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O UNBFGVQVQGXXCK-KKUMJFAQSA-N 0.000 description 2
- VDTYRPWRWRCROL-UFYCRDLUSA-N Phe-Val-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 VDTYRPWRWRCROL-UFYCRDLUSA-N 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- DEDANIDYQAPTFI-IHRRRGAJSA-N Pro-Asp-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O DEDANIDYQAPTFI-IHRRRGAJSA-N 0.000 description 2
- CLNJSLSHKJECME-BQBZGAKWSA-N Pro-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1 CLNJSLSHKJECME-BQBZGAKWSA-N 0.000 description 2
- JMVQDLDPDBXAAX-YUMQZZPRSA-N Pro-Gly-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 JMVQDLDPDBXAAX-YUMQZZPRSA-N 0.000 description 2
- HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-N 0.000 description 2
- ZLXKLMHAMDENIO-DCAQKATOSA-N Pro-Lys-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLXKLMHAMDENIO-DCAQKATOSA-N 0.000 description 2
- GMJDSFYVTAMIBF-FXQIFTODSA-N Pro-Ser-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GMJDSFYVTAMIBF-FXQIFTODSA-N 0.000 description 2
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 2
- WDXYVIIVDIDOSX-DCAQKATOSA-N Ser-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N WDXYVIIVDIDOSX-DCAQKATOSA-N 0.000 description 2
- QFBNNYNWKYKVJO-DCAQKATOSA-N Ser-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N QFBNNYNWKYKVJO-DCAQKATOSA-N 0.000 description 2
- OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 2
- UBRXAVQWXOWRSJ-ZLUOBGJFSA-N Ser-Asn-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CO)N)C(=O)N UBRXAVQWXOWRSJ-ZLUOBGJFSA-N 0.000 description 2
- ZOHGLPQGEHSLPD-FXQIFTODSA-N Ser-Gln-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZOHGLPQGEHSLPD-FXQIFTODSA-N 0.000 description 2
- MIJWOJAXARLEHA-WDSKDSINSA-N Ser-Gly-Glu Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O MIJWOJAXARLEHA-WDSKDSINSA-N 0.000 description 2
- GVIGVIOEYBOTCB-XIRDDKMYSA-N Ser-Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CC(C)C)C(O)=O)=CNC2=C1 GVIGVIOEYBOTCB-XIRDDKMYSA-N 0.000 description 2
- XUDRHBPSPAPDJP-SRVKXCTJSA-N Ser-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO XUDRHBPSPAPDJP-SRVKXCTJSA-N 0.000 description 2
- 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 2
- XGQKSRGHEZNWIS-IHRRRGAJSA-N Ser-Pro-Tyr Chemical compound N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O XGQKSRGHEZNWIS-IHRRRGAJSA-N 0.000 description 2
- PYTKULIABVRXSC-BWBBJGPYSA-N Ser-Ser-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PYTKULIABVRXSC-BWBBJGPYSA-N 0.000 description 2
- IAOHCSQDQDWRQU-GUBZILKMSA-N Ser-Val-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IAOHCSQDQDWRQU-GUBZILKMSA-N 0.000 description 2
- 102000007000 Tenascin Human genes 0.000 description 2
- 108010008125 Tenascin Proteins 0.000 description 2
- TZKPNGDGUVREEB-FOHZUACHSA-N Thr-Asn-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O TZKPNGDGUVREEB-FOHZUACHSA-N 0.000 description 2
- ASJDFGOPDCVXTG-KATARQTJSA-N Thr-Cys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O ASJDFGOPDCVXTG-KATARQTJSA-N 0.000 description 2
- BDGBHYCAZJPLHX-HJGDQZAQSA-N Thr-Lys-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BDGBHYCAZJPLHX-HJGDQZAQSA-N 0.000 description 2
- LHNNQVXITHUCAB-QTKMDUPCSA-N Thr-Met-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O LHNNQVXITHUCAB-QTKMDUPCSA-N 0.000 description 2
- OLFOOYQTTQSSRK-UNQGMJICSA-N Thr-Pro-Phe Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OLFOOYQTTQSSRK-UNQGMJICSA-N 0.000 description 2
- 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 2
- YRJOLUDFVAUXLI-GSSVUCPTSA-N Thr-Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O YRJOLUDFVAUXLI-GSSVUCPTSA-N 0.000 description 2
- BBPCSGKKPJUYRB-UVOCVTCTSA-N Thr-Thr-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O BBPCSGKKPJUYRB-UVOCVTCTSA-N 0.000 description 2
- BEZTUFWTPVOROW-KJEVXHAQSA-N Thr-Tyr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O BEZTUFWTPVOROW-KJEVXHAQSA-N 0.000 description 2
- NJGMALCNYAMYCB-JRQIVUDYSA-N Thr-Tyr-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O NJGMALCNYAMYCB-JRQIVUDYSA-N 0.000 description 2
- AVYVKJMBNLPWRX-WFBYXXMGSA-N Trp-Ala-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 AVYVKJMBNLPWRX-WFBYXXMGSA-N 0.000 description 2
- UTQBQJNSNXJNIH-IHPCNDPISA-N Trp-Asn-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N UTQBQJNSNXJNIH-IHPCNDPISA-N 0.000 description 2
- CZSMNLQMRWPGQF-XEGUGMAKSA-N Trp-Gln-Ala Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O CZSMNLQMRWPGQF-XEGUGMAKSA-N 0.000 description 2
- MKDXQPMIQPTTAW-SIXJUCDHSA-N Trp-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N MKDXQPMIQPTTAW-SIXJUCDHSA-N 0.000 description 2
- WMIUTJPFHMMUGY-ZFWWWQNUSA-N Trp-Pro-Gly Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)NCC(=O)O WMIUTJPFHMMUGY-ZFWWWQNUSA-N 0.000 description 2
- UJGDFQRPYGJBEH-AAEUAGOBSA-N Trp-Ser-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N UJGDFQRPYGJBEH-AAEUAGOBSA-N 0.000 description 2
- GSCPHMSPGQSZJT-JYBASQMISA-N Trp-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O GSCPHMSPGQSZJT-JYBASQMISA-N 0.000 description 2
- BURPTJBFWIOHEY-UWJYBYFXSA-N Tyr-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BURPTJBFWIOHEY-UWJYBYFXSA-N 0.000 description 2
- SCCKSNREWHMKOJ-SRVKXCTJSA-N Tyr-Asn-Ser Chemical compound N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O SCCKSNREWHMKOJ-SRVKXCTJSA-N 0.000 description 2
- BEIGSKUPTIFYRZ-SRVKXCTJSA-N Tyr-Asp-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O BEIGSKUPTIFYRZ-SRVKXCTJSA-N 0.000 description 2
- TZXFLDNBYYGLKA-BZSNNMDCSA-N Tyr-Asp-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 TZXFLDNBYYGLKA-BZSNNMDCSA-N 0.000 description 2
- HDSKHCBAVVWPCQ-FHWLQOOXSA-N Tyr-Glu-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HDSKHCBAVVWPCQ-FHWLQOOXSA-N 0.000 description 2
- HIINQLBHPIQYHN-JTQLQIEISA-N Tyr-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HIINQLBHPIQYHN-JTQLQIEISA-N 0.000 description 2
- STTVVMWQKDOKAM-YESZJQIVSA-N Tyr-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O STTVVMWQKDOKAM-YESZJQIVSA-N 0.000 description 2
- NXRGXTBPMOGFID-CFMVVWHZSA-N Tyr-Ile-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O NXRGXTBPMOGFID-CFMVVWHZSA-N 0.000 description 2
- DZKFGCNKEVMXFA-JUKXBJQTSA-N Tyr-Ile-His Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O DZKFGCNKEVMXFA-JUKXBJQTSA-N 0.000 description 2
- OLYXUGBVBGSZDN-ACRUOGEOSA-N Tyr-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 OLYXUGBVBGSZDN-ACRUOGEOSA-N 0.000 description 2
- SINRIKQYQJRGDQ-MEYUZBJRSA-N Tyr-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SINRIKQYQJRGDQ-MEYUZBJRSA-N 0.000 description 2
- QPBJXNYYQTUTDD-KKUMJFAQSA-N Tyr-Met-Gln Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N QPBJXNYYQTUTDD-KKUMJFAQSA-N 0.000 description 2
- XGZBEGGGAUQBMB-KJEVXHAQSA-N Tyr-Pro-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC2=CC=C(C=C2)O)N)O XGZBEGGGAUQBMB-KJEVXHAQSA-N 0.000 description 2
- NHOVZGFNTGMYMI-KKUMJFAQSA-N Tyr-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NHOVZGFNTGMYMI-KKUMJFAQSA-N 0.000 description 2
- NZBSVMQZQMEUHI-WZLNRYEVSA-N Tyr-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N NZBSVMQZQMEUHI-WZLNRYEVSA-N 0.000 description 2
- XFEMMSGONWQACR-KJEVXHAQSA-N Tyr-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O XFEMMSGONWQACR-KJEVXHAQSA-N 0.000 description 2
- MWUYSCVVPVITMW-IGNZVWTISA-N Tyr-Tyr-Ala Chemical compound C([C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 MWUYSCVVPVITMW-IGNZVWTISA-N 0.000 description 2
- SLLKXDSRVAOREO-KZVJFYERSA-N Val-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N)O SLLKXDSRVAOREO-KZVJFYERSA-N 0.000 description 2
- NMPXRFYMZDIBRF-ZOBUZTSGSA-N Val-Asn-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N NMPXRFYMZDIBRF-ZOBUZTSGSA-N 0.000 description 2
- QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 2
- CJDZKZFMAXGUOJ-IHRRRGAJSA-N Val-Cys-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N CJDZKZFMAXGUOJ-IHRRRGAJSA-N 0.000 description 2
- VCAWFLIWYNMHQP-UKJIMTQDSA-N Val-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)N VCAWFLIWYNMHQP-UKJIMTQDSA-N 0.000 description 2
- DJEVQCWNMQOABE-RCOVLWMOSA-N Val-Gly-Asp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N DJEVQCWNMQOABE-RCOVLWMOSA-N 0.000 description 2
- HVRRJRMULCPNRO-BZSNNMDCSA-N Val-Trp-Arg Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 HVRRJRMULCPNRO-BZSNNMDCSA-N 0.000 description 2
- QHSSPPHOHJSTML-HOCLYGCPSA-N Val-Trp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)NCC(=O)O)N QHSSPPHOHJSTML-HOCLYGCPSA-N 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 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
- 230000003321 amplification Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 108010060035 arginylproline Proteins 0.000 description 2
- 108010038633 aspartylglutamate Proteins 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000005880 cancer cell killing Effects 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000011022 operating instruction Methods 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 108010029020 prolylglycine Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 108010080629 tryptophan-leucine Proteins 0.000 description 2
- 108010084932 tryptophyl-proline Proteins 0.000 description 2
- 230000005740 tumor formation Effects 0.000 description 2
- 108010079202 tyrosyl-alanyl-cysteine Proteins 0.000 description 2
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 2
- 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 1
- IESDGNYHXIOKRW-YXMSTPNBSA-N (2s)-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s,3r)-2-amino-3-hydroxybutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IESDGNYHXIOKRW-YXMSTPNBSA-N 0.000 description 1
- IGXNPQWXIRIGBF-KEOOTSPTSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoic acid Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 IGXNPQWXIRIGBF-KEOOTSPTSA-N 0.000 description 1
- DIBLBAURNYJYBF-XLXZRNDBSA-N (2s)-2-[[(2s)-2-[[2-[[(2s)-6-amino-2-[[(2s)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 DIBLBAURNYJYBF-XLXZRNDBSA-N 0.000 description 1
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-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
- HXNNRBHASOSVPG-GUBZILKMSA-N Ala-Glu-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O HXNNRBHASOSVPG-GUBZILKMSA-N 0.000 description 1
- OMMDTNGURYRDAC-NRPADANISA-N Ala-Glu-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OMMDTNGURYRDAC-NRPADANISA-N 0.000 description 1
- SIGTYDNEPYEXGK-ZANVPECISA-N Ala-Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CNC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 SIGTYDNEPYEXGK-ZANVPECISA-N 0.000 description 1
- YYAVDNKUWLAFCV-ACZMJKKPSA-N Ala-Ser-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O YYAVDNKUWLAFCV-ACZMJKKPSA-N 0.000 description 1
- PEEYDECOOVQKRZ-DLOVCJGASA-N Ala-Ser-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PEEYDECOOVQKRZ-DLOVCJGASA-N 0.000 description 1
- UCDOXFBTMLKASE-HERUPUMHSA-N Ala-Ser-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N UCDOXFBTMLKASE-HERUPUMHSA-N 0.000 description 1
- AOAKQKVICDWCLB-UWJYBYFXSA-N Ala-Tyr-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N AOAKQKVICDWCLB-UWJYBYFXSA-N 0.000 description 1
- XKXAZPSREVUCRT-BPNCWPANSA-N Ala-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=C(O)C=C1 XKXAZPSREVUCRT-BPNCWPANSA-N 0.000 description 1
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 1
- GIVATXIGCXFQQA-FXQIFTODSA-N Arg-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N GIVATXIGCXFQQA-FXQIFTODSA-N 0.000 description 1
- UFBURHXMKFQVLM-CIUDSAMLSA-N Arg-Glu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O UFBURHXMKFQVLM-CIUDSAMLSA-N 0.000 description 1
- CYXCAHZVPFREJD-LURJTMIESA-N Arg-Gly-Gly Chemical compound NC(=N)NCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O CYXCAHZVPFREJD-LURJTMIESA-N 0.000 description 1
- NKNILFJYKKHBKE-WPRPVWTQSA-N Arg-Gly-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O NKNILFJYKKHBKE-WPRPVWTQSA-N 0.000 description 1
- MMGCRPZQZWTZTA-IHRRRGAJSA-N Arg-His-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N MMGCRPZQZWTZTA-IHRRRGAJSA-N 0.000 description 1
- OOIMKQRCPJBGPD-XUXIUFHCSA-N Arg-Ile-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O OOIMKQRCPJBGPD-XUXIUFHCSA-N 0.000 description 1
- FNXCAFKDGBROCU-STECZYCISA-N Arg-Ile-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FNXCAFKDGBROCU-STECZYCISA-N 0.000 description 1
- GMFAGHNRXPSSJS-SRVKXCTJSA-N Arg-Leu-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GMFAGHNRXPSSJS-SRVKXCTJSA-N 0.000 description 1
- SLQQPJBDBVPVQV-JYJNAYRXSA-N Arg-Phe-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O SLQQPJBDBVPVQV-JYJNAYRXSA-N 0.000 description 1
- LRPZJPMQGKGHSG-XGEHTFHBSA-N Arg-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)O LRPZJPMQGKGHSG-XGEHTFHBSA-N 0.000 description 1
- INOIAEUXVVNJKA-XGEHTFHBSA-N Arg-Thr-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O INOIAEUXVVNJKA-XGEHTFHBSA-N 0.000 description 1
- JRVABKHPWDRUJF-UBHSHLNASA-N Asn-Asn-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)N JRVABKHPWDRUJF-UBHSHLNASA-N 0.000 description 1
- XWFPGQVLOVGSLU-CIUDSAMLSA-N Asn-Gln-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N XWFPGQVLOVGSLU-CIUDSAMLSA-N 0.000 description 1
- PTSDPWIHOYMRGR-UGYAYLCHSA-N Asn-Ile-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O PTSDPWIHOYMRGR-UGYAYLCHSA-N 0.000 description 1
- KMCRKVOLRCOMBG-DJFWLOJKSA-N Asn-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KMCRKVOLRCOMBG-DJFWLOJKSA-N 0.000 description 1
- ACKNRKFVYUVWAC-ZPFDUUQYSA-N Asn-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ACKNRKFVYUVWAC-ZPFDUUQYSA-N 0.000 description 1
- HDHZCEDPLTVHFZ-GUBZILKMSA-N Asn-Leu-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O HDHZCEDPLTVHFZ-GUBZILKMSA-N 0.000 description 1
- DOURAOODTFJRIC-CIUDSAMLSA-N Asn-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N DOURAOODTFJRIC-CIUDSAMLSA-N 0.000 description 1
- WUQXMTITJLFXAU-JIOCBJNQSA-N Asn-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N)O WUQXMTITJLFXAU-JIOCBJNQSA-N 0.000 description 1
- YSYTWUMRHSFODC-QWRGUYRKSA-N Asn-Tyr-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O YSYTWUMRHSFODC-QWRGUYRKSA-N 0.000 description 1
- DATSKXOXPUAOLK-KKUMJFAQSA-N Asn-Tyr-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O DATSKXOXPUAOLK-KKUMJFAQSA-N 0.000 description 1
- LRCIOEVFVGXZKB-BZSNNMDCSA-N Asn-Tyr-Tyr Chemical compound [H]N[C@@H](CC(N)=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 LRCIOEVFVGXZKB-BZSNNMDCSA-N 0.000 description 1
- QXNGSPZMGFEZNO-QRTARXTBSA-N Asn-Val-Trp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O QXNGSPZMGFEZNO-QRTARXTBSA-N 0.000 description 1
- OERMIMJQPQUIPK-FXQIFTODSA-N Asp-Arg-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O OERMIMJQPQUIPK-FXQIFTODSA-N 0.000 description 1
- TVVYVAUGRHNTGT-UGYAYLCHSA-N Asp-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O TVVYVAUGRHNTGT-UGYAYLCHSA-N 0.000 description 1
- VFUXXFVCYZPOQG-WDSKDSINSA-N Asp-Glu-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VFUXXFVCYZPOQG-WDSKDSINSA-N 0.000 description 1
- 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 1
- ODNWIBOCFGMRTP-SRVKXCTJSA-N Asp-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CN=CN1 ODNWIBOCFGMRTP-SRVKXCTJSA-N 0.000 description 1
- KTTCQQNRRLCIBC-GHCJXIJMSA-N Asp-Ile-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O KTTCQQNRRLCIBC-GHCJXIJMSA-N 0.000 description 1
- OAMLVOVXNKILLQ-BQBZGAKWSA-N Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O OAMLVOVXNKILLQ-BQBZGAKWSA-N 0.000 description 1
- UZFHNLYQWMGUHU-DCAQKATOSA-N Asp-Lys-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UZFHNLYQWMGUHU-DCAQKATOSA-N 0.000 description 1
- NVFSJIXJZCDICF-SRVKXCTJSA-N Asp-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N NVFSJIXJZCDICF-SRVKXCTJSA-N 0.000 description 1
- NZWDWXSWUQCNMG-GARJFASQSA-N Asp-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N)C(=O)O NZWDWXSWUQCNMG-GARJFASQSA-N 0.000 description 1
- CUQDCPXNZPDYFQ-ZLUOBGJFSA-N Asp-Ser-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O CUQDCPXNZPDYFQ-ZLUOBGJFSA-N 0.000 description 1
- OZBXOELNJBSJOA-UBHSHLNASA-N Asp-Ser-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N OZBXOELNJBSJOA-UBHSHLNASA-N 0.000 description 1
- RSMZEHCMIOKNMW-GSSVUCPTSA-N Asp-Thr-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RSMZEHCMIOKNMW-GSSVUCPTSA-N 0.000 description 1
- JDDYEZGPYBBPBN-JRQIVUDYSA-N Asp-Thr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JDDYEZGPYBBPBN-JRQIVUDYSA-N 0.000 description 1
- XWKBWZXGNXTDKY-ZKWXMUAHSA-N Asp-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O XWKBWZXGNXTDKY-ZKWXMUAHSA-N 0.000 description 1
- PLOKOIJSGCISHE-BYULHYEWSA-N Asp-Val-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PLOKOIJSGCISHE-BYULHYEWSA-N 0.000 description 1
- GYNUXDMCDILYIQ-QRTARXTBSA-N Asp-Val-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(=O)O)N GYNUXDMCDILYIQ-QRTARXTBSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- VTJLJQGUMBWHBP-GUBZILKMSA-N Cys-His-Gln Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N VTJLJQGUMBWHBP-GUBZILKMSA-N 0.000 description 1
- BLGNLNRBABWDST-CIUDSAMLSA-N Cys-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N BLGNLNRBABWDST-CIUDSAMLSA-N 0.000 description 1
- ZXCAQANTQWBICD-DCAQKATOSA-N Cys-Lys-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N ZXCAQANTQWBICD-DCAQKATOSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- RZSLYUUFFVHFRQ-FXQIFTODSA-N Gln-Ala-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O RZSLYUUFFVHFRQ-FXQIFTODSA-N 0.000 description 1
- JFOKLAPFYCTNHW-SRVKXCTJSA-N Gln-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N JFOKLAPFYCTNHW-SRVKXCTJSA-N 0.000 description 1
- XOKGKOQWADCLFQ-GARJFASQSA-N Gln-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XOKGKOQWADCLFQ-GARJFASQSA-N 0.000 description 1
- KZEUVLLVULIPNX-GUBZILKMSA-N Gln-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N KZEUVLLVULIPNX-GUBZILKMSA-N 0.000 description 1
- 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 1
- GPISLLFQNHELLK-DCAQKATOSA-N Gln-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](CCC(=O)N)N GPISLLFQNHELLK-DCAQKATOSA-N 0.000 description 1
- RBWKVOSARCFSQQ-FXQIFTODSA-N Gln-Gln-Ser Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O RBWKVOSARCFSQQ-FXQIFTODSA-N 0.000 description 1
- 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 1
- XFAUJGNLHIGXET-AVGNSLFASA-N Gln-Leu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XFAUJGNLHIGXET-AVGNSLFASA-N 0.000 description 1
- ILKYYKRAULNYMS-JYJNAYRXSA-N Gln-Lys-Phe Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ILKYYKRAULNYMS-JYJNAYRXSA-N 0.000 description 1
- ROHVCXBMIAAASL-HJGDQZAQSA-N Gln-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)N)N)O ROHVCXBMIAAASL-HJGDQZAQSA-N 0.000 description 1
- SXFPZRRVWSUYII-KBIXCLLPSA-N Gln-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N SXFPZRRVWSUYII-KBIXCLLPSA-N 0.000 description 1
- LPIKVBWNNVFHCQ-GUBZILKMSA-N Gln-Ser-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O LPIKVBWNNVFHCQ-GUBZILKMSA-N 0.000 description 1
- HLRLXVPRJJITSK-IFFSRLJSSA-N Gln-Thr-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HLRLXVPRJJITSK-IFFSRLJSSA-N 0.000 description 1
- QXQDADBVIBLBHN-FHWLQOOXSA-N Gln-Tyr-Phe Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QXQDADBVIBLBHN-FHWLQOOXSA-N 0.000 description 1
- VYOILACOFPPNQH-UMNHJUIQSA-N Gln-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N VYOILACOFPPNQH-UMNHJUIQSA-N 0.000 description 1
- HUWSBFYAGXCXKC-CIUDSAMLSA-N Glu-Ala-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(O)=O HUWSBFYAGXCXKC-CIUDSAMLSA-N 0.000 description 1
- GLWXKFRTOHKGIT-ACZMJKKPSA-N Glu-Asn-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O GLWXKFRTOHKGIT-ACZMJKKPSA-N 0.000 description 1
- SBCYJMOOHUDWDA-NUMRIWBASA-N Glu-Asp-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SBCYJMOOHUDWDA-NUMRIWBASA-N 0.000 description 1
- YLJHCWNDBKKOEB-IHRRRGAJSA-N Glu-Glu-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YLJHCWNDBKKOEB-IHRRRGAJSA-N 0.000 description 1
- OAGVHWYIBZMWLA-YFKPBYRVSA-N Glu-Gly-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)NCC(O)=O OAGVHWYIBZMWLA-YFKPBYRVSA-N 0.000 description 1
- FBEJIDRSQCGFJI-GUBZILKMSA-N Glu-Leu-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FBEJIDRSQCGFJI-GUBZILKMSA-N 0.000 description 1
- PMSMKNYRZCKVMC-DRZSPHRISA-N Glu-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)N PMSMKNYRZCKVMC-DRZSPHRISA-N 0.000 description 1
- BPCLDCNZBUYGOD-BPUTZDHNSA-N Glu-Trp-Glu Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 BPCLDCNZBUYGOD-BPUTZDHNSA-N 0.000 description 1
- ZSIDREAPEPAPKL-XIRDDKMYSA-N Glu-Trp-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCC(=O)O)N ZSIDREAPEPAPKL-XIRDDKMYSA-N 0.000 description 1
- BKMOHWJHXQLFEX-IRIUXVKKSA-N Glu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCC(=O)O)N)O BKMOHWJHXQLFEX-IRIUXVKKSA-N 0.000 description 1
- LJPIRKICOISLKN-WHFBIAKZSA-N Gly-Ala-Ser Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O LJPIRKICOISLKN-WHFBIAKZSA-N 0.000 description 1
- GRIRDMVMJJDZKV-RCOVLWMOSA-N Gly-Asn-Val Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O GRIRDMVMJJDZKV-RCOVLWMOSA-N 0.000 description 1
- MOJKRXIRAZPZLW-WDSKDSINSA-N Gly-Glu-Ala Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O MOJKRXIRAZPZLW-WDSKDSINSA-N 0.000 description 1
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 1
- ZQIMMEYPEXIYBB-IUCAKERBSA-N Gly-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN ZQIMMEYPEXIYBB-IUCAKERBSA-N 0.000 description 1
- 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 1
- IKAIKUBBJHFNBZ-LURJTMIESA-N Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-LURJTMIESA-N 0.000 description 1
- WDEHMRNSGHVNOH-VHSXEESVSA-N Gly-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)CN)C(=O)O WDEHMRNSGHVNOH-VHSXEESVSA-N 0.000 description 1
- IGOYNRWLWHWAQO-JTQLQIEISA-N Gly-Phe-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IGOYNRWLWHWAQO-JTQLQIEISA-N 0.000 description 1
- IALQAMYQJBZNSK-WHFBIAKZSA-N Gly-Ser-Asn Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O IALQAMYQJBZNSK-WHFBIAKZSA-N 0.000 description 1
- JKSMZVCGQWVTBW-STQMWFEESA-N Gly-Trp-Asn Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(O)=O JKSMZVCGQWVTBW-STQMWFEESA-N 0.000 description 1
- DNVDEMWIYLVIQU-RCOVLWMOSA-N Gly-Val-Asp Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O DNVDEMWIYLVIQU-RCOVLWMOSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- MBSSHYPAEHPSGY-LSJOCFKGSA-N His-Ala-Met Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(O)=O MBSSHYPAEHPSGY-LSJOCFKGSA-N 0.000 description 1
- WMKXFMUJRCEGRP-SRVKXCTJSA-N His-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N WMKXFMUJRCEGRP-SRVKXCTJSA-N 0.000 description 1
- ALPXXNRQBMRCPZ-MEYUZBJRSA-N His-Thr-Phe Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ALPXXNRQBMRCPZ-MEYUZBJRSA-N 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- RSDHVTMRXSABSV-GHCJXIJMSA-N Ile-Asn-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N RSDHVTMRXSABSV-GHCJXIJMSA-N 0.000 description 1
- SLQVFYWBGNNOTK-BYULHYEWSA-N Ile-Gly-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)N)C(=O)O)N SLQVFYWBGNNOTK-BYULHYEWSA-N 0.000 description 1
- CDGLBYSAZFIIJO-RCOVLWMOSA-N Ile-Gly-Gly Chemical compound CC[C@H](C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O CDGLBYSAZFIIJO-RCOVLWMOSA-N 0.000 description 1
- PARSHQDZROHERM-NHCYSSNCSA-N Ile-Lys-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)O)N PARSHQDZROHERM-NHCYSSNCSA-N 0.000 description 1
- YSGBJIQXTIVBHZ-AJNGGQMLSA-N Ile-Lys-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O YSGBJIQXTIVBHZ-AJNGGQMLSA-N 0.000 description 1
- 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 1
- JNLSTRPWUXOORL-MMWGEVLESA-N Ile-Ser-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N JNLSTRPWUXOORL-MMWGEVLESA-N 0.000 description 1
- DGTOKVBDZXJHNZ-WZLNRYEVSA-N Ile-Thr-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N DGTOKVBDZXJHNZ-WZLNRYEVSA-N 0.000 description 1
- QHUREMVLLMNUAX-OSUNSFLBSA-N Ile-Thr-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)O)N QHUREMVLLMNUAX-OSUNSFLBSA-N 0.000 description 1
- YBHKCXNNNVDYEB-SPOWBLRKSA-N Ile-Trp-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CO)C(=O)O)N YBHKCXNNNVDYEB-SPOWBLRKSA-N 0.000 description 1
- NSPNUMNLZNOPAQ-SJWGOKEGSA-N Ile-Tyr-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N NSPNUMNLZNOPAQ-SJWGOKEGSA-N 0.000 description 1
- JERJIYYCOGBAIJ-OBAATPRFSA-N Ile-Tyr-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N JERJIYYCOGBAIJ-OBAATPRFSA-N 0.000 description 1
- NXRNRBOKDBIVKQ-CXTHYWKRSA-N Ile-Tyr-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N NXRNRBOKDBIVKQ-CXTHYWKRSA-N 0.000 description 1
- ZSESFIFAYQEKRD-CYDGBPFRSA-N Ile-Val-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(=O)O)N ZSESFIFAYQEKRD-CYDGBPFRSA-N 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 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 1
- UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 description 1
- 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 1
- CLVUXCBGKUECIT-HJGDQZAQSA-N Leu-Asp-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CLVUXCBGKUECIT-HJGDQZAQSA-N 0.000 description 1
- KGCLIYGPQXUNLO-IUCAKERBSA-N Leu-Gly-Glu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O KGCLIYGPQXUNLO-IUCAKERBSA-N 0.000 description 1
- POZULHZYLPGXMR-ONGXEEELSA-N Leu-Gly-Val Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O POZULHZYLPGXMR-ONGXEEELSA-N 0.000 description 1
- HNDWYLYAYNBWMP-AJNGGQMLSA-N Leu-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(C)C)N HNDWYLYAYNBWMP-AJNGGQMLSA-N 0.000 description 1
- QLDHBYRUNQZIJQ-DKIMLUQUSA-N Leu-Ile-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QLDHBYRUNQZIJQ-DKIMLUQUSA-N 0.000 description 1
- ZRHDPZAAWLXXIR-SRVKXCTJSA-N Leu-Lys-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O ZRHDPZAAWLXXIR-SRVKXCTJSA-N 0.000 description 1
- KPYAOIVPJKPIOU-KKUMJFAQSA-N Leu-Lys-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O KPYAOIVPJKPIOU-KKUMJFAQSA-N 0.000 description 1
- WBRJVRXEGQIDRK-XIRDDKMYSA-N Leu-Trp-Ser Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 WBRJVRXEGQIDRK-XIRDDKMYSA-N 0.000 description 1
- NNCDAORZCMPZPX-GUBZILKMSA-N Lys-Gln-Ser Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N NNCDAORZCMPZPX-GUBZILKMSA-N 0.000 description 1
- 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 1
- XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 1
- ISHNZELVUVPCHY-ZETCQYMHSA-N Lys-Gly-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O ISHNZELVUVPCHY-ZETCQYMHSA-N 0.000 description 1
