CN112094353A - 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) - Google Patents
具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) Download PDFInfo
- Publication number
- CN112094353A CN112094353A CN202010859460.5A CN202010859460A CN112094353A CN 112094353 A CN112094353 A CN 112094353A CN 202010859460 A CN202010859460 A CN 202010859460A CN 112094353 A CN112094353 A CN 112094353A
- Authority
- CN
- China
- Prior art keywords
- ser
- gly
- ala
- thr
- leu
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000027455 binding Effects 0.000 title claims abstract description 67
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 title abstract description 100
- 239000000427 antigen Substances 0.000 title abstract description 48
- 108091007433 antigens Proteins 0.000 title abstract description 47
- 102000036639 antigens Human genes 0.000 title abstract description 47
- 108091008874 T cell receptors Proteins 0.000 title description 101
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title description 92
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 275
- 206010042971 T-cell lymphoma Diseases 0.000 claims abstract description 50
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims abstract description 40
- 208000000389 T-cell leukemia Diseases 0.000 claims abstract description 31
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims abstract description 28
- 101000662909 Homo sapiens T cell receptor beta constant 1 Proteins 0.000 claims abstract 12
- 102100037272 T cell receptor beta constant 1 Human genes 0.000 claims abstract 12
- 238000000034 method Methods 0.000 claims description 79
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 70
- 230000003211 malignant effect Effects 0.000 claims description 54
- 230000014509 gene expression Effects 0.000 claims description 34
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 claims description 31
- 206010002449 angioimmunoblastic T-cell lymphoma Diseases 0.000 claims description 25
- 239000012634 fragment Substances 0.000 claims description 25
- 239000011230 binding agent Substances 0.000 claims description 24
- 239000013598 vector Substances 0.000 claims description 23
- 201000005962 mycosis fungoides Diseases 0.000 claims description 22
- 150000007523 nucleic acids Chemical class 0.000 claims description 22
- 208000002460 Enteropathy-Associated T-Cell Lymphoma Diseases 0.000 claims description 21
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 claims description 15
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 claims description 15
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 claims description 15
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 claims description 15
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 claims description 12
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 12
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 claims description 11
- 108020004707 nucleic acids Proteins 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 11
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 11
- 206010066957 hepatosplenic T-cell lymphoma Diseases 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 8
- 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 claims description 7
- 208000000814 primary cutaneous anaplastic large cell lymphoma Diseases 0.000 claims description 7
- 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 101000662902 Homo sapiens T cell receptor beta constant 2 Proteins 0.000 claims 6
- 102100037298 T cell receptor beta constant 2 Human genes 0.000 claims 6
- 210000004027 cell Anatomy 0.000 abstract description 176
- 238000011282 treatment Methods 0.000 abstract description 11
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 250
- 239000013256 coordination polymer Substances 0.000 description 232
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 78
- 239000003795 chemical substances by application Substances 0.000 description 70
- 108090000765 processed proteins & peptides Proteins 0.000 description 66
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 36
- 206010028980 Neoplasm Diseases 0.000 description 35
- 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 34
- 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 33
- 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 33
- 150000001413 amino acids Chemical class 0.000 description 31
- 108090000623 proteins and genes Proteins 0.000 description 30
- MGSVBZIBCCKGCY-ZLUOBGJFSA-N Asp-Ser-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MGSVBZIBCCKGCY-ZLUOBGJFSA-N 0.000 description 28
- 102000004196 processed proteins & peptides Human genes 0.000 description 28
- 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 27
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 26
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 26
- 125000006850 spacer group Chemical group 0.000 description 25
- 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 24
- 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 24
- LOJYQMFIIJVETK-WDSKDSINSA-N Gln-Gln Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(O)=O LOJYQMFIIJVETK-WDSKDSINSA-N 0.000 description 23
- 210000000822 natural killer cell Anatomy 0.000 description 22
- 108010070409 phenylalanyl-glycyl-glycine Proteins 0.000 description 22
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 21
- 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 20
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 20
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 20
- 206010025323 Lymphomas Diseases 0.000 description 20
- 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 20
- 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 19
- 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 19
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 19
- 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 19
- 108010008355 arginyl-glutamine Proteins 0.000 description 19
- 210000003719 b-lymphocyte Anatomy 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 238000010186 staining Methods 0.000 description 19
- 108010089804 glycyl-threonine Proteins 0.000 description 18
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 17
- 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 17
- 201000010099 disease Diseases 0.000 description 17
- 210000005259 peripheral blood Anatomy 0.000 description 17
- 239000011886 peripheral blood Substances 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 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 16
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 16
- 108010057821 leucylproline Proteins 0.000 description 16
- 239000003550 marker Substances 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 15
- 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 14
- 108010079364 N-glycylalanine Proteins 0.000 description 14
- 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 14
- 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 14
- 108010081404 acein-2 Proteins 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 14
- 230000036210 malignancy Effects 0.000 description 14
- 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 13
- 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 13
- 241000880493 Leptailurus serval Species 0.000 description 13
- 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 13
- OLKICIBQRVSQMA-SRVKXCTJSA-N Ser-Ser-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OLKICIBQRVSQMA-SRVKXCTJSA-N 0.000 description 13
- 229940024606 amino acid Drugs 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 108010037850 glycylvaline Proteins 0.000 description 13
- 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 12
- 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 12
- 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 12
- 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 12
- 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 12
- 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 12
- DANHCMVVXDXOHN-SRVKXCTJSA-N Tyr-Asp-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DANHCMVVXDXOHN-SRVKXCTJSA-N 0.000 description 12
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 12
- 238000000684 flow cytometry Methods 0.000 description 12
- 230000003053 immunization Effects 0.000 description 12
- 238000002649 immunization Methods 0.000 description 12
- 210000001165 lymph node Anatomy 0.000 description 12
- 238000002823 phage display Methods 0.000 description 12
- 108010044292 tryptophyltyrosine Proteins 0.000 description 12
- 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 11
- 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 11
- 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 11
- 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 11
- 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 11
- 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 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 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 11
- 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 11
- 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 11
- 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 11
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 11
- 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 11
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 11
- 108010078144 glutaminyl-glycine Proteins 0.000 description 11
- 210000003289 regulatory T cell Anatomy 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 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 10
- UTLCRGFJFSZWAW-OLHMAJIHSA-N Asp-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O UTLCRGFJFSZWAW-OLHMAJIHSA-N 0.000 description 10
- 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 10
- 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 10
- 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 10
- 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 10
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 10
- BSKMOCNNLNDIMU-CDMKHQONSA-N Phe-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O BSKMOCNNLNDIMU-CDMKHQONSA-N 0.000 description 10
- 108010090804 Streptavidin Proteins 0.000 description 10
- 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 10
- 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 10
- 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 10
- 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 10
- 108010060035 arginylproline Proteins 0.000 description 10
- 108010050848 glycylleucine Proteins 0.000 description 10
- 108010087823 glycyltyrosine Proteins 0.000 description 10
- 208000032839 leukemia Diseases 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 230000001177 retroviral effect Effects 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 108010061238 threonyl-glycine Proteins 0.000 description 10
- 108010073969 valyllysine Proteins 0.000 description 10
- FRBAHXABMQXSJQ-FXQIFTODSA-N Arg-Ser-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O FRBAHXABMQXSJQ-FXQIFTODSA-N 0.000 description 9
- 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 9
- 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 9
- 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 9
- 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 9
- 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 9
- 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 9
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 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 9
- 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 9
- 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 9
- 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 9
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 9
- 108010015792 glycyllysine Proteins 0.000 description 9
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108010003137 tyrosyltyrosine Proteins 0.000 description 9
- 108090000672 Annexin A5 Proteins 0.000 description 8
- 102000004121 Annexin A5 Human genes 0.000 description 8
- 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 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 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 8
- 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 8
- CCQOOWAONKGYKQ-BYPYZUCNSA-N Gly-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)CN CCQOOWAONKGYKQ-BYPYZUCNSA-N 0.000 description 8
- 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 8
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 8
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 8
- 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 8
- 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 8
- 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 8
- 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 8
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 8
- 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 8
- 229940098773 bovine serum albumin Drugs 0.000 description 8
- 108010075431 glycyl-alanyl-phenylalanine Proteins 0.000 description 8
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 108010038320 lysylphenylalanine Proteins 0.000 description 8
- 108010026333 seryl-proline Proteins 0.000 description 8
- 230000009258 tissue cross reactivity Effects 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 108010005834 tyrosyl-alanyl-glycine Proteins 0.000 description 8
- AWAXZRDKUHOPBO-GUBZILKMSA-N Ala-Gln-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O AWAXZRDKUHOPBO-GUBZILKMSA-N 0.000 description 7
- NBTGEURICRTMGL-WHFBIAKZSA-N Ala-Gly-Ser Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O NBTGEURICRTMGL-WHFBIAKZSA-N 0.000 description 7
- MAEQBGQTDWDSJQ-LSJOCFKGSA-N Ala-Met-His Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N MAEQBGQTDWDSJQ-LSJOCFKGSA-N 0.000 description 7
- KLALXKYLOMZDQT-ZLUOBGJFSA-N Ala-Ser-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(N)=O KLALXKYLOMZDQT-ZLUOBGJFSA-N 0.000 description 7