- PBLLTSKBTAHDNA-KBPBESRZSA-N Lys-Gly-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PBLLTSKBTAHDNA-KBPBESRZSA-N 0.000 description 1
- PRCHKVGXZVTALR-KKUMJFAQSA-N Lys-His-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCCCN)N PRCHKVGXZVTALR-KKUMJFAQSA-N 0.000 description 1
- PRSBSVAVOQOAMI-BJDJZHNGSA-N Lys-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN PRSBSVAVOQOAMI-BJDJZHNGSA-N 0.000 description 1
- ONPDTSFZAIWMDI-AVGNSLFASA-N Lys-Leu-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O ONPDTSFZAIWMDI-AVGNSLFASA-N 0.000 description 1
- YXPJCVNIDDKGOE-MELADBBJSA-N Lys-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N)C(=O)O YXPJCVNIDDKGOE-MELADBBJSA-N 0.000 description 1
- ZJSZPXISKMDJKQ-JYJNAYRXSA-N Lys-Phe-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=CC=C1 ZJSZPXISKMDJKQ-JYJNAYRXSA-N 0.000 description 1
- AFLBTVGQCQLOFJ-AVGNSLFASA-N Lys-Pro-Arg Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O AFLBTVGQCQLOFJ-AVGNSLFASA-N 0.000 description 1
- WZVSHTFTCYOFPL-GARJFASQSA-N Lys-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCCN)N)C(=O)O WZVSHTFTCYOFPL-GARJFASQSA-N 0.000 description 1
- QWTGQXGNNMIUCW-BPUTZDHNSA-N Met-Asn-Trp Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O QWTGQXGNNMIUCW-BPUTZDHNSA-N 0.000 description 1
- FVKRQMQQFGBXHV-QXEWZRGKSA-N Met-Asp-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O FVKRQMQQFGBXHV-QXEWZRGKSA-N 0.000 description 1
- JPCHYAUKOUGOIB-HJGDQZAQSA-N Met-Glu-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JPCHYAUKOUGOIB-HJGDQZAQSA-N 0.000 description 1
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 1
- PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 description 1
- 108010066427 N-valyltryptophan Proteins 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- LSXGADJXBDFXQU-DLOVCJGASA-N Phe-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 LSXGADJXBDFXQU-DLOVCJGASA-N 0.000 description 1
- NOFBJKKOPKJDCO-KKXDTOCCSA-N Phe-Ala-Tyr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NOFBJKKOPKJDCO-KKXDTOCCSA-N 0.000 description 1
- MPFGIYLYWUCSJG-AVGNSLFASA-N Phe-Glu-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 MPFGIYLYWUCSJG-AVGNSLFASA-N 0.000 description 1
- MSHZERMPZKCODG-ACRUOGEOSA-N Phe-Leu-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 MSHZERMPZKCODG-ACRUOGEOSA-N 0.000 description 1
- KNYPNEYICHHLQL-ACRUOGEOSA-N Phe-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 KNYPNEYICHHLQL-ACRUOGEOSA-N 0.000 description 1
- PHJUFDQVVKVOPU-ULQDDVLXSA-N Phe-Lys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=CC=C1)N PHJUFDQVVKVOPU-ULQDDVLXSA-N 0.000 description 1
- 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 1
- GNRMAQSIROFNMI-IXOXFDKPSA-N Phe-Thr-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GNRMAQSIROFNMI-IXOXFDKPSA-N 0.000 description 1
- BAONJAHBAUDJKA-BZSNNMDCSA-N Phe-Tyr-Asp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(O)=O)C(O)=O)C1=CC=CC=C1 BAONJAHBAUDJKA-BZSNNMDCSA-N 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- ZCXQTRXYZOSGJR-FXQIFTODSA-N Pro-Asp-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O ZCXQTRXYZOSGJR-FXQIFTODSA-N 0.000 description 1
- TUYWCHPXKQTISF-LPEHRKFASA-N Pro-Cys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N2CCC[C@@H]2C(=O)O TUYWCHPXKQTISF-LPEHRKFASA-N 0.000 description 1
- HQVPQXMCQKXARZ-FXQIFTODSA-N Pro-Cys-Ser Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O HQVPQXMCQKXARZ-FXQIFTODSA-N 0.000 description 1
- FKLSMYYLJHYPHH-UWVGGRQHSA-N Pro-Gly-Leu Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O FKLSMYYLJHYPHH-UWVGGRQHSA-N 0.000 description 1
- RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 description 1
- RNEFESSBTOQSAC-DCAQKATOSA-N Pro-Ser-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O RNEFESSBTOQSAC-DCAQKATOSA-N 0.000 description 1
- KIDXAAQVMNLJFQ-KZVJFYERSA-N Pro-Thr-Ala Chemical compound C[C@@H](O)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](C)C(O)=O KIDXAAQVMNLJFQ-KZVJFYERSA-N 0.000 description 1
- GZNYIXWOIUFLGO-ZJDVBMNYSA-N Pro-Thr-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZNYIXWOIUFLGO-ZJDVBMNYSA-N 0.000 description 1
- CWZUFLWPEFHWEI-IHRRRGAJSA-N Pro-Tyr-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O CWZUFLWPEFHWEI-IHRRRGAJSA-N 0.000 description 1
- QKWYXRPICJEQAJ-KJEVXHAQSA-N Pro-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@@H]2CCCN2)O QKWYXRPICJEQAJ-KJEVXHAQSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- SSJMZMUVNKEENT-IMJSIDKUSA-N Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CO SSJMZMUVNKEENT-IMJSIDKUSA-N 0.000 description 1
- MWMKFWJYRRGXOR-ZLUOBGJFSA-N Ser-Ala-Asn Chemical compound N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)CC(N)=O)C)CO MWMKFWJYRRGXOR-ZLUOBGJFSA-N 0.000 description 1
- KAAPNMOKUUPKOE-SRVKXCTJSA-N Ser-Asn-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KAAPNMOKUUPKOE-SRVKXCTJSA-N 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
- KMWFXJCGRXBQAC-CIUDSAMLSA-N Ser-Cys-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N KMWFXJCGRXBQAC-CIUDSAMLSA-N 0.000 description 1
- HVKMTOIAYDOJPL-NRPADANISA-N Ser-Gln-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVKMTOIAYDOJPL-NRPADANISA-N 0.000 description 1
- HJEBZBMOTCQYDN-ACZMJKKPSA-N Ser-Glu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HJEBZBMOTCQYDN-ACZMJKKPSA-N 0.000 description 1
- OHKFXGKHSJKKAL-NRPADANISA-N Ser-Glu-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OHKFXGKHSJKKAL-NRPADANISA-N 0.000 description 1
- WSTIOCFMWXNOCX-YUMQZZPRSA-N Ser-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N WSTIOCFMWXNOCX-YUMQZZPRSA-N 0.000 description 1
- UIPXCLNLUUAMJU-JBDRJPRFSA-N Ser-Ile-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O UIPXCLNLUUAMJU-JBDRJPRFSA-N 0.000 description 1
- ZOPISOXXPQNOCO-SVSWQMSJSA-N Ser-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CO)N ZOPISOXXPQNOCO-SVSWQMSJSA-N 0.000 description 1
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 1
- UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 description 1
- NIOYDASGXWLHEZ-CIUDSAMLSA-N Ser-Met-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(O)=O NIOYDASGXWLHEZ-CIUDSAMLSA-N 0.000 description 1
- ATEQEHCGZKBEMU-GQGQLFGLSA-N Ser-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CO)N ATEQEHCGZKBEMU-GQGQLFGLSA-N 0.000 description 1
- PLQWGQUNUPMNOD-KKUMJFAQSA-N Ser-Tyr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O PLQWGQUNUPMNOD-KKUMJFAQSA-N 0.000 description 1
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 1
- JGUWRQWULDWNCM-FXQIFTODSA-N Ser-Val-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O JGUWRQWULDWNCM-FXQIFTODSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- DGDCHPCRMWEOJR-FQPOAREZSA-N Thr-Ala-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 DGDCHPCRMWEOJR-FQPOAREZSA-N 0.000 description 1
- UKBSDLHIKIXJKH-HJGDQZAQSA-N Thr-Arg-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O UKBSDLHIKIXJKH-HJGDQZAQSA-N 0.000 description 1
- DCLBXIWHLVEPMQ-JRQIVUDYSA-N Thr-Asp-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 DCLBXIWHLVEPMQ-JRQIVUDYSA-N 0.000 description 1
- NRUPKQSXTJNQGD-XGEHTFHBSA-N Thr-Cys-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NRUPKQSXTJNQGD-XGEHTFHBSA-N 0.000 description 1
- KWQBJOUOSNJDRR-XAVMHZPKSA-N Thr-Cys-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N)O KWQBJOUOSNJDRR-XAVMHZPKSA-N 0.000 description 1
- DSLHSTIUAPKERR-XGEHTFHBSA-N Thr-Cys-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O DSLHSTIUAPKERR-XGEHTFHBSA-N 0.000 description 1
- OQCXTUQTKQFDCX-HTUGSXCWSA-N Thr-Glu-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N)O OQCXTUQTKQFDCX-HTUGSXCWSA-N 0.000 description 1
- LKEKWDJCJSPXNI-IRIUXVKKSA-N Thr-Glu-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 LKEKWDJCJSPXNI-IRIUXVKKSA-N 0.000 description 1
- NCXVJIQMWSGRHY-KXNHARMFSA-N Thr-Leu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O NCXVJIQMWSGRHY-KXNHARMFSA-N 0.000 description 1
- ABWNZPOIUJMNKT-IXOXFDKPSA-N Thr-Phe-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O ABWNZPOIUJMNKT-IXOXFDKPSA-N 0.000 description 1
- MXNAOGFNFNKUPD-JHYOHUSXSA-N Thr-Phe-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MXNAOGFNFNKUPD-JHYOHUSXSA-N 0.000 description 1
- PRTHQBSMXILLPC-XGEHTFHBSA-N Thr-Ser-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PRTHQBSMXILLPC-XGEHTFHBSA-N 0.000 description 1
- RVMNUBQWPVOUKH-HEIBUPTGSA-N Thr-Ser-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RVMNUBQWPVOUKH-HEIBUPTGSA-N 0.000 description 1
- GRIUMVXCJDKVPI-IZPVPAKOSA-N Thr-Thr-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GRIUMVXCJDKVPI-IZPVPAKOSA-N 0.000 description 1
- LVRFMARKDGGZMX-IZPVPAKOSA-N Thr-Tyr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CC1=CC=C(O)C=C1 LVRFMARKDGGZMX-IZPVPAKOSA-N 0.000 description 1
- KVEWWQRTAVMOFT-KJEVXHAQSA-N Thr-Tyr-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O KVEWWQRTAVMOFT-KJEVXHAQSA-N 0.000 description 1
- 208000000728 Thymus Neoplasms Diseases 0.000 description 1
- RSUXQZNWAOTBQF-XIRDDKMYSA-N Trp-Arg-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N RSUXQZNWAOTBQF-XIRDDKMYSA-N 0.000 description 1
- ZCPCXVJOMUPIDD-IHPCNDPISA-N Trp-Asp-Phe Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=CC=C1 ZCPCXVJOMUPIDD-IHPCNDPISA-N 0.000 description 1
- DQDXHYIEITXNJY-BPUTZDHNSA-N Trp-Gln-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N DQDXHYIEITXNJY-BPUTZDHNSA-N 0.000 description 1
- NXQAOORHSYJRGH-AAEUAGOBSA-N Trp-Gly-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 NXQAOORHSYJRGH-AAEUAGOBSA-N 0.000 description 1
- KIMOCKLJBXHFIN-YLVFBTJISA-N Trp-Ile-Gly Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O)=CNC2=C1 KIMOCKLJBXHFIN-YLVFBTJISA-N 0.000 description 1
- SAKLWFSRZTZQAJ-GQGQLFGLSA-N Trp-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N SAKLWFSRZTZQAJ-GQGQLFGLSA-N 0.000 description 1
- UJRIVCPPPMYCNA-HOCLYGCPSA-N Trp-Leu-Gly Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N UJRIVCPPPMYCNA-HOCLYGCPSA-N 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- CDRYEAWHKJSGAF-BPNCWPANSA-N Tyr-Ala-Met Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(O)=O CDRYEAWHKJSGAF-BPNCWPANSA-N 0.000 description 1
- CRWOSTCODDFEKZ-HRCADAONSA-N Tyr-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O CRWOSTCODDFEKZ-HRCADAONSA-N 0.000 description 1
- DYEGCOJHFNJBKB-UFYCRDLUSA-N Tyr-Arg-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 DYEGCOJHFNJBKB-UFYCRDLUSA-N 0.000 description 1
- MBFJIHUHHCJBSN-AVGNSLFASA-N Tyr-Asn-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MBFJIHUHHCJBSN-AVGNSLFASA-N 0.000 description 1
- NLMXVDDEQFKQQU-CFMVVWHZSA-N Tyr-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NLMXVDDEQFKQQU-CFMVVWHZSA-N 0.000 description 1
- MNMYOSZWCKYEDI-JRQIVUDYSA-N Tyr-Asp-Thr 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@@H](C)O)C(O)=O MNMYOSZWCKYEDI-JRQIVUDYSA-N 0.000 description 1
- SMLCYZYQFRTLCO-UWJYBYFXSA-N Tyr-Cys-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O SMLCYZYQFRTLCO-UWJYBYFXSA-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
- XDGPTBVOSHKDFT-KKUMJFAQSA-N Tyr-Met-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(O)=O XDGPTBVOSHKDFT-KKUMJFAQSA-N 0.000 description 1
- YYLHVUCSTXXKBS-IHRRRGAJSA-N Tyr-Pro-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O YYLHVUCSTXXKBS-IHRRRGAJSA-N 0.000 description 1
- RWOKVQUCENPXGE-IHRRRGAJSA-N Tyr-Ser-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RWOKVQUCENPXGE-IHRRRGAJSA-N 0.000 description 1
- ITDWWLTTWRRLCC-KJEVXHAQSA-N Tyr-Thr-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ITDWWLTTWRRLCC-KJEVXHAQSA-N 0.000 description 1
- BIVIUZRBCAUNPW-JRQIVUDYSA-N Tyr-Thr-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O BIVIUZRBCAUNPW-JRQIVUDYSA-N 0.000 description 1
- RIVVDNTUSRVTQT-IRIUXVKKSA-N Tyr-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O RIVVDNTUSRVTQT-IRIUXVKKSA-N 0.000 description 1
- ZZDYJFVIKVSUFA-WLTAIBSBSA-N Tyr-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O ZZDYJFVIKVSUFA-WLTAIBSBSA-N 0.000 description 1
- LDKDSFQSEUOCOO-RPTUDFQQSA-N Tyr-Thr-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LDKDSFQSEUOCOO-RPTUDFQQSA-N 0.000 description 1
- KLQPIEVIKOQRAW-IZPVPAKOSA-N Tyr-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O KLQPIEVIKOQRAW-IZPVPAKOSA-N 0.000 description 1
- WYOBRXPIZVKNMF-IRXDYDNUSA-N Tyr-Tyr-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(O)=O)C1=CC=C(O)C=C1 WYOBRXPIZVKNMF-IRXDYDNUSA-N 0.000 description 1
- KRXFXDCNKLANCP-CXTHYWKRSA-N Tyr-Tyr-Ile Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 KRXFXDCNKLANCP-CXTHYWKRSA-N 0.000 description 1
- KSGKJSFPWSMJHK-JNPHEJMOSA-N Tyr-Tyr-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KSGKJSFPWSMJHK-JNPHEJMOSA-N 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- DDRBQONWVBDQOY-GUBZILKMSA-N Val-Ala-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O DDRBQONWVBDQOY-GUBZILKMSA-N 0.000 description 1
- LTFLDDDGWOVIHY-NAKRPEOUSA-N Val-Ala-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N LTFLDDDGWOVIHY-NAKRPEOUSA-N 0.000 description 1
- RKIGNDAHUOOIMJ-BQFCYCMXSA-N Val-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 RKIGNDAHUOOIMJ-BQFCYCMXSA-N 0.000 description 1
- MJXNDRCLGDSBBE-FHWLQOOXSA-N Val-His-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N MJXNDRCLGDSBBE-FHWLQOOXSA-N 0.000 description 1
- MYLNLEIZWHVENT-VKOGCVSHSA-N Val-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](C(C)C)N MYLNLEIZWHVENT-VKOGCVSHSA-N 0.000 description 1
- QRVPEKJBBRYISE-XUXIUFHCSA-N Val-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N QRVPEKJBBRYISE-XUXIUFHCSA-N 0.000 description 1
- YMTOEGGOCHVGEH-IHRRRGAJSA-N Val-Lys-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O YMTOEGGOCHVGEH-IHRRRGAJSA-N 0.000 description 1
- HPANGHISDXDUQY-ULQDDVLXSA-N Val-Lys-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N HPANGHISDXDUQY-ULQDDVLXSA-N 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- MGSDFCKWGHNUSM-QVPNGJTFSA-N alpha-L-Fucp-(1->2)-beta-D-Galp-(1->3)-beta-D-GlcpNAc Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]([C@H](O)O[C@H](CO)[C@H]2O)NC(C)=O)O[C@H](CO)[C@H](O)[C@@H]1O MGSDFCKWGHNUSM-QVPNGJTFSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 1
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 1
- 108010020688 glycylhistidine Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 108010005942 methionylglycine Proteins 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012634 optical imaging Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 108010083476 phenylalanyltryptophan Proteins 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 108010048818 seryl-histidine Proteins 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 101150047061 tag-72 gene Proteins 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 201000009377 thymus cancer Diseases 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
- C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464403—Receptors for growth factors
- A61K39/464404—Epidermal growth factor receptors [EGFR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464493—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; Prostatic acid phosphatase [PAP]; Prostate-specific G-protein-coupled receptor [PSGR]
- A61K39/464495—Prostate specific membrane antigen [PSMA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3007—Carcino-embryonic Antigens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/49—Breast
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/54—Pancreas
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/11—Epidermal growth factor [EGF]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/15—Transforming growth factor beta (TGF-β)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2302—Interleukin-2 (IL-2)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2307—Interleukin-7 (IL-7)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/51—B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/515—CD3, T-cell receptor complex
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/599—Cell markers; Cell surface determinants with CD designations not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/998—Proteins not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
- C12N5/0637—Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Pregnancy & Childbirth (AREA)
- General Chemical & Material Sciences (AREA)
- Gynecology & Obstetrics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Engineering & Computer Science (AREA)
- Developmental Biology & Embryology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本揭示內容係關於用以誘發T細胞分化及/或增生的方法及其用途。在本發明方法中,將分離自一個體的周邊血液單核球細胞(peripheral blood mononuclear cell,PBMC)與雙功抗體(bi-specific antibody,BsAb)培養在一培養液中,據以使該PBMC分化為T細胞。各T細胞表面具有一抗-腫瘤抗原部及一抗-CD3部。本揭示內容亦提供用以治療罹患癌症之個體的方法及醫藥套組。
Description
本揭示內容係關於癌症治療。具體來說,本揭示內容係關於具抗原專一性的T細胞及其於抑制癌症生長或轉移的用途。
T細胞為一種數量稀少的細胞群,在周邊血液中僅可發現5至10%的CD4+
T細胞。藉由細胞激素(例如IL-2、IL-4及IL-5)刺激,加上抗-CD28抗體,可促進T細胞增生。然而,其數量仍不足以進行任何臨床應用,例如涉及增加活化的T細胞數量,再將其移轉回人體(例如嵌合抗原受體(chimeric antigen receptor,CAR)T細胞治療)的應用。
用以活化T細胞或誘發T細胞分化的其中一種方式係利用抗-CD3抗體來活化由CD3調節的訊息傳導路徑來達成。及至目前為止,曾有研究人員以小鼠之抗-人類IgG2a同型(OKT3)單株抗體進行由CD3抗原複合物誘導的人類T細胞活化,其係誘發一種等同於伴刀豆球蛋白A(concanavalin A,Con A)誘導的細胞分裂反應而造成。然而,使用非人類來源的單株抗體(例如鼠類OKT3抗體)主要顧慮之一在於其免疫原性對接受者造成的影響,在某些個案中,會引起致命的過敏反應。鼠類OKT3抗體活化的人類T細胞,將不可避免地在該T細胞表面攜帶鼠類蛋白片段,因而對其接受者構成潛在威脅。
有鑑於前述情形,相關領域仍需研發可取代鼠類OKT3抗體的低免疫原性抗體,以及排除使用鼠類OKT3抗體來活化人類T細胞的改良方法。
本揭示內容提供藉由本揭示內容雙功抗體(bi-specific antibody,BsAb)來分化及增生的T細胞,及其於治療癌症的用途。
因此,本揭示內容的第一態樣提供了一種用以誘發T細胞分化及/或增生的方法,其中各T細胞表面具有一抗-腫瘤抗原部(anti-tumor antigen moiety)及一抗-CD3部(anti-CD3 moiety)。該方法包括,將一周邊血液單核球細胞(peripheral blood mononuclear cell,PBMC)與一雙功抗體培養在一培養液中,據以使該PBMC分化為T細胞,其中各BsAb包含一對應至該T細胞之抗-腫瘤抗原部的腫瘤抗原結合位點,以及一對應至該T細胞之抗-CD3部的CD3結合位點,且該BsAb非鼠類OKT3抗體。
依據本揭示內容的實施方式,各BsAb具有一單鏈變異片段(single chain variable fragment,scFv)、一抗原結合片段(Fab)、一F(ab’)2
或一IgG的結構。
依據本揭示內容的實施方式,各BsAb的腫瘤抗原結合位點可結合至上皮生長因子受器(epidermal growth factor receptor,EGFR)、計畫性細胞死亡-配體1(programmed cell death-ligand 1,PD-L1)或前列腺專一性的膜抗原(prostate specific membrane antigen,PSMA)。
依據本揭示內容非必要的實施方式,該培養液更包含一細胞激素,該細胞激素係選自由IL-2、TGF-β及其組合所組成的群組。在一較佳實施方式中,該培養液包含IL-2及TGF-β,且所生成的T細胞為調控型T細胞(regulatory T cell)。
依據本揭示內容的實施方式,在各BsAb中,該腫瘤抗原結合位點包含一與序列編號:69、77、84、90、96、102、108、114或120具有至少90%序列相似度的抗-腫瘤抗原scFv;以及該CD3結合位點包含一與序列編號:67具有至少90%序列相似度的抗-CD3 VL-Ck域(domain),以及一與序列編號:68具有至少90%序列相似度的抗-CD3 VH-CH1域。
依據本揭示內容的實施方式,在各BsAb中,該腫瘤抗原結合位點包含一與序列編號:70、78、85、91、97、109或121具有至少90%序列相似度的抗-腫瘤抗原scFv;以及該CD3結合位點包含一與序列編號:66或79具有至少90%序列相似度的抗-CD3 scFv。
依據本揭示內容的實施方式,在各BsAb中,該腫瘤抗原結合位點包含一與序列編號:64、75、82、88、94、100、106、112或118具有至少90%序列相似度的抗-腫瘤抗原VL-Ck域;以及一與序列編號:65、76、83、89、95、101、107、113或119具有至少90%序列相似度的抗-腫瘤抗原VH-CH1域;以及該CD3結合位點包含一與序列編號:66或79具有至少90%序列相似度的抗-CD3 scFv。
依據本揭示內容的實施方式,在各BsAb中,該腫瘤抗原結合位點包含一與序列編號:73、80、86、92、98、104、110、116或122具有至少90%序列相似度的抗-腫瘤抗原VL-Ck域,以及一與序列編號:74、81、87、93、99、105、111、117,或123具有至少90%序列相似度的抗-腫瘤抗原VH-CH1-Fc域;以及該CD3結合位點包含一與序列編號:71具有至少90%序列相似度的抗-CD3 VL-Ck域,以及一與序列編號:72具有至少90%序列相似度的抗-CD3 VH-CH1-Fc域。
實務上,可將依據本發明方法所製備的具抗原專一性T細胞與上述人源化之BsAb混和成一混合物,接著將該混合物投予至一有需要癌症治療之個體。
因此,本揭示內容的第三態樣提供了一種用以癌症治療的醫藥套組。該醫藥套組包含依據本發明方法分化及增生的T細胞,以及本揭示內容的人源化BsAb。
本揭示內容的第四態樣提供了一種用以治療一罹患癌症之個體的方法。該方法包括,對該個體投予一有效量之藉由上述方法所製備的T細胞,或一有效量之經本揭示內容BsAb修飾的鼠類OKT3 T細胞。
依據某些實施方式,將鼠類OKT3 T細胞與本揭示內容BsAb培養在一培養液中,可將該T細胞進行修飾而使其表面攜帶(arm)本揭示內容BsAb。此外或非必要地,該培養液更包含一細胞激素,該細胞激素係選自由IL-2、IL-7及其組合所組成的群組。
較佳地,對個體投予本揭示內容T細胞的數量為該個體每公斤體重1×104
至1×107
個細胞。該數量可以單一劑量形式,或以一劑以上的較小劑量形式投予。
本發明方法可用以治療不同癌症,特別是會表現EGFR、PSMA或PD-L1的癌症。例示性之可利用本發明方法來治療之癌症包括,但不限於,膀胱癌、膽癌、骨癌、腦瘤、乳癌、子宮頸癌、結直腸癌、大腸癌、食道癌、上皮癌、胃癌、胃腸基質瘤(gastrointestinal stromal tumor,GIST)、神經膠質瘤、淋巴譜系之造血組織腫瘤、肝癌、非何杰金氏淋巴癌(non-Hodgkin’s lymphoma)、卡波西氏肉瘤、白血病、肺癌、淋巴瘤、小腸癌、黑色素瘤、骨髓性白血病、胰臟癌、前列腺癌、視網膜母細胞瘤、卵巢癌、腎細胞癌、脾臟癌、鱗狀細胞癌、甲狀腺癌及濾泡狀甲狀腺癌。
依據本揭示內容一具體實施方式,該癌症為三陰性乳癌。依據本揭示內容另一具體實施方式,該癌症為惡性胰臟癌。
本揭示內容一或多個實施方式的詳細內容及說明闡述如下。在參閱以下的詳細說明及申請專利範圍後,本揭示內容的其餘特徵及優點將顯而易見。
下文提供了詳細說明及附隨圖式係為了使本揭示內容實施例的敘述更加詳盡與完備,而非代表用以理解或運用本揭示內容實施例的唯一形式。本說明書闡述實施例的功能以及用以建構與操作此等實施例的步驟順序。然而,亦可利用其他實施例來達成相同或均等的功能與步驟順序。
I. 定義
「抗體」(antibody)一詞係以最廣泛的意義使用,具體涵蓋單株抗體、多株抗體、多重專一性抗體(例如雙功抗體),以及抗體片段(只要其展現欲求的生物學活性即可),也就是說,當處於一蛋白及/或其他分子的複合混合物中,抗體會優先辨識其標的抗原時並專一結合該抗原。
在此使用之「單株抗體」(monoclonal antibody)係指一種自一實質上同質的抗體群中所獲得的抗體,且無須藉由任何特定方法製備該抗體。與多株抗體相反的是,多株抗體通常包括對抗不同抗原決定位(epitope)的不同抗體,而不同的單株抗體各自對抗抗原上的單一決定位置(即抗原決定位)。本揭示內容單株抗體可藉由融合瘤方法(hybridoma method)或藉由重組DNA方法來製備。單株抗體在本文中具體包括「嵌合」(chimeric)或「重組」(recombinant)抗體,其中重鏈及/或輕鏈的一部分係相同於或同源對應於一衍生自一特定物種或屬於一抗體種類(class)或亞種(subclass)的抗體序列,而該鏈的其餘部分則相同於或同源對應於一衍生自另一物種或屬於另一抗體種類或亞種,以及此類抗體片段的抗體序列,只要其展現欲求的生物學活性即可。
非人類(例如鼠類)抗體的「人源化」(humanized)形式為嵌合抗體(chimeric antibodies),其含有最少的衍生自非人類免疫球蛋白(non-human immunoglobulin)序列。人源化抗體為人類免疫球蛋白,其高度變異區殘基(hypervariable region residues)由非人類物種(例如小鼠、大鼠、兔子或非人類靈長類)中具有欲求的專一性或親和性的高度變異區殘基所取代。在某些情形下,人類免疫球蛋白的Fv框架區(framework region,FR)殘基由對應的非人類殘基所取代。一般來說,人源化抗體會包含實質上所有的至少一個(通常為兩個)的變異域,其中所有的或實質上所有的FR區為人類免疫球蛋白序列。人源化抗體非必要性地包含至少一部分的免疫球蛋白恆定區(constant region,Fc),其通常為一人類免疫球蛋白之Fc。
「雙功抗體(bi-specific antibody,BsAb)」一詞係指一抗體具有至少兩種不同的抗原專一性。在較佳實施方式中,本揭示內容BsAb具有二個抗原結合位點,其中一個對抗一腫瘤抗原(例如EGFR、PD-L1、HER2、PSMA及其他),而另一個對抗一T細胞受體(例如CD3)。
「鏈接物」(linker)或「胜肽鏈接物」(peptide linker)一詞在本揭示內容中可交替使用,係指一種具有天然或合成胺基酸殘基,用於連接二種多肽的胜肽。舉例來說,胜肽鏈接物可用於連接VH及VL,以形成單鏈變異片段(例如scFv);或將scFv連接全長抗體以形成本揭示內容BsAb。較佳地,鏈接物為一具有至少5個胺基酸殘基長度的胜肽,例如5至100個胺基酸殘基長度,更佳地,10至30胺基酸殘基長度。scFv中的鏈接物為一具有至少5個胺基酸殘基長度的胜肽,較佳地為15至20個胺基酸殘基長度。較佳地,鏈接物包含一序列的(Gn
S)m
,其中G = 甘胺酸(glycine),S = 絲胺酸(serine),且n及m為一介於1至4之間各自獨立的數字。在一實施例中,鏈接物包含一(G2
S)4
的序列。在另一實施例中,鏈接物包含一(G4
S)3
的序列。
「癌症」(cancer)或「腫瘤」(tumor)一詞在本揭示內容中可交替使用,較佳地,係指在哺乳動物(特別是人類)中的生理條件下通常具有未受控制的細胞生長特性。在此方面的癌症包括轉移癌(metastases cancer),及/或抗藥性癌症(drug-resistant cancer)。就癌症來說,較佳的為該些會展現下列分子:αvβ3、α5β1、癌胚胎抗原(carcinoembryonic antigen,CEA)、細胞毒性T-淋巴球相關抗原4(cytotoxic T-lymphocyte–associated antigen 4,CTLA4)、CD3、CD19、CD20、CD30、CD50、CIAX、cMuc1、ED-B、表皮生長因子受體(epidermal growth factor receptor,EGFR)、表皮細胞黏附分子(epithelia cell adhesion molecules,EpCAM)、生成促紅血球形成素之肝細胞A3(erythropoietin-producing hepatocellular A3,EPHA3)、家族性腺瘤息肉症(familial adenomatous polyposis,FAP)、gpA33、Globo-H、人類表皮生長因子受體2(human epidermal growth factor receptor 2,HER2)、HER3、類胰島素生長因子1受體(insulin like growth factor 1 receptor,IGF1R)、OC183B2、血小板-衍生生長因子受體(platelet-derived growth factor receptor,PDGFR)、計畫性細胞死亡-配體1(programmed cell death-ligand 1,PD-L1)、前列腺專一性的膜抗原(prostate specific membrane antigen,PSMA)、Ley
、MET、腫瘤-相關醣蛋白72(tumor-associated glycoprotein 72,TAG72)、生腱蛋白(tenascin)、血管內皮生長因子受體(vascular endothelial growth factor receptor,VEGFR)、VEGFR-2及/或VEGFR-3表現量增加的癌症。因此,可利用本揭示內容治療的癌症或腫瘤為乳癌、肺癌、大腸癌、結直腸癌、脾臟癌、腎癌、肝癌、膀胱癌、頭頸部癌、卵巢癌、前列腺癌、腦癌、胰臟癌、皮膚癌、骨癌、血癌、胸腺癌、子宮癌、睾丸癌、子宮頸癌和神經元癌。更具體來說,該癌症係選自由膀胱癌、膽癌、骨癌、腦瘤、乳癌、子宮頸癌、結直腸癌、大腸癌、食道癌、上皮癌、胃癌、胃腸基質瘤(GIST)、神經膠質瘤、淋巴譜系之造血組織腫瘤、肝癌、非何杰金氏淋巴癌、卡波西氏肉瘤、白血病、肺癌、淋巴瘤、小腸癌、黑色素瘤、骨髓性白血病、胰臟癌、前列腺癌、視網膜母細胞瘤、卵巢癌、腎細胞癌、脾臟癌、鱗狀細胞癌、甲狀腺癌及濾泡狀甲狀腺癌所組成的群組。在一實施例中,該癌症為惡性胰臟癌。在另一實施例中,該癌症為三陰性乳癌(TNBC)。
在此使用之「一有效量」(an effective amount)一詞係指一有效的量,在劑量及必要的時間內,對癌症治療可達到欲求的治療結果。
「投予」(administered、administering或administration)一詞在本文中可交替使用,係指直接投予本揭示內容BsAb或其組合來分化及增生T細胞。
「個體」(subject)或「病患」(patient)一詞係指一種可用本揭示內容組合物及/或方法治療的動物,包括人類。除非有具體指出其中一種性別,「個體」或「病患」一詞意指男性及女性二者。因此,「個體」或「病患」一詞包含任一種可自癌症治療獲益的哺乳動物。例示性之「個體」或「病患」包括,但不限於,人、大鼠、小鼠、豚鼠、猴子、豬、山羊、牛、馬、狗、貓、鳥及雞。在一例示性實施方式中,該病患為人類。
在此使用之「相同」(identical)或「相似度百分比」(percent identity)一詞係指當比較及排列序列(即序列比對)求最大序列對應值時,兩個或兩個以上序列或次序列相同或特定百分比的胺基酸殘基相同。為確認相似度百分比,序列以求取最佳排列結果為目的來進行排列(例如可在一第一胺基酸序列中引入間隙來達到與一第二胺基酸序列的最佳排列)。接著比較在對應的胺基酸位置上的胺基酸殘基。當該第一序列的一個位置由該第二序列對應位置的相同胺基酸殘基佔據時,則該分子在該位置是相同的。二序列之間的相似度百分比為該二序列共有的相同位置數目的函數(即%相似度 = 相同位置/位置的總數(例如,重疊位置)×100)。在某些實施例中,兩個序列長度相同。
除非上下文另有明確說明,單數形式「一」(a或an)及「該」(the)在本文中包括複數對象。
II. 發明敍述
因此,本揭示內容的第一態樣係提供具抗原專一性T細胞,特別是指藉由本揭示內容重組的雙功抗體(BsAb)活化(或誘發分化)的T細胞,該T細胞係由周邊血液單核球細胞(PBMC)轉換成表面帶有專一性抗-腫瘤抗原及抗-CD3片段的T細胞。因此,該些具抗原專一性T細胞將會更強有力地結合腫瘤細胞(包括惡性腫瘤細胞及三陰性乳癌(TNBC)細胞),因而可抑制該腫瘤細胞的生長及轉移。
1. 本揭示內容之BsAb
抗體屬於免疫球蛋白,其包括IgG、IgA、IgE、IgM及IgD等種類。血清中發現含量最豐富的免疫球蛋白為IgG,其結構具有四條鏈,兩條輕鏈及兩條重鏈;每一輕鏈具有二個結構域(domain)且每一重鏈具有四個結構域。抗原結合位點係位於片段抗原結合(Fab)區,該Fab包含變異輕鏈(variable light,VL)及變異重鏈(variable heavy,VH)結構域,以及恆定輕鏈(constant light,CL)及恆定重鏈(constant heavy,CH1)結構域。該重鏈的CH2及CH3結構域稱為可結晶片段(fragment crystallizable,Fc)區域。因此,全長的抗體重鏈自N端至C端為一種由一VH、一CH1、一絞鏈區(hinge region,HR)、一CH2及一CH3所組成的多肽;簡稱為VH-CH1-HR-CH2-CH3。全長的抗體輕鏈自N端往C端方向為一種由一VL及一CL所組成的多肽,簡稱為VL-CL,其中該CL可為κ(kappa)或λ(lambda)。目前認為IgG係一種藉由雙硫鍵(disulfide bonds,-S-S-)將二個重鏈結合在一起的異四聯體(heterotetramer),其中該雙硫鍵係介於CL結構域與CH1結構域之間及介於兩個重鏈的鉸鏈區之間。
如在上文「定義」章節所述,BsAb係指對不同抗原具有專一性的抗體;因此,本揭示內容之BsAb為一種重組抗體,其經改造而包含能夠分別結合二種不同抗原的序列,其中該二抗原為一腫瘤抗原及一CD3抗原。因此,本揭示內容的各BsAb包含一抗-腫瘤抗原序列及一抗-CD3序列。本揭示內容研發不同的重組BsAb,並利用其來誘發單核球細胞分化及/或增生為表面帶有對應該BsAb抗原之具抗原專一性T細胞。
第1圖為闡述本揭示內容BsAb之結構示意圖。
在某些實施方式中,本揭示內容BsAb係單體(monomeric)二價(divalent)的雙功抗體,其中對抗一腫瘤抗原(即抗-腫瘤抗原Fab)的一VH-CH1域及一輕鏈VL-Ck係融合至一抗-CD3 scFv(scFv),其中該scFv由一重鏈變異域(VH)及一輕鏈變異域(VL)所組成,簡稱為VH-VL(第1圖之圖A)。在其他實施方式中,該單體二價BsAb在其結構中包含一抗-CD3 Fab,其中該抗-CD3 Fab係由對抗CD3的一VH-CH1域及一輕鏈VL-Ck所組成,且該抗-CD3 Fab係經由一胜肽鏈接物融合至一對抗一腫瘤抗原scFv(第1圖之圖B)。在其他實施方式中,本揭示內容的單體二價BsAb係由一抗-腫瘤抗原scFv及一抗-CD3 scFv所組成,其中該二個scFv係經由一胜肽鏈接物連接(第1圖之圖C)。在再其他實施方式中,本揭示內容之BsAb具有一「孔中球」(knob into hole)的結構,其中第一重鏈CH3域的球狀凸起部分係藉由將數個胺基酸側鏈取代為替代胺基酸而造成,且第二重鏈CH3域對應於該球狀凸起部分的孔狀凹陷部分係藉由將適當胺基酸側鏈取代為替代胺基酸而造成。該BsAb「孔中球」結構的示意圖繪示於第1圖之圖D。該孔中球技術為本領域習知技藝人士所熟知,且可方便地用來製備本揭示內容之BsAb。
編碼本揭示內容BsAb的DNA係衍生自已知抗體,將其基因進行選殖及融合來建立具有欲求的人源化BsAb之DNA構築載體。詳細的製備方法闡述於實施例。
因此,可建立具有雙結合位點的重組BsAb,其中該結合位點可結合至一T細胞之CD3及一腫瘤抗原,且該腫瘤抗原係選自由PSMA、EGFR、PD-L1、CEA、FAP、EpCAM、HER2及VCAM-1所組成的群組。