- ALMIMUZAWTUNIO-BZSNNMDCSA-N Asp-Tyr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ALMIMUZAWTUNIO-BZSNNMDCSA-N 0.000 description 7
- OVQXQLWWJSNYFV-XEGUGMAKSA-N Gln-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCC(N)=O)C)C(O)=O)=CNC2=C1 OVQXQLWWJSNYFV-XEGUGMAKSA-N 0.000 description 7
- 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 7
- IKFZXRLDMYWNBU-YUMQZZPRSA-N Gln-Gly-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N IKFZXRLDMYWNBU-YUMQZZPRSA-N 0.000 description 7
- 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 7
- 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 7
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 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 7
- 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 7
- 108010058846 Ovalbumin Proteins 0.000 description 7
- 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 7
- 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 7
- 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 7
- 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 7
- 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 7
- 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 7
- USXYVSTVPHELAF-RCWTZXSCSA-N Val-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](C(C)C)N)O USXYVSTVPHELAF-RCWTZXSCSA-N 0.000 description 7
- 108010087924 alanylproline Proteins 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 239000000562 conjugate Substances 0.000 description 7
- 230000003325 follicular Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 108010010147 glycylglutamine Proteins 0.000 description 7
- 108010081551 glycylphenylalanine Proteins 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 108010087904 neutravidin Proteins 0.000 description 7
- 229940092253 ovalbumin Drugs 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 108010051242 phenylalanylserine Proteins 0.000 description 7
- 108010029020 prolylglycine Proteins 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000007790 solid phase Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 108010038745 tryptophylglycine Proteins 0.000 description 7
- 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 6
- 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 6
- 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 6
- 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 6
- 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 6
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 6
- 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
- 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 6
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 6
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 6
- 102100027208 T-cell antigen CD7 Human genes 0.000 description 6
- GLQFKOVWXPPFTP-VEVYYDQMSA-N Thr-Arg-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GLQFKOVWXPPFTP-VEVYYDQMSA-N 0.000 description 6
- 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 6
- WPSKTVVMQCXPRO-BWBBJGPYSA-N Thr-Ser-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WPSKTVVMQCXPRO-BWBBJGPYSA-N 0.000 description 6
- NDZYTIMDOZMECO-SHGPDSBTSA-N Thr-Thr-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O NDZYTIMDOZMECO-SHGPDSBTSA-N 0.000 description 6
- 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 6
- LUMQYLVYUIRHHU-YJRXYDGGSA-N Tyr-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LUMQYLVYUIRHHU-YJRXYDGGSA-N 0.000 description 6
- 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 6
- 108010064997 VPY tripeptide Proteins 0.000 description 6
- QPPZEDOTPZOSEC-RCWTZXSCSA-N Val-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](C(C)C)N)O QPPZEDOTPZOSEC-RCWTZXSCSA-N 0.000 description 6
- CKTMJBPRVQWPHU-JSGCOSHPSA-N Val-Phe-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)O)N CKTMJBPRVQWPHU-JSGCOSHPSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 6
- 108010068265 aspartyltyrosine Proteins 0.000 description 6
- 210000001185 bone marrow Anatomy 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 230000001472 cytotoxic effect Effects 0.000 description 6
- 108010049041 glutamylalanine Proteins 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 230000002147 killing effect Effects 0.000 description 6
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 6
- 210000005170 neoplastic cell Anatomy 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 6
- 108010020532 tyrosyl-proline Proteins 0.000 description 6
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 5
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 5
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 5
- 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 5
- MNBHKGYCLBUIBC-UFYCRDLUSA-N Arg-Phe-Phe Chemical compound C([C@H](NC(=O)[C@H](CCCNC(N)=N)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 MNBHKGYCLBUIBC-UFYCRDLUSA-N 0.000 description 5
- PPMTUXJSQDNUDE-CIUDSAMLSA-N Asn-Glu-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PPMTUXJSQDNUDE-CIUDSAMLSA-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
- XTMZYFMTYJNABC-ZLUOBGJFSA-N Asn-Ser-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N XTMZYFMTYJNABC-ZLUOBGJFSA-N 0.000 description 5
- 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 5
- DTNUIAJCPRMNBT-WHFBIAKZSA-N Asp-Gly-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O DTNUIAJCPRMNBT-WHFBIAKZSA-N 0.000 description 5
- XXAMCEGRCZQGEM-ZLUOBGJFSA-N Asp-Ser-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O XXAMCEGRCZQGEM-ZLUOBGJFSA-N 0.000 description 5
- 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 5
- PRBLYKYHAJEABA-SRVKXCTJSA-N Gln-Arg-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O PRBLYKYHAJEABA-SRVKXCTJSA-N 0.000 description 5
- 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 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
- 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 5
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 5
- FQZPTCNSNPWHLJ-AVGNSLFASA-N Leu-Gln-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O FQZPTCNSNPWHLJ-AVGNSLFASA-N 0.000 description 5
- 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 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
- 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 5
- 208000008771 Lymphadenopathy Diseases 0.000 description 5
- 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 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 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 5
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 5
- 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 5
- MPPHJZYXDVDGOF-BWBBJGPYSA-N Ser-Cys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CO MPPHJZYXDVDGOF-BWBBJGPYSA-N 0.000 description 5
- 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 5
- 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 5
- 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 5
- DIPIPFHFLPTCLK-LOKLDPHHSA-N Thr-Gln-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O DIPIPFHFLPTCLK-LOKLDPHHSA-N 0.000 description 5
- 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 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
- NQQMWWVVGIXUOX-SVSWQMSJSA-N Thr-Ser-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NQQMWWVVGIXUOX-SVSWQMSJSA-N 0.000 description 5
- XYNFFTNEQDWZNY-ULQDDVLXSA-N Tyr-Met-His Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N XYNFFTNEQDWZNY-ULQDDVLXSA-N 0.000 description 5
- 102000006707 alpha-beta T-Cell Antigen Receptors Human genes 0.000 description 5
- 108010087408 alpha-beta T-Cell Antigen Receptors Proteins 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 230000000973 chemotherapeutic effect Effects 0.000 description 5
- 231100000433 cytotoxic Toxicity 0.000 description 5
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 5
- 210000000285 follicular dendritic cell Anatomy 0.000 description 5
- 108010057083 glutamyl-aspartyl-leucine Proteins 0.000 description 5
- 238000011835 investigation Methods 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 108010000761 leucylarginine Proteins 0.000 description 5
- 208000018555 lymphatic system disease Diseases 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 210000003071 memory t lymphocyte Anatomy 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000000877 morphologic effect Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 108010070643 prolylglutamic acid Proteins 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000010361 transduction Methods 0.000 description 5
- 230000026683 transduction Effects 0.000 description 5
- NIZKGBJVCMRDKO-KWQFWETISA-N Ala-Gly-Tyr Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NIZKGBJVCMRDKO-KWQFWETISA-N 0.000 description 4
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 4
- 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 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
- 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 4
- 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 4
- OOXUBGLNDRGOKT-FXQIFTODSA-N Asn-Ser-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OOXUBGLNDRGOKT-FXQIFTODSA-N 0.000 description 4
- 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 4
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 4
- 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 4
- 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 4
- ZGHMRONFHDVXEF-AVGNSLFASA-N Gln-Ser-Phe Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ZGHMRONFHDVXEF-AVGNSLFASA-N 0.000 description 4
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 4
- 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 4
- UGVQELHRNUDMAA-BYPYZUCNSA-N Gly-Ala-Gly Chemical compound [NH3+]CC(=O)N[C@@H](C)C(=O)NCC([O-])=O UGVQELHRNUDMAA-BYPYZUCNSA-N 0.000 description 4
- GNPVTZJUUBPZKW-WDSKDSINSA-N Gly-Gln-Ser Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GNPVTZJUUBPZKW-WDSKDSINSA-N 0.000 description 4
- FXGRXIATVXUAHO-WEDXCCLWSA-N Gly-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN FXGRXIATVXUAHO-WEDXCCLWSA-N 0.000 description 4
- 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 4
- 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 4
- FBOMZVOKCZMDIG-XQQFMLRXSA-N His-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N FBOMZVOKCZMDIG-XQQFMLRXSA-N 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 108010065920 Insulin Lispro Proteins 0.000 description 4
- 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 4
- 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 4
- LAPSXOAUPNOINL-YUMQZZPRSA-N Leu-Gly-Asp Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O LAPSXOAUPNOINL-YUMQZZPRSA-N 0.000 description 4
- FKQPWMZLIIATBA-AJNGGQMLSA-N Leu-Lys-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FKQPWMZLIIATBA-AJNGGQMLSA-N 0.000 description 4
- 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 4
- 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 4
- 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 4
- 102000019298 Lipocalin Human genes 0.000 description 4
- 108050006654 Lipocalin Proteins 0.000 description 4
- YLLWCSDBVGZLOW-CIUDSAMLSA-N Met-Gln-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O YLLWCSDBVGZLOW-CIUDSAMLSA-N 0.000 description 4
- 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 4
- 108010066427 N-valyltryptophan Proteins 0.000 description 4
- NAXPHWZXEXNDIW-JTQLQIEISA-N Phe-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 NAXPHWZXEXNDIW-JTQLQIEISA-N 0.000 description 4
- ACJULKNZOCRWEI-ULQDDVLXSA-N Phe-Met-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O ACJULKNZOCRWEI-ULQDDVLXSA-N 0.000 description 4
- 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 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
- FIODMZKLZFLYQP-GUBZILKMSA-N Pro-Val-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O FIODMZKLZFLYQP-GUBZILKMSA-N 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 208000003251 Pruritus Diseases 0.000 description 4
- ICHZYBVODUVUKN-SRVKXCTJSA-N Ser-Asn-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ICHZYBVODUVUKN-SRVKXCTJSA-N 0.000 description 4
- 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 4
- 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 4
- BKZYBLLIBOBOOW-GHCJXIJMSA-N Ser-Ile-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O BKZYBLLIBOBOOW-GHCJXIJMSA-N 0.000 description 4
- 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 4
- 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 4
- 208000009359 Sezary Syndrome Diseases 0.000 description 4
- 208000021388 Sezary disease Diseases 0.000 description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
- 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 4
- 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 4
- 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 4
- 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 4
- 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 4
- ILUOMMDDGREELW-OSUNSFLBSA-N Thr-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O ILUOMMDDGREELW-OSUNSFLBSA-N 0.000 description 4
- OEVJGIHPQOXYFE-SRVKXCTJSA-N Tyr-Asn-Asp 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](CC(O)=O)C(O)=O OEVJGIHPQOXYFE-SRVKXCTJSA-N 0.000 description 4
- XMNDQSYABVWZRK-BZSNNMDCSA-N Tyr-Asn-Phe 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](CC1=CC=CC=C1)C(O)=O XMNDQSYABVWZRK-BZSNNMDCSA-N 0.000 description 4
- 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 4
- 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 4
- HKYTWJOWZTWBQB-AVGNSLFASA-N Tyr-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=C(O)C=C1 HKYTWJOWZTWBQB-AVGNSLFASA-N 0.000 description 4
- 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 4
- UPODKYBYUBTWSV-BZSNNMDCSA-N Tyr-Phe-Cys Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CS)C(O)=O)C1=CC=C(O)C=C1 UPODKYBYUBTWSV-BZSNNMDCSA-N 0.000 description 4
- 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 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