依據某些實施方式,可製備抗-PSMA/抗-CD3 BsAb。在一實施例中,該抗-PSMA/抗-CD3 BsAb包含一PSMA結合位點(包含一序列編號:65的VH-CH1域及一序列編號:64的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-PSMA/抗-CD3 BsAb包含一PSMA結合位點(包含一序列編號:69的抗-PSMA scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-PSMA/抗-CD3 BsAb包含一PSMA結合位點(包含一序列編號:70的抗-PSMA scFv);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在再一其他實施例中,該抗-PSMA/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該PSMA結合位點包含一序列編號:73的VL-Ck及一序列編號:74的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-EGFR/抗-CD3 BsAb。在一實施例中,該抗-EGFR/抗-CD3 BsAb包含一EGFR結合位點(包含一序列編號:76的VH-CH1域及一序列編號:75的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-EGFR/抗-CD3 BsAb包含一EGFR結合位點(包含一序列編號:77的抗-EGFR scFv;以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-EGFR/抗-CD3 BsAb包含一EGFR結合位點(包含一序列編號:78的抗-EGFR scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-EGFR/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該EGFR結合位點包含一序列編號:80的VL-Ck及一序列編號:81的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-PD-L1/抗-CD3 BsAb。在一實施例中,該抗-PD-L1/抗-CD3 BsAb包含一PD-L1結合位點(包含一序列編號:83的VH-CH1域及一序列編號:82的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-PD-L1/抗-CD3 BsAb包含一PD-L1結合位點(包含一序列編號:84的抗-PD-L1 scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-PD-L1/抗-CD3 BsAb包含一PD-L1結合位點(包含一序列編號:85的抗-PD-L1 scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-PD-L1/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該PD-L1結合位點包含一序列編號:86的VL-Ck及一序列編號:87的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-HER2/抗-CD3 BsAb。在一實施例中,該抗-HER2/抗-CD3 BsAb包含一HER2結合位點(包含一序列編號:89的VH-CH1域及一序列編號:88的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-HER2/抗-CD3 BsAb包含一HER2結合位點(包含一序列編號:90的抗-HER2 scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-HER2/抗-CD3 BsAb包含一HER2結合位點(包含一序列編號:91的抗-HER2 scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-HER2/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該HER2結合位點包含一序列編號:92的VL-Ck及一序列編號:93的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-FAP/抗-CD3 BsAb。在一實施例中,該抗-FAP/抗-CD3 BsAb包含一FAP結合位點(包含一序列編號:95的VH-CH1域及一序列編號:94的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-FAP/抗-CD3 BsAb包含一FAP結合位點(包含一序列編號:96的抗-FAP scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-FAP/抗-CD3 BsAb包含一FAP結合位點(包含一序列編號:97的抗-FAP scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-FAP/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該FAP結合位點包含一序列編號:98的VL-Ck及一序列編號:99的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-EpCAM(MOC31)/抗-CD3 BsAb。在一實施例中,該抗-EpCAM(MOC31)/抗-CD3 BsAb包含一EpCAM(MOC31)結合位點(包含一序列編號:101的VH-CH1域及一序列編號:100的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-EpCAM(MOC31)/抗-CD3 BsAb包含一EpCAM(MOC31)結合位點(包含一序列編號:102的抗-EpCAM(MOC31) scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-EpCAM(MOC31)/抗-CD3 BsAb包含一EpCAM(MOC31)結合位點(包含一序列編號:103的抗-EpCAM(MOC31) scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-EpCAM(MOC31)/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該EpCAM(MOC31)結合位點包含一序列編號:104的VL-Ck及一序列編號:105的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-EpCAM(MT201)/抗-CD3 BsAb。在一實施例中,該抗-EpCAM(MT201)/抗-CD3 BsAb包含一EpCAM(MT201)結合位點(包含一序列編號:107的VH-CH1域及一序列編號:106的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-EpCAM(MT201)/抗-CD3 BsAb包含一EpCAM(MT201)結合位點(包含一序列編號:108的抗-EpCAM(MT201) scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-EpCAM(MT201)/抗-CD3 BsAb包含一EpCAM(MT201)結合位點(包含一序列編號:109的抗-EpCAM(MT201) scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-EpCAM(MT201)/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該EpCAM(MT201)結合位點包含一序列編號:110的VL-Ck及一序列編號:111的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-CEA/抗-CD3 BsAb。在一實施例中,該抗-CEA/抗-CD3 BsAb包含一CEA結合位點(包含一序列編號:113的VH-CH1域及一序列編號:112的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-CEA/抗-CD3 BsAb包含一CEA結合位點(包含一序列編號:114的抗-CEA scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-CEA/抗-CD3 BsAb包含一CEA結合位點(包含一序列編號:115的抗-CEA scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-CEA/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該CEA結合位點包含一序列編號:116的VL-Ck及一序列編號:117的VH1-CH1-Fc孔狀凹陷域。
依據某些實施方式,可製備抗-VCAM1/抗-CD3 BsAb。在一實施例中,該抗-VCAM1/抗-CD3 BsAb包含一VCAM1結合位點(包含一序列編號:119的VH-CH1域及一序列編號:118的VL-Ck域);以及一CD3結合位點(包含一序列編號:66的抗-CD3 scFv)。在另一實施例中,該抗-VCAM1/抗-CD3 BsAb包含一VCAM1結合位點(包含一序列編號:120的抗-VCAM1 scFv);以及一CD3結合位點(包含一序列編號:68的VH-CH1域及一序列編號:67的VL-Ck域)。在一其他實施例中,該抗-VCAM1/抗-CD3 BsAb包含一VCAM1結合位點(包含一序列編號:121的抗-VCAM1 scFv);以及一CD3結合位點(包含一序列編號:79的抗-CD3 scFv)。在再一其他實施例中,該抗-VCAM1/抗-CD3 BsAb具有一「孔中球」結構,其中該CD3結合位點包含一序列編號:71的VL-Ck及一序列編號:72的VH-CH1-Fc球狀凸起域;以及該VCAM1結合位點包含一序列編號:122的VL-Ck及一序列編號:123的VH1-CH1-Fc孔狀凹陷域。
依據本揭示內容的其他實施方式,可製備抗-CD3 VH及CL的人源化OKT3,該些序列(參照表39至42)可與本揭示內容所述相關抗-腫瘤抗原序列融合以製備欲求的BsAb。
2. 藉由本揭示內容BsAb活化具抗原專一性T細胞
可利用本揭示內容BsAb來誘發單核球細胞(例如周邊血液單核球細胞)分化及增生成本揭示內容具抗原專一性T細胞。因此,本揭示內容一態樣係關於製備具抗原專一性的T細胞,其表面分別包含一抗-腫瘤抗原部及一抗-CD3部。
因此,本揭示內容涵蓋一種用以誘發T細胞分化及/或增生的方法。該方法包含,將採集自一個體的周邊血液單核球細胞(PBMC)與本揭示內容雙功抗體(BsAb)培養在一培養液中,據以使該PBMC分化為T細胞,並將該分化的T細胞進行增殖,其中,各BsAb包含一對應至各T細胞上之抗-腫瘤抗原部的腫瘤抗原結合位點,及一對應至各T細胞上之抗-CD3部的CD3結合位點,且該BsAb非鼠類OKT3抗體。
可利用本領域習知技藝人士所知的任一方法自一個體的新鮮血液中分離PBMC,例如藉由等密度離心(density centrifugation)(Ficoll-Paque),因血液的不同成分具有不同的密度而可據以分離。
為達到T細胞的分化及增生,可將分離的PBMC與本揭示內容任一BsAb培養在一普通培養液中一段足夠的時間,舉例來說,至少7天,例如7、8、9、10、11、12、13及14天;較佳地,至少14天。在某些實施方式中,培養7天後CD3+
T細胞的數量倍增。在其他實施方式中,繼續培養14天,CD3+
T細胞的數量增加3倍。此外或非必要地,培養液可包括細胞激素,例如IL-2、IL-7及其組合。
依據本揭示內容的實施方式,所製備的T細胞表面,分別包含一對應至BsAb抗-腫瘤抗原的抗-腫瘤抗原部,及一對應至BsAb抗-CD3的抗-CD3部。在某些實施例中,所製備的T細胞表面分別包含抗-PSMA及抗-CD3部。在其他實施例中,所製備的T細胞表面分別包含抗-EGFR及抗-CD3部。在再其他實施例中,所製備的T細胞表面分別包含抗-PD-L1及抗-CD3部。
依據本揭示內容的再其他實施方式,將PBMC與該本揭示內容BsAb培養至少7天後,可製備周邊衍生調控型T細胞,該T細胞表面出現細胞標識分子FoxP3。在此情形下,該培養液除細胞激素IL-2之外,更包含抗-CD28抗體。
依據本揭示內容的實施方式,本揭示內容具抗原專一性T細胞(包括周邊衍生調控型T細胞)不僅對於腫瘤細胞展現強有力的結合親和力,亦生產較高量的細胞激素,包括,但不限於,IL-2、IFN-γ、TNF-α、顆粒酶B及穿孔素。因此,相較於藉由鼠類OKT3抗體活化的T細胞,上述該些T細胞對於腫瘤細胞(包括惡性癌細胞及TNBC細胞)具有更高的細胞毒性功效。
3. 治療癌症的方法
3.1 利用具抗原專一性的T細胞來治療癌症
因此,本揭示內容的再一態樣係提供一種用以治療癌症的方法。該方法利用第2章節所述具抗原專一性T細胞的優勢,對一罹患癌症之個體投予一有效量之T細胞,或進一步以BsAb修飾的T細胞,據以抑制(suppress或inhibit)癌細胞的生長。
第2A圖為本發明方法之示意圖,首先自一個體的新鮮血液中分離PBMC,接著以一步法擴增及分化處理該分離的PBMC,以使該分化的T細胞攜帶分別對應該BsAb抗-腫瘤抗原及抗-CD3的部分。具體來說,該一步法擴增及分化處理,包括將PBMC與本揭示內容BsAb培養在一培養液中至少7天,更佳地,至少14天,直到製備足夠數量的欲求的T細胞。此外或非必要地,可進一步以BsAb修飾製得的具抗原專一性T細胞,在此情形下,將本揭示內容具抗原專一性T細胞進一步與本揭示內容BsAb作用的步驟稱為「一步法擴增、分化及修飾」(one-step expanding, differentiation and modification)處理,如第2A圖所述。
在某些實施方式中,對個體直接投予一有效量之該具抗原專一性T細胞(即未進一步以BsAb修飾)來治療癌症。在其他實施方式中,對該個體投予一有效量之該進一步以BsAb修飾的具抗原專一性T細胞來治療癌症。投予該個體的T細胞數量可約為個體每公斤體重1×104
至1×107
個細胞。在特定實施方式中,投予該個體的T細胞數量可約為個體每公斤體重1×105
至1×106
細胞。該劑量可以單一劑量形式,或選擇性地以一劑以上的較小劑量形式投予。
3.2 利用經本揭示內容BsAb修飾的鼠類OKT3 T細胞來治療癌症
在某些實施方式中,並非利用上述在第2章節中的具抗原專一性T細胞,而是利用進一步以本揭示內容BsAb修飾的鼠類OKT3 T細胞(即經由鼠類OKT3抗體活化PBMC所衍生的T細胞)來治療癌症。參照第2B圖,其類似於第2A圖,除鼠類OKT3 T細胞係經本揭示內容BsAb修飾,並投予該個體。類似於第2A圖的是,係藉由將鼠類OKT3 T細胞與本揭示內容BsAb培養來進行該修飾,據以使鼠類OKT3 T細胞攜帶該BsAb的抗-腫瘤抗原及抗-CD3。
依據本揭示內容的實施方式,至少500奈克,例如500、600、700、800、900、1,000、1,100、1,200、1,300、1,400、1,500、1,600、1,700、1,800、1,900、2,000、2,100、2,200、2,300、2,400、2,500、2,600、2,700、2,800、2,900及3,000奈克的本揭示內容BsAb方足以修飾鼠類OKT3 T細胞(例如3×105
細胞),以致使欲求的本揭示內容BsAb的抗-腫瘤抗原表現在該T細胞表面。在某些實施例中,鼠類OKT3 T細胞進一步以本揭示內容抗-PSMA/抗-CD3 BsAb修飾。在其他實施例中,相較於未經修飾的鼠類OKT3 T細胞,經本揭示內容抗-PSMA/抗-CD3 BsAb修飾的鼠類OKT3 T細胞可生產更高量的細胞激素,包括,但不限於,IL-2、IFN-γ、TNF-α、顆粒酶B及穿孔素。因此,相較於未經修飾的鼠類OKT3 T細胞,該些經修飾的鼠類OKT3 T細胞對於腫瘤細胞(包括惡性癌細胞及TNBC細胞)具有更高的細胞毒性功效。
可藉由任一種可有效將BsAb或T細胞傳遞至特定作用位置的途徑,對一哺乳動物(較佳為人類)投予本揭示內容之BsAb、具抗原專一性的T細胞,以及經修飾的鼠類OKT3 T細胞,例如經口、經鼻、經肺、經皮膚,例如被動式或離子導入輸送(iontophoretic delivery),或非經腸,例如經直腸、經儲槽(depot)、皮下、靜脈內、肌肉內、鼻內、小腦內(intracerebellar)、眼藥水或軟膏。當可理解,本揭示內容的劑量會隨病患而有所不同,不僅由於所選擇的癌症治療藥劑、投予途徑,以及該BsAb、該T細胞及/或其組合,在該病患體內引發欲求反應之能力,並可因下列因素:欲緩解病狀的疾病病況或嚴重程度、病患年齡、性別、體重、病患的狀態及所治療病理病狀的嚴重程度、病患隨後遵循的並行藥物或特殊飲食,以及本領域習知技藝人士將辨識的其他因素,該適當劑量最終由主治醫師裁量。可調節劑量以改進治療反應。治療有效量亦為一種癌症治療藥劑的治療有益效應超過任何毒性或有害效應的量。較佳地,BsAb、T細胞或其組合,係以癌細胞生長受到抑制的劑量投予一段時間。
現將參考以下實施方式更具體地描述本揭示內容,該等實施方式係出於示範性而非限制性的目的而提供。
實施例
材料及方法
細胞及動物
本揭示內容使用人類T淋巴球細胞株Jurkat T細胞(CD3+
)、人類前列腺腺癌細胞株LNCaP(PSMA+
/PD-L1+
)、人類大腸腺癌細胞株HT-29(EGFR+
)、惡性胰臟癌細胞株MIA PaCa-2(PD-L1+
)、三陰性乳癌(TNBC)細胞株MDA-MB-231(EGFR+
/PD-L1+
)及Expi293細胞。
一般來說,在37°C、5%CO2
下,將HT-29、MIA PaCa-2及MDA-MB-231細胞培養在基礎培養液(Dulbecco’s modified Eagle’s medium)(Sigma,St Louis,MO,USA)中,輔以10%的胎牛血清(FCS,HyClone,Logan,UT)、每毫升100單位之青黴素及每毫升100微克之鏈黴素。將Jurkat T及LNCaP細胞培養在包含具有相同補充物的RPMI-1640中。在37°C、5%CO2
下,將Expi293細胞培養在Expi293™表現培養液中。
SCID小鼠(6–8週齡)得自臺灣臺北市國家實驗研究院國家實驗動物中心。所有動物實驗皆依現行制度規範執行,並取得臺北醫學大學(臺灣臺北市)實驗室動物設施及病理學核心委員會核准。
製備重組BsAb
為製備本揭示內容之BsAb,將編碼抗-腫瘤抗原(例如抗-PSMA、抗-EGFR、抗-PD-L1及其他)及抗-CD3的核酸與其他DNA序列(例如訊息胜肽、IRES、鏈接物及其他)以全基因合成方式進行移植及融合,以建構欲求的構築載體。
接著在37°C、8%CO2
下,在Expi293細胞中(每25.5毫升7.5×107
細胞,加入30微克之核酸以進行轉染)將所製備的DNA構築載體進行增殖。藉由鎳-親和力層析法,自6天後收集的培養液中純化BsAb,並利用Pierce™之BCA蛋白分析套組來確認該BsAb的濃度。
製備人源化OKT3之VH及VL
為選擇用以進行互補性決定區(complementarity-determining region,CDR)移植的人類框架序列,發明人利用IgBLAST程式,將OKT3之VH及VL序列與美國國家生物技術資訊中心資料庫的人類生殖細胞系免疫球蛋白變異區及連接區的序列進行比較。發明人發現IGHV1-46^03/IGHJ4與OKT3之VH的變異區/連接區最為相似。發明人並發現IGKV1-39^01/IgKJ4與OKT3之VL的變異區及連接區最為相似。為建構人源化OKT3之VH,該CDR藉由Kabat等人(Sequences of Proteins of Immunological Interest. 5th ed. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health; 1991:103–511)的法則來確認,且將OKT3 VH的2個殘基(Thr 71及Lys 73)植入IGHV1-46^03/IGHJ4。為建構人源化OKT3之VL,該CDR藉由Kabat等人的法則來確認,且OKT3 VL的1個殘基(Tyr 71)植入IGKV1-39^01/IgKJ4。該人源化OKT3之VH及VL片段係以全基因合成方式建構。
分析純化之BsAb
將BsAb以10%的SDS-PAGE凝膠、在還原或非還原條件下進行電泳,接著以考馬斯藍(Coomassie Blue)進行染色。
分化T細胞
CD8+
T細胞。將分離自健康個體血液的周邊血液單核球細胞(PBMC)或初始的CD8+
T細胞以磷酸鹽緩衝生理鹽水(phosphate buffer solution,PBS)清洗,並以每毫升2×106
個細胞的濃度懸浮在AIM-V培養液中。接著在37°C、5%CO2
下,將該些懸浮細胞與BsAb(每毫升1-1,000奈克)及人源化IL-2(每毫升3,000國際單位)培養一段指定時間。在第7天及第14天分別收集部分該T細胞,並利用流式細胞分析進行分析。
CD4+
T細胞。CD4+
T細胞分化方法類似於CD8+
T細胞,除將PBMC以每毫升1×106
個細胞的濃度懸浮,並培養在具有BsAb(每毫升1-1,000奈克)及人源化IL-2(每毫升2,000國際單位)及IL-7(每毫升20國際單位)的AIM-V培養液中。
調控型T細胞。調控型T細胞的分化方法類似於CD8+
T細胞,除將PBMC或初始的CD4+
T細胞以每毫升1×106
個細胞的濃度懸浮,並培養在具有BsAb(每毫升1-1,000奈克)、抗-CD28抗體(每毫升100奈克),人源化IL-2(每毫升2,000國際單位)及D-甘露糖(每升25毫摩爾)的AIM-V培養液中。
流式細胞儀分析
辨識及/或標定(targeting)腫瘤專一性抗原。在4°C下,將BsAb(每毫升1微克)與LNCaP(PSMA+
/PD-L1+
)、HT-29(EGFR+
)、MDA-MB-231(EGFR+
/PD-L1+
)、MIA PaCa-2(PD-L1+
)或Jurkat(CD3+
)細胞(3×105
個細胞)作用60分鐘,接著在4°C下作用與小鼠抗-組胺酸抗體(每毫升1微克)及FITC標記的山羊F(ab)2抗-小鼠免疫球蛋白二級抗體(每毫升1微克)。利用FACSCalibur流式細胞儀(Becton Dickinson,Mountain View,CA,USA)測量螢光,接著以Flowjo(Tree Star Inc.,San Carlos,CA,USA)軟體進行分析。
T細胞分化。在4°C下,將分化的T細胞(3×105
個細胞)與FITC標記的抗-人類CD3抗體(每毫升1微克)、FITC標記的抗-人類CD4抗體(每毫升1微克)、FITC標記的抗-人類CD8抗體(每毫升1微克)或PE標記的抗-人類FoxP3抗體混和。以冷的PBS清洗後,利用FACSCalibur流式細胞儀(Becton Dickinson,Mountain View,CA,USA)測量活細胞數之螢光,接著以Flowjo(Tree Star Inc.,San Carlos,CA,USA)軟體進行分析。
殘留在T細胞表面之BsAb量。將T細胞或攜帶實施例1 BsAb的T細胞(3×105
個細胞)培養在一包含20%FCS的培養液中,及分別在0、24、48及72小時採集樣本。以PBS清洗後,在4°C下,將採集的T細胞與小鼠抗-組胺酸抗體(每毫升1微克)及FITC標記的山羊F(ab)2抗-小鼠免疫球蛋白二級抗體(每毫升1微克)混和。接著利用FACSCalibur流式細胞儀(Becton Dickinson,Mountain View,CA,USA)測量螢光,接著以Flowjo(Tree Star Inc.,San Carlos,CA,USA)軟體進行分析。
細胞毒性分析
將腫瘤細胞(每孔104
個細胞)種在96孔盤中並在37°C、5%CO2
下培養24小時。接著,將分化的T細胞(例如實施例2之T細胞)或OKT3 T細胞以3:1、5:1或10:1的E/T比例加入腫瘤細胞,並繼續培養16小時。之後採集該細胞及上清液,並利用CytoTox96®
非放射性細胞毒性套組分析來評估各分化的T細胞之細胞毒性功效。
酵素連結免疫吸附分析法(ELISA)
利用市售的ELISA套組,並依據使用操作說明分別測量分泌自分化的T細胞的IL-2、INF-γ、TNF-α、顆粒酶B及穿孔素量。簡單來說,收集以實施例2之T細胞的或OKT3 T細胞處理的腫瘤細胞上清液,將其注入96-孔盤(每孔100微升)中,並在36°C之培養箱中作用1.5小時。之後以清洗緩衝液清洗,加入抗體(每孔100微升),並將該混合物置回培養箱,在36°C下繼續作用1小時。在清洗後,加入辣根過氧化物酶(horse radish peroxidase,HRP)(每孔100微升)並繼續作用30分鐘。在清洗後,加入四甲基聯苯胺(tetramethylbenzidine,TMB)(每孔100微升),並將該混合物在36°C下避光作用15分鐘。接著,加入終止反應溶液(每孔100微升),並利用微孔盤光譜分析儀測量每孔吸光值(405奈米)。
活體攝影帶有EGFR+
腫瘤的SCID小鼠
將SCID小鼠背部分別注射HT-29(EGFR+
)細胞(每100微升2×106
個細胞)以誘發腫瘤形成。使腫瘤生長14-17天,直到其體積大小約為80-100立方毫米,接著將NIR797標記進一步以抗-EGFR/抗-CD3 BsAb修飾的OKT3 T細胞(107
個細胞)以靜脈注射方式注射該動物。在注射後4及24小時,分別將戊巴比妥(Pentobarbital)麻醉的小鼠利用IVIS光譜光學攝影系統(激發波長,745奈米;放射波長,840奈米;Perkin-Elmer,Inc.,MA,USA)進行攝影。接著犧牲小鼠,收集腫瘤及器官(包括心臟、肺臟、腎臟、肝臟、胃、肌肉、骨骼、大腸、小腸、胰臟及血液),並利用IVIS光譜光學攝影系統進行分析。
治療帶有EGFR+
腫瘤的SCID小鼠
將SCID小鼠背部分別注射HT-29(EGFR+
)細胞(每100微升2×106
個細胞)以誘發腫瘤形成。使腫瘤生長10-14天,直到其體積大小約為30-50立方毫米,接著將NIR797標記進一步以抗-EGFR/抗-CD3 BsAb修飾的T細胞(每小鼠107
個細胞)以靜脈注射方式注射該動物。在治療期間每週二次紀錄各小鼠之體重及測量腫瘤體積大小(長×寬×高×1/2)。接著犧牲小鼠,並將腫瘤進行解剖及進行H&E染色或以抗-CD3抗體進行免疫染色分析。
統計分析
利用JMP 9.0軟體(SAS Institute,Inc.,Cary,NC)(藉由非參數式的Mann–Whitney檢定)估計介於各平均值之間差異的統計顯著性。在細胞毒性分析及活體毒性分析中P值>0.05,以及在活體治療中P值>0.01認為具有統計顯著性。
實施例1 製備及確認人源化抗-腫瘤/抗-CD3之抗體
1.1 製備抗-腫瘤/抗-CD3 BsAb
在此實施例中,分別具有如第1圖所示的結構之重組人源化雙功抗體,經由使用如第3圖所示的DNA構築載體來製備。就抗-腫瘤Fab/抗-CD3 scFv BsAb來說,該構築載體依序包含IgG訊息胜肽(LS)、抗-腫瘤 VL-CK(例如抗-EGFR之VL-CK)、內部核糖體進入位點(internal ribosomal entry site,IRES)、LS、抗-腫瘤VH-CH1(例如抗-EGFR VH-CH1)、鏈接胜肽(L)及抗-CD3 VH-VL(第3圖之圖A)。就抗-CD3 Fab/抗-腫瘤scFv BsAb來說,該構築載體依序包含LS、抗-CD3 VL-CK、IRES、LS、抗-CD3 VH-CH1、L及抗-腫瘤VH-VL(第3圖之圖B)。就抗-腫瘤scFv/抗-CD3 scFv BsAb來說,該構築載體依序包含LS、抗-腫瘤VL-VH、L及抗-CD3 VH-VL(第3圖之圖C)。就抗-CD3球狀凸起/抗-腫瘤孔狀凹陷BsAb來說,該抗-CD3球狀凸起構築載體依序包含LS、抗-CD3 VL-CK、IRES、LS及抗-CD3 VH-CH1-球狀凸起Fc,而該抗-腫瘤孔狀凹陷依序包含LS、抗-腫瘤 VL-CK、IRES、LS及抗-腫瘤VH-CH1-孔狀凹陷Fc(第3圖之圖D)。
因此,製備包含一抗-CD3及一抗-腫瘤抗原(即抗-PSMA、抗-EGFR、抗-PD-L1、抗-HER2、抗-FAP、抗-EpCAM(MOC31)、抗-EpCAM(MO201)、抗-CEA及抗-VCAM-1)之BsAb。本揭示內容BsAb的成分及各自的核酸及胺基酸序列為總結在表1至表36中。BsAb係經由Expi-293™表現系統所製備,且每一BsAb的產率高於每升100毫克,並具有超過95%的組裝準確率。
1.2 確認抗-PSMA Fab/抗-CD3 scFv、抗-CD3 Fab/抗-PSMA scFv、抗-PSMA scFv/抗-CD3 scFv及抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb
第4圖闡述SDS-PAGE分析抗-PSMA Fab/抗-CD3 scFv、抗-CD3 Fab/抗-PSMA scFv、抗-EGFR Fab/抗-CD3 scFv及抗-CD3 Fab/抗-PD-L1 scFv BsAb,在還原條件下其分別由一約95千道爾頓的Fab片段所組成;另一方面,在非還原條件下分別觀察到一170千道爾頓的抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb及一50千道爾頓的抗-PSMAscFv/抗-CD3 scFv。SDS-PAGE尚包括抗-EGFR之抗體爾必得舒(Erbitux)作為正控制組。
在此實施例中藉由利用流式細胞分析來檢驗BsAb的雙功能活性。實驗結果繪示於第3圖。
抗-PSMA Fab/抗-CD3 scFv、抗-CD3 Fab/抗-PSMA scFv、抗-PSMA scFv/抗-CD3 scFv及抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb能夠各別結合CD3-陽性的T細胞(即Jurkat T細胞)及PSMA-陽性的前列腺癌細胞(即LNCaP細胞),而抗-EGFR Fab/抗-CD3 scFv可專一辨識EGFR-陽性的癌細胞(即HT29細胞);以及抗-CD3 Fab/抗-PD-L1 scFv可專一辨識CD3-陽性的T細胞(即Jurkat T細胞)及PD-L1-陽性的前列腺癌細胞(即LNCaP細胞)。第5圖的實驗數據確認實施例1的抗體確實具備對二種不同抗原的專一性。
1.3 製備人源化OKT3之抗-腫瘤/抗-CD3 BsAb
在此實施例中,依據「材料及方法」章節所述的步驟來製備重組人源化OKT3之VH及VL序列。表37及表38提供該人源化OKT3之VH及VL胺基酸序列及各別的CDR。
可將人源化OKT3之VH及VL序列與上述在表1至表36中的抗-腫瘤序列融合,從而建構欲求的人源化OKT3之抗-腫瘤/抗-CD3 BsAb。表39提供用以建構抗-腫瘤Fab/抗-CD3 scFv之人源化OKT3之抗-CD3 scFv序列;表40提供用以建構抗-CD3 Fab/抗-腫瘤scFv之人源化OKT3之抗-CD3 VL-CK及VH-CH1序列;表41提供用以建構抗-腫瘤scFv/抗-CD3 scFv之人源化OKT3之抗-CD3 scFv序列;以及表42提供用以建構抗-CD3球狀凸起/抗-腫瘤孔狀凹陷之人源化OKT3之抗-CD3 VL球狀凸起及VH球狀凸起序列。
實施例2 增生及確認藉由實施例1 BsAb所分化的CD3+
/CD8+
細胞
為製備攜帶實施例1 BsAb的T細胞,可將周邊血液單核球細胞(PBMC)自健康個體血液中分離,並培養在一包含細胞激素IL-2加上鼠類單株抗體OKT3或細胞激素IL-2加上實施例1.2 BsAb(即抗-PSMA Fab/抗-CD3 scFv、抗-CD3 Fab/抗-PSMA scFv、抗-PSMA scFv/抗-CD3 scFv及抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb)的培養液中進行分化。培養的細胞分別在第7天及第14天採集,並利用FITC接合的抗-CD3、抗-CD4及抗-CD8抗體進行流式細胞儀分析。定量結果總結在表43及第6圖中。
表43的實驗數據指出實施例1.2人類BsAb與鼠類OKT3在誘發PBMC分化為CD3+
/CD8+
細胞上同樣有效。進一步地,除該些藉由抗-PSMA scFv/抗-CD3 scFv BsAb誘發的細胞之外,藉由實施例1.2 BsAb誘發的CD3+
細胞群在培養7天後超過80%,在培養14天後超過90%,且在培養18天後CD3+
/CD8+
細胞的總數增加約4-5倍(第6圖)。
為確認分化的T細胞是否確實已攜帶實施例1.2 BsAb,可利用FITC接合的山羊抗-人類Fab抗體藉由流式細胞儀分析該些增生的T細胞表面的抗-抗原片段(例如抗-PSMA及抗-CD3)。實驗結果繪示於第7圖。
第7圖的實驗數據確認,藉由表面攜帶實施例1.2 BsAb的抗-PSMA之片段的作用,與實施例1.2 BsAb培養14天後的PBMC成功地分化為PSMA專一性的T細胞。
實施例3 實施例2之T細胞對癌細胞的功效
3.1 實施例2之T細胞的細胞毒性功效
利用CytoTox 96®
非放射性細胞毒性分析套組(Promega,G1780),並依據該廠商的使用操作說明來評估分別藉由鼠類OKT3及實施例1.2 BsAb分化的CD3+
/CD8+
T細胞在LNCaP(PSMA+
)細胞中的癌細胞殺害功效。實驗結果總結在表44及第8圖中。
發明人發現在不同的效應細胞:標的細胞比例(E/T比例):3:1、5:1及10:1下,藉由鼠類OKT3誘發的CD3+
/CD8+
T細胞分別殺害約8.4%、11.6%及19.3%的LNCaP細胞;而在相同的E/T比例下,攜帶抗-PSMA Fab/抗-CD3 scFv BsAb的T細胞殺害約65%、87%及97%的LNCaP細胞。類似的改進細胞毒性效應亦發現在攜帶抗-CD3 Fab/抗-PSMA scFv、抗-PSMA scFv/抗-CD3 scFv及抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb的T細胞上(第8圖)。
攝影分析進一步顯示,當一接觸腫瘤細胞,大量的實施例2之T細胞(或攜帶實施例1抗-CD3 Fab/抗-PSMA scFv、抗-PSMA scFv/抗-CD3 scFv或抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb的T細胞)專一結合在LNCaP細胞表面,然而藉由鼠類OKT3分化的T細胞甚至在作用8小時後大部分仍未結合(第9圖)。
3.2 確認實施例2之T細胞的癌細胞殺害功效
為進一步分析實施例2之T細胞(攜帶實施例1 BsAb的CD3+
/CD8+
T細胞)所展現的癌細胞殺害功效,收集該些T細胞所分泌的細胞激素並利用ELSA進行分析,而實驗結果指出IL-2、INF-γ、TNF-α、顆粒酶B及穿孔素的量全部皆顯著高於藉由鼠類OKT3分化的T細胞所分泌的細胞激素(第10圖)。
3.3 經修飾的實施例2之T細胞(進一步經實施例1.2 BsAb修飾)可增強癌細胞殺害功效
在此實施例中,進一步將實施例1.2 BsAb以E/T為3:1、5:1及10:1的比例加入培養實施例2之T細胞的培養液中,並培養18小時,接著將該混合物加至PSMA+
癌細胞(即LNCaP細胞)。藉由實施例3.1中所述之細胞毒性分析來評估癌細胞殺害功效,且藉由ELISA分析收集自LNCaP細胞的上清液中細胞激素量。實驗結果繪示於第11及12圖。
如第11圖所示,經修飾的實施例2之T細胞(進一步經實施例1.2 BsAb修飾)可展現更高的細胞殺害功效,在E/T比例為10:1時具有超過90%的殺害功效,而藉由鼠類OKT3分化的T細胞在相同的E/T比例下僅有約20%的量。如意料中的,各別的細胞激素(包括IL-2、INF-γ、TNF-α、顆粒酶B及穿孔素)量亦更高於控制組細胞(即藉由鼠類OKT3分化的T細胞)的細胞激素量(第12圖)。
3.4 攜帶實施例1抗-CD3/抗-PD-L1 BsAb的T細胞對惡性胰臟癌或三陰性乳癌(TNBC)的功效
惡性胰臟癌及三陰性乳癌(TNBC)二者皆以高死亡率及極低治癒率著稱。在此實施例中,利用惡性胰臟癌細胞株MIA PaCa-2及TNBC細胞株MDA-MB-231來測試攜帶實施例1.2抗-CD3/抗-PD-L1 BsAb的T細胞對該二種惡性癌症的效應。
在惡性胰臟癌細胞中,相較於控制組T細胞(即藉由鼠類OKT3誘發分化的T細胞)的細胞毒性效應,攜帶實施例1.2抗-CD3/抗-PD-L1 BsAb的T細胞的可展現更高的細胞毒性效應,且若該T細胞進一步以實施例1.2抗-CD3/抗-PD-L1 BsAb修飾後,其殺害功效增強更多。攜帶實施例1.2抗-CD3/抗-PD-L1 BsAb的T細胞對TNBC細胞的癌症殺害功效甚至更為顯著,甚至在3:1的低E/T比例時,仍具有近乎100%的殺害功效;而控制組T細胞在相同比例時僅展現10%的 殺害功效(第13圖)。
攝影分析顯示,藉由鼠類OKT3分化的T細胞大部分未結合MIA PaCa-2及MDA-MB-231細胞二者,而大量的MIA PaCa-2及MDA-MB-231細胞在與進一步以實施例1.2抗-CD3/抗-PD-L1 BsAb修飾的T細胞作用後呈現出細胞凋亡徵象(第14A及14B圖)。
3.5 殘留在T細胞表面的BsAb量的時間效應
將實施例1.2抗-PSMA/抗-CD3 BsAb與血清作用不同時間(即0、24、48及72小時),並利用流式細胞分析來評估殘留在T細胞表面的BsAb的殘留量。實驗結果繪示於第15圖。
T細胞表面的BsAb量隨著時間遞減,在四種類型或結構的BsAb中,抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb受降解影響程度最低,在72小時後約47%的BsAb仍殘留在T細胞表面,而殘留在T細胞表面的抗-PSMA scFv/抗-CD3 scFv量驟降至15%的低量。
實施例4 經實施例1.2 BsAb修飾的鼠類OKT3 T細胞的效應
如在實施例1至4中所提供的發現結果,鼠類OKT3分化的T細胞在癌症殺害功效方面並非如實施例2之T細胞(即攜帶實施例1 BsAb的T細胞)一樣有效,係導因於其對癌細胞的低結合親和力及低細胞激素分泌量。因此,在此實施例中,將鼠類OKT3 T細胞藉由與實施例1.2 BsAb共同作用來進行修飾,接著評估其對癌細胞的細胞毒性效應。
4.1 經實施例1.2 BsAb修飾的鼠類OKT3 T細胞
為將鼠類OKT3 T細胞進行修飾,將約3×105
個鼠類OKT3 T細胞與不同數量(8、24、120、600及3,000奈克)的實施例1.2抗-PSMA/抗-CD3 BsAb混和並利用流式細胞分析進行分析。實驗結果指出,約600奈克的實施例1.2 BsAb足以將實施例1.2 BsAb覆蓋於鼠類OKT3 T細胞表面(實驗數據未顯示)。
4.2 經實施例1.2 BsAb修飾的鼠類OKT3 T細胞對PSMA+
細胞的效應
如意料中的,相較於修飾前,經實施例1 BsAb(包括抗-PSMA Fab/抗-CD3 scFv、抗-CD3 Fab/抗-PSMA scFv、抗-PSMA scFv/抗-CD3 scFv及抗-CD3球狀凸起/抗-PSMA孔狀凹陷)修飾的鼠類OKT3分化的T細胞對於LNCaP細胞(PSMA+
)的癌細胞殺害能力顯著增加。其中,在E/T比例為10:1時,經抗-PSMA Fab/抗-CD3 scFv修飾的鼠類OKT3 T細胞可展現近乎100%的細胞殺害功效(第16圖)。相較於未經修飾的控制組T細胞,分泌自經實施例1.2 BsAb修飾的鼠類OKT3 T細胞的各細胞激素(包括IL-2、INF-γ、TNF-α、顆粒酶B及穿孔素)量亦顯著增加(第17圖)。
攝影分析顯示,相較於未經修飾的OKT3 T細胞,經抗-PSMA Fab/抗-CD3 scFv、抗-CD3 Fab/抗-PSMA scFv、抗-PSMA scFv/抗-CD3 scFv或抗-CD3球狀凸起/抗-PSMA孔狀凹陷BsAb修飾的鼠類OKT3 T細胞更專一結合LNCaP細胞表面(第18圖)。
4.3 經實施例1.2 BsAb修飾的鼠類OKT3 T細胞對EGFR+
細胞的效應
在此實施例中,將鼠類OKT3 T細胞以實施例1.2抗-EGFR Fab/抗-CD3 scFv BsAb進行修飾,並進行分析來評估其殺害EGFR+
癌細胞(即HT29 細胞)的能力。
類似於實施例5.1的發現結果,經實施例1.2抗-EGFR Fab/抗-CD3 scFv BsAb修飾後,鼠類OKT3 T細胞可展現增強的細胞毒性功效,在E/T比例為10:1時具有約50%的細胞殺害功效(第19A圖),以及具有增加的細胞激素(INF-γ、TNF-α、顆粒酶B及穿孔素)量(第19B圖)。
攝影分析顯示,相較於未經修飾的OKT3 T細胞,經抗-EGFR Fab/抗-CD3 scFv BsAb修飾的鼠類OKT3 T細胞更專一結合HT29細胞表面(第20圖)。
4.4 經實施例1.2 BsAb修飾的鼠類OKT3 T細胞對PD-L1+
細胞的效應
在此實施例中,將鼠類OKT3 T細胞以實施例1.2抗-CD3 Fab/抗-PD-L1 scFv BsAb進行修飾,並進行分析來評估其殺害PD-L1+
癌細胞(即LNCaP細胞)的能力。
類似於實施例5.1及5.2的發現結果,經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv BsAb修飾後,鼠類OKT3 T細胞可展現增強的細胞毒性功效,在E/T比例為10:1時具有約92%的細胞殺害功效(第21A圖),以及具有增加的細胞激素(INF-γ、TNF-α、顆粒酶B及穿孔素)量(第21B圖)。
攝影分析顯示,相較於未經修飾的OKT3 T細胞,經抗-CD3 Fab/抗-PD-L1 scFv BsAb修飾的鼠類OKT3 T細胞更專一結合LNCaP細胞表面(第22圖)。
4.5 經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv修飾的鼠類OKT3 T細胞對惡性胰臟癌細胞及TNBC細胞的效應
在此實施例中,依據實施例3.4所述之類似步驟來測試經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv BsAb修飾的鼠類OKT3 T細胞對惡性胰臟癌細胞株MIA PaCa-2(PD-L1+
細胞)及TNBC細胞(MDA-MB-231細胞)的癌症殺害功效。
在惡性胰臟癌細胞中,相較於控制組T細胞(即未經修飾的鼠類OKT3 T細胞),經實施例1抗-CD3 Fab/抗-PD-L1 scFv BsAb修飾的鼠類OKT3 T細胞可展現更高的細胞毒性功效(殺害約40%的癌細胞)。在TNBC細胞中癌症殺害功效更為顯著,甚至在3:1的低E/T比例時,仍可殺害近乎80%的癌細胞;而該控制組T細胞在相同比例時僅展現20-30%的殺害功效(第23圖)。
攝影分析顯示,相較於未經修飾的OKT3 T細胞,經抗-CD3 Fab/抗-PD-L1 scFv BsAb修飾的鼠類OKT3 T細胞專一結合MIA PaCa-2細胞(第24A圖)及MDA-MB-231細胞(第24B圖)表面,並增強癌細胞的細胞凋亡。
實施例5 經實施例1 BsAb修飾的鼠類OKT3 T細胞的活體內效應
為探討實施例1 BsAb是否可改進鼠類OKT3 T細胞的標定功效(targeting effect),將鼠類OKT3 T細胞以實施例1.2抗-EGFR/抗-CD3 BsAb進行修飾同時,一併進行螢光指示劑-NIR797標記。接著,將該修飾及標記的鼠類OKT3 T細胞以IV注射方式注射至帶有異質的EGFR+
腫瘤(HT29細胞)之SCID小鼠體內,並分別在第4及24小時利用IVIS攝影系統進行活體攝影。24小時後犧牲該動物,並採集腫瘤本身及包括心臟、肺臟、腎臟、脾臟、肝臟、胃、肌肉、骨骼、大腸、小腸、胰臟、及血液等器官,分別利用IVIS攝影系統進行分析。實驗結果繪示於第25及26圖。
第25圖的影像顯示,相較於以未經修飾的鼠類OKT3 T細胞處理的動物,以經修飾的OKT3 T細胞處理的動物體內發現螢光強度主要集中在腫瘤位點。該實驗結果確認以實施例1 BsAb修飾的鼠類OKT3 T細胞確實標定至該腫瘤,因而增強在腫瘤位點的螢光強度。
此外,發現經修飾的T細胞除集中在EGFR+
腫瘤本身之外,其餘在活體內分布情形類似於該些經修飾的T細胞在普通健康動物體內的分布情形(第26圖)。
此外,當以經修飾的鼠類OKT3 T細胞處理後,腫瘤體積大小及其重量受到顯著抑制(第27圖之圖A及C),而該動物的體重在25天的治療時程內僅有輕微減少(第27圖之圖B)。
將採集自動物的腫瘤進一步利用免疫組織化學(IHC)染色及H&E染色進行分析,其實驗結果如第28圖所示。發現經修飾的鼠類OKT3 T細胞主要集中在腫瘤的附近區域。
實施例6 實施例2之T細胞及實施例4經修飾的鼠類OKT3細胞的比較性研究
在此實施例中,比較藉由實施例1.2 BsAb(即抗-PSMA Fab/抗-CD3 scFv及抗-PSMA scFv/抗-CD3 scFv)及鼠類OKT3所誘發的T細胞分化及增生。實驗結果繪示於第29至32圖。
如第29A圖所示,實施例1.2 BsAb的(即抗-PSMA Fab/抗-CD3 scFv及抗-PSMA scFv/抗-CD3 scFv)及鼠類OKT3二者皆能夠誘發PBMC分化為CD3+
細胞,且超過95%的細胞成為CD3+
細胞。至於CD4+
細胞部分,實施例1.2 BsAb(即抗-PSMA Fab/抗-CD3 scFv及抗-PSMA scFv/抗-CD3 scFv)較鼠類OKT3更可有效誘發PBMC分化為CD4+
T細胞,以實施例1.2 BsAb處理後,有超過90%的PBMC分化為CD4+
細胞,而鼠類OKT3處理後,僅有約75%的PBMC轉變成CD4+
細胞。進一步地,藉由實施例1.2 BsAb誘發的T細胞增生比例,亦高於藉由鼠類OKT3 T細胞誘發的T細胞增生比例(第29B圖)。利用流式細胞分析進一步確認類似於藉由鼠類OKT3抗體誘發的T細胞,該抗體出現在OKT3 T細胞表面;二種實施例1.2 BsAb各自所攜帶的抗體片段亦出現在其所誘發的T細胞表面(第30圖)。
鼠類OKT3 T細胞及實施例2之T細胞對細胞毒性的比較性研究提供於第31圖。如圖所示,OKT3 T細胞能夠殺害PSMA+
細胞(LNCaP細胞),而實施例2之T細胞(或藉由實施例1 BsAb誘發的T細胞)展現至少50%的細胞毒性,且若其進一步以實施例1.2 BsAb修飾,則該T細胞的細胞毒性將會進一步增加。舉例來說,藉由抗-CD3 Fab/抗-PSMA scFv分化的T細胞,在E/T比例為5:1及10:1時,其細胞毒性分別約51.32%及60.97%;若進一步以抗-CD3 Fab/抗-PSMA scFv修飾後,在E/T比例為5:1及10:1時,其細胞毒性增加至約78.15%及81.75%。類似的觀察亦發現在藉由抗-PSMA scFv/抗-CD3 scFv誘發的T細胞中。
實施例7 藉由實施例1.2 BsAb進行一步法分化及增生調控型T細胞
在此實施例中,藉由實施例1.2 BsAb誘發及生成調控型T細胞。簡單來說,自健康人類個體分離PBMC並將其與實施例1.2抗-CD3 Fab/抗-PSMA scFv或抗-PSMA scFv/的抗-CD3 scFv培養7天,在任一情形下,該培養液亦包含IL-2、TGF-β及抗-CD28抗體。接著,採集分化的T細胞並利用流式細胞分析進行分析。實驗結果繪示於第32圖。
實驗數據指出,抗-CD3 Fab/抗-PSMA scFv BsAb及抗-PSMA scFv/抗-CD3 scFv可分別誘發約19.3%(第32圖之圖A)及7.2%的(第32圖之圖B)的CD4+
FoxP3+
調控型T細胞的形成。
雖然上文實施方式中揭露本揭示內容的具體實施例,本發明所屬技術領域中具有通常知識者當可對其進行各種更動與修飾。上文的說明書、實施例及實驗數據對本揭示內容作為例示性實施方式中的結構及使用方式做出完整的描述。儘管上文已描述本揭示內容中各種實施方式有一定程度的特性,或參照一或多個各別實施方式,本發明所屬領域技術具有通常知識者仍能在不悖離本揭示內容精神及範圍情形下,對已揭示的實施方式進行眾多修改。
無
在參閱以下的詳細說明、申請專利範圍及附隨圖式後,本揭示內容及其他特徵、態樣及優點將更明顯易懂,其中:
第1圖為本揭示內容BsAb的結構示意圖:(A)抗-抗原Fab/抗-CD3 scFv、(B)抗-CD3 Fab/抗-抗原scFv、(C)抗-CD3 scFv/抗-抗原scFv及(D)抗-CD3球狀凸起(knob)/抗-抗原孔狀凹陷(hole);
第2A圖為以具抗原專一性T細胞來治療一個體的示意圖,其中係藉由本揭示內容BsAb以一步法擴增、分化及/或修飾來製備該T細胞;
第2B圖為以鼠類OKT3 T細胞來治療一個體的示意圖,其中係藉由本揭示內容BsAb以一步法修飾來製備該T細胞;
第3圖為用以表現本揭示內容BsAb之DNA構築載體的示意圖;
第4圖闡述實施例1.2 BsAb在非還原條件(左欄)及還原條件下(右欄)以SDS-PAGE分析的結果;
第5圖闡述實施例1.2 BsAb以流式細胞分析的結果;
第6圖闡述藉由本揭示內容實施例2之鼠類OKT3抗體及BsAb來誘發T細胞分化及增生的結果;
第7圖為依據本揭示內容一實施方式所繪示之流式細胞分析結果,其係關於增生T細胞的表面抗-抗原片段;
第8圖為依據本揭示內容一實施方式所繪示之細胞毒性分析結果,其係關於鼠類OKT3 T細胞及實施例2之T細胞於前列腺癌細胞株LNCaP的細胞毒性作用;
第9圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及實施例2之T細胞分別結合腫瘤細胞的結果;
第10圖為依據本揭示內容一實施方式所繪示之細胞激素量的長條圖,其係關於在不同效應細胞:標的細胞比例(E/T比例)下,鼠類OKT3 T細胞及實施例2之T細胞分別分泌細胞激素量的結果;
第11圖為依據本揭示內容一實施方式所繪示之細胞毒性分析折線圖,其係關於在不同E/T比例下,鼠類OKT3 T細胞及經修飾的實施例2之T細胞(進一步經實施例1.2 BsAb修飾)於LNCaP細胞的細胞毒性分析結果;
第12圖為依據本揭示內容一實施方式所繪示之細胞激素量的長條圖,其係關於在不同E/T比例下,鼠類OKT3 T細胞及經修飾的實施例2之T細胞(進一步經實施例1.2 BsAb修飾)分別分泌細胞激素量的結果;
第13圖為依據本揭示內容一實施方式所繪示之細胞毒性分析結果,其係關於鼠類OKT3 T細胞、實施例2之T細胞或經修飾的實施例2之T細胞(進一步經抗-CD3 Fab/抗-PD-L1 scFv BsAb修飾)於惡性胰臟癌細胞株MIA PaCa-2及三陰性乳癌(TNBC)細胞株MDA-MB-231的細胞毒性作用;
第14A圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及實施例2之T細胞分別結合MIA PaCa-2細胞的結果;
第14B圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及實施例2之T細胞分別結合MDA-MB-231細胞的結果;
第15圖為依據本揭示內容一實施方式所繪示之結果,其係關於實施例1.2 BsAb在T細胞表面的殘留量之時程變化;
第16圖為依據本揭示內容一實施方式所繪示之細胞毒性分析結果,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2 BsAb修飾)於前列腺癌細胞株LNCaP的細胞毒性作用;
第17圖為依據本揭示內容一實施方式所繪示之細胞激素量的長條圖,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1 BsAb修飾)分別分泌細胞激素量的結果;
第18圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2 BsAb修飾)分別結合前列腺腫瘤細胞(LNCaP細胞)的結果;
第19A圖為依據本揭示內容一實施方式所繪示之細胞毒性分析結果,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)於HT29細胞的細胞毒性作用;
第19B圖為依據本揭示內容一實施方式所繪示之細胞激素量的長條圖,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1抗-EGFR Fab/抗-CD3 scFv修飾)分別分泌細胞激素量的結果;
第20圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)分別結合HT29細胞的結果;
第21A圖為依據本揭示內容一實施方式所繪示之細胞毒性分析結果,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv修飾)於LNCaP細胞的細胞毒性作用;
第21B圖為依據本揭示內容一實施方式所繪示之細胞激素量的長條圖,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv修飾)分別分泌細胞激素量的結果;
第22圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv修飾)分別結合LNCaP細胞的結果;
第23圖為依據本揭示內容一實施方式所繪示之細胞毒性分析結果,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經抗-CD3 Fab/抗-PD-L1 scFv BsAb修飾)於惡性胰臟癌細胞株MIA PaCa-2及三陰性乳癌(TNBC)細胞株MDA-MB-231的細胞毒性作用;
第24A圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv修飾)分別結合MIA PaCa-2細胞的結果;
第24B圖為依據本揭示內容一實施方式所得之影像,其係關於鼠類OKT3 T細胞及經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-CD3 Fab/抗-PD-L1 scFv修飾)分別結合MDA-MB-231細胞的結果;
第25圖為依據本揭示內容一實施方式所得之活體內結果,其係關於將鼠類OKT3 T細胞或經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)投予動物體內並定量螢光強度的結果;
第26圖為依據本揭示內容一實施方式所繪示之活體內結果,其係關於鼠類OKT3 T細胞或經修飾的鼠類OKT3 T細胞(進一步經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)於受試動物體內不同器官的分布情形;
第27A圖為依據本揭示內容一實施方式所繪示之腫瘤體積大小變化的折線圖,其係關於以實施例1.2 BsAb、鼠類OKT3 T細胞或經修飾的鼠類OKT3 T細胞(經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)治療腫瘤並記錄腫瘤體積大小變化的結果;
第27B圖為依據本揭示內容一實施方式所繪示之體重變化的折線圖,其係關於將實施例1.2 BsAb、鼠類OKT3 T細胞或經修飾的鼠類OKT3 T細胞(經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)投予受試動物並記錄體重變化的結果;
第27C圖為依據本揭示內容一實施方式所得之腫瘤重量的結果,其係關於以實施例1.2 BsAb、鼠類OKT3 T細胞或經修飾的鼠類OKT3 T細胞(經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)治療腫瘤並記錄腫瘤重量的變化;
第28圖為依據本揭示內容一實施方式所得之影像,其係關於以實施例1.2 BsAb、鼠類OKT3 T細胞或經修飾的鼠類OKT3 T細胞(經實施例1.2抗-EGFR Fab/抗-CD3 scFv修飾)治療腫瘤後的免疫組織化學(immunohistochemical,IHC) 染色及H&E染色結果;
第29A圖為依據本揭示內容一實施方式所繪示之流式細胞分析結果,其係關於利用流式細胞分析分析藉由鼠類OKT3、及抗-PSMA Fab/抗-CD3 scFv或抗-PSMA scFv/抗-CD3 scFv分化的T細胞;
第29B圖為依據本揭示內容一實施方式所繪示之式細胞分析結果,其係關於藉由鼠類OKT3、及抗-CD3 Fab/抗-PSMA scFv或抗-PSMA scFv/抗-CD3 scFv分別分化的T細胞增生結果;
第30圖為依據本揭示內容一實施方式所繪示之流式細胞分析結果,其係關於利用流式細胞分析分析OKT3 T細胞,或攜帶抗-CD3 Fab/抗-PSMA scFv或抗-PSMA scFv/抗-CD3 scFv的T細胞所攜帶的二種類型抗體片段結果;
第31圖為依據本揭示內容一實施方式所繪示之細胞毒性分析結果,其係關於鼠類OKT3 T細胞及實施例2之T細胞分別於LNCaP細胞的細胞毒性作用;以及
第32圖為依據本揭示內容一實施方式所繪示之流式細胞分析結果,其係關於藉由抗-CD3 Fab/抗-PSMA scFv及抗-PSMA scFv/抗-CD3 scFv BsAb來誘發CD4+
FoxP3+
調控型T細胞結果。