- 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 4
- BVWPHWLFGRCECJ-JSGCOSHPSA-N Val-Gly-Tyr Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N BVWPHWLFGRCECJ-JSGCOSHPSA-N 0.000 description 4
- HQYVQDRYODWONX-DCAQKATOSA-N Val-His-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CO)C(=O)O)N HQYVQDRYODWONX-DCAQKATOSA-N 0.000 description 4
- 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 4
- 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 4
- 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 4
- 230000004913 activation Effects 0.000 description 4
- 210000002203 alpha-beta t lymphocyte Anatomy 0.000 description 4
- 108010068380 arginylarginine Proteins 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 230000000779 depleting effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 108010092114 histidylphenylalanine Proteins 0.000 description 4
- 108010018006 histidylserine Proteins 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000007803 itching Effects 0.000 description 4
- 208000007282 lymphomatoid papulosis Diseases 0.000 description 4
- 108010003700 lysyl aspartic acid Proteins 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000001613 neoplastic effect Effects 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 210000004180 plasmocyte Anatomy 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 230000002463 transducing effect Effects 0.000 description 4
- 108010000998 wheylin-2 peptide Proteins 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 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 3
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 3
- 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 3
- VNYMOTCMNHJGTG-JBDRJPRFSA-N Ala-Ile-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O VNYMOTCMNHJGTG-JBDRJPRFSA-N 0.000 description 3
- 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 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
- 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 3
- 108700028369 Alleles Proteins 0.000 description 3
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 3
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 3
- PHHRSPBBQUFULD-UWVGGRQHSA-N Arg-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N PHHRSPBBQUFULD-UWVGGRQHSA-N 0.000 description 3
- 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 3
- LXMKTIZAGIBQRX-HRCADAONSA-N Arg-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O LXMKTIZAGIBQRX-HRCADAONSA-N 0.000 description 3
- ADPACBMPYWJJCE-FXQIFTODSA-N Arg-Ser-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O ADPACBMPYWJJCE-FXQIFTODSA-N 0.000 description 3
- XVVOVPFMILMHPX-ZLUOBGJFSA-N Asn-Asp-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XVVOVPFMILMHPX-ZLUOBGJFSA-N 0.000 description 3
- 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 3
- SUIJFTJDTJKSRK-IHRRRGAJSA-N Asn-Pro-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 SUIJFTJDTJKSRK-IHRRRGAJSA-N 0.000 description 3
- SNYCNNPOFYBCEK-ZLUOBGJFSA-N Asn-Ser-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O SNYCNNPOFYBCEK-ZLUOBGJFSA-N 0.000 description 3
- NJIKKGUVGUBICV-ZLUOBGJFSA-N Asp-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O NJIKKGUVGUBICV-ZLUOBGJFSA-N 0.000 description 3
- QXHVOUSPVAWEMX-ZLUOBGJFSA-N Asp-Asp-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O QXHVOUSPVAWEMX-ZLUOBGJFSA-N 0.000 description 3
- 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 3
- AYFVRYXNDHBECD-YUMQZZPRSA-N Asp-Leu-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AYFVRYXNDHBECD-YUMQZZPRSA-N 0.000 description 3
- DPNWSMBUYCLEDG-CIUDSAMLSA-N Asp-Lys-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O DPNWSMBUYCLEDG-CIUDSAMLSA-N 0.000 description 3
- KOWYNSKRPUWSFG-IHPCNDPISA-N Asp-Phe-Trp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)NC(=O)[C@H](CC(=O)O)N KOWYNSKRPUWSFG-IHPCNDPISA-N 0.000 description 3
- 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 3
- 208000015943 Coeliac disease Diseases 0.000 description 3
- 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 3
- 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 3
- 108020004414 DNA Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 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 3
- 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 3
- FNAJNWPDTIXYJN-CIUDSAMLSA-N Gln-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O FNAJNWPDTIXYJN-CIUDSAMLSA-N 0.000 description 3
- 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 3
- 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 3
- OCQUNKSFDYDXBG-QXEWZRGKSA-N Gly-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OCQUNKSFDYDXBG-QXEWZRGKSA-N 0.000 description 3
- DUYYPIRFTLOAJQ-YUMQZZPRSA-N Gly-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)CN DUYYPIRFTLOAJQ-YUMQZZPRSA-N 0.000 description 3
- 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 3
- 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 3
- 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 3
- KAJAOGBVWCYGHZ-JTQLQIEISA-N Gly-Gly-Phe Chemical compound [NH3+]CC(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 KAJAOGBVWCYGHZ-JTQLQIEISA-N 0.000 description 3
- 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 3
- 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 3
- IRJWAYCXIYUHQE-WHFBIAKZSA-N Gly-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CN IRJWAYCXIYUHQE-WHFBIAKZSA-N 0.000 description 3
- 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 3
- 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 3
- BXDLTKLPPKBVEL-FJXKBIBVSA-N Gly-Thr-Met Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(O)=O BXDLTKLPPKBVEL-FJXKBIBVSA-N 0.000 description 3
- ZHHLTWUOWXHVQJ-YUMQZZPRSA-N His-Ser-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N ZHHLTWUOWXHVQJ-YUMQZZPRSA-N 0.000 description 3
- 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 3
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 3
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 3
- 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 3
- KUHFPGIVBOCRMV-MNXVOIDGSA-N Ile-Gln-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)O)N KUHFPGIVBOCRMV-MNXVOIDGSA-N 0.000 description 3
- ODPKZZLRDNXTJZ-WHOFXGATSA-N Ile-Gly-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N ODPKZZLRDNXTJZ-WHOFXGATSA-N 0.000 description 3
- HQLSBZFLOUHQJK-STECZYCISA-N Ile-Tyr-Arg Chemical compound CC[C@H](C)[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 HQLSBZFLOUHQJK-STECZYCISA-N 0.000 description 3
- OMDWJWGZGMCQND-CFMVVWHZSA-N Ile-Tyr-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N OMDWJWGZGMCQND-CFMVVWHZSA-N 0.000 description 3
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 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
- 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 3
- FIYMBBHGYNQFOP-IUCAKERBSA-N Leu-Gly-Gln Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)O)N FIYMBBHGYNQFOP-IUCAKERBSA-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