序列表 <110> 臺北醫學大學 <120> 具抗原專一性的T細胞及其用途 <150> US62/478,280 <151> 2017-03-29 <160> 143 <170> BiSSAP 1.3.6 <210> 1 <211> 63 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 1 atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggt 60 gac 63 <210> 2 <211> 645 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 2 gacatcgtga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagagtgacc 60 atcacctgca aggccagcca ggacgtgggc accgccgtgg actggtacca gcagaagccc 120 ggcaaggccc ccaagctgct gatctactgg gccagcacca gacacaccgg cgtgcccgac 180 agattcaccg gcagcggcag cggcaccgac ttcaccctga ccatcagcag cctgcagccc 240 gaggacttcg ccgactactt ctgccagcag tacaacagct accccctgac cttcggcggc 300 ggcaccaagc tggagatcaa gagaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa ctctacgcct gcgaagtcac ccatcagggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gctga 645 <210> 3 <211> 585 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 3 gcccctctcc ctcccccccc cctaacgtta ctggccgaag ccgcttggaa taaggccggt 60 gtgcgtttgt ctatatgtta ttttccacca tattgccgtc ttttggcaat gtgagggccc 120 ggaaacctgg ccctgtcttc ttgacgagca ttcctagggg tctttcccct ctcgccaaag 180 gaatgcaagg tctgttgaat gtcgtgaagg aagcagttcc tctggaagct tcttgaagac 240 aaacaacgtc tgtagcgacc ctttgcaggc agcggaaccc cccacctggc gacaggtgcc 300 tctgcggcca aaagccacgt gtataagata cacctgcaaa ggcggcacaa ccccagtgcc 360 acgttgtgag ttggatagtt gtggaaagag tcaaatggct ctcctcaagc gtattcaaca 420 aggggctgaa ggatgcccag aaggtacccc attgtatggg atctgatctg gggcctcggt 480 gcacatgctt tacatgtgtt tagtcgaggt taaaaaaacg tctaggcccc ccgaaccacg 540 gggacgtggt tttcctttga aaaacacgat gataatatgg ccaca 585 <210> 4 <211> 660 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 4 gaggtgcagc tggtgcagag cggcgccgag gtgaagaagc ccggcgccag cgtgaagatc 60 agctgcaaga ccagcggcta caccttcacc gagtacacca tccactgggt gaagcaggcc 120 agcggcaagg gcctggagtg gatcggcaac atcaacccca acaacggcgg caccacctac 180 aaccagaagt tcgaggacag agccaccctg accgtggaca agagcaccag caccgcctac 240 atggagctga gcagcctgag aagcgaggac accgccgtgt actactgcgc cgccggctgg 300 aacttcgact actggggcca gggcaccacc gtgaccgtga gcagcgcctc caccaagggc 360 ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagagagttg agcccaaatc ttgtgacaaa 660 <210> 5 <211> 774 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 5 ggtggcggct caggtggagg cgacatcaag ctgcagcaga gcggcgccga gctggccaga 60 cccggcgcca gcgtgaagat gagctgcaag accagcggct acaccttcac cagatacacc 120 atgcactggg tgaagcagag acccggccag ggcctggagt ggatcggcta catcaacccc 180 agcagaggct acaccaacta caaccagaag ttcaaggaca aggccaccct gaccaccgac 240 aagagcagca gcaccgccta catgcagctg agcagcctga ccagcgagga cagcgccgtg 300 tactactgcg ccagatacta cgacgaccac tactgcctgg actactgggg ccagggcacc 360 accctgaccg tgagcagcgt ggagggcggc agcggcggca gcggcggcag cggcggcagc 420 ggcggcgtgg acgacatcca gctgacccag agccccgcca tcatgagcgc cagccccggc 480 gagaaggtga ccatgacctg cagagccagc agcagcgtga gctacatgaa ctggtaccag 540 cagaagagcg gcaccagccc caagagatgg atctacgaca ccagcaaggt ggccagcggc 600 gtgccctaca gattcagcgg cagcggcagc ggcaccagct acagcctgac catcagcagc 660 atggaggccg aggacgccgc cacctactac tgccagcagt ggagcagcaa ccccctgacc 720 ttcggcgctg gcaccaagct ggagctgaag agacaccacc accaccacca ctga 774 <210> 6 <211> 642 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 6 gacatccagc tgacccagag ccccgccatc atgagcgcca gccccggcga gaaggtgacc 60 atgacctgca gagccagcag cagcgtgagc tacatgaact ggtaccagca gaagagcggc 120 accagcccca agagatggat ctacgacacc agcaaggtgg ccagcggcgt gccctacaga 180 ttcagcggca gcggcagcgg caccagctac agcctgacca tcagcagcat ggaggccgag 240 gacgccgcca cctactactg ccagcagtgg agcagcaacc ccctgacctt cggcgctggc 300 accaagctgg agctgaagag aactgtggct gcaccatctg tcttcatctt cccgccatct 360 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540 agcaaagcag actacgagaa acacaaactc tacgcctgcg aagtcaccca tcagggcctg 600 agctcgcccg tcacaaagag cttcaacagg ggagagtgct ga 642 <210> 7 <211> 651 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 7 gacatcaagc tgcagcagag cggcgccgag ctggccagac ccggcgccag cgtgaagatg 60 agctgcaaga ccagcggcta caccttcacc agatacacca tgcactgggt gaagcagaga 120 cccggccagg gcctggagtg gatcggctac atcaacccca gcagaggcta caccaactac 180 aaccagaagt tcaaggacaa ggccaccctg accaccgaca agagcagcag caccgcctac 240 atgcagctga gcagcctgac cagcgaggac agcgccgtgt actactgcgc cagatactac 300 gacgaccact actgcctgga ctactggggc cagggcacca ccctgaccgt gagcagcgcc 360 tccaccaaag gtccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 420 acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ctctgaccag cggcgtgcac accttcccag ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac 600 acctgcaacg tagatcacaa gcccagtaac accaaggtgg acaagacagt t 651 <210> 8 <211> 759 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 8 ggcggcggca gcggcggcgg cgaggtgcag ctggtgcaga gcggcgccga ggtgaagaag 60 cccggcgcca gcgtgaagat cagctgcaag accagcggct acaccttcac cgagtacacc 120 atccactggg tgaagcaggc cagcggcaag ggcctggagt ggatcggcaa catcaacccc 180 aacaacggcg gcaccaccta caaccagaag ttcgaggaca gagccaccct gaccgtggac 240 aagagcacca gcaccgccta catggagctg agcagcctga gaagcgagga caccgccgtg 300 tactactgcg ccgccggctg gaacttcgac tactggggcc agggcaccac cgtgaccgtg 360 agcagcgccg gtggaggcgg ttcaggcgga ggtggctctg gcggtggcgg atcggacatc 420 gtgatgaccc agagccccag cagcctgagc gccagcgtgg gcgacagagt gaccatcacc 480 tgcaaggcca gccaggacgt gggcaccgcc gtggactggt accagcagaa gcccggcaag 540 gcccccaagc tgctgatcta ctgggccagc accagacaca ccggcgtgcc cgacagattc 600 accggcagcg gcagcggcac cgacttcacc ctgaccatca gcagcctgca gcccgaggac 660 ttcgccgact acttctgcca gcagtacaac agctaccccc tgaccttcgg cggcggcacc 720 aagctggaga tcaagagaca ccaccaccac caccactga 759 <210> 9 <211> 717 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 9 gacatcgtga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagagtgacc 60 atcacctgca aggccagcca ggacgtgggc accgccgtgg actggtacca gcagaagccc 120 ggcaaggccc ccaagctgct gatctactgg gccagcacca gacacaccgg cgtgcccgac 180 agattcaccg gcagcggcag cggcaccgac ttcaccctga ccatcagcag cctgcagccc 240 gaggacttcg ccgactactt ctgccagcag tacaacagct accccctgac cttcggcggc 300 ggcaccaagc tggagatcaa gagaggtgga ggcggttcag gcggaggtgg ctctggcggt 360 ggcggatcgg aggtgcagct ggtgcagagc ggcgccgagg tgaagaagcc cggcgccagc 420 gtgaagatca gctgcaagac cagcggctac accttcaccg agtacaccat ccactgggtg 480 aagcaggcca gcggcaaggg cctggagtgg attggcaaca tcaaccccaa caacggcggc 540 accacctaca accagaagtt cgaggacaga gccaccctga ccgtggacaa gagcaccagc 600 accgcctaca tggagctgag cagcctgaga agcgaggaca ccgccgtgta ctactgcgcc 660 gctggctgga acttcgacta ctggggccag ggcaccaccg tgaccgtgag cagcgcc 717 <210> 10 <211> 672 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 10 gacatccagc tgacccagag cccagcaatc atgtctgcca gcccaggaga gaaggtgacc 60 atgacatgcc gggccagcag cagcgtgagc tacatgaact ggtatcagcg gaagagcggc 120 acctccccta agagatggat ctacgacaca tctaaggtgg ccagcggcgt gccatatagg 180 ttctccggct ctggcagcgg cacctcctac tctctgacaa tcagctccat ggaggccgag 240 gatgccgcca cctactattg ccagcagtgg tctagcaatc ccctgacctt tggcgccggc 300 acaaagctgg agctgaagag gaccgtggca gcacctagcg tgttcatctt tcccccttcc 360 gacgagcagc tgaagtccgg cacagcctct gtggtgtgcc tgctgaacaa tttctatcca 420 cgcgaggcca aggtgcagtg gaaggtggat aacgccctgc agtctggcaa tagccaggag 480 tccgtgaccg agcaggactc taaggatagc acatactccc tgtcctctac cctgacactg 540 agcaaggccg attacgagaa gcacaagctg tatgcatgcg aggtgaccca ccagggcctg 600 agctccccag tgacaaagtc ttttaaccgg ggcgagtgtg gcggcggctc ccaccaccac 660 caccaccact ga 672 <210> 11 <211> 1350 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 11 gacatcaagc tgcagcagag cggagcagag ctggccaggc ccggagcctc tgtgaagatg 60 agctgcaaga cctccggcta caccttcaca cggtatacaa tgcactgggt gaagtacaga 120 cctggccagg gcctggagtg gatcggctat atcaacccat cccgcggcta caccaactat 180 aatcagaagt ttaaggacaa ggccaccctg accacagata agagctcctc tacagcctac 240 atgcagctga gctccctgac ctctgaggac agcgccgtgt actattgcgc ccggtactat 300 gacgatcact actgtctgga ttattggggc cagggcacca cactgaccgt gtctagcgcc 360 tctacaaagg gacctagcgt gttcccactg gcaccctcct ctaagtccac ctctggagga 420 acagccgccc tgggatgcct ggtgaaggat tacttcccag agcccgtgac cgtgtcctgg 480 aactctggcg ccctgaccag cggagtgcac acatttcctg ccgtgctgca gagctccggc 540 ctgtactccc tgtctagcgt ggtgacagtg ccatcctcta gcctgggcac ccagacatat 600 atctgcaacg tgaatcacaa gccaagcaat accaaggtcg acaagaaggt ggagcccaag 660 tcctgtgata agacccacac atgcccccct tgtcctgcac cagagctgct gggaggacca 720 agcgtgttcc tgtttccacc caagcctaag gacaccctga tgatctctcg gaccccagag 780 gtgacatgcg tggtggtgga cgtgagccac gaggatcccg aggtgaagtt taactggtac 840 gtggatggcg tggaggtgca caatgccaag accaagccca gggaggagca gtacaattcc 900 acctatcgcg tggtgtctgt gctgacagtg ctgcaccagg actggctgaa cggcaaggag 960 tataagtgca aggtgtccaa taaggccctg cccgccccta tcgagaagac aatctctaag 1020 gcaaagggac agcctcggga gccacaggtg tacaccctgc ctccatccag agatgagctg 1080 accaagaacc aggtgtctct gacatgtctg gtgaagggct tctatccctc tgacatcgcc 1140 gtggagtggg agagcaatgg ccagcctgag aacaattacg ataccacacc ccctgtgctg 1200 gacagcgatg gctccttctt tctgtatagc gacctgacag tggataagtc cagatggcag 1260 cagggcaacg tgtttagctg ttccgtgatg cacgaggccc tgcacaatca ctacacccag 1320 aagtctctga gcctgtcccc cggcaagtaa 1350 <210> 12 <211> 684 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 12 aggatcgtga tgacccagtc tcctagctcc ctgagcgcct ccgtgggcga ccgcgtgacc 60 atcacatgca aggccagcca ggatgtggga accgcagtgg actggtacca ggataagcca 120 ggcaaggccc ccaagctgct gatctattgg gcctccacca ggcacacagg agtgccagac 180 agattcaccg gctctggcag cggcacagac ttcaccctga caatctctag cctgcagccc 240 gaggacttcg ccgattactt ttgccagcag tacaacagct atcctctgac cttcggcggc 300 ggcacaaagc tggagatcaa gaggaccgtg gcagcaccat ccgtgttcat ctttccccct 360 tctgacgagc agctgaagtc tggcacagcc agcgtggtgt gctacctgaa caacttctac 420 cccagggagg ccaaggtgca gtggaaggtg gataacgccc tgcagtccgg caattctcag 480 gagagcgtga ccgagcagga ctccaaggat tctacataca gcctgtggtc caccctgaca 540 ctgtccaagg ccgactacga gaagcacaag ctgtatgcat gcgaggtgac ccaccagggc 600 ctgtcctctc ccgtgacaaa gagcttcaat aggggagagt gtggaggagg atcctaccct 660 tatgacgtgc cagattatgc ctaa 684 <210> 13 <211> 1338 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 13 gaggtgcagc tggtgcagtc cggagcagag gtgaagaagc ctggagcctc tgtgaagatc 60 agctgcaaga cctccggcta caccttcaca gagtatacaa tccactgggt gaagaaggcc 120 agcggcaagg gcctggagtg gatcggcaac atcaatccaa acaatggcgg caccacatac 180 aaccaggagt ttgaggaccg ggccaccctg acagtggata agtccacctc tacagcctat 240 atggagctga gctccctgag atccgaggac accgccgtgt actattgcgc cgccggctgg 300 aatttcgatt actggggcca gggcaccaca gtgaccgtgt ctagcgcctc tacaaaggga 360 ccaagcgtgt ttccactggc accctcctct aagagcacct ccggaggaac agccgccctg 420 ggctgtctgg tgaaggacta tttcccagag cccgtgaccg tgtcctggaa ctctggcgcc 480 ctgacctccg gagtggcaac aggaccagcc gtgctgcaga gctccggcct gtacagcctg 540 tctagcgtgg tgaccgtgcc ctcctctagc ctgggcaccc agacatatat ctgcaacgtg 600 aatcacaagc caagcaatac aaaggtcgac aagaaggtgg agcccaagtc ctgtgataag 660 acccacacat gccccccttg tcctgcacca gagctgctgg gaggaccaag cgtgttcctg 720 tttccaccca agcctaagga caccctgatg atctctagga cccccgaggt gacatgcgtg 780 gtggtggacg tgagccacga ggatcctgag gtgaagttta actggtacgt ggatggcgtg 840 gaggtgcaca atgccaagac caagccccgg gaggagcagt acaactccac ctatagagtg 900 gtgtctgtgc tgacagtgct gcaccaggac tggctgaacg gcaaggagta taagtgcaag 960 gtgtccaata aggccctgcc cgcccctatc gagaagacca tctctaaggc caagggccag 1020 cctagggagc cacaggtgta cacactgcct ccatcccgca aggagctgac caagaaccag 1080 gtgtctctga catgtctggt gaagggcttc tatccttctg atatcgccgt ggagtgggag 1140 agcaatggcc agccagagaa caattacaag accacacccc ctgtgctgaa gagcgacggc 1200 tccttctttc tgtatagcaa gctgaccgtg gataagtcca gatggcagca gggcaacgtg 1260 ttttcttgta gcgtgatgca cgaggccctg cacaatcact acacacagaa gtccctgtct 1320 ctgagccctg gcaagtaa 1338 <210> 14 <211> 645 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 14 gatattctgc tgacccagag cccggttatt ctgagcgtta gcccgggtga acgtgttagc 60 tttagctgtc gtgcaagcca gagcattggt accaatattc attggtatca gcagcgtacc 120 aatggtagcc cgcgtctgct gattaaatat gcaagcgaaa gcattagcgg tattccgagc 180 cgttttagcg gtagcggtag cggtaccgat tttaccctga gcattaatag cgttgaaagc 240 gaagatattg cagattatta ttgtcagcag aataataatt ggccgaccac ctttggtgca 300 ggtaccaaac tggaactgaa acgtactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa ctctacgcct gcgaagtcac ccatcagggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gctga 645 <210> 15 <211> 672 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 15 caggttcagc tgaaacagag cggtccgggt ctggttcagc cgagccagag cctgagcatt 60 acctgtaccg ttagcggttt tagcctgacc aattatggtg ttcattgggt tcgtcagagc 120 ccgggtaaag gtctggaatg gctgggtgtt atttggagcg gtggtaatac cgattataat 180 accccgttta ccagccgtct gagcattaat aaagataata gcaaaagcca ggtttttttt 240 aaaatgaata gcctgcagag caatgatacc gcaatttatt attgtgcacg tgcactgacc 300 tattatgatt atgaatttgc atattggggt cagggtaccc tggttaccgt tagcgcagcc 360 tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420 acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600 atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagagagt tgagcccaaa 660 tcttgtgaca aa 672 <210> 16 <211> 768 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 16 ggcggcggca gcggcggcgg ccaggttcag ctgaaacaga gcggtccggg tctggttcag 60 ccgagccaga gcctgagcat tacctgtacc gttagcggtt ttagcctgac caattatggt 120 gttcattggg ttcgtcagag cccgggtaaa ggtctggaat ggctgggtgt tatttggagc 180 ggtggtaata ccgattataa taccccgttt accagccgtc tgagcattaa taaagataat 240 agcaaaagcc aggttttttt taaaatgaat agcctgcaga gcaatgatac cgcaatttat 300 tattgtgcac gtgcactgac ctattatgat tatgaatttg catattgggg tcagggtacc 360 ctggttaccg ttagcgcagg cggcggcggc agcggcggcg gcggcagcgg cggcggcggc 420 agcgatattc tgctgaccca gagcccggtt attctgagcg ttagcccggg tgaacgtgtt 480 agctttagct gtcgtgcaag ccagagcatt ggtaccaata ttcattggta tcagcagcgt 540 accaatggta gcccgcgtct gctgattaaa tatgcaagcg aaagcattag cggtattccg 600 agccgtttta gcggtagcgg tagcggtacc gattttaccc tgagcattaa tagcgttgaa 660 agcgaagata ttgcagatta ttattgtcag cagaataata attggccgac cacctttggt 720 gcaggtacca aactggaact gaaacgtcac caccaccacc accactga 768 <210> 17 <211> 726 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 17 gatattctgc tgacccagag cccggttatt ctgagcgtta gcccgggtga acgtgttagc 60 tttagctgtc gtgcaagcca gagcattggt accaatattc attggtatca gcagcgtacc 120 aatggtagcc cgcgtctgct gattaaatat gcaagcgaaa gcattagcgg tattccgagc 180 cgttttagcg gtagcggtag cggtaccgat tttaccctga gcattaatag cgttgaaagc 240 gaagatattg cagattatta ttgtcagcag aataataatt ggccgaccac ctttggtgca 300 ggtaccaaac tggaactgaa acgtggtgga ggcggttcag gcggaggtgg ctctggcggt 360 ggcggatcgc aggttcagct gaaacagagc ggtccgggtc tggttcagcc gagccagagc 420 ctgagcatta cctgtaccgt tagcggtttt agcctgacca attatggtgt tcattgggtt 480 cgtcagagcc cgggtaaagg tctggaatgg ctgggtgtta tttggagcgg tggtaatacc 540 gattataata ccccgtttac cagccgtctg agcattaata aagataatag caaaagccag 600 gtttttttta aaatgaatag cctgcagagc aatgataccg caatttatta ttgtgcacgt 660 gcactgacct attatgatta tgaatttgca tattggggtc agggtaccct ggttaccgtt 720 agcgca 726 <210> 18 <211> 765 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 18 ggcggtggat cagacatcaa gctgcagcag agcggcgccg agctggccag acccggcgcc 60 agcgtgaaga tgagctgcaa gaccagcggc tacaccttca ccagatacac catgcactgg 120 gtgaagcaga gacccggcca gggcctggag tggatcggct acatcaaccc cagcagaggc 180 tacaccaact acaaccagaa gttcaaggac aaggccaccc tgaccaccga caagagcagc 240 agcaccgcct acatgcagct gagcagcctg accagcgagg acagcgccgt gtactactgc 300 gccagatact acgacgacca ctactgcctg gactactggg gccagggcac caccctgacc 360 gtgagcagcg tggagggcgg cagcggcggc agcggcggca gcggcggcag cggcggcgtg 420 gacgacatcc agctgaccca gagccccgcc atcatgagcg ccagccccgg cgagaaggtg 480 accatgacct gcagagccag cagcagcgtg agctacatga actggtacca gcagaagagc 540 ggcaccagcc ccaagagatg gatctacgac accagcaagg tggccagcgg cgtgccctac 600 agattcagcg gcagcggcag cggcaccagc tacagcctga ccatcagcag catggaggcc 660 gaggacgccg ccacctacta ctgccagcag tggagcagca accccctgac cttcggcgct 720 ggcaccaagc tggagctgaa gagacaccac caccaccacc actga 765 <210> 19 <211> 684 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 19 aggattctgc tgacccagag cccggttatt ctgagcgtta gcccgggtga acgtgttagc 60 tttagctgtc gtgcaagcca gagcattggt accaatattc attggtatca ggatcgtacc 120 aatggtagcc cgcgtctgct gattaaatat gcaagcgaaa gcattagcgg tattccgagc 180 cgttttagcg gtagcggtag cggtaccgat tttaccctga gcattaatag cgttgaaagc 240 gaagatattg cagattatta ttgtcagcag aataataatt ggccgaccac ctttggtgca 300 ggtaccaaac tggaactgaa acgtaccgtg gcagcaccat ccgtgttcat ctttccccct 360 tctgacgagc agctgaagtc tggcacagcc agcgtggtgt gctacctgaa caacttctac 420 cccagggagg ccaaggtgca gtggaaggtg gataacgccc tgcagtccgg caattctcag 480 gagagcgtga ccgagcagga ctccaaggat tctacataca gcctgtggtc caccctgaca 540 ctgtccaagg ccgactacga gaagcacaag ctgtatgcat gcgaggtgac ccaccagggc 600 ctgtcctctc ccgtgacaaa gagcttcaat aggggagagt gtggaggagg atcctaccct 660 tatgacgtgc cagattatgc ctaa 684 <210> 20 <211> 1350 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 20 caggttcagc tgaaacagag cggtccgggt ctggttcagc cgagccagag cctgagcatt 60 acctgtaccg ttagcggttt tagcctgacc aattatggtg ttcattgggt tcgtaagagc 120 ccgggtaaag gtctggaatg gctgggtgtt atttggagcg gtggtaatac cgattataat 180 accgagttta ccagccgtct gagcattaat aaagataata gcaaaagcca ggtttttttt 240 aaaatgaata gcctgcagag caatgatacc gcaatttatt attgtgcacg tgcactgacc 300 tattatgatt atgaatttgc atattggggt cagggtaccc tggttaccgt tagcgcagcc 360 tctacaaagg gaccaagcgt gtttccactg gcaccctcct ctaagagcac ctccggagga 420 acagccgccc tgggctgtct ggtgaaggac tatttcccag agcccgtgac cgtgtcctgg 480 aactctggcg ccctgacctc cggagtggca acaggaccag ccgtgctgca gagctccggc 540 ctgtacagcc tgtctagcgt ggtgaccgtg ccctcctcta gcctgggcac ccagacatat 600 atctgcaacg tgaatcacaa gccaagcaat acaaaggtcg acaagaaggt ggagcccaag 660 tcctgtgata agacccacac atgcccccct tgtcctgcac cagagctgct gggaggacca 720 agcgtgttcc tgtttccacc caagcctaag gacaccctga tgatctctag gacccccgag 780 gtgacatgcg tggtggtgga cgtgagccac gaggatcctg aggtgaagtt taactggtac 840 gtggatggcg tggaggtgca caatgccaag accaagcccc gggaggagca gtacaactcc 900 acctatagag tggtgtctgt gctgacagtg ctgcaccagg actggctgaa cggcaaggag 960 tataagtgca aggtgtccaa taaggccctg cccgccccta tcgagaagac catctctaag 1020 gccaagggcc agcctaggga gccacaggtg tacacactgc ctccatcccg caaggagctg 1080 accaagaacc aggtgtctct gacatgtctg gtgaagggct tctatccttc tgatatcgcc 1140 gtggagtggg agagcaatgg ccagccagag aacaattaca agaccacacc ccctgtgctg 1200 aagagcgacg gctccttctt tctgtatagc aagctgaccg tggataagtc cagatggcag 1260 cagggcaacg tgttttcttg tagcgtgatg cacgaggccc tgcacaatca ctacacacag 1320 aagtccctgt ctctgagccc tggcaagtaa 1350 <210> 21 <211> 645 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 21 gatatccaga tgacccagag ccctagctcc ctgagcgcct ccgtgggcga cagggtgacc 60 atcacatgta gggcatccca ggacgtgagc accgcagtgg cctggtatca gcagaagccc 120 ggcaaggccc ctaagctgct gatctactct gccagcttcc tgtatagcgg cgtgccttcc 180 agattttccg gatctggaag cggaaccgac ttcaccctga caatctctag cctgcagcca 240 gaggattttg ccacatacta ttgccagcag tacctgtatc acccagcaac cttcggacag 300 ggcacaaaag tggaaatcaa gcggactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa ctctacgcct gcgaagtcac ccatcagggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gctga 645 <210> 22 <211> 669 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 22 gaggtgcagc tggtggaaag cgggggagga ctggtgcagc ctggggggtc actgagactg 60 agttgcgccg cctccggctt caccttttcc gactcttgga tccactgggt gaggcaggca 120 ccaggcaagg gcctggagtg ggtggcctgg atctctccct acggcggcag cacctactat 180 gccgactccg tgaagggccg gtttacaatc tctgccgata ccagcaagaa cacagcctat 240 ctgcagatga attctctgag agccgaggac accgccgtgt actattgcgc acggagacac 300 tggccaggag gattcgatta ctggggacag ggcaccctgg tgacagtgtc cgccgcctcc 360 accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 420 gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540 tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 600 tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agagagttga gcccaaatct 660 tgtgacaaa 669 <210> 23 <211> 774 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 23 gggggcggga gcgggggcgg cgaggtgcag ctggtggaaa gcgggggagg actggtgcag 60 cctggggggt cactgagact gagttgcgcc gcctccggct tcaccttttc cgactcttgg 120 atccactggg tgaggcaggc accaggcaag ggcctggagt gggtggcctg gatctctccc 180 tacggcggca gcacctacta tgccgactcc gtgaagggcc ggtttacaat ctctgccgat 240 accagcaaga acacagccta tctgcagatg aattctctga gagccgagga caccgccgtg 300 tactattgcg cacggagaca ctggccagga ggattcgatt actggggaca gggcaccctg 360 gtgacagtgt ccgccgtgga gggaggatcc ggaggatctg gaggaagcgg cggctccggc 420 ggcgtggacg atatccagat gacccagagc cctagctccc tgagcgcctc cgtgggcgac 480 agggtgacca tcacatgtag ggcatcccag gacgtgagca ccgcagtggc ctggtatcag 540 cagaagcccg gcaaggcccc taagctgctg atctactctg ccagcttcct gtatagcggc 600 gtgccttcca gattttccgg atctggaagc ggaaccgact tcaccctgac aatctctagc 660 ctgcagccag aggattttgc cacatactat tgccagcagt acctgtatca cccagcaacc 720 ttcggacagg gcacaaaagt ggaaatcaag cggcatcatc atcatcacca ttaa 774 <210> 24 <211> 723 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 24 gatatccaga tgacccagag ccctagctcc ctgagcgcct ccgtgggcga cagggtgacc 60 atcacatgta gggcatccca ggacgtgagc accgcagtgg cctggtatca gcagaagccc 120 ggcaaggccc ctaagctgct gatctactct gccagcttcc tgtatagcgg cgtgccttcc 180 agattttccg gatctggaag cggaaccgac ttcaccctga caatctctag cctgcagcca 240 gaggattttg ccacatacta ttgccagcag tacctgtatc acccagcaac cttcggacag 300 ggcacaaaag tggaaatcaa gcggggtgga ggcggttcag gcggaggtgg ctctggcggt 360 ggcggatcgg aggtgcagct ggtggaaagc gggggaggac tggtgcagcc tggggggtca 420 ctgagactga gttgcgccgc ctccggcttc accttttccg actcttggat ccactgggtg 480 aggcaggcac caggcaaggg cctggagtgg gtggcctgga tctctcccta cggcggcagc 540 acctactatg ccgactccgt gaagggccgg tttacaatct ctgccgatac cagcaagaac 600 acagcctatc tgcagatgaa ttctctgaga gccgaggaca ccgccgtgta ctattgcgca 660 cggagacact ggccaggagg attcgattac tggggacagg gcaccctggt gacagtgtcc 720 gcc 723 <210> 25 <211> 684 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 25 aggatccaga tgacccagag ccctagctcc ctgagcgcct ccgtgggcga cagggtgacc 60 atcacatgta gggcatccca ggacgtgagc accgcagtgg cctggtatca ggataagccc 120 ggcaaggccc ctaagctgct gatctactct gccagcttcc tgtatagcgg cgtgccttcc 180 agattttccg gatctggaag cggaaccgac ttcaccctga caatctctag cctgcagcca 240 gaggattttg ccacatacta ttgccagcag tacctgtatc acccagcaac cttcggacag 300 ggcacaaaag tggaaatcaa gcggaccgtg gcagcaccat ccgtgttcat ctttccccct 360 tctgacgagc agctgaagtc tggcacagcc agcgtggtgt gctacctgaa caacttctac 420 cccagggagg ccaaggtgca gtggaaggtg gataacgccc tgcagtccgg caattctcag 480 gagagcgtga ccgagcagga ctccaaggat tctacataca gcctgtggtc caccctgaca 540 ctgtccaagg ccgactacga gaagcacaag ctgtatgcat gcgaggtgac ccaccagggc 600 ctgtcctctc ccgtgacaaa gagcttcaat aggggagagt gtggaggagg atcctaccct 660 tatgacgtgc cagattatgc ctaa 684 <210> 26 <211> 1347 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 26 gaggtgcagc tggtggaaag cgggggagga ctggtgcagc ctggggggtc actgagactg 60 agttgcgccg cctccggctt caccttttcc gactcttgga tccactgggt gaggaaggca 120 ccaggcaagg gcctggagtg ggtggcctgg atctctccct acggcggcag cacctactat 180 gccgactccg tgaagggcga gtttacaatc tctgccgata ccagcaagaa cacagcctat 240 ctgcagatga attctctgag agccgaggac accgccgtgt actattgcgc acggagacac 300 tggccaggag gattcgatta ctggggacag ggcaccctgg tgacagtgtc cgccgcctct 360 acaaagggac caagcgtgtt tccactggca ccctcctcta agagcacctc cggaggaaca 420 gccgccctgg gctgtctggt gaaggactat ttcccagagc ccgtgaccgt gtcctggaac 480 tctggcgccc tgacctccgg agtggcaaca ggaccagccg tgctgcagag ctccggcctg 540 tacagcctgt ctagcgtggt gaccgtgccc tcctctagcc tgggcaccca gacatatatc 600 tgcaacgtga atcacaagcc aagcaataca aaggtcgaca agaaggtgga gcccaagtcc 660 tgtgataaga cccacacatg ccccccttgt cctgcaccag agctgctggg aggaccaagc 720 gtgttcctgt ttccacccaa gcctaaggac accctgatga tctctaggac ccccgaggtg 780 acatgcgtgg tggtggacgt gagccacgag gatcctgagg tgaagtttaa ctggtacgtg 840 gatggcgtgg aggtgcacaa tgccaagacc aagccccggg aggagcagta caactccacc 900 tatagagtgg tgtctgtgct gacagtgctg caccaggact ggctgaacgg caaggagtat 960 aagtgcaagg tgtccaataa ggccctgccc gcccctatcg agaagaccat ctctaaggcc 1020 aagggccagc ctagggagcc acaggtgtac acactgcctc catcccgcaa ggagctgacc 1080 aagaaccagg tgtctctgac atgtctggtg aagggcttct atccttctga tatcgccgtg 1140 gagtgggaga gcaatggcca gccagagaac aattacaaga ccacaccccc tgtgctgaag 1200 agcgacggct ccttctttct gtatagcaag ctgaccgtgg ataagtccag atggcagcag 1260 ggcaacgtgt tttcttgtag cgtgatgcac gaggccctgc acaatcacta cacacagaag 1320 tccctgtctc tgagccctgg caagtaa 1347 <210> 27 <211> 645 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 27 gacatccaga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagagtgacc 60 atcacctgca gagccagcca ggacgtgaac accgccgtgg cctggtacca gcagaagccc 120 ggcaaggccc ccaagctgct gatctacagc gccagcttcc tgtacagcgg cgtgcccagc 180 agattcagcg gcagcagaag cggcaccgac ttcaccctga ccatcagcag cctgcagccc 240 gaggacttcg ccacctacta ctgccagcag cactacacca ccccccccac cttcggccag 300 ggcaccaagg tggagatcaa gagaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa ctctacgcct gcgaagtcac ccatcagggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gctga 645 <210> 28 <211> 675 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 28 gaggtgcagc tggtggagag cggcggcggc ctggtgcagc ccggcggcag cctgagactg 60 agctgcgccg ccagcggctt caacatcaag gacacctaca tccactgggt gagacaggcc 120 cccggcaagg gcctggagtg ggtggccaga atctacccca ccaacggcta caccagatac 180 gccgacagcg tgaagggcag attcaccatc agcgccgaca ccagcaagaa caccgcctac 240 ctgcagatga acagcctgag agccgaggac accgccgtgt actactgcag cagatggggc 300 ggcgacggct tctacgccat ggactactgg ggccagggca ccctggtgac cgtgagcagc 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 660 aaatcttgtg acaaa 675 <210> 29 <211> 759 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 29 ggcggcggca gcggcggcgg cgaggtgcag ctggtgcaga gcggcgccga ggtgaagaag 60 cccggcgcca gcgtgaagat cagctgcaag accagcggct acaccttcac cgagtacacc 120 atccactggg tgaagcaggc cagcggcaag ggcctggagt ggatcggcaa catcaacccc 180 aacaacggcg gcaccaccta caaccagaag ttcgaggaca gagccaccct gaccgtggac 240 aagagcacca gcaccgccta catggagctg agcagcctga gaagcgagga caccgccgtg 300 tactactgcg ccgccggctg gaacttcgac tactggggcc agggcaccac cgtgaccgtg 360 agcagcgccg gtggaggcgg ttcaggcgga ggtggctctg gcggtggcgg atcggacatc 420 gtgatgaccc agagccccag cagcctgagc gccagcgtgg gcgacagagt gaccatcacc 480 tgcaaggcca gccaggacgt gggcaccgcc gtggactggt accagcagaa gcccggcaag 540 gcccccaagc tgctgatcta ctgggccagc accagacaca ccggcgtgcc cgacagattc 600 accggcagcg gcagcggcac cgacttcacc ctgaccatca gcagcctgca gcccgaggac 660 ttcgccgact acttctgcca gcagtacaac agctaccccc tgaccttcgg cggcggcacc 720 aagctggaga tcaagagaca ccaccaccac caccactga 759 <210> 30 <211> 729 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 30 gacatccaga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagagtgacc 60 atcacctgca gagccagcca ggacgtgaac accgccgtgg cctggtacca gcagaagccc 120 ggcaaggccc ccaagctgct gatctacagc gccagcttcc tgtacagcgg cgtgcccagc 180 agattcagcg gcagcagaag cggcaccgac ttcaccctga ccatcagcag cctgcagccc 240 gaggacttcg ccacctacta ctgccagcag cactacacca ccccccccac cttcggccag 300 ggcaccaagg tggagatcaa gagaggtgga ggcggttcag gcggaggtgg ctctggcggt 360 ggcggatcgg aggtgcagct ggtggagagc ggcggcggcc tggtgcagcc cggcggcagc 420 ctgagactga gctgcgccgc cagcggcttc aacatcaagg acacctacat ccactgggtg 480 agacaggccc ccggcaaggg cctggagtgg gtggccagaa tctaccccac caacggctac 540 accagatacg ccgacagcgt gaagggcaga ttcaccatca gcgccgacac cagcaagaac 600 accgcctacc tgcagatgaa cagcctgaga gccgaggaca ccgccgtgta ctactgcagc 660 agatggggcg gcgacggctt ctacgccatg gactactggg gccagggcac cctggtgacc 720 gtgagcagc 729 <210> 31 <211> 684 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 31 aggatccaga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagagtgacc 60 atcacctgca gagccagcca ggacgtgaac accgccgtgg cctggtacca ggataagccc 120 ggcaaggccc ccaagctgct gatctacagc gccagcttcc tgtacagcgg cgtgcccagc 180 agattcagcg gcagcagaag cggcaccgac ttcaccctga ccatcagcag cctgcagccc 240 gaggacttcg ccacctacta ctgccagcag cactacacca ccccccccac cttcggccag 300 ggcaccaagg tggagatcaa gagaaccgtg gcagcaccat ccgtgttcat ctttccccct 360 tctgacgagc agctgaagtc tggcacagcc agcgtggtgt gctacctgaa caacttctac 420 cccagggagg ccaaggtgca gtggaaggtg gataacgccc tgcagtccgg caattctcag 480 gagagcgtga ccgagcagga ctccaaggat tctacataca gcctgtggtc caccctgaca 540 ctgtccaagg ccgactacga gaagcacaag ctgtatgcat gcgaggtgac ccaccagggc 600 ctgtcctctc ccgtgacaaa gagcttcaat aggggagagt gtggaggagg atcctaccct 660 tatgacgtgc cagattatgc ctaa 684 <210> 32 <211> 1353 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 32 gaggtgcagc tggtggagag cggcggcggc ctggtgcagc ccggcggcag cctgagactg 60 agctgcgccg ccagcggctt caacatcaag gacacctaca tccactgggt gagaaaggcc 120 cccggcaagg gcctggagtg ggtggccaga atctacccca ccaacggcta caccagatac 180 gccgacagcg tgaagggcag gttcaccatc agcgccgaca ccagcaagaa caccgcctac 240 ctgcagatga acagcctgag agccgaggac accgccgtgt actactgcag cagatggggc 300 ggcgacggct tctacgccat ggactactgg ggccagggca ccctggtgac cgtgagcagc 360 gcctctacaa agggaccaag cgtgtttcca ctggcaccct cctctaagag cacctccgga 420 ggaacagccg ccctgggctg tctggtgaag gactatttcc cagagcccgt gaccgtgtcc 480 tggaactctg gcgccctgac ctccggagtg gcaacaggac cagccgtgct gcagagctcc 540 ggcctgtaca gcctgtctag cgtggtgacc gtgccctcct ctagcctggg cacccagaca 600 tatatctgca acgtgaatca caagccaagc aatacaaagg tcgacaagaa ggtggagccc 660 aagtcctgtg ataagaccca cacatgcccc ccttgtcctg caccagagct gctgggagga 720 ccaagcgtgt tcctgtttcc acccaagcct aaggacaccc tgatgatctc taggaccccc 780 gaggtgacat gcgtggtggt ggacgtgagc cacgaggatc ctgaggtgaa gtttaactgg 840 tacgtggatg gcgtggaggt gcacaatgcc aagaccaagc cccgggagga gcagtacaac 900 tccacctata gagtggtgtc tgtgctgaca gtgctgcacc aggactggct gaacggcaag 960 gagtataagt gcaaggtgtc caataaggcc ctgcccgccc ctatcgagaa gaccatctct 1020 aaggccaagg gccagcctag ggagccacag gtgtacacac tgcctccatc ccgcaaggag 1080 ctgaccaaga accaggtgtc tctgacatgt ctggtgaagg gcttctatcc ttctgatatc 1140 gccgtggagt gggagagcaa tggccagcca gagaacaatt acaagaccac accccctgtg 1200 ctgaagagcg acggctcctt ctttctgtat agcaagctga ccgtggataa gtccagatgg 1260 cagcagggca acgtgttttc ttgtagcgtg atgcacgagg ccctgcacaa tcactacaca 1320 cagaagtccc tgtctctgag ccctggcaag taa 1353 <210> 33 <211> 660 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 33 gacattgtga tgacccagtc ccctgacagc ctggctgtga gcctgggaga gagggccacc 60 atcaactgca agagcagcca gagcctgctg tacagcagaa accagaaaaa ctacctggcc 120 tggtaccagc agaaacccgg ccagcctccc aagctgctga tcttctgggc cagcaccaga 180 gagagcggcg tgcctgacag attcagcggc tccggcttcg gcaccgactt caccctgacc 240 atcagcagcc tccaggccga ggatgtcgcc gtgtattact gccagcagta cttctcctat 300 cccctcacct tcggccaagg caccaaggtg gagatcaaga ctgtggctgc accatctgtc 360 ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 420 ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 480 tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 540 agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaactcta cgcctgcgaa 600 gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgctga 660 <210> 34 <211> 687 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 34 caagtgcagc tggtgcagtc cggcgctgag gtgaagaagc ccggagcctc cgtgaaggtg 60 tcctgcaaga cctccaggta caccttcaca gagtacacca tccactgggt gagacaggct 120 cccggccaga ggctggagtg gattggcggc attaacccca acaacggcat ccccaactac 180 aaccagaagt tcaagggcag ggtgaccatc acagttgata catccgccag cacagcctat 240 atggaactga gctccctgag gagcgaggac acagccgtgt actactgcgc caggaggagg 300 attgcctacg gctatgatga gggccatgcc atggactact ggggacaggg caccctggtg 360 acagtctcca gcgcctccac caagggccca tcggtcttcc ccctggcacc ctcctccaag 420 agcacctctg ggggcacagc ggccctgggc tgcctggtca aggactactt ccccgaaccg 480 gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 540 ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 600 ggcacccaga cctacatctg caacgtgaat cacaagccca gcaacaccaa ggtggacaag 660 agagttgagc ccaaatcttg tgacaaa 687 <210> 35 <211> 807 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 35 ggcggcggca gcggcggcgg ccaagtgcag ctggtgcagt ccggcgctga ggtgaagaag 60 cccggagcct ccgtgaaggt gtcctgcaag acctccaggt acaccttcac agagtacacc 120 atccactggg tgagacaggc tcccggccag aggctggagt ggattggcgg cattaacccc 180 aacaacggca tccccaacta caaccagaag ttcaagggca gggtgaccat cacagttgat 240 acatccgcca gcacagccta tatggaactg agctccctga ggagcgagga cacagccgtg 300 tactactgcg ccaggaggag gattgcctac ggctatgatg agggccatgc catggactac 360 tggggacagg gcaccctggt gacagtctcc agcggcagca ccagcggatc cggaaagcct 420 ggcagcggag agggaagcac caagggcgac attgtgatga cccagtcccc tgacagcctg 480 gctgtgagcc tgggagagag ggccaccatc aactgcaaga gcagccagag cctgctgtac 540 agcagaaacc agaaaaacta cctggcctgg taccagcaga aacccggcca gcctcccaag 600 ctgctgatct tctgggccag caccagagag agcggcgtgc ctgacagatt cagcggctcc 660 ggcttcggca ccgacttcac cctgaccatc agcagcctcc aggccgagga tgtcgccgtg 720 tattactgcc agcagtactt ctcctatccc ctcaccttcg gccaaggcac caaggtggag 780 atcaagcacc accaccacca ccactga 807 <210> 36 <211> 756 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 36 gacattgtga tgacccagtc ccctgacagc ctggctgtga gcctgggaga gagggccacc 60 atcaactgca agagcagcca gagcctgctg tacagcagaa accagaaaaa ctacctggcc 120 tggtaccagc agaaacccgg ccagcctccc aagctgctga tcttctgggc cagcaccaga 180 gagagcggcg tgcctgacag attcagcggc tccggcttcg gcaccgactt caccctgacc 240 atcagcagcc tccaggccga ggatgtcgcc gtgtattact gccagcagta cttctcctat 300 cccctcacct tcggccaagg caccaaggtg gagatcaagg gtggaggcgg ttcaggcgga 360 ggtggctctg gcggtggcgg atcgcaagtg cagctggtgc agtccggcgc tgaggtgaag 420 aagcccggag cctccgtgaa ggtgtcctgc aagacctcca ggtacacctt cacagagtac 480 accatccact gggtgagaca ggctcccggc cagaggctgg agtggattgg cggcattaac 540 cccaacaacg gcatccccaa ctacaaccag aagttcaagg gcagggtgac catcacagtt 600 gatacatccg ccagcacagc ctatatggaa ctgagctccc tgaggagcga ggacacagcc 660 gtgtactact gcgccaggag gaggattgcc tacggctatg atgagggcca tgccatggac 720 tactggggac agggcaccct ggtgacagtc tccagc 756 <210> 37 <211> 699 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 37 aggattgtga tgacccagtc ccctgacagc ctggctgtga gcctgggaga gagggccacc 60 atcaactgca agagcagcca gagcctgctg tacagcagaa accagaaaaa ctacctggcc 120 tggtaccagg ataaacccgg ccagcctccc aagctgctga tcttctgggc cagcaccaga 180 gagagcggcg tgcctgacag attcagcggc tccggcttcg gcaccgactt caccctgacc 240 atcagcagcc tccaggccga ggatgtcgcc gtgtattact gccagcagta cttctcctat 300 cccctcacct tcggccaagg caccaaggtg gagatcaaga ccgtggcagc accatccgtg 360 ttcatctttc ccccttctga cgagcagctg aagtctggca cagccagcgt ggtgtgctac 420 ctgaacaact tctaccccag ggaggccaag gtgcagtgga aggtggataa cgccctgcag 480 tccggcaatt ctcaggagag cgtgaccgag caggactcca aggattctac atacagcctg 540 tggtccaccc tgacactgtc caaggccgac tacgagaagc acaagctgta tgcatgcgag 600 gtgacccacc agggcctgtc ctctcccgtg acaaagagct tcaatagggg agagtgtgga 660 ggaggatcct acccttatga cgtgccagat tatgcctaa 699 <210> 38 <211> 1365 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 38 caagtgcagc tggtgcagtc cggcgctgag gtgaagaagc ccggagcctc cgtgaaggtg 60 tcctgcaaga cctccaggta caccttcaca gagtacacca tccactgggt gagaaaggct 120 cccggccaga ggctggagtg gattggcggc attaacccca acaacggcat ccccaactac 180 aaccagaggt tcaagggcag ggtgaccatc acagttgata catccgccag cacagcctat 240 atggaactga gctccctgag gagcgaggac acagccgtgt actactgcgc caggaggagg 300 attgcctacg gctatgatga gggccatgcc atggactact ggggacaggg caccctggtg 360 acagtctcca gcgcctctac aaagggacca agcgtgtttc cactggcacc ctcctctaag 420 agcacctccg gaggaacagc cgccctgggc tgtctggtga aggactattt cccagagccc 480 gtgaccgtgt cctggaactc tggcgccctg acctccggag tggcaacagg accagccgtg 540 ctgcagagct ccggcctgta cagcctgtct agcgtggtga ccgtgccctc ctctagcctg 600 ggcacccaga catatatctg caacgtgaat cacaagccaa gcaatacaaa ggtcgacaag 660 aaggtggagc ccaagtcctg tgataagacc cacacatgcc ccccttgtcc tgcaccagag 720 ctgctgggag gaccaagcgt gttcctgttt ccacccaagc ctaaggacac cctgatgatc 780 tctaggaccc ccgaggtgac atgcgtggtg gtggacgtga gccacgagga tcctgaggtg 840 aagtttaact ggtacgtgga tggcgtggag gtgcacaatg ccaagaccaa gccccgggag 900 gagcagtaca actccaccta tagagtggtg tctgtgctga cagtgctgca ccaggactgg 960 ctgaacggca aggagtataa gtgcaaggtg tccaataagg ccctgcccgc ccctatcgag 1020 aagaccatct ctaaggccaa gggccagcct agggagccac aggtgtacac actgcctcca 1080 tcccgcaagg agctgaccaa gaaccaggtg tctctgacat gtctggtgaa gggcttctat 1140 ccttctgata tcgccgtgga gtgggagagc aatggccagc cagagaacaa ttacaagacc 1200 acaccccctg tgctgaagag cgacggctcc ttctttctgt atagcaagct gaccgtggat 1260 aagtccagat ggcagcaggg caacgtgttt tcttgtagcg tgatgcacga ggccctgcac 1320 aatcactaca cacagaagtc cctgtctctg agccctggca agtaa 1365 <210> 39 <211> 657 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 39 gatattcaga tgacccagag cccttcaagc ctgtccgcca gcgtcgggga tagagtgacc 60 attacttgcc ggagcaccaa gtccctgctg cactccaacg gcatcacata cctgtattgg 120 taccagcaga agcccggcaa ggcccctaag ctgctgatct atcagatgtc caatctggcc 180 tctggcgtgc caagcagatt cagctcctct ggcagcggca ccgactttac cctgacaatc 240 agctccctgc agcccgagga tttcgccaca tactattgcg cccagaacct ggagatccct 300 aggacctttg gccagggcac aaaggtggag ctgaagactg tggctgcacc atctgtcttc 360 atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 420 aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 480 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 540 agcaccctga cgctgagcaa agcagactac gagaaacaca aactctacgc ctgcgaagtc 600 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgctga 657 <210> 40 <211> 663 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 40 gaggtgcagc tggtgcagtc cggacctggc ctggtgcagc caggaggctc cgtgaggatc 60 tcttgtgccg ccagcggcta taccttcaca aactacggca tgaattgggt gaagcaggca 120 cctggcaagg gcctggagtg gatgggctgg atcaacacct atacaggcga gtccacctac 180 gccgactctt ttaagggcag attcaccttt tctctggata catccgcctc tgccgcctac 240 ctgcagatca atagcctgcg ggccgaggac acagccgtgt actattgtgc cagattcgcc 300 atcaaagggg actactgggg acagggcaca ctgctgaccg tctcaagcgc ctccaccaag 360 ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 420 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 480 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 540 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 600 gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 660 aaa 663 <210> 41 <211> 771 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 41 ggcggcggca gcggcggcgg cgaggtgcag ctggtgcagt ccggacctgg cctggtgcag 60 ccaggaggct ccgtgaggat ctcttgtgcc gccagcggct ataccttcac aaactacggc 120 atgaattggg tgaagcaggc acctggcaag ggcctggagt ggatgggctg gatcaacacc 180 tatacaggcg agtccaccta cgccgactct tttaagggca gattcacctt ttctctggat 240 acatccgcct ctgccgccta cctgcagatc aatagcctgc gggccgagga cacagccgtg 300 tactattgtg ccagattcgc catcaaaggg gactactggg gacagggcac actgctgacc 360 gtctcaagcg gtggaggcgg ttcaggcgga ggtggctctg gcggtggcgg atcggatatt 420 cagatgaccc agagcccttc aagcctgtcc gccagcgtcg gggatagagt gaccattact 480 tgccggagca ccaagtccct gctgcactcc aacggcatca catacctgta ttggtaccag 540 cagaagcccg gcaaggcccc taagctgctg atctatcaga tgtccaatct ggcctctggc 600 gtgccaagca gattcagctc ctctggcagc ggcaccgact ttaccctgac aatcagctcc 660 ctgcagcccg aggatttcgc cacatactat tgcgcccaga acctggagat ccctaggacc 720 tttggccagg gcacaaaggt ggagctgaag caccaccacc accaccactg a 771 <210> 42 <211> 762 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 42 gatattcaga tgacccagag cccttcaagc ctgtccgcca gcgtcgggga tagagtgacc 60 attacttgcc ggagcaccaa gtccctgctg cactccaacg gcatcacata cctgtattgg 120 taccagcaga agcccggcaa ggcccctaag ctgctgatct atcagatgtc caatctggcc 180 tctggcgtgc caagcagatt cagctcctct ggcagcggca ccgactttac cctgacaatc 240 agctccctgc agcccgagga tttcgccaca tactattgcg cccagaacct ggagatccct 300 aggacctttg gccagggcac aaaggtggag ctgaagcgcg ccaccccctc tcacaacagc 360 caccaggtgc caagcgccgg aggaccaacc gccaattccg gcacatctgg aagcgaggtg 420 cagctggtgc agtccggacc tggcctggtg cagccaggag gctccgtgag gatctcttgt 480 gccgccagcg gctatacctt cacaaactac ggcatgaatt gggtgaagca ggcacctggc 540 aagggcctgg agtggatggg ctggatcaac acctatacag gcgagtccac ctacgccgac 600 tcttttaagg gcagattcac cttttctctg gatacatccg cctctgccgc ctacctgcag 660 atcaatagcc tgcgggccga ggacacagcc gtgtactatt gtgccagatt cgccatcaaa 720 ggggactact ggggacaggg cacactgctg accgtctcaa gc 762 <210> 43 <211> 696 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 43 aggattcaga tgacccagag cccttcaagc ctgtccgcca gcgtcgggga tagagtgacc 60 attacttgcc ggagcaccaa gtccctgctg cactccaacg gcatcacata cctgtattgg 120 taccaggata agcccggcaa ggcccctaag ctgctgatct atcagatgtc caatctggcc 180 tctggcgtgc caagcagatt cagctcctct ggcagcggca ccgactttac cctgacaatc 240 agctccctgc agcccgagga tttcgccaca tactattgcg cccagaacct ggagatccct 300 aggacctttg gccagggcac aaaggtggag ctgaagaccg tggcagcacc atccgtgttc 360 atctttcccc cttctgacga gcagctgaag tctggcacag ccagcgtggt gtgctacctg 420 aacaacttct accccaggga ggccaaggtg cagtggaagg tggataacgc cctgcagtcc 480 ggcaattctc aggagagcgt gaccgagcag gactccaagg attctacata cagcctgtgg 540 tccaccctga cactgtccaa ggccgactac gagaagcaca agctgtatgc atgcgaggtg 600 acccaccagg gcctgtcctc tcccgtgaca aagagcttca ataggggaga gtgtggagga 660 ggatcctacc cttatgacgt gccagattat gcctaa 696 <210> 44 <211> 1341 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 44 gaggtgcagc tggtgcagtc cggacctggc ctggtgcagc caggaggctc cgtgaggatc 60 tcttgtgccg ccagcggcta taccttcaca aactacggca tgaattgggt gaagaaggca 120 cctggcaagg gcctggagtg gatgggctgg atcaacacct atacaggcga gtccacctac 180 gccgactctt ttaagggcga gttcaccttt tctctggata catccgcctc tgccgcctac 240 ctgcagatca atagcctgcg ggccgaggac acagccgtgt actattgtgc cagattcgcc 300 atcaaagggg actactgggg acagggcaca ctgctgaccg tctcaagcgc ctctacaaag 360 ggaccaagcg tgtttccact ggcaccctcc tctaagagca cctccggagg aacagccgcc 420 ctgggctgtc tggtgaagga ctatttccca gagcccgtga ccgtgtcctg gaactctggc 480 gccctgacct ccggagtggc aacaggacca gccgtgctgc agagctccgg cctgtacagc 540 ctgtctagcg tggtgaccgt gccctcctct agcctgggca cccagacata tatctgcaac 600 gtgaatcaca agccaagcaa tacaaaggtc gacaagaagg tggagcccaa gtcctgtgat 660 aagacccaca catgcccccc ttgtcctgca ccagagctgc tgggaggacc aagcgtgttc 720 ctgtttccac ccaagcctaa ggacaccctg atgatctcta ggacccccga ggtgacatgc 780 gtggtggtgg acgtgagcca cgaggatcct gaggtgaagt ttaactggta cgtggatggc 840 gtggaggtgc acaatgccaa gaccaagccc cgggaggagc agtacaactc cacctataga 900 gtggtgtctg tgctgacagt gctgcaccag gactggctga acggcaagga gtataagtgc 960 aaggtgtcca ataaggccct gcccgcccct atcgagaaga ccatctctaa ggccaagggc 1020 cagcctaggg agccacaggt gtacacactg cctccatccc gcaaggagct gaccaagaac 1080 caggtgtctc tgacatgtct ggtgaagggc ttctatcctt ctgatatcgc cgtggagtgg 1140 gagagcaatg gccagccaga gaacaattac aagaccacac cccctgtgct gaagagcgac 1200 ggctccttct ttctgtatag caagctgacc gtggataagt ccagatggca gcagggcaac 1260 gtgttttctt gtagcgtgat gcacgaggcc ctgcacaatc actacacaca gaagtccctg 1320 tctctgagcc ctggcaagta a 1341 <210> 45 <211> 642 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 45 gagctgcaga tgacccagtc ccctagctct ttaagcgctt ccgtgggcga cagagtgacc 60 atcacatgtc gtacctccca gagcatcagc tcctatttaa actggtacca gcagaagccc 120 ggacagcccc ccaagctgct gatctactgg gcttccactc gtgaaagcgg cgtgcccgat 180 cgtttttccg gcagcggcag cggcaccgac tttactttaa ccatctcctc tttacagccc 240 gaggatagcg ccacctacta ctgccagcag agctacgaca tcccctacac attcggccaa 300 ggtaccaagc tggaaatcaa aactgtggct gcaccatctg tcttcatctt cccgccatct 360 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540 agcaaagcag actacgagaa acacaaactc tacgcctgcg aagtcaccca tcagggcctg 600 agctcgcccg tcacaaagag cttcaacagg ggagagtgct ga 642 <210> 46 <211> 696 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 46 gaagtgcagc tgctggagag cggaggcgga gtggtgcaac ccggtcgttc tttaaggctg 60 agctgcgctg ccagcggctt caccttcagc agctatggca tgcactgggt gagacaagct 120 cccggaaaag gtttagagtg ggtggccgtg atctcctacg acggcagcaa caagtactac 180 gccgacagcg tgaagggtcg tttcaccatc tctcgtgaca actccaagaa cactttatac 240 ctccagatga actctttaag ggccgaggac accgccgtgt actactgtgc caaggacatg 300 ggctggggca gcggatggag gccctactac tactacggca tggacgtgtg gggccaaggt 360 acaaccgtga ccgtgtccag cgcctccacc aagggcccat cggtcttccc cctggcaccc 420 tcctccaaga gcacctctgg gggcacagcg gccctgggct gcctggtcaa ggactacttc 480 cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc 540 ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 600 agcagcttgg gcacccagac ctacatctgc aacgtgaatc acaagcccag caacaccaag 660 gtggacaaga gagttgagcc caaatcttgt gacaaa 696 <210> 47 <211> 789 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 47 ggcggcggca gcggcggcgg cgaagtgcag ctgctggaga gcggaggcgg agtggtgcaa 60 cccggtcgtt ctttaaggct gagctgcgct gccagcggct tcaccttcag cagctatggc 120 atgcactggg tgagacaagc tcccggaaaa ggtttagagt gggtggccgt gatctcctac 180 gacggcagca acaagtacta cgccgacagc gtgaagggtc gtttcaccat ctctcgtgac 240 aactccaaga acactttata cctccagatg aactctttaa gggccgagga caccgccgtg 300 tactactgtg ccaaggacat gggctggggc agcggatgga ggccctacta ctactacggc 360 atggacgtgt ggggccaagg tacaaccgtg accgtgtcca gcggtggagg cggttcaggc 420 ggaggtggct ctggcggtgg cggatcggag ctgcagatga cccagtcccc tagctcttta 480 agcgcttccg tgggcgacag agtgaccatc acatgtcgta cctcccagag catcagctcc 540 tatttaaact ggtaccagca gaagcccgga cagcccccca agctgctgat ctactgggct 600 tccactcgtg aaagcggcgt gcccgatcgt ttttccggca gcggcagcgg caccgacttt 660 actttaacca tctcctcttt acagcccgag gatagcgcca cctactactg ccagcagagc 720 tacgacatcc cctacacatt cggccaaggt accaagctgg aaatcaaaca ccaccaccac 780 caccactga 789 <210> 48 <211> 747 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 48 gagctgcaga tgacccagtc ccctagctct ttaagcgctt ccgtgggcga cagagtgacc 60 atcacatgtc gtacctccca gagcatcagc tcctatttaa actggtacca gcagaagccc 120 ggacagcccc ccaagctgct gatctactgg gcttccactc gtgaaagcgg cgtgcccgat 180 cgtttttccg gcagcggcag cggcaccgac tttactttaa ccatctcctc tttacagccc 240 gaggatagcg ccacctacta ctgccagcag agctacgaca tcccctacac attcggccaa 300 ggtaccaagc tggaaatcaa aggcggcggc ggcagcggcg gcggcggctc cggcggagga 360 ggctccgaag tgcagctgct ggagagcgga ggcggagtgg tgcaacccgg tcgttcttta 420 aggctgagct gcgctgccag cggcttcacc ttcagcagct atggcatgca ctgggtgaga 480 caagctcccg gaaaaggttt agagtgggtg gccgtgatct cctacgacgg cagcaacaag 540 tactacgccg acagcgtgaa gggtcgtttc accatctctc gtgacaactc caagaacact 600 ttatacctcc agatgaactc tttaagggcc gaggacaccg ccgtgtacta ctgtgccaag 660 gacatgggct ggggcagcgg atggaggccc tactactact acggcatgga cgtgtggggc 720 caaggtacaa ccgtgaccgt gtccagc 747 <210> 49 <211> 681 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 49 aggctgcaga tgacccagtc ccctagctct ttaagcgctt ccgtgggcga cagagtgacc 60 atcacatgtc gtacctccca gagcatcagc tcctatttaa actggtacca ggataagccc 120 ggacagcccc ccaagctgct gatctactgg gcttccactc gtgaaagcgg cgtgcccgat 180 cgtttttccg gcagcggcag cggcaccgac tttactttaa ccatctcctc tttacagccc 240 gaggatagcg ccacctacta ctgccagcag agctacgaca tcccctacac attcggccaa 300 ggtaccaagc tggaaatcaa aaccgtggca gcaccatccg tgttcatctt tcccccttct 360 gacgagcagc tgaagtctgg cacagccagc gtggtgtgct acctgaacaa cttctacccc 420 agggaggcca aggtgcagtg gaaggtggat aacgccctgc agtccggcaa ttctcaggag 480 agcgtgaccg agcaggactc caaggattct acatacagcc tgtggtccac cctgacactg 540 tccaaggccg actacgagaa gcacaagctg tatgcatgcg aggtgaccca ccagggcctg 600 tcctctcccg tgacaaagag cttcaatagg ggagagtgtg gaggaggatc ctacccttat 660 gacgtgccag attatgccta a 681 <210> 50 <211> 1374 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 50 gaagtgcagc tgctggagag cggaggcgga gtggtgcaac ccggtcgttc tttaaggctg 60 agctgcgctg ccagcggctt caccttcagc agctatggca tgcactgggt gagaaaggct 120 cccggaaaag gtttagagtg ggtggccgtg atctcctacg acggcagcaa caagtactac 180 gccgacagcg tgaagggtga gttcaccatc tctcgtgaca actccaagaa cactttatac 240 ctccagatga actctttaag ggccgaggac accgccgtgt actactgtgc caaggacatg 300 ggctggggca gcggatggag gccctactac tactacggca tggacgtgtg gggccaaggt 360 acaaccgtga ccgtgtccag cgcctctaca aagggaccaa gcgtgtttcc actggcaccc 420 tcctctaaga gcacctccgg aggaacagcc gccctgggct gtctggtgaa ggactatttc 480 ccagagcccg tgaccgtgtc ctggaactct ggcgccctga cctccggagt ggcaacagga 540 ccagccgtgc tgcagagctc cggcctgtac agcctgtcta gcgtggtgac cgtgccctcc 600 tctagcctgg gcacccagac atatatctgc aacgtgaatc acaagccaag caatacaaag 660 gtcgacaaga aggtggagcc caagtcctgt gataagaccc acacatgccc cccttgtcct 720 gcaccagagc tgctgggagg accaagcgtg ttcctgtttc cacccaagcc taaggacacc 780 ctgatgatct ctaggacccc cgaggtgaca tgcgtggtgg tggacgtgag ccacgaggat 840 cctgaggtga agtttaactg gtacgtggat ggcgtggagg tgcacaatgc caagaccaag 900 ccccgggagg agcagtacaa ctccacctat agagtggtgt ctgtgctgac agtgctgcac 960 caggactggc tgaacggcaa ggagtataag tgcaaggtgt ccaataaggc cctgcccgcc 1020 cctatcgaga agaccatctc taaggccaag ggccagccta gggagccaca ggtgtacaca 1080 ctgcctccat cccgcaagga gctgaccaag aaccaggtgt ctctgacatg tctggtgaag 1140 ggcttctatc cttctgatat cgccgtggag tgggagagca atggccagcc agagaacaat 1200 tacaagacca caccccctgt gctgaagagc gacggctcct tctttctgta tagcaagctg 1260 accgtggata agtccagatg gcagcagggc aacgtgtttt cttgtagcgt gatgcacgag 1320 gccctgcaca atcactacac acagaagtcc ctgtctctga gccctggcaa gtaa 1374 <210> 51 <211> 648 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 51 gatattcaga tgacccagag cccgagcagc ctgagcgcaa gcgttggtga tcgtgttacc 60 attacctgta aagcaagcca gaccgttagc gcaaatgttg catggtatca gcagaaaccg 120 ggtaaagcac cgaaactgct gatttatctg gcaagctatc gttatcgtgg tgttccgagc 180 cgttttagcg gtagcggtag cggtaccgat tttaccctga ccattagcag cctgcagccg 240 gaagattttg caacctatta ttgtcatcag tattatacct atccgctgtt tacctttggt 300 cagggtacca aactggaaat taaacgtact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaactctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgctga 648 <210> 52 <211> 678 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 52 caggttcagc tggttcagag cggtagcgaa ctgaaaaaac cgggtgcaag cgttaaagtt 60 agctgtaaag caagcggtta tacctttacc gaatatggta tgaatgtttg gcgtcaggca 120 ccgggtcagg gtctggaatg gatgggttgg attaatacca aaagcggtga agcaacctat 180 gttgaagaat ttaaaggtcg ttttgttttt agcctggata ccagcgttag caccgcatat 240 ctgcagatta gcagcctgaa agcagaagat accgcagttt attattgtgc acgttgggat 300 ttttatgatt atgttgatga agcaatgtat tggggtcagg gtaccaccgt taccgttagc 360 agcgcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct 420 gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 480 tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 540 tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcacccag 600 acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gagagttgag 660 cccaaatctt gtgacaaa 678 <210> 53 <211> 777 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 53 ggcggcggca gcggcggcgg ccaggttcag ctggttcaga gcggtagcga actgaaaaaa 60 ccgggtgcaa gcgttaaagt tagctgtaaa gcaagcggtt atacctttac cgaatatggt 120 atgaatgttt ggcgtcaggc accgggtcag ggtctggaat ggatgggttg gattaatacc 180 aaaagcggtg aagcaaccta tgttgaagaa tttaaaggtc gttttgtttt tagcctggat 240 accagcgtta gcaccgcata tctgcagatt agcagcctga aagcagaaga taccgcagtt 300 tattattgtg cacgttggga tttttatgat tatgttgatg aagcaatgta ttggggtcag 360 ggtaccaccg ttaccgttag cagcggtgga ggcggttcag gcggaggtgg ctctggcggt 420 ggcggatcgg atattcagat gacccagagc ccgagcagcc tgagcgcaag cgttggtgat 480 cgtgttacca ttacctgtaa agcaagccag accgttagcg caaatgttgc atggtatcag 540 cagaaaccgg gtaaagcacc gaaactgctg atttatctgg caagctatcg ttatcgtggt 600 gttccgagcc gttttagcgg tagcggtagc ggtaccgatt ttaccctgac cattagcagc 660 ctgcagccgg aagattttgc aacctattat tgtcatcagt attataccta tccgctgttt 720 acctttggtc agggtaccaa actggaaatt aaacgtcacc accaccacca ccactga 777 <210> 54 <211> 735 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 54 gatattcaga tgacccagag cccgagcagc ctgagcgcaa gcgttggtga tcgtgttacc 60 attacctgta aagcaagcca gaccgttagc gcaaatgttg catggtatca gcagaaaccg 120 ggtaaagcac cgaaactgct gatttatctg gcaagctatc gttatcgtgg tgttccgagc 180 cgttttagcg gtagcggtag cggtaccgat tttaccctga ccattagcag cctgcagccg 240 gaagattttg caacctatta ttgtcatcag tattatacct atccgctgtt tacctttggt 300 cagggtacca aactggaaat taaacgtggt ggaggcggtt caggcggagg tggctctggc 360 ggtggcggat cgcaggttca gctggttcag agcggtagcg aactgaaaaa accgggtgca 420 agcgttaaag ttagctgtaa agcaagcggt tataccttta ccgaatatgg tatgaatgtt 480 tggcgtcagg caccgggtca gggtctggaa tggatgggtt ggattaatac caaaagcggt 540 gaagcaacct atgttgaaga atttaaaggt cgttttgttt ttagcctgga taccagcgtt 600 agcaccgcat atctgcagat tagcagcctg aaagcagaag ataccgcagt ttattattgt 660 gcacgttggg atttttatga ttatgttgat gaagcaatgt attggggtca gggtaccacc 720 gttaccgtta gcagc 735 <210> 55 <211> 687 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 55 aggattcaga tgacccagag cccgagcagc ctgagcgcaa gcgttggtga tcgtgttacc 60 attacctgta aagcaagcca gaccgttagc gcaaatgttg catggtatca ggataaaccg 120 ggtaaagcac cgaaactgct gatttatctg gcaagctatc gttatcgtgg tgttccgagc 180 cgttttagcg gtagcggtag cggtaccgat tttaccctga ccattagcag cctgcagccg 240 gaagattttg caacctatta ttgtcatcag tattatacct atccgctgtt tacctttggt 300 cagggtacca aactggaaat taaacgtacc gtggcagcac catccgtgtt catctttccc 360 ccttctgacg agcagctgaa gtctggcaca gccagcgtgg tgtgctacct gaacaacttc 420 taccccaggg aggccaaggt gcagtggaag gtggataacg ccctgcagtc cggcaattct 480 caggagagcg tgaccgagca ggactccaag gattctacat acagcctgtg gtccaccctg 540 acactgtcca aggccgacta cgagaagcac aagctgtatg catgcgaggt gacccaccag 600 ggcctgtcct ctcccgtgac aaagagcttc aataggggag agtgtggagg aggatcctac 660 ccttatgacg tgccagatta tgcctaa 687 <210> 56 <211> 1356 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 56 caggttcagc tggttcagag cggtagcgaa ctgaaaaaac cgggtgcaag cgttaaagtt 60 agctgtaaag caagcggtta tacctttacc gaatatggta tgaatgtttg gcgtaaggca 120 ccgggtcagg gtctggaatg gatgggttgg attaatacca aaagcggtga agcaacctat 180 gttgaagaat ttaaaggtcg ttttgttttt agcctggata ccagcgttag caccgcatat 240 ctgcagatta gcagcctgaa agcagaagat accgcagttt attattgtgc acgttgggat 300 ttttatgatt atgttgatga agcaatgtat tggggtcagg gtaccaccgt taccgttagc 360 agcgcctcta caaagggacc aagcgtgttt ccactggcac cctcctctaa gagcacctcc 420 ggaggaacag ccgccctggg ctgtctggtg aaggactatt tcccagagcc cgtgaccgtg 480 tcctggaact ctggcgccct gacctccgga gtggcaacag gaccagccgt gctgcagagc 540 tccggcctgt acagcctgtc tagcgtggtg accgtgccct cctctagcct gggcacccag 600 acatatatct gcaacgtgaa tcacaagcca agcaatacaa aggtcgacaa gaaggtggag 660 cccaagtcct gtgataagac ccacacatgc cccccttgtc ctgcaccaga gctgctggga 720 ggaccaagcg tgttcctgtt tccacccaag cctaaggaca ccctgatgat ctctaggacc 780 cccgaggtga catgcgtggt ggtggacgtg agccacgagg atcctgaggt gaagtttaac 840 tggtacgtgg atggcgtgga ggtgcacaat gccaagacca agccccggga ggagcagtac 900 aactccacct atagagtggt gtctgtgctg acagtgctgc accaggactg gctgaacggc 960 aaggagtata agtgcaaggt gtccaataag gccctgcccg cccctatcga gaagaccatc 1020 tctaaggcca agggccagcc tagggagcca caggtgtaca cactgcctcc atcccgcaag 1080 gagctgacca agaaccaggt gtctctgaca tgtctggtga agggcttcta tccttctgat 1140 atcgccgtgg agtgggagag caatggccag ccagagaaca attacaagac cacaccccct 1200 gtgctgaaga gcgacggctc cttctttctg tatagcaagc tgaccgtgga taagtccaga 1260 tggcagcagg gcaacgtgtt ttcttgtagc gtgatgcacg aggccctgca caatcactac 1320 acacagaagt ccctgtctct gagccctggc aagtaa 1356 <210> 57 <211> 654 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 57 gatattcaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60 attacctgcc aggcgagcca gagcattagc agcagctatc tgagctggta tcagcagaaa 120 ccgggcaaag cgccgaaact gctgatttat gcggtgagct atctggcgag cggcgtgccg 180 agccgcttta gcggcagcgg cagcggcacc gatttcaccc tgaccattag cagcctgcag 240 ccggaagatt ttgcgaccta ttattgccag agcggctatt atagcgcggg cgatctgacc 300 tttggccagg gcaccaaagt ggaaattaaa cgcactgtgg ctgcaccatc tgtcttcatc 360 ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420 aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480 aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540 accctgacgc tgagcaaagc agactacgag aaacacaaac tctacgcctg cgaagtcacc 600 catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg ctga 654 <210> 58 <211> 660 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 58 gaagtgcagc tggtggaaag cggcggcggc ctggtgcagc cgggcggcag cctgcgcctg 60 agctgcgcgg cgagcggctt tagcctgagc aactattata ttaactgggt gcgccaggcg 120 ccgggcaaag gcctggaatg ggtggcgatt attttttgcg cgggcaacgc gtataacgcg 180 agctgggcga aaggccgctt taccattagc cgcgatgata gcaaaaacac cctgtatctg 240 cagatgaaca gcctgcgcgc ggaagatacc gcggtgtatt attgcgcgcg cggctggcag 300 gcgctggtga actggggcca gggcaccctg gtgaccgtga gcagcgcctc caccaagggc 360 ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagagagttg agcccaaatc ttgtgacaaa 660 <210> 59 <211> 765 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 59 ggcggcggca gcggcggcgg cgaagtgcag ctggtggaaa gcggcggcgg cctggtgcag 60 ccgggcggca gcctgcgcct gagctgcgcg gcgagcggct ttagcctgag caactattat 120 attaactggg tgcgccaggc gccgggcaaa ggcctggaat gggtggcgat tattttttgc 180 gcgggcaacg cgtataacgc gagctgggcg aaaggccgct ttaccattag ccgcgatgat 240 agcaaaaaca ccctgtatct gcagatgaac agcctgcgcg cggaagatac cgcggtgtat 300 tattgcgcgc gcggctggca ggcgctggtg aactggggcc agggcaccct ggtgaccgtg 360 agcagcggcg gcggcggcag cggcggcggc ggcagcggcg gcggcggcag cgatattcag 420 atgacccaga gcccgagcag cctgagcgcg agcgtgggcg atcgcgtgac cattacctgc 480 caggcgagcc agagcattag cagcagctat ctgagctggt atcagcagaa accgggcaaa 540 gcgccgaaac tgctgattta tgcggtgagc tatctggcga gcggcgtgcc gagccgcttt 600 agcggcagcg gcagcggcac cgatttcacc ctgaccatta gcagcctgca gccggaagat 660 tttgcgacct attattgcca gagcggctat tatagcgcgg gcgatctgac ctttggccag 720 ggcaccaaag tggaaattaa acgccaccac caccaccacc actga 765 <210> 60 <211> 723 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 60 gatattcaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60 attacctgcc aggcgagcca gagcattagc agcagctatc tgagctggta tcagcagaaa 120 ccgggcaaag cgccgaaact gctgatttat gcggtgagct atctggcgag cggcgtgccg 180 agccgcttta gcggcagcgg cagcggcacc gatttcaccc tgaccattag cagcctgcag 240 ccggaagatt ttgcgaccta ttattgccag agcggctatt atagcgcggg cgatctgacc 300 tttggccagg gcaccaaagt ggaaattaaa cgcggtggag gcggttcagg cggaggtggc 360 tctggcggtg gcggatcgga agtgcagctg gtggaaagcg gcggcggcct ggtgcagccg 420 ggcggcagcc tgcgcctgag ctgcgcggcg agcggcttta gcctgagcaa ctattatatt 