- CCQLQKZTXZBXTN-NHCYSSNCSA-N Leu-Gly-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O CCQLQKZTXZBXTN-NHCYSSNCSA-N 0.000 description 3
- OYQUOLRTJHWVSQ-SRVKXCTJSA-N Leu-His-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O OYQUOLRTJHWVSQ-SRVKXCTJSA-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
- 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 3
- 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 3
- 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 3
- 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 3
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- CGOMLCQJEMWMCE-STQMWFEESA-N Phe-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 CGOMLCQJEMWMCE-STQMWFEESA-N 0.000 description 3
- 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 3
- 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 3
- DZZCICYRSZASNF-FXQIFTODSA-N Pro-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 DZZCICYRSZASNF-FXQIFTODSA-N 0.000 description 3
- KPDRZQUWJKTMBP-DCAQKATOSA-N Pro-Asp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1 KPDRZQUWJKTMBP-DCAQKATOSA-N 0.000 description 3
- 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 3
- JLMZKEQFMVORMA-SRVKXCTJSA-N Pro-Pro-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 JLMZKEQFMVORMA-SRVKXCTJSA-N 0.000 description 3
- BGWKULMLUIUPKY-BQBZGAKWSA-N Pro-Ser-Gly Chemical compound OC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 BGWKULMLUIUPKY-BQBZGAKWSA-N 0.000 description 3
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 3
- WXUBSIDKNMFAGS-IHRRRGAJSA-N Ser-Arg-Tyr Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@H](CO)N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WXUBSIDKNMFAGS-IHRRRGAJSA-N 0.000 description 3
- GHPQVUYZQQGEDA-BIIVOSGPSA-N Ser-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N)C(=O)O GHPQVUYZQQGEDA-BIIVOSGPSA-N 0.000 description 3
- 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 3
- DKGRNFUXVTYRAS-UBHSHLNASA-N Ser-Ser-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O DKGRNFUXVTYRAS-UBHSHLNASA-N 0.000 description 3
- 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 3
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 3
- 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 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
- 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 3
- 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 3
- DVLHKUWLNKDINO-PMVMPFDFSA-N Trp-Tyr-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O DVLHKUWLNKDINO-PMVMPFDFSA-N 0.000 description 3
- PEVVXUGSAKEPEN-AVGNSLFASA-N Tyr-Asn-Glu 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(O)=O)C(O)=O PEVVXUGSAKEPEN-AVGNSLFASA-N 0.000 description 3
- YKCXQOBTISTQJD-BZSNNMDCSA-N Tyr-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N YKCXQOBTISTQJD-BZSNNMDCSA-N 0.000 description 3
- 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 3
- UMSZZGTXGKHTFJ-SRVKXCTJSA-N Tyr-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 UMSZZGTXGKHTFJ-SRVKXCTJSA-N 0.000 description 3
- 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 3
- 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 3
- SMUWZUSWMWVOSL-JYJNAYRXSA-N Tyr-Val-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N SMUWZUSWMWVOSL-JYJNAYRXSA-N 0.000 description 3
- PIFJAFRUVWZRKR-QMMMGPOBSA-N Val-Gly-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O PIFJAFRUVWZRKR-QMMMGPOBSA-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
- 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 3
- 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 3
- 238000007792 addition Methods 0.000 description 3
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 3
- 108010041407 alanylaspartic acid Proteins 0.000 description 3
- 108010047495 alanylglycine Proteins 0.000 description 3
- 108010070783 alanyltyrosine Proteins 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 108010047857 aspartylglycine Proteins 0.000 description 3
- 108010092854 aspartyllysine Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000002771 cell marker Substances 0.000 description 3
- 230000005754 cellular signaling Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 3
- 229960002074 flutamide Drugs 0.000 description 3
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 3
- 108010050475 glycyl-leucyl-tyrosine Proteins 0.000 description 3
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 3
- 108010077515 glycylproline Proteins 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 108010077112 prolyl-proline Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 210000003660 reticulum Anatomy 0.000 description 3
- 108010048818 seryl-histidine Proteins 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 210000001541 thymus gland Anatomy 0.000 description 3
- 108010084932 tryptophyl-proline Proteins 0.000 description 3
- 108010027345 wheylin-1 peptide 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
- JAMAWBXXKFGFGX-KZVJFYERSA-N Ala-Arg-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JAMAWBXXKFGFGX-KZVJFYERSA-N 0.000 description 2
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 2
- VBRDBGCROKWTPV-XHNCKOQMSA-N Ala-Glu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N VBRDBGCROKWTPV-XHNCKOQMSA-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
- 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 2
- XHNLCGXYBXNRIS-BJDJZHNGSA-N Ala-Lys-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XHNLCGXYBXNRIS-BJDJZHNGSA-N 0.000 description 2
- CHFFHQUVXHEGBY-GARJFASQSA-N Ala-Lys-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N CHFFHQUVXHEGBY-GARJFASQSA-N 0.000 description 2
- BFMIRJBURUXDRG-DLOVCJGASA-N Ala-Phe-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 BFMIRJBURUXDRG-DLOVCJGASA-N 0.000 description 2
- IPZQNYYAYVRKKK-FXQIFTODSA-N Ala-Pro-Ala Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IPZQNYYAYVRKKK-FXQIFTODSA-N 0.000 description 2
- OLVCTPPSXNRGKV-GUBZILKMSA-N Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OLVCTPPSXNRGKV-GUBZILKMSA-N 0.000 description 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
- 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 2
- 206010002412 Angiocentric lymphomas Diseases 0.000 description 2
- 102000008102 Ankyrins Human genes 0.000 description 2
- 108010049777 Ankyrins Proteins 0.000 description 2
- NUBPTCMEOCKWDO-DCAQKATOSA-N Arg-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N NUBPTCMEOCKWDO-DCAQKATOSA-N 0.000 description 2
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 2
- DIIGDGJKTMLQQW-IHRRRGAJSA-N Arg-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N DIIGDGJKTMLQQW-IHRRRGAJSA-N 0.000 description 2
- 108010051330 Arg-Pro-Gly-Pro Proteins 0.000 description 2
- ASQKVGRCKOFKIU-KZVJFYERSA-N Arg-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ASQKVGRCKOFKIU-KZVJFYERSA-N 0.000 description 2
- AUZAXCPWMDBWEE-HJGDQZAQSA-N Arg-Thr-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O AUZAXCPWMDBWEE-HJGDQZAQSA-N 0.000 description 2