480 aactgggtgc gccaggcgcc gggcaaaggc ctggaatggg tggcgattat tttttgcgcg 540 ggcaacgcgt ataacgcgag ctgggcgaaa ggccgcttta ccattagccg cgatgatagc 600 aaaaacaccc tgtatctgca gatgaacagc ctgcgcgcgg aagataccgc ggtgtattat 660 tgcgcgcgcg gctggcaggc gctggtgaac tggggccagg gcaccctggt gaccgtgagc 720 agc 723 <210> 61 <211> 693 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 61 aggattcaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60 attacctgcc aggcgagcca gagcattagc agcagctatc tgagctggta tcaggataaa 120 ccgggcaaag cgccgaaact gctgatttat gcggtgagct atctggcgag cggcgtgccg 180 agccgcttta gcggcagcgg cagcggcacc gatttcaccc tgaccattag cagcctgcag 240 ccggaagatt ttgcgaccta ttattgccag agcggctatt atagcgcggg cgatctgacc 300 tttggccagg gcaccaaagt ggaaattaaa cgcaccgtgg cagcaccatc cgtgttcatc 360 tttccccctt ctgacgagca gctgaagtct ggcacagcca gcgtggtgtg ctacctgaac 420 aacttctacc ccagggaggc caaggtgcag tggaaggtgg ataacgccct gcagtccggc 480 aattctcagg agagcgtgac cgagcaggac tccaaggatt ctacatacag cctgtggtcc 540 accctgacac tgtccaaggc cgactacgag aagcacaagc tgtatgcatg cgaggtgacc 600 caccagggcc tgtcctctcc cgtgacaaag agcttcaata ggggagagtg tggaggagga 660 tcctaccctt atgacgtgcc agattatgcc taa 693 <210> 62 <211> 1338 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 62 gaagtgcagc tggtggaaag cggcggcggc ctggtgcagc cgggcggcag cctgcgcctg 60 agctgcgcgg cgagcggctt tagcctgagc aactattata ttaactgggt gcgcaaggcg 120 ccgggcaaag gcctggaatg ggtggcgatt attttttgcg cgggcaacgc gtataacgcg 180 agctgggcga aaggcgagtt taccattagc cgcgatgata gcaaaaacac cctgtatctg 240 cagatgaaca gcctgcgcgc ggaagatacc gcggtgtatt attgcgcgcg cggctggcag 300 gcgctggtga actggggcca gggcaccctg gtgaccgtga gcagcgcctc tacaaaggga 360 ccaagcgtgt ttccactggc accctcctct aagagcacct ccggaggaac agccgccctg 420 ggctgtctgg tgaaggacta tttcccagag cccgtgaccg tgtcctggaa ctctggcgcc 480 ctgacctccg gagtggcaac aggaccagcc gtgctgcaga gctccggcct gtacagcctg 540 tctagcgtgg tgaccgtgcc ctcctctagc ctgggcaccc agacatatat ctgcaacgtg 600 aatcacaagc caagcaatac aaaggtcgac aagaaggtgg agcccaagtc ctgtgataag 660 acccacacat gccccccttg tcctgcacca gagctgctgg gaggaccaag cgtgttcctg 720 tttccaccca agcctaagga caccctgatg atctctagga cccccgaggt gacatgcgtg 780 gtggtggacg tgagccacga ggatcctgag gtgaagttta actggtacgt ggatggcgtg 840 gaggtgcaca atgccaagac caagccccgg gaggagcagt acaactccac ctatagagtg 900 gtgtctgtgc tgacagtgct gcaccaggac tggctgaacg gcaaggagta taagtgcaag 960 gtgtccaata aggccctgcc cgcccctatc gagaagacca tctctaaggc caagggccag 1020 cctagggagc cacaggtgta cacactgcct ccatcccgca aggagctgac caagaaccag 1080 gtgtctctga catgtctggt gaagggcttc tatccttctg atatcgccgt ggagtgggag 1140 agcaatggcc agccagagaa caattacaag accacacccc ctgtgctgaa gagcgacggc 1200 tccttctttc tgtatagcaa gctgaccgtg gataagtcca gatggcagca gggcaacgtg 1260 ttttcttgta gcgtgatgca cgaggccctg cacaatcact acacacagaa gtccctgtct 1320 ctgagccctg gcaagtaa 1338 <210> 63 <211> 21 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 63 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp 20 <210> 64 <211> 214 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 64 Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala 20 25 30 Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Asp Tyr Phe Cys Gln Gln Tyr Asn Ser Tyr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210 <210> 65 <211> 220 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 65 Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Glu Tyr 20 25 30 Thr Ile His Trp Val Lys Gln Ala Ser Gly Lys Gly Leu Glu Trp Ile 35 40 45 Gly Asn Ile Asn Pro Asn Asn Gly Gly Thr Thr Tyr Asn Gln Lys Phe 50 55 60 Glu Asp Arg Ala Thr Leu Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ala Gly Trp Asn Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 <210> 66 <211> 257 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 66 Gly Gly Gly Ser Gly Gly Gly Asp Ile Lys Leu Gln Gln Ser Gly Ala 1 5 10 15 Glu Leu Ala Arg Pro Gly Ala Ser Val Lys Met Ser Cys Lys Thr Ser 20 25 30 Gly Tyr Thr Phe Thr Arg Tyr Thr Met His Trp Val Lys Gln Arg Pro 35 40 45 Gly Gln Gly Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr 50 55 60 Thr Asn Tyr Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Thr Asp 65 70 75 80 Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu 85 90 95 Asp Ser Ala Val Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys 100 105 110 Leu Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Val Glu 115 120 125 Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Val Asp 130 135 140 Asp Ile Gln Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly 145 150 155 160 Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met 165 170 175 Asn Trp Tyr Gln Gln Lys Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr 180 185 190 Asp Thr Ser Lys Val Ala Ser Gly Val Pro Tyr Arg Phe Ser Gly Ser 195 200 205 Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu 210 215 220 Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr 225 230 235 240 Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg His His His His His 245 250 255 His <210> 67 <211> 213 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 67 Asp Ile Gln Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly 1 5 10 15 Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met 20 25 30 Asn Trp Tyr Gln Gln Lys Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr 35 40 45 Asp Thr Ser Lys Val Ala Ser Gly Val Pro Tyr Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu 65 70 75 80 Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr 85 90 95 Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala Pro 100 105 110 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 115 120 125 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 145 150 155 160 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr Ala 180 185 190 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205 Asn Arg Gly Glu Cys 210 <210> 68 <211> 217 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 68 Asp Ile Lys Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala 1 5 10 15 Ser Val Lys Met Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Asn Gln Lys Phe 50 55 60 Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser Ser Thr Ala Tyr 65 70 75 80 Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly 100 105 110 Thr Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 115 120 125 Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu 130 135 140 Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 145 150 155 160 Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 165 170 175 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 180 185 190 Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro 195 200 205 Ser Asn Thr Lys Val Asp Lys Thr Val 210 215 <210> 69 <211> 252 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 69 Gly Gly Gly Ser Gly Gly Gly Glu Val Gln Leu Val Gln Ser Gly Ala 1 5 10 15 Glu Val Lys Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser 20 25 30 Gly Tyr Thr Phe Thr Glu Tyr Thr Ile His Trp Val Lys Gln Ala Ser 35 40 45 Gly Lys Gly Leu Glu Trp Ile Gly Asn Ile Asn Pro Asn Asn Gly Gly 50 55 60 Thr Thr Tyr Asn Gln Lys Phe Glu Asp Arg Ala Thr Leu Thr Val Asp 65 70 75 80 Lys Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Trp Asn Phe Asp Tyr Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Gly Gly Gly Gly Ser 115 120 125 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln 130 135 140 Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 145 150 155 160 Cys Lys Ala Ser Gln Asp Val Gly Thr Ala Val Asp Trp Tyr Gln Gln 165 170 175 Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg 180 185 190 His Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp 195 200 205 Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Asp Tyr 210 215 220 Phe Cys Gln Gln Tyr Asn Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr 225 230 235 240 Lys Leu Glu Ile Lys Arg His His His His His His 245 250 <210> 70 <211> 239 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 70 Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala 20 25 30 Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Asp Tyr Phe Cys Gln Gln Tyr Asn Ser Tyr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Ile Ser 130 135 140 Cys Lys Thr Ser Gly Tyr Thr Phe Thr Glu Tyr Thr Ile His Trp Val 145 150 155 160 Lys Gln Ala Ser Gly Lys Gly Leu Glu Trp Ile Gly Asn Ile Asn Pro 165 170 175 Asn Asn Gly Gly Thr Thr Tyr Asn Gln Lys Phe Glu Asp Arg Ala Thr 180 185 190 Leu Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Trp Asn 210 215 220 Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala 225 230 235 <210> 71 <211> 223 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 71 Asp Ile Gln Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly 1 5 10 15 Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met 20 25 30 Asn Trp Tyr Gln Arg Lys Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr 35 40 45 Asp Thr Ser Lys Val Ala Ser Gly Val Pro Tyr Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu 65 70 75 80 Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr 85 90 95 Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala Pro 100 105 110 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 115 120 125 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 145 150 155 160 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr Ala 180 185 190 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205 Asn Arg Gly Glu Cys Gly Gly Gly Ser His His His His His His 210 215 220 <210> 72 <211> 449 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 72 Asp Ile Lys Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala 1 5 10 15 Ser Val Lys Met Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Thr Met His Trp Val Lys Tyr Arg Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Asn Gln Lys Phe 50 55 60 Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser Ser Thr Ala Tyr 65 70 75 80 Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly 100 105 110 Thr Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 115 120 125 Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 130 135 140 Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 145 150 155 160 Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 165 170 175 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 180 185 190 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 195 200 205 Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 260 265 270 Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Asp Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Asp Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 445 Lys <210> 73 <211> 227 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 73 Arg Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala 20 25 30 Val Asp Trp Tyr Gln Asp Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Asp Tyr Phe Cys Gln Gln Tyr Asn Ser Tyr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Trp 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro Tyr Asp Val Pro 210 215 220 Asp Tyr Ala 225 <210> 74 <211> 445 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 74 Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Glu Tyr 20 25 30 Thr Ile His Trp Val Lys Lys Ala Ser Gly Lys Gly Leu Glu Trp Ile 35 40 45 Gly Asn Ile Asn Pro Asn Asn Gly Gly Thr Thr Tyr Asn Gln Glu Phe 50 55 60 Glu Asp Arg Ala Thr Leu Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ala Gly Trp Asn Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val Ala Thr Gly Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220 Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 225 230 235 240 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320 Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 340 345 350 Arg Lys Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 355 360 365 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 370 375 380 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Lys Ser Asp Gly 385 390 395 400 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 405 410 415 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 75 <211> 214 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 75 Asp Ile Leu Leu Thr Gln Ser Pro Val Ile Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn 20 25 30 Ile His Trp Tyr Gln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile 35 40 45 Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Ser 65 70 75 80 Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr 85 90 95 Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210 <210> 76 <211> 224 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 76 Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln 1 5 10 15 Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr 20 25 30 Gly Val His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu 35 40 45 Gly Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr 50 55 60 Ser Arg Leu Ser Ile Asn Lys Asp Asn Ser Lys Ser Gln Val Phe Phe 65 70 75 80 Lys Met Asn Ser Leu Gln Ser Asn Asp Thr Ala Ile Tyr Tyr Cys Ala 85 90 95 Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe 115 120 125 Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 130 135 140 Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 145 150 155 160 Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 165 170 175 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 180 185 190 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 195 200 205 Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 <210> 77 <211> 255 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 77 Gly Gly Gly Ser Gly Gly Gly Gln Val Gln Leu Lys Gln Ser Gly Pro 1 5 10 15 Gly Leu Val Gln Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser 20 25 30 Gly Phe Ser Leu Thr Asn Tyr Gly Val His Trp Val Arg Gln Ser Pro 35 40 45 Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser Gly Gly Asn Thr 50 55 60 Asp Tyr Asn Thr Pro Phe Thr Ser Arg Leu Ser Ile Asn Lys Asp Asn 65 70 75 80 Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu Gln Ser Asn Asp 85 90 95 Thr Ala Ile Tyr Tyr Cys Ala Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu 100 105 110 Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly 115 120 125 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Leu 130 135 140 Leu Thr Gln Ser Pro Val Ile Leu Ser Val Ser Pro Gly Glu Arg Val 145 150 155 160 Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn Ile His Trp 165 170 175 Tyr Gln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile Lys Tyr Ala 180 185 190 Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser 195 200 205 Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Ser Glu Asp Ile 210 215 220 Ala Asp Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr Thr Phe Gly 225 230 235 240 Ala Gly Thr Lys Leu Glu Leu Lys Arg His His His His His His 245 250 255 <210> 78 <211> 242 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 78 Asp Ile Leu Leu Thr Gln Ser Pro Val Ile Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn 20 25 30 Ile His Trp Tyr Gln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile 35 40 45 Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Ser 65 70 75 80 Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr 85 90 95 Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Lys 115 120 125 Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln Ser Leu Ser Ile Thr 130 135 140 Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr Gly Val His Trp Val 145 150 155 160 Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser 165 170 175 Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr Ser Arg Leu Ser Ile 180 185 190 Asn Lys Asp Asn Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu 195 200 205 Gln Ser Asn Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Ala Leu Thr Tyr 210 215 220 Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ala <210> 79 <211> 254 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 79 Gly Gly Gly Ser Asp Ile Lys Leu Gln Gln Ser Gly Ala Glu Leu Ala 1 5 10 15 Arg Pro Gly Ala Ser Val Lys Met Ser Cys Lys Thr Ser Gly Tyr Thr 20 25 30 Phe Thr Arg Tyr Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly 35 40 45 Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr 50 55 60 Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser 65 70 75 80 Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala 85 90 95 Val Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr 100 105 110 Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Val Glu Gly Gly Ser 115 120 125 Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Val Asp Asp Ile Gln 130 135 140 Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val 145 150 155 160 Thr Met Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met Asn Trp Tyr 165 170 175 Gln Gln Lys Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr Asp Thr Ser 180 185 190 Lys Val Ala Ser Gly Val Pro Tyr Arg Phe Ser Gly Ser Gly Ser Gly 195 200 205 Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu Asp Ala Ala 210 215 220 Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Ala 225 230 235 240 Gly Thr Lys Leu Glu Leu Lys Arg His His His His His His 245 250 <210> 80 <211> 227 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 80 Arg Ile Leu Leu Thr Gln Ser Pro Val Ile Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn 20 25 30 Ile His Trp Tyr Gln Asp Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile 35 40 45 Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Ser 65 70 75 80 Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr 85 90 95 Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Trp 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro Tyr Asp Val Pro 210 215 220 Asp Tyr Ala 225 <210> 81 <211> 449 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 81 Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln 1 5 10 15 Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr 20 25 30 Gly Val His Trp Val Arg Lys Ser Pro Gly Lys Gly Leu Glu Trp Leu 35 40 45 Gly Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Glu Phe Thr 50 55 60 Ser Arg Leu Ser Ile Asn Lys Asp Asn Ser Lys Ser Gln Val Phe Phe 65 70 75 80 Lys Met Asn Ser Leu Gln Ser Asn Asp Thr Ala Ile Tyr Tyr Cys Ala 85 90 95 Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe 115 120 125 Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 130 135 140 Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 145 150 155 160 Asn Ser Gly Ala Leu Thr Ser Gly Val Ala Thr Gly Pro Ala Val Leu 165 170 175 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 180 185 190 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 195 200 205 Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 260 265 270 Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Ser Arg Lys Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 445 Lys <210> 82 <211> 214 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 82 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210 <210> 83 <211> 223 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 83 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser 20 25 30 Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Arg His Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 115 120 125 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 130 135 140 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 145 150 155 160 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 165 170 175 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 180 185 190 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 195 200 205 Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 <210> 84 <211> 257 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 84 Gly Gly Gly Ser Gly Gly Gly Glu Val Gln Leu Val Glu Ser Gly Gly 1 5 10 15 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 30 Gly Phe Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro 35 40 45 Gly Lys Gly Leu Glu Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser 50 55 60 Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp 65 70 75 80 Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Arg His Trp Pro Gly Gly Phe 100 105 110 Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Val Glu Gly 115 120 125 Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Val Asp Asp 130 135 140 Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 145 150 155 160 Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala Val 165 170 175 Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 180 185 190 Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 195 200 205 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 210 215 220 Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala Thr 225 230 235 240 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg His His His His His 245 250 255 His <210> 85 <211> 241 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 85 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val 115 120 125 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 130 135 140 Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser Trp Ile His Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Trp Ile Ser Pro 165 170 175 Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Arg His Trp 210 215 220 Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 225 230 235 240 Ala <210> 86 <211> 227 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 86 Arg Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala 20 25 30 Val Ala Trp Tyr Gln Asp Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Trp 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro Tyr Asp Val Pro 210 215 220 Asp Tyr Ala 225 <210> 87 <211> 448 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 87 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser 20 25 30 Trp Ile His Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Glu Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Arg His Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 115 120 125 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 130 135 140 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 145 150 155 160 Ser Gly Ala Leu Thr Ser Gly Val Ala Thr Gly Pro Ala Val Leu Gln 165 170 175 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 180 185 190 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 195 200 205 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 210 215 220 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 260 265 270 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Arg Lys Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Lys 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 88 <211> 214 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 88 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210 <210> 89 <211> 225 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 89 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys 225 <210> 90 <211> 256 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 90 Gly Gly Gly Ser Gly Gly Gly Glu Val Gln Leu Val Glu Ser Gly Gly 1 5 10 15 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 30 Gly Phe Asn Ile Lys Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro 35 40 45 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr 50 55 60 Thr Arg Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp 65 70 75 80 Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr 100 105 110 Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly 115 120 125 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile 130 135 140 Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg 145 150 155 160 Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala Val Ala 165 170 175 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ser 180 185 190 Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Arg 195 200 205 Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp 210 215 220 Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro Thr Phe 225 230 235 240 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg His His His His His His 245 250 255 <210> 91 <211> 243 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 91 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val 115 120 125 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 130 135 140 Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr Tyr Ile His Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Tyr Pro 165 170 175 Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser Arg Trp Gly Gly 210 215 220 Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 225 230 235 240 Val Ser Ser <210> 92 <211> 227 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 92 Arg Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala 20 25 30 Val Ala Trp Tyr Gln Asp Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Trp 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro Tyr Asp Val Pro 210 215 220 Asp Tyr Ala 225 <210> 93 <211> 450 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 93 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 20 25 30 Tyr Ile His Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val Ala Thr Gly Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 340 345 350 Thr Leu Pro Pro Ser Arg Lys Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Lys 450 <210> 94 <211> 219 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 94 Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 20 25 30 Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 35 40 45 Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 85 90 95 Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 100 105 110 Lys Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 95 <211> 229 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 95 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe Thr Glu Tyr 20 25 30 Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile 35 40 45 Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His Ala Met Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 115 120 125 Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 130 135 140 Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 145 150 155 160 Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 165 170 175 Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 180 185 190 Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 195 200 205 Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro 210 215 220 Lys Ser Cys Asp Lys 225 <210> 96 <211> 268 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 96 Gly Gly Gly Ser Gly Gly Gly Gln Val Gln Leu Val Gln Ser Gly Ala 1 5 10 15 Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser 20 25 30 Arg Tyr Thr Phe Thr Glu Tyr Thr Ile His Trp Val Arg Gln Ala Pro 35 40 45 Gly Gln Arg Leu Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Ile 50 55 60 Pro Asn Tyr Asn Gln Lys Phe Lys Gly Arg Val Thr Ile Thr