- CPTXATAOUQJQRO-GUBZILKMSA-N Arg-Val-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O CPTXATAOUQJQRO-GUBZILKMSA-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
- HUZGPXBILPMCHM-IHRRRGAJSA-N Asn-Arg-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HUZGPXBILPMCHM-IHRRRGAJSA-N 0.000 description 2
- DXVMJJNAOVECBA-WHFBIAKZSA-N Asn-Gly-Asn Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O DXVMJJNAOVECBA-WHFBIAKZSA-N 0.000 description 2
- IICZCLFBILYRCU-WHFBIAKZSA-N Asn-Gly-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IICZCLFBILYRCU-WHFBIAKZSA-N 0.000 description 2
- JLNFZLNDHONLND-GARJFASQSA-N Asn-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N JLNFZLNDHONLND-GARJFASQSA-N 0.000 description 2
- LSJQOMAZIKQMTJ-SRVKXCTJSA-N Asn-Phe-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O LSJQOMAZIKQMTJ-SRVKXCTJSA-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
- MYTHOBCLNIOFBL-SRVKXCTJSA-N Asn-Ser-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MYTHOBCLNIOFBL-SRVKXCTJSA-N 0.000 description 2
- SLHOOKXYTYAJGQ-XVYDVKMFSA-N Asp-Ala-His Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 SLHOOKXYTYAJGQ-XVYDVKMFSA-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
- QQXOYLWJQUPXJU-WHFBIAKZSA-N Asp-Cys-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O QQXOYLWJQUPXJU-WHFBIAKZSA-N 0.000 description 2
- GISFCCXBVJKGEO-QEJZJMRPSA-N Asp-Glu-Trp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O GISFCCXBVJKGEO-QEJZJMRPSA-N 0.000 description 2
- PZXPWHFYZXTFBI-YUMQZZPRSA-N Asp-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O PZXPWHFYZXTFBI-YUMQZZPRSA-N 0.000 description 2
- UZNSWMFLKVKJLI-VHWLVUOQSA-N Asp-Ile-Trp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O UZNSWMFLKVKJLI-VHWLVUOQSA-N 0.000 description 2
- RQHLMGCXCZUOGT-ZPFDUUQYSA-N Asp-Leu-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RQHLMGCXCZUOGT-ZPFDUUQYSA-N 0.000 description 2
- 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 2
- HJZLUGQGJWXJCJ-CIUDSAMLSA-N Asp-Pro-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJZLUGQGJWXJCJ-CIUDSAMLSA-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
- 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 2
- WOKXEQLPBLLWHC-IHRRRGAJSA-N Asp-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 WOKXEQLPBLLWHC-IHRRRGAJSA-N 0.000 description 2
- XWKPSMRPIKKDDU-RCOVLWMOSA-N Asp-Val-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O XWKPSMRPIKKDDU-RCOVLWMOSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- HHABWQIFXZPZCK-ACZMJKKPSA-N Cys-Gln-Ser Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CS)N HHABWQIFXZPZCK-ACZMJKKPSA-N 0.000 description 2
- SRIRHERUAMYIOQ-CIUDSAMLSA-N Cys-Leu-Ser Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O SRIRHERUAMYIOQ-CIUDSAMLSA-N 0.000 description 2
- 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 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229910052693 Europium Inorganic materials 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- LLQPHQFNMLZJMP-UHFFFAOYSA-N Fentrazamide Chemical compound N1=NN(C=2C(=CC=CC=2)Cl)C(=O)N1C(=O)N(CC)C1CCCCC1 LLQPHQFNMLZJMP-UHFFFAOYSA-N 0.000 description 2
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 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
- CKNUKHBRCSMKMO-XHNCKOQMSA-N Gln-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O CKNUKHBRCSMKMO-XHNCKOQMSA-N 0.000 description 2
- CRRFJBGUGNNOCS-PEFMBERDSA-N Gln-Asp-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O CRRFJBGUGNNOCS-PEFMBERDSA-N 0.000 description 2
- 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 2
- 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 2
- OACQOWPRWGNKTP-AVGNSLFASA-N Gln-Tyr-Asp 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](CC(O)=O)C(O)=O OACQOWPRWGNKTP-AVGNSLFASA-N 0.000 description 2
- FTMLQFPULNGION-ZVZYQTTQSA-N Gln-Val-Trp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O FTMLQFPULNGION-ZVZYQTTQSA-N 0.000 description 2
- WZZSKAJIHTUUSG-ACZMJKKPSA-N Glu-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O WZZSKAJIHTUUSG-ACZMJKKPSA-N 0.000 description 2
- 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 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
- BUAKRRKDHSSIKK-IHRRRGAJSA-N Glu-Glu-Tyr Chemical compound OC(=O)CC[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 BUAKRRKDHSSIKK-IHRRRGAJSA-N 0.000 description 2
- LRPXYSGPOBVBEH-IUCAKERBSA-N Glu-Gly-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O LRPXYSGPOBVBEH-IUCAKERBSA-N 0.000 description 2
- HMJULNMJWOZNFI-XHNCKOQMSA-N Glu-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N)C(=O)O HMJULNMJWOZNFI-XHNCKOQMSA-N 0.000 description 2
- MLILEEIVMRUYBX-NHCYSSNCSA-N Glu-Val-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O MLILEEIVMRUYBX-NHCYSSNCSA-N 0.000 description 2
- MZZSCEANQDPJER-ONGXEEELSA-N Gly-Ala-Phe Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MZZSCEANQDPJER-ONGXEEELSA-N 0.000 description 2
- QIZJOTQTCAGKPU-KWQFWETISA-N Gly-Ala-Tyr Chemical compound [NH3+]CC(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 QIZJOTQTCAGKPU-KWQFWETISA-N 0.000 description 2
- JRDYDYXZKFNNRQ-XPUUQOCRSA-N Gly-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN JRDYDYXZKFNNRQ-XPUUQOCRSA-N 0.000 description 2
- UPOJUWHGMDJUQZ-IUCAKERBSA-N Gly-Arg-Arg Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UPOJUWHGMDJUQZ-IUCAKERBSA-N 0.000 description 2
- CLODWIOAKCSBAN-BQBZGAKWSA-N Gly-Arg-Asp Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(O)=O)C(O)=O CLODWIOAKCSBAN-BQBZGAKWSA-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
- HQRHFUYMGCHHJS-LURJTMIESA-N Gly-Gly-Arg Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N HQRHFUYMGCHHJS-LURJTMIESA-N 0.000 description 2
- AAHSHTLISQUZJL-QSFUFRPTSA-N Gly-Ile-Ile Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AAHSHTLISQUZJL-QSFUFRPTSA-N 0.000 description 2
- 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 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
- ZWRDOVYMQAAISL-UWVGGRQHSA-N Gly-Met-Lys Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCCN ZWRDOVYMQAAISL-UWVGGRQHSA-N 0.000 description 2
- IBYOLNARKHMLBG-WHOFXGATSA-N Gly-Phe-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IBYOLNARKHMLBG-WHOFXGATSA-N 0.000 description 2
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-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
- VNNRLUNBJSWZPF-ZKWXMUAHSA-N Gly-Ser-Ile Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNNRLUNBJSWZPF-ZKWXMUAHSA-N 0.000 description 2
- DNAZKGFYFRGZIH-QWRGUYRKSA-N Gly-Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 DNAZKGFYFRGZIH-QWRGUYRKSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- VIJMRAIWYWRXSR-CIUDSAMLSA-N His-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CN=CN1 VIJMRAIWYWRXSR-CIUDSAMLSA-N 0.000 description 2
- FFKJUTZARGRVTH-KKUMJFAQSA-N His-Ser-Tyr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O FFKJUTZARGRVTH-KKUMJFAQSA-N 0.000 description 2