Val Asp 65 70 75 80 Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Arg Arg Ile Ala Tyr Gly Tyr 100 105 110 Asp Glu Gly His Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 115 120 125 Val Ser Ser Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu 130 135 140 Gly Ser Thr Lys Gly Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu 145 150 155 160 Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln 165 170 175 Ser Leu Leu Tyr Ser Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln 180 185 190 Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr 195 200 205 Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr 210 215 220 Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val 225 230 235 240 Tyr Tyr Cys Gln Gln Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly 245 250 255 Thr Lys Val Glu Ile Lys His His His His His His 260 265 <210> 97 <211> 252 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 97 Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 20 25 30 Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 35 40 45 Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 85 90 95 Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 100 105 110 Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 115 120 125 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 130 135 140 Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe Thr Glu Tyr 145 150 155 160 Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile 165 170 175 Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn Gln Lys Phe 180 185 190 Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr 195 200 205 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 210 215 220 Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His Ala Met Asp 225 230 235 240 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 245 250 <210> 98 <211> 232 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 98 Arg Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 20 25 30 Arg Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Asp Lys Pro Gly Gln 35 40 45 Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 Pro Asp Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 85 90 95 Tyr Phe Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 100 105 110 Lys Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Trp Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr 210 215 220 Pro Tyr Asp Val Pro Asp Tyr Ala 225 230 <210> 99 <211> 454 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 99 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Thr Ser Arg Tyr Thr Phe Thr Glu Tyr 20 25 30 Thr Ile His Trp Val Arg Lys Ala Pro Gly Gln Arg Leu Glu Trp Ile 35 40 45 Gly Gly Ile Asn Pro Asn Asn Gly Ile Pro Asn Tyr Asn Gln Arg Phe 50 55 60 Lys Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Arg Arg Ile Ala Tyr Gly Tyr Asp Glu Gly His Ala Met Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 115 120 125 Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 130 135 140 Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 145 150 155 160 Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val Ala Thr 165 170 175 Gly Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 180 185 190 Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 195 200 205 Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro 210 215 220 Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 225 230 235 240 Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 245 250 255 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 260 265 270 Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 275 280 285 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 290 295 300 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 305 310 315 320 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 325 330 335 Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 340 345 350 Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Lys Glu Leu Thr Lys Asn 355 360 365 Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 370 375 380 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 385 390 395 400 Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 405 410 415 Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 420 425 430 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 435 440 445 Ser Leu Ser Pro Gly Lys 450 <210> 100 <211> 218 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 100 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Thr Lys Ser Leu Leu His Ser 20 25 30 Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Gln Met Ser Asn Leu Ala Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Ser Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gln Asn 85 90 95 Leu Glu Ile Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Leu Lys 100 105 110 Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 115 120 125 Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 130 135 140 Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 145 150 155 160 Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 165 170 175 Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 180 185 190 His Lys Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 195 200 205 Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 101 <211> 221 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 101 Glu Val Gln Leu Val Gln Ser Gly Pro Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Val Arg Ile Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala Asp Ser Phe 50 55 60 Lys Gly Arg Phe Thr Phe Ser Leu Asp Thr Ser Ala Ser Ala Ala Tyr 65 70 75 80 Leu Gln Ile Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Phe Ala Ile Lys Gly Asp Tyr Trp Gly Gln Gly Thr Leu Leu 100 105 110 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 115 120 125 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 130 135 140 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 145 150 155 160 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 165 170 175 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 180 185 190 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 195 200 205 Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 <210> 102 <211> 256 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 102 Gly Gly Gly Ser Gly Gly Gly Glu Val Gln Leu Val Gln Ser Gly Pro 1 5 10 15 Gly Leu Val Gln Pro Gly Gly Ser Val Arg Ile Ser Cys Ala Ala Ser 20 25 30 Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Ala Pro 35 40 45 Gly Lys Gly Leu Glu Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu 50 55 60 Ser Thr Tyr Ala Asp Ser Phe Lys Gly Arg Phe Thr Phe Ser Leu Asp 65 70 75 80 Thr Ser Ala Ser Ala Ala Tyr Leu Gln Ile Asn Ser Leu Arg Ala Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Phe Ala Ile Lys Gly Asp Tyr 100 105 110 Trp Gly Gln Gly Thr Leu Leu Thr Val Ser Ser Gly Gly Gly Gly Ser 115 120 125 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln 130 135 140 Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 145 150 155 160 Cys Arg Ser Thr Lys Ser Leu Leu His Ser Asn Gly Ile Thr Tyr Leu 165 170 175 Tyr Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 180 185 190 Gln Met Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Ser Ser 195 200 205 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 210 215 220 Asp Phe Ala Thr Tyr Tyr Cys Ala Gln Asn Leu Glu Ile Pro Arg Thr 225 230 235 240 Phe Gly Gln Gly Thr Lys Val Glu Leu Lys His His His His His His 245 250 255 <210> 103 <211> 254 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 103 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Thr Lys Ser Leu Leu His Ser 20 25 30 Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Gln Met Ser Asn Leu Ala Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Ser Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gln Asn 85 90 95 Leu Glu Ile Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Leu Lys 100 105 110 Arg Ala Thr Pro Ser His Asn Ser His Gln Val Pro Ser Ala Gly Gly 115 120 125 Pro Thr Ala Asn Ser Gly Thr Ser Gly Ser Glu Val Gln Leu Val Gln 130 135 140 Ser Gly Pro Gly Leu Val Gln Pro Gly Gly Ser Val Arg Ile Ser Cys 145 150 155 160 Ala Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Lys 165 170 175 Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly Trp Ile Asn Thr Tyr 180 185 190 Thr Gly Glu Ser Thr Tyr Ala Asp Ser Phe Lys Gly Arg Phe Thr Phe 195 200 205 Ser Leu Asp Thr Ser Ala Ser Ala Ala Tyr Leu Gln Ile Asn Ser Leu 210 215 220 Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Phe Ala Ile Lys 225 230 235 240 Gly Asp Tyr Trp Gly Gln Gly Thr Leu Leu Thr Val Ser Ser 245 250 <210> 104 <211> 231 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 104 Arg Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Thr Lys Ser Leu Leu His Ser 20 25 30 Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Gln Asp Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Gln Met Ser Asn Leu Ala Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Ser Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gln Asn 85 90 95 Leu Glu Ile Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Leu Lys 100 105 110 Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 115 120 125 Leu Lys Ser Gly Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr 130 135 140 Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 145 150 155 160 Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 165 170 175 Tyr Ser Leu Trp Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 180 185 190 His Lys Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 195 200 205 Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro 210 215 220 Tyr Asp Val Pro Asp Tyr Ala 225 230 <210> 105 <211> 446 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 105 Glu Val Gln Leu Val Gln Ser Gly Pro Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Val Arg Ile Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Gly Met Asn Trp Val Lys Lys Ala Pro Gly Lys Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala Asp Ser Phe 50 55 60 Lys Gly Glu Phe Thr Phe Ser Leu Asp Thr Ser Ala Ser Ala Ala Tyr 65 70 75 80 Leu Gln Ile Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Phe Ala Ile Lys Gly Asp Tyr Trp Gly Gln Gly Thr Leu Leu 100 105 110 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 115 120 125 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 130 135 140 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 145 150 155 160 Ala Leu Thr Ser Gly Val Ala Thr Gly Pro Ala Val Leu Gln Ser Ser 165 170 175 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 180 185 190 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 195 200 205 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 210 215 220 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 225 230 235 240 Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 245 250 255 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 260 265 270 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 275 280 285 Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 290 295 300 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 305 310 315 320 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 325 330 335 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 340 345 350 Ser Arg Lys Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 355 360 365 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 370 375 380 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Lys Ser Asp 385 390 395 400 Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 405 410 415 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 420 425 430 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 106 <211> 213 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 106 Glu Leu Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Thr Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile 35 40 45 Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Ser Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Asp Ile Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Val Ala Ala Pro 100 105 110 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 115 120 125 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 145 150 155 160 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr Ala 180 185 190 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205 Asn Arg Gly Glu Cys 210 <210> 107 <211> 232 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 107 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Met Gly Trp Gly Ser Gly Trp Arg Pro Tyr Tyr Tyr Tyr 100 105 110 Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala 115 120 125 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser 130 135 140 Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 145 150 155 160 Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 165 170 175 Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 180 185 190 Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 195 200 205 Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 210 215 220 Val Glu Pro Lys Ser Cys Asp Lys 225 230 <210> 108 <211> 262 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 108 Gly Gly Gly Ser Gly Gly Gly Glu Val Gln Leu Leu Glu Ser Gly Gly 1 5 10 15 Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 30 Gly Phe Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro 35 40 45 Gly Lys Gly Leu Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn 50 55 60 Lys Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 65 70 75 80 Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Lys Asp Met Gly Trp Gly Ser Gly 100 105 110 Trp Arg Pro Tyr Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr 115 120 125 Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 130 135 140 Gly Gly Gly Gly Ser Glu Leu Gln Met Thr Gln Ser Pro Ser Ser Leu 145 150 155 160 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Thr Ser Gln 165 170 175 Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro 180 185 190 Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro 195 200 205 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 210 215 220 Ser Ser Leu Gln Pro Glu Asp Ser Ala Thr Tyr Tyr Cys Gln Gln Ser 225 230 235 240 Tyr Asp Ile Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 245 250 255 His His His His His His 260 <210> 109 <211> 249 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 109 Glu Leu Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Thr Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile 35 40 45 Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Ser Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Asp Ile Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 100 105 110 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu 115 120 125 Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys 130 135 140 Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile Ser Tyr Asp 165 170 175 Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile 180 185 190 Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu 195 200 205 Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Asp Met Gly Trp 210 215 220 Gly Ser Gly Trp Arg Pro Tyr Tyr Tyr Tyr Gly Met Asp Val Trp Gly 225 230 235 240 Gln Gly Thr Thr Val Thr Val Ser Ser 245 <210> 110 <211> 226 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 110 Arg Leu Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Thr Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Asp Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile 35 40 45 Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Ser Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Asp Ile Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Val Ala Ala Pro 100 105 110 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 115 120 125 Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 145 150 155 160 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Trp Ser 165 170 175 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr Ala 180 185 190 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205 Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro Tyr Asp Val Pro Asp 210 215 220 Tyr Ala 225 <210> 111 <211> 457 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 111 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Gly Met His Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Glu Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Met Gly Trp Gly Ser Gly Trp Arg Pro Tyr Tyr Tyr Tyr 100 105 110 Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala 115 120 125 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser 130 135 140 Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 145 150 155 160 Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 165 170 175 Val Ala Thr Gly Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 180 185 190 Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 195 200 205 Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys 210 215 220 Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 225 230 235 240 Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 245 250 255 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 260 265 270 Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 275 280 285 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 290 295 300 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 305 310 315 320 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 325 330 335 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 340 345 350 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Lys Glu Leu 355 360 365 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 370 375 380 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 385 390 395 400 Tyr Lys Thr Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu 405 410 415 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 420 425 430 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 435 440 445 Lys Ser Leu Ser Leu Ser Pro Gly Lys 450 455 <210> 112 <211> 215 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 112 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Thr Val Ser Ala Asn 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Leu Ala Ser Tyr Arg Tyr Arg Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys His Gln Tyr Tyr Thr Tyr Pro Leu 85 90 95 Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala 100 105 110 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 115 120 125 Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 130 135 140 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 145 150 155 160 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 165 170 175 Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu 180 185 190 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 195 200 205 Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 113 <211> 226 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 113 Gln Val Gln Leu Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Tyr 20 25 30 Gly Met Asn Val Trp Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Thr Lys Ser Gly Glu Ala Thr Tyr Val Glu Glu Phe 50 55 60 Lys Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 65 70 75 80 Leu Gln Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Trp Asp Phe Tyr Asp Tyr Val Asp Glu Ala Met Tyr Trp Gly 100 105 110 Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 195 200 205 Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220 Asp Lys 225 <210> 114 <211> 258 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 114 Gly Gly Gly Ser Gly Gly Gly Gln Val Gln Leu Val Gln Ser Gly Ser 1 5 10 15 Glu Leu Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser 20 25 30 Gly Tyr Thr Phe Thr Glu Tyr Gly Met Asn Val Trp Arg Gln Ala Pro 35 40 45 Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Thr Lys Ser Gly Glu 50 55 60 Ala Thr Tyr Val Glu Glu Phe Lys Gly Arg Phe Val Phe Ser Leu Asp 65 70 75 80 Thr Ser Val Ser Thr Ala Tyr Leu Gln Ile Ser Ser Leu Lys Ala Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Trp Asp Phe Tyr Asp Tyr Val 100 105 110 Asp Glu Ala Met Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 125 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 130 135 140 Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 145 150 155 160 Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Thr Val Ser Ala Asn Val 165 170 175 Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 180 185 190 Leu Ala Ser Tyr Arg Tyr Arg Gly Val Pro Ser Arg Phe Ser Gly Ser 195 200 205 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 210 215 220 Asp Phe Ala Thr Tyr Tyr Cys His Gln Tyr Tyr Thr Tyr Pro Leu Phe 225 230 235 240 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg His His His His 245 250 255 His His <210> 115 <211> 245 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 115 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Thr Val Ser Ala Asn 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Leu Ala Ser Tyr Arg Tyr Arg Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys His Gln Tyr Tyr Thr Tyr Pro Leu 85 90 95 Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Gly Gly Gly 100 105 110 Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu 115 120 125 Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala Ser Val Lys Val 130 135 140 Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Tyr Gly Met Asn Val 145 150 155 160 Trp Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn 165 170 175 Thr Lys Ser Gly Glu Ala Thr Tyr Val Glu Glu Phe Lys Gly Arg Phe 180 185 190 Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr Leu Gln Ile Ser 195 200 205 Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Trp Asp 210 215 220 Phe Tyr Asp Tyr Val Asp Glu Ala Met Tyr Trp Gly Gln Gly Thr Thr 225 230 235 240 Val Thr Val Ser Ser 245 <210> 116 <211> 228 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 116 Arg Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Thr Val Ser Ala Asn 20 25 30 Val Ala Trp Tyr Gln Asp Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Leu Ala Ser Tyr Arg Tyr Arg Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys His Gln Tyr Tyr Thr Tyr Pro Leu 85 90 95 Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala 100 105 110 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 115 120 125 Gly Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr Pro Arg Glu 130 135 140 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 145 150 155 160 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 165 170 175 Trp Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu 180 185 190 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 195 200 205 Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro Tyr Asp Val 210 215 220 Pro Asp Tyr Ala 225 <210> 117 <211> 451 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 117 Gln Val Gln Leu Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Tyr 20 25 30 Gly Met Asn Val Trp Arg Lys Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Thr Lys Ser Gly Glu Ala Thr Tyr Val Glu Glu Phe 50 55 60 Lys Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 65 70 75 80 Leu Gln Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Trp Asp Phe Tyr Asp Tyr Val Asp Glu Ala Met Tyr Trp Gly 100 105 110 Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val Ala Thr Gly Pro Ala 165 170 175 Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 195 200 205 Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys 210 215 220 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240 Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270 Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 290 295 300 Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 305 310 315 320 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 340 345 350 Tyr Thr Leu Pro Pro Ser Arg Lys Glu Leu Thr Lys Asn Gln Val Ser 355 360 365 Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400 Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415 Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 435 440 445 Pro Gly Lys 450 <210> 118 <211> 217 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 118 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Ser 20 25 30 Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Val Ser Tyr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 65 70 75 80 Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Gly Tyr Tyr Ser Ala 85 90 95 Gly Asp Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 100 105 110 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 115 120 125 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 130 135 140 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 145 150 155 160 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 165 170 175 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 180 185 190 Lys Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 195 200 205 Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 119 <211> 220 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 119 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr 20 25 30 Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Ile Ile Phe Cys Ala Gly Asn Ala Tyr Asn Ala Ser Trp Ala Lys 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Arg Gly Trp Gln Ala Leu Val Asn Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 <210> 120 <211> 254 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 120 Gly Gly Gly Ser Gly Gly Gly Glu Val Gln Leu Val Glu Ser Gly Gly 1 5 10 15 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 30 Gly Phe Ser Leu Ser Asn Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro 35 40 45 Gly Lys Gly Leu Glu Trp Val Ala Ile Ile Phe Cys Ala Gly Asn Ala 50 55 60 Tyr Asn Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp 65 70 75 80 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 85 90 95 Thr Ala Val Tyr Tyr Cys Ala Arg Gly Trp Gln Ala Leu Val Asn Trp 100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 115 120 125 Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser 130 135 140 Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 145 150 155 160 Gln Ala Ser Gln Ser Ile Ser Ser Ser Tyr Leu Ser Trp Tyr Gln Gln 165 170 175 Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Val Ser Tyr Leu 180 185 190 Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 195 200 205 Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 210 215 220 Tyr Cys Gln Ser Gly Tyr Tyr Ser Ala Gly Asp Leu Thr Phe Gly Gln 225 230 235 240 Gly Thr Lys Val Glu Ile Lys Arg His His His His His His 245 250 <210> 121 <211> 241 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 121 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Ser 20 25 30 Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Val Ser Tyr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 65 70 75 80 Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Gly