- JGFWUKYIQAEYAH-DCAQKATOSA-N His-Ser-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JGFWUKYIQAEYAH-DCAQKATOSA-N 0.000 description 2
- 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 2
- FOCSWPCHUDVNLP-PMVMPFDFSA-N His-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](CC4=CN=CN4)N FOCSWPCHUDVNLP-PMVMPFDFSA-N 0.000 description 2
- SYPULFZAGBBIOM-GVXVVHGQSA-N His-Val-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N SYPULFZAGBBIOM-GVXVVHGQSA-N 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 2
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- CYHYBSGMHMHKOA-CIQUZCHMSA-N Ile-Ala-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N CYHYBSGMHMHKOA-CIQUZCHMSA-N 0.000 description 2
- YBJWJQQBWRARLT-KBIXCLLPSA-N Ile-Gln-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O YBJWJQQBWRARLT-KBIXCLLPSA-N 0.000 description 2
- FUOYNOXRWPJPAN-QEWYBTABSA-N Ile-Glu-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N FUOYNOXRWPJPAN-QEWYBTABSA-N 0.000 description 2
- GLYJPWIRLBAIJH-UHFFFAOYSA-N Ile-Lys-Pro Natural products CCC(C)C(N)C(=O)NC(CCCCN)C(=O)N1CCCC1C(O)=O GLYJPWIRLBAIJH-UHFFFAOYSA-N 0.000 description 2
- SHVFUCSSACPBTF-VGDYDELISA-N Ile-Ser-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N SHVFUCSSACPBTF-VGDYDELISA-N 0.000 description 2
- WKSHBPRUIRGWRZ-KCTSRDHCSA-N Ile-Trp-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)NCC(=O)O)N WKSHBPRUIRGWRZ-KCTSRDHCSA-N 0.000 description 2
- JZBVBOKASHNXAD-NAKRPEOUSA-N Ile-Val-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N JZBVBOKASHNXAD-NAKRPEOUSA-N 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 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 2
- VCSBGUACOYUIGD-CIUDSAMLSA-N Leu-Asn-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VCSBGUACOYUIGD-CIUDSAMLSA-N 0.000 description 2
- JKGHDYGZRDWHGA-SRVKXCTJSA-N Leu-Asn-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JKGHDYGZRDWHGA-SRVKXCTJSA-N 0.000 description 2
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 2
- 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 2
- BOFAFKVZQUMTID-AVGNSLFASA-N Leu-Gln-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N BOFAFKVZQUMTID-AVGNSLFASA-N 0.000 description 2
- CIVKXGPFXDIQBV-WDCWCFNPSA-N Leu-Gln-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CIVKXGPFXDIQBV-WDCWCFNPSA-N 0.000 description 2
- 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 2
- ZFNLIDNJUWNIJL-WDCWCFNPSA-N Leu-Glu-Thr 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)O)C(O)=O ZFNLIDNJUWNIJL-WDCWCFNPSA-N 0.000 description 2
- MPSBSKHOWJQHBS-IHRRRGAJSA-N Leu-His-Met Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCSC)C(=O)O)N MPSBSKHOWJQHBS-IHRRRGAJSA-N 0.000 description 2
- 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 2
- 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 2
- RGUXWMDNCPMQFB-YUMQZZPRSA-N Leu-Ser-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RGUXWMDNCPMQFB-YUMQZZPRSA-N 0.000 description 2
- HWMQRQIFVGEAPH-XIRDDKMYSA-N Leu-Ser-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 HWMQRQIFVGEAPH-XIRDDKMYSA-N 0.000 description 2
- WUHBLPVELFTPQK-KKUMJFAQSA-N Leu-Tyr-Asn 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](CC(N)=O)C(O)=O WUHBLPVELFTPQK-KKUMJFAQSA-N 0.000 description 2
- 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 2
- LMDVGHQPPPLYAR-IHRRRGAJSA-N Leu-Val-His Chemical compound N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O LMDVGHQPPPLYAR-IHRRRGAJSA-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
- 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 2
- ULUQBUKAPDUKOC-GVXVVHGQSA-N Lys-Glu-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O ULUQBUKAPDUKOC-GVXVVHGQSA-N 0.000 description 2
- 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 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
- 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 2
- 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 2
- QVTDVTONTRSQMF-WDCWCFNPSA-N Lys-Thr-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CCCCN QVTDVTONTRSQMF-WDCWCFNPSA-N 0.000 description 2
- 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 2
- OXHSZBRPUGNMKW-DCAQKATOSA-N Met-Gln-Arg Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OXHSZBRPUGNMKW-DCAQKATOSA-N 0.000 description 2
- UOENBSHXYCHSAU-YUMQZZPRSA-N Met-Gln-Gly Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O UOENBSHXYCHSAU-YUMQZZPRSA-N 0.000 description 2
- UZWMJZSOXGOVIN-LURJTMIESA-N Met-Gly-Gly Chemical compound CSCC[C@H](N)C(=O)NCC(=O)NCC(O)=O UZWMJZSOXGOVIN-LURJTMIESA-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
- 102100034256 Mucin-1 Human genes 0.000 description 2
- 108010008707 Mucin-1 Proteins 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- YMORXCKTSSGYIG-IHRRRGAJSA-N Phe-Arg-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N YMORXCKTSSGYIG-IHRRRGAJSA-N 0.000 description 2
- ZWJKVFAYPLPCQB-UNQGMJICSA-N Phe-Arg-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O ZWJKVFAYPLPCQB-UNQGMJICSA-N 0.000 description 2
- IUVYJBMTHARMIP-PCBIJLKTSA-N Phe-Asp-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O IUVYJBMTHARMIP-PCBIJLKTSA-N 0.000 description 2
- 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 2
- YFXXRYFWJFQAFW-JHYOHUSXSA-N Phe-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=CC=C1)N)O YFXXRYFWJFQAFW-JHYOHUSXSA-N 0.000 description 2
- ZVJGAXNBBKPYOE-HKUYNNGSSA-N Phe-Trp-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(O)=O)C1=CC=CC=C1 ZVJGAXNBBKPYOE-HKUYNNGSSA-N 0.000 description 2
- IEIFEYBAYFSRBQ-IHRRRGAJSA-N Phe-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N IEIFEYBAYFSRBQ-IHRRRGAJSA-N 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- LCRSGSIRKLXZMZ-BPNCWPANSA-N Pro-Ala-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LCRSGSIRKLXZMZ-BPNCWPANSA-N 0.000 description 2
- LNLNHXIQPGKRJQ-SRVKXCTJSA-N Pro-Arg-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1 LNLNHXIQPGKRJQ-SRVKXCTJSA-N 0.000 description 2
- 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 2
- 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 2
- DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 2
- MRYUJHGPZQNOAD-IHRRRGAJSA-N Pro-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 MRYUJHGPZQNOAD-IHRRRGAJSA-N 0.000 description 2
- LEIKGVHQTKHOLM-IUCAKERBSA-N Pro-Pro-Gly Chemical compound OC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 LEIKGVHQTKHOLM-IUCAKERBSA-N 0.000 description 2
- 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 2
- 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 2
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 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 2
- HBOABDXGTMMDSE-GUBZILKMSA-N Ser-Arg-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O HBOABDXGTMMDSE-GUBZILKMSA-N 0.000 description 2
- FIDMVVBUOCMMJG-CIUDSAMLSA-N Ser-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO FIDMVVBUOCMMJG-CIUDSAMLSA-