Tyr Tyr Ser Ala 85 90 95 Gly Asp Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly 100 105 110 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 115 120 125 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 130 135 140 Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr Tyr Ile 145 150 155 160 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Ile 165 170 175 Ile Phe Cys Ala Gly Asn Ala Tyr Asn Ala Ser Trp Ala Lys Gly Arg 180 185 190 Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met 195 200 205 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly 210 215 220 Trp Gln Ala Leu Val Asn Trp Gly Gln Gly Thr Leu Val Thr Val Ser 225 230 235 240 Ser <210> 122 <211> 230 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 122 Arg Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Ser 20 25 30 Tyr Leu Ser Trp Tyr Gln Asp Lys Pro Gly Lys Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Val Ser Tyr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 65 70 75 80 Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Gly Tyr Tyr Ser Ala 85 90 95 Gly Asp Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 100 105 110 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 115 120 125 Lys Ser Gly Thr Ala Ser Val Val Cys Tyr Leu Asn Asn Phe Tyr Pro 130 135 140 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 145 150 155 160 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 165 170 175 Ser Leu Trp Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 180 185 190 Lys Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 195 200 205 Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Ser Tyr Pro Tyr 210 215 220 Asp Val Pro Asp Tyr Ala 225 230 <210> 123 <211> 445 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 123 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr 20 25 30 Tyr Ile Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Ile Ile Phe Cys Ala Gly Asn Ala Tyr Asn Ala Ser Trp Ala Lys 50 55 60 Gly Glu Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Arg Gly Trp Gln Ala Leu Val Asn Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val Ala Thr Gly Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220 Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 225 230 235 240 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320 Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 340 345 350 Arg Lys Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 355 360 365 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 370 375 380 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Lys Ser Asp Gly 385 390 395 400 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 405 410 415 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 124 <211> 119 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 124 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Thr Asp Lys Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly 100 105 110 Thr Thr Val Thr Val Ser Ser 115 <210> 125 <211> 5 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 125 Arg Tyr Thr Met His 1 5 <210> 126 <211> 17 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 126 Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <210> 127 <211> 10 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 127 Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr 1 5 10 <210> 128 <211> 107 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 128 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met 20 25 30 Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 35 40 45 Asp Thr Ser Lys Val Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 75 80 Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr 85 90 95 Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> 129 <211> 10 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 129 Arg Ala Ser Ser Ser Val Ser Tyr Met Asn 1 5 10 <210> 130 <211> 7 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 130 Asp Thr Ser Lys Val Ala Ser 1 5 <210> 131 <211> 9 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 131 Gln Gln Trp Ser Ser Asn Pro Leu Thr 1 5 <210> 132 <211> 774 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 132 ggtggcggct caggtggagg ccaggtgcag ctggtgcaga gcggcgcgga agtgaaaaaa 60 ccgggcgcga gcgtgaaagt gagctgcaaa gcgagcggct atacctttac ccgctatacc 120 atgcattggg tgcgccaggc gccgggccag ggcctggaat ggatgggcta tattaacccg 180 agccgcggct ataccagcta tgcgcagaaa tttcagggcc gcgtgaccat gaccaccgat 240 aaaagcacca gcaccgtgta tatggaactg agcagcctgc gcagcgaaga taccgcggtg 300 tattattgcg cgcgctatta tgatgatcat tattgcctgg attattgggg ccagggcacc 360 accgtgaccg tgagcagcgt ggagggcggc agcggcggca gcggcggcag cggcggcagc 420 ggcggcgtgg acgatattca gatgacccag agcccgagca gcctgagcgc gagcgtgggc 480 gatcgcgtga ccattacctg ccgcgcgagc agcagcgtga gctatatgaa ctggtatcag 540 cagaaaccgg gcaaagcgcc gaaactgctg atttatgata ccagcaaagt ggcgagcggc 600 gtgccgagcc gctttagcgg cagcggcagc ggcaccgatt ataccctgac cattagcagc 660 ctgcagccgg aagattttgc gacctattat tgccagcagt ggagcagcaa cccgctgacc 720 tttggcggcg gcaccaaagt ggaaattaaa cgccaccacc accaccacca ctga 774 <210> 133 <211> 257 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 133 Gly Gly Gly Ser Gly Gly Gly Gln Val Gln Leu Val Gln Ser Gly Ala 1 5 10 15 Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser 20 25 30 Gly Tyr Thr Phe Thr Arg Tyr Thr Met His Trp Val Arg Gln Ala Pro 35 40 45 Gly Gln Gly Leu Glu Trp Met Gly Tyr Ile Asn Pro Ser Arg Gly Tyr 50 55 60 Thr Ser Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp 65 70 75 80 Lys Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys 100 105 110 Leu Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Val Glu 115 120 125 Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Val Asp 130 135 140 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 145 150 155 160 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met 165 170 175 Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 180 185 190 Asp Thr Ser Lys Val Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 195 200 205 Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 210 215 220 Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr 225 230 235 240 Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg His His His His His 245 250 255 His <210> 134 <211> 642 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 134 gatattcaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60 attacctgcc gcgcgagcag cagcgtgagc tatatgaact ggtatcagca gaaaccgggc 120 aaagcgccga aactgctgat ttatgatacc agcaaagtgg cgagcggcgt gccgagccgc 180 tttagcggca gcggcagcgg caccgattat accctgacca ttagcagcct gcagccggaa 240 gattttgcga cctattattg ccagcagtgg agcagcaacc cgctgacctt tggcggcggc 300 accaaagtgg aaattaaacg cactgtggct gcaccatctg tcttcatctt cccgccatct 360 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540 agcaaagcag actacgagaa acacaaactc tacgcctgcg aagtcaccca tcagggcctg 600 agctcgcccg tcacaaagag cttcaacagg ggagagtgct ga 642 <210> 135 <211> 213 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 135 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met 20 25 30 Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 35 40 45 Asp Thr Ser Lys Val Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 75 80 Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr 85 90 95 Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 100 105 110 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 115 120 125 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 145 150 155 160 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr Ala 180 185 190 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205 Asn Arg Gly Glu Cys 210 <210> 136 <211> 651 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 136 caggtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60 agctgcaaag cgagcggcta tacctttacc cgctatacca tgcattgggt gcgccaggcg 120 ccgggccagg gcctggaatg gatgggctat attaacccga gccgcggcta taccagctat 180 gcgcagaaat ttcagggccg cgtgaccatg accaccgata aaagcaccag caccgtgtat 240 atggaactga gcagcctgcg cagcgaagat accgcggtgt attattgcgc gcgctattat 300 gatgatcatt attgcctgga ttattggggc cagggcacca ccgtgaccgt gagcagcgcc 360 tccaccaaag gtccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 420 acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ctctgaccag cggcgtgcac accttcccag ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac 600 acctgcaacg tagatcacaa gcccagtaac accaaggtgg acaagacagt t 651 <210> 137 <211> 217 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 137 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Thr Asp Lys Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly 100 105 110 Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 115 120 125 Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu 130 135 140 Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 145 150 155 160 Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 165 170 175 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 180 185 190 Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro 195 200 205 Ser Asn Thr Lys Val Asp Lys Thr Val 210 215 <210> 138 <211> 765 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 138 ggcggtggat cacaggtgca gctggtgcag agcggcgcgg aagtgaaaaa accgggcgcg 60 agcgtgaaag tgagctgcaa agcgagcggc tataccttta cccgctatac catgcattgg 120 gtgcgccagg cgccgggcca gggcctggaa tggatgggct atattaaccc gagccgcggc 180 tataccagct atgcgcagaa atttcagggc cgcgtgacca tgaccaccga taaaagcacc 240 agcaccgtgt atatggaact gagcagcctg cgcagcgaag ataccgcggt gtattattgc 300 gcgcgctatt atgatgatca ttattgcctg gattattggg gccagggcac caccgtgacc 360 gtgagcagcg tggagggcgg cagcggcggc agcggcggca gcggcggcag cggcggcgtg 420 gacgatattc agatgaccca gagcccgagc agcctgagcg cgagcgtggg cgatcgcgtg 480 accattacct gccgcgcgag cagcagcgtg agctatatga actggtatca gcagaaaccg 540 ggcaaagcgc cgaaactgct gatttatgat accagcaaag tggcgagcgg cgtgccgagc 600 cgctttagcg gcagcggcag cggcaccgat tataccctga ccattagcag cctgcagccg 660 gaagattttg cgacctatta ttgccagcag tggagcagca acccgctgac ctttggcggc 720 ggcaccaaag tggaaattaa acgccaccac caccaccacc actga 765 <210> 139 <211> 254 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 139 Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 1 5 10 15 Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 20 25 30 Phe Thr Arg Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 35 40 45 Leu Glu Trp Met Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Ser Tyr 50 55 60 Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Lys Ser Thr 65 70 75 80 Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 85 90 95 Val Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr 100 105 110 Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Val Glu Gly Gly Ser 115 120 125 Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Val Asp Asp Ile Gln 130 135 140 Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val 145 150 155 160 Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met Asn Trp Tyr 165 170 175 Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp Thr Ser 180 185 190 Lys Val Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 195 200 205 Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala 210 215 220 Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Gly 225 230 235 240 Gly Thr Lys Val Glu Ile Lys Arg His His His His His His 245 250 <210> 140 <211> 672 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 140 gatattcaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60 attacctgcc gcgcgagcag cagcgtgagc tatatgaact ggtatcagcg taaaccgggc 120 aaagcgccga aactgctgat ttatgatacc agcaaagtgg cgagcggcgt gccgagccgc 180 tttagcggca gcggcagcgg caccgattat accctgacca ttagcagcct gcagccggaa 240 gattttgcga cctattattg ccagcagtgg agcagcaacc cgctgacctt tggcggcggc 300 accaaagtgg aaattaaacg caccgtggca gcacctagcg tgttcatctt tcccccttcc 360 gacgagcagc tgaagtccgg cacagcctct gtggtgtgcc tgctgaacaa tttctatcca 420 cgcgaggcca aggtgcagtg gaaggtggat aacgccctgc agtctggcaa tagccaggag 480 tccgtgaccg agcaggactc taaggatagc acatactccc tgtcctctac cctgacactg 540 agcaaggccg attacgagaa gcacaagctg tatgcatgcg aggtgaccca ccagggcctg 600 agctccccag tgacaaagtc ttttaaccgg ggcgagtgtg gcggcggctc ccaccaccac 660 caccaccact ga 672 <210> 141 <211> 223 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 141 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Met 20 25 30 Asn Trp Tyr Gln Arg Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 35 40 45 Asp Thr Ser Lys Val Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 75 80 Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr 85 90 95 Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 100 105 110 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 115 120 125 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 145 150 155 160 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr Ala 180 185 190 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205 Asn Arg Gly Glu Cys Gly Gly Gly Ser His His His His His His 210 215 220 <210> 142 <211> 1350 <212> DNA <213> 人工序列 <220> <223> 合成序列 <400> 142 caggtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60 agctgcaaag cgagcggcta tacctttacc cgctatacca tgcattgggt gcgctatgcg 120 ccgggccagg gcctggaatg gatgggctat attaacccga gccgcggcta taccagctat 180 gcgcagaaat ttcagggccg cgtgaccatg accaccgata aaagcaccag caccgtgtat 240 atggaactga gcagcctgcg cagcgaagat accgcggtgt attattgcgc gcgctattat 300 gatgatcatt attgcctgga ttattggggc cagggcacca ccgtgaccgt gagcagcgcc 360 tctacaaagg gacctagcgt gttcccactg gcaccctcct ctaagtccac ctctggagga 420 acagccgccc tgggatgcct ggtgaaggat tacttcccag agcccgtgac cgtgtcctgg 480 aactctggcg ccctgaccag cggagtgcac acatttcctg ccgtgctgca gagctccggc 540 ctgtactccc tgtctagcgt ggtgacagtg ccatcctcta gcctgggcac ccagacatat 600 atctgcaacg tgaatcacaa gccaagcaat accaaggtcg acaagaaggt ggagcccaag 660 tcctgtgata agacccacac atgcccccct tgtcctgcac cagagctgct gggaggacca 720 agcgtgttcc tgtttccacc caagcctaag gacaccctga tgatctctcg gaccccagag 780 gtgacatgcg tggtggtgga cgtgagccac gaggatcccg aggtgaagtt taactggtac 840 gtggatggcg tggaggtgca caatgccaag accaagccca gggaggagca gtacaattcc 900 acctatcgcg tggtgtctgt gctgacagtg ctgcaccagg actggctgaa cggcaaggag 960 tataagtgca aggtgtccaa taaggccctg cccgccccta tcgagaagac aatctctaag 1020 gcaaagggac agcctcggga gccacaggtg tacaccctgc ctccatccag agatgagctg 1080 accaagaacc aggtgtctct gacatgtctg gtgaagggct tctatccctc tgacatcgcc 1140 gtggagtggg agagcaatgg ccagcctgag aacaattacg ataccacacc ccctgtgctg 1200 gacagcgatg gctccttctt tctgtatagc gacctgacag tggataagtc cagatggcag 1260 cagggcaacg tgtttagctg ttccgtgatg cacgaggccc tgcacaatca ctacacccag 1320 aagtctctga gcctgtcccc cggcaagtaa 1350 <210> 143 <211> 449 <212> PRT <213> 人工序列 <220> <223> 合成序列 <400> 143 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Thr Met His Trp Val Arg Tyr Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Thr Asp Lys Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly 100 105 110 Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 115 120 125 Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 130 135 140 Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 145 150 155 160 Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 165 170 175 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 180 185 190 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 195 200 205 Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys 210 215 220 Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 260 265 270 Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Asp Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Asp Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 445 Lys
Claims (16)
- 一種用以誘發一T細胞分化及/或增生的方法,其中該T細胞表面具有一抗-腫瘤抗原部(anti-tumor antigen moiety)及一抗-CD3部(anti-CD3 moiety),該方法包含:將一周邊血液單核球細胞(peripheral blood mononuclear cell,PBMC)與一雙功抗體(bi-specific antibody,BsAb)培養在一培養液中,據以使該PBMC分化為T細胞,其中,該BsAb包含一對應至該T細胞之該抗-腫瘤抗原部的腫瘤抗原結合位點,以及一對應至該T細胞之該抗-CD3部的CD3結合位點,以及該BsAb非鼠類OKT3抗體;以及在該BsAb中,該腫瘤抗原結合位點包含一與序列編號:70、78、85、91、97、103、109、115或121具有至少90%序列相似度的抗-腫瘤抗原scFv;以及該CD3結合位點包含一與序列編號:66或79具有至少90%序列相似度的抗-CD3 scFv;或是該腫瘤抗原結合位點包含一與序列編號:64、75、82、88、94、100、106、112或118具有至少90%序列相似度的抗-腫瘤抗原VL-Ck域;以及一與序列編號:65、76、83、89、95、101、107、113或119具有至少90%序列相似度的抗-腫瘤抗原VH-CH1域;以及該CD3結合位點包含一與序列編號:66或79具有至少90%序列相似度的抗-CD3 scFv。
- 一種用以誘發一T細胞分化及/或增生的方法,包含: 將一PBMC與一多肽培養在一培養液中,據以使該PBMC分化為T細胞,其中,該多肽包含一與序列編號:124具有至少90%序列相似度的抗-CD3 VH序列,以及一與序列編號:128具有至少90%序列相似度的抗-CD3 VL序列。
- 如請求項1或2所述之方法,其中該培養液更包含一細胞激素,且該細胞激素係選自由IL-2、IL-7、TGF-β及其組合所組成的群組。
- 如請求項3所述之方法,其中該培養液包含IL-2、IL-7及TGF-β的組合;且利用該方法所製備的T細胞為一調控型T細胞。
- 一種利用請求項1至4之任一方法所製備的T細胞。
- 一種雙功抗體,包含:一腫瘤抗原結合位點包含一與序列編號:70、78、85、91、97、103、109、115或121具有至少90%序列相似度的抗-腫瘤抗原scFv;以及一CD3結合位點包含一與序列編號:66或79具有至少90%序列相似度的抗-CD3 scFv;或是一腫瘤抗原結合位點包含一與序列編號:64、75、82、88、94、100、106、112或118具有至少90%序列相似度的抗-腫瘤抗原VL-Ck域;以及一與序列編號:65、76、83、89、95、101、107、113或119具有至少90%序列相似度的抗-腫瘤抗原VH-CH1域;以及一CD3結合位點包含一與序列編號:66或79具有至少90%序列相似度的抗-CD3 scFv。
- 一種多肽,包含:一與序列編號:124具有至少90%序列相似度的抗-CD3 VH序列,以及一與序列編號:128具有至少90%序列相似度的抗-CD3 VL序列。
- 一種T細胞於製備一藥物之用途,其中該藥物係用以治療癌症,其中該T細胞是一種如請求項5所述之T細胞,或一種經由如請求項6所述之雙功抗體所修飾,或經由如請求項7所述之多肽所修飾的鼠類OKT3 T細胞。
- 如請求項8所述之用途,其中係藉由將一周邊血液單核球細胞(PBMC)與一鼠類OKT3單株抗體培養在一培養液以製備該鼠類OKT3 T細胞。
- 如請求項9所述之用途,其中可進一步以如請求項6所述之BsAb或以如請求項7所述之多肽來修飾該如請求項5所述之T細胞或該經修飾的鼠類OKT3 T細胞,其中係藉由將該如請求項5所述之T細胞或該經修飾的鼠類OKT3 T細胞培養在一具有如請求項6所述之BsAb或具有如請求項7所述之多肽的培養液中來進行該修飾。
- 如請求項10所述之用途,其中該培養液更包含一細胞激素,該細胞激素係選自由IL-2、IL-7及其組合所組成的群組。
- 如請求項11所述之用途,其中該培養液更包含抗-CD28抗體。
- 如請求項8所述之用途,其中該癌症係EGFR+、PSMA+或PD-L1+之癌症。
- 如請求項8所述之用途,其中該癌症係膀胱癌、膽癌、骨癌、腦瘤、乳癌、子宮頸癌、結直腸癌、大腸癌、食道癌、上皮癌、胃癌、胃腸基質瘤(gastrointestinal stromal tumor,GIST)、神經膠質瘤、淋巴譜系之造血組織腫瘤、肝癌、非何杰金氏淋巴癌(non-Hodgkin’s lymphoma)、卡波西氏肉瘤、白血病、肺癌、淋巴瘤、小腸癌、黑色素瘤、骨髓性白血病、胰臟癌、前列腺癌、視網膜母細胞瘤、卵巢癌、腎細胞癌、脾臟癌、鱗狀細胞癌、甲狀腺癌或濾泡狀甲狀腺癌。
- 如請求項14所述之用途,其中該乳癌係三陰性乳癌。
- 一種醫藥套組,包含該如請求項5所述之T細胞,或該經如請求項6所述之BsAb或該經如請求項7所述之多肽修飾的鼠類OKT3 T細胞;以及該如請求項6所述之BsAb或該如請求項7所述之多肽。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762478280P | 2017-03-29 | 2017-03-29 | |
US62478280 | 2017-03-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201945541A TW201945541A (zh) | 2019-12-01 |
TWI710637B true TWI710637B (zh) | 2020-11-21 |
Family
ID=63674272
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW107110908A TWI676681B (zh) | 2017-03-29 | 2018-03-29 | 具抗原專一性的t細胞及其用途 |
TW108129663A TWI710637B (zh) | 2017-03-29 | 2018-03-29 | 具抗原專一性的t細胞及其用途 |
TW109143906A TW202122576A (zh) | 2017-03-29 | 2018-03-29 | 具抗原專一性的t細胞及其用途 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW107110908A TWI676681B (zh) | 2017-03-29 | 2018-03-29 | 具抗原專一性的t細胞及其用途 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW109143906A TW202122576A (zh) | 2017-03-29 | 2018-03-29 | 具抗原專一性的t細胞及其用途 |
Country Status (8)
Country | Link |
---|---|
US (1) | US11913025B2 (zh) |
EP (1) | EP3607053A4 (zh) |
JP (1) | JP7029822B2 (zh) |
KR (1) | KR102367658B1 (zh) |
CN (1) | CN110520523A (zh) |
AU (2) | AU2018243114C1 (zh) |
TW (3) | TWI676681B (zh) |
WO (1) | WO2018177371A1 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI676681B (zh) * | 2017-03-29 | 2019-11-11 | 臺北醫學大學 | 具抗原專一性的t細胞及其用途 |
JP7137696B2 (ja) | 2019-05-14 | 2022-09-14 | プロヴェンション・バイオ・インコーポレイテッド | 1型糖尿病を予防するための方法および組成物 |
JP7337373B2 (ja) * | 2019-07-29 | 2023-09-04 | サイアス株式会社 | 抗原特異的t細胞の製造方法 |
WO2021252917A2 (en) | 2020-06-11 | 2021-12-16 | Provention Bio, Inc. | Methods and compositions for preventing type 1 diabetes |
CN114621351B (zh) * | 2022-04-27 | 2023-01-03 | 华羊生物技术股份有限公司 | 多特异性抗体及其治疗癌症的用途 |
WO2023230626A2 (en) * | 2022-05-27 | 2023-11-30 | Bighat Biosciences, Inc. | Ph-selective anti-cd3 antibodies and use of the same |
WO2024044709A2 (en) * | 2022-08-24 | 2024-02-29 | The Research Foundation For The State University Of New York | Anti-monomethyl auristatin antibodies and antibody fragments |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011062112A1 (ja) * | 2009-11-18 | 2011-05-26 | 国立大学法人東北大学 | ヒト型化抗egfr抗体可変領域の高機能性変異体 |
CN102245640A (zh) * | 2008-12-09 | 2011-11-16 | 霍夫曼-拉罗奇有限公司 | 抗-pd-l1抗体及它们用于增强t细胞功能的用途 |
WO2016179518A2 (en) * | 2015-05-06 | 2016-11-10 | Janssen Biotech, Inc. | Prostate specific membrane antigen (psma) bispecific binding agents and uses thereof |
WO2016204966A1 (en) * | 2015-06-16 | 2016-12-22 | Genentech, Inc. | Anti-cd3 antibodies and methods of use |
TWI676681B (zh) * | 2017-03-29 | 2019-11-11 | 臺北醫學大學 | 具抗原專一性的t細胞及其用途 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003015705A2 (en) | 2001-08-17 | 2003-02-27 | Roger Williams Hospital | In situ immunization |
WO2005056598A2 (en) | 2003-12-12 | 2005-06-23 | Novo Nordisk A/S | Laminin-5 modulators and uses thereof |
CA2738565C (en) * | 2008-10-01 | 2023-10-10 | Micromet Ag | Cross-species-specific psmaxcd3 bispecific single chain antibody |
TWI629357B (zh) * | 2009-10-02 | 2018-07-11 | 安進研究(慕尼黑)有限責任公司 | 跨物種特異性的PSMAxCD3雙特異性單鏈抗體 |
EP2506876B1 (en) * | 2009-12-02 | 2016-10-12 | Imaginab, Inc. | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (psma) and methods for their use |
TWI653333B (zh) * | 2010-04-01 | 2019-03-11 | 安進研究(慕尼黑)有限責任公司 | 跨物種專一性之PSMAxCD3雙專一性單鏈抗體 |
CN102250245B (zh) | 2010-05-27 | 2014-05-14 | 四川大学 | 抗b细胞淋巴瘤的双特异性抗体及其用途 |
CN103842383B (zh) * | 2011-05-16 | 2017-11-03 | 健能隆医药技术(上海)有限公司 | 多特异性fab融合蛋白及其使用方法 |
CA2837975C (en) | 2011-08-23 | 2022-04-05 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
KR20150064068A (ko) | 2012-10-08 | 2015-06-10 | 로슈 글리카트 아게 | 2개의 Fab 단편을 포함하는 FC-부재 항체 및 이용 방법 |
KR101911438B1 (ko) * | 2012-10-31 | 2018-10-24 | 삼성전자주식회사 | 이중 특이 항원 결합 단백질 복합체 및 이중 특이 항체의 제조 방법 |
US9562110B2 (en) * | 2012-11-21 | 2017-02-07 | Wuhan Yzy Biopharma Co., Ltd. | Bispecific antibody |
CN103965359B (zh) * | 2013-01-24 | 2016-08-03 | 上海市肿瘤研究所 | 抗上皮细胞粘附分子和t细胞抗原的双特异性抗体 |
WO2015013671A1 (en) | 2013-07-25 | 2015-01-29 | Cytomx Therapeutics, Inc. | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
JP2017520575A (ja) * | 2014-07-01 | 2017-07-27 | ファイザー・インク | 二重特異的ヘテロ二量体ダイアボディおよびその使用 |
CN104592391B (zh) | 2015-01-21 | 2020-08-21 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体EpCAM×CD3的构建及应用 |
CN104829728B (zh) * | 2015-01-21 | 2019-03-12 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体her2xcd3的构建及应用 |
CN104558191B (zh) * | 2015-01-21 | 2020-08-21 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体cd20×cd3的构建及应用 |
CN104829729B (zh) * | 2015-04-03 | 2018-08-14 | 复旦大学 | 一种携带抗Her2/CD3双特异性功能蛋白的人T细胞制备 |
IL274151B (en) * | 2015-05-21 | 2022-07-01 | Harpoon Therapeutics Inc | Trispecific binding proteins and methods of use |
EP4137158A1 (en) * | 2015-08-07 | 2023-02-22 | Imaginab, Inc. | Antigen binding constructs to target molecules |
-
2018
- 2018-03-29 TW TW107110908A patent/TWI676681B/zh active
- 2018-03-29 AU AU2018243114A patent/AU2018243114C1/en active Active
- 2018-03-29 US US16/497,805 patent/US11913025B2/en active Active
- 2018-03-29 KR KR1020197030438A patent/KR102367658B1/ko active IP Right Grant
- 2018-03-29 TW TW108129663A patent/TWI710637B/zh active
- 2018-03-29 EP EP18777422.9A patent/EP3607053A4/en active Pending
- 2018-03-29 TW TW109143906A patent/TW202122576A/zh unknown
- 2018-03-29 CN CN201880021557.XA patent/CN110520523A/zh active Pending
- 2018-03-29 WO PCT/CN2018/081084 patent/WO2018177371A1/en unknown
- 2018-03-29 JP JP2019553936A patent/JP7029822B2/ja active Active
-
2022
- 2022-02-28 AU AU2022201375A patent/AU2022201375A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102245640A (zh) * | 2008-12-09 | 2011-11-16 | 霍夫曼-拉罗奇有限公司 | 抗-pd-l1抗体及它们用于增强t细胞功能的用途 |
WO2011062112A1 (ja) * | 2009-11-18 | 2011-05-26 | 国立大学法人東北大学 | ヒト型化抗egfr抗体可変領域の高機能性変異体 |
WO2016179518A2 (en) * | 2015-05-06 | 2016-11-10 | Janssen Biotech, Inc. | Prostate specific membrane antigen (psma) bispecific binding agents and uses thereof |
WO2016204966A1 (en) * | 2015-06-16 | 2016-12-22 | Genentech, Inc. | Anti-cd3 antibodies and methods of use |
TWI676681B (zh) * | 2017-03-29 | 2019-11-11 | 臺北醫學大學 | 具抗原專一性的t細胞及其用途 |
Non-Patent Citations (3)
Title |
---|
Klein, S. C., et al. "Release of cytokines and soluble cell surface molecules by PBMC after activation with the bispecific antibody CD3× CD19." Scandinavian journal of immunology 46.5 (1997): 452-458. |
Mack, Matthias, et al. "Biologic properties of a bispecific single-chain antibody directed against 17-1A (EpCAM) and CD3: tumor cell-dependent T cell stimulation and cytotoxic activity." the Journal of Immunology 158.8 (1997): 3965-3970. |
Mack, Matthias, et al. "Biologic properties of a bispecific single-chain antibody directed against 17-1A (EpCAM) and CD3: tumor cell-dependent T cell stimulation and cytotoxic activity." the Journal of Immunology 158.8 (1997): 3965-3970. Klein, S. C., et al. "Release of cytokines and soluble cell surface molecules by PBMC after activation with the bispecific antibody CD3× CD19." Scandinavian journal of immunology 46.5 (1997): 452-458. * |
Also Published As
Publication number | Publication date |
---|---|
TWI676681B (zh) | 2019-11-11 |
JP7029822B2 (ja) | 2022-03-04 |
AU2022201375A1 (en) | 2022-03-24 |
KR20190130141A (ko) | 2019-11-21 |
EP3607053A4 (en) | 2021-04-07 |
TW201945541A (zh) | 2019-12-01 |
AU2018243114B2 (en) | 2021-12-09 |
JP2020512003A (ja) | 2020-04-23 |
EP3607053A1 (en) | 2020-02-12 |
US20210139851A1 (en) | 2021-05-13 |
AU2018243114A1 (en) | 2019-10-17 |
AU2018243114C1 (en) | 2022-05-05 |
KR102367658B1 (ko) | 2022-02-25 |
US11913025B2 (en) | 2024-02-27 |
CN110520523A (zh) | 2019-11-29 |
WO2018177371A1 (en) | 2018-10-04 |
TW202122576A (zh) | 2021-06-16 |
TW201842182A (zh) | 2018-12-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI710637B (zh) | 具抗原專一性的t細胞及其用途 | |
RU2761115C1 (ru) | Биспецифические антитела, специфические в отношении костимуляторного tnf-рецептора | |
AU2021203876A1 (en) | Anti-CD3 antibodies, activatable anti-CD3 antibodies, multispecific anti-CD3 antibodies, multispecific activatable anti-CD3 antibodies, and methods of using the same | |
KR102182485B1 (ko) | 단백질 약물의 불활성화를 위한 항체 로커 | |
AU2021254602A1 (en) | Humanized anti-MUC1* antibodies | |
KR101963923B1 (ko) | 이중특이적 t 세포 활성화 항원 결합 분자 | |
DK2519543T3 (en) | HETERODIMER BINDING PROTEINS AND USE THEREOF | |
CN111954680B (zh) | IL2Rβ/共同γ链抗体 | |
KR20230002261A (ko) | 항-sars-cov-2 중화 항체 및 이의 사용 방법 | |
CN110862454A (zh) | 一种抗Claudin18_2抗体及其应用 | |
KR20180054877A (ko) | 공자극 tnf 수용체에 대해 4가를 갖는 이중특이적 항체 | |
KR20150122203A (ko) | T 세포 활성화 이중특이적 항원 결합 분자 | |
KR20150122761A (ko) | T 세포 활성화 항원 결합 분자 | |
KR20190141655A (ko) | 종양 형질도입용 조성물 및 방법 | |
CA2527726A1 (en) | De-immunized anti-cd3 antibody | |
WO2020168555A1 (zh) | Cd3抗原结合片段及其应用 | |
KR20200003367A (ko) | 암 치료용 조성물 및 방법 | |
KR20200139130A (ko) | 유도 및 네비게이션 제어 단백질의 제조 및 사용 방법 | |
CN110382542A (zh) | 针对共刺激性tnf受体的双特异性抗原结合分子 | |
KR102569068B1 (ko) | 항pd-l1 항체 | |
RU2770620C1 (ru) | Связывающие молекулы, вызывающие клеточную активацию | |
KR20230059789A (ko) | 항-가변 muc1* 항체 및 이의 용도 | |
KR20220154710A (ko) | 소형 유도 및 항법 제어(miniGNC) 항체-유사 단백질 및 이의 제조 및 사용 방법 | |
AU2016280190A1 (en) | Cys80 conjugated immunoglobulins | |
CN109836502B (zh) | 一种双特异性抗体及其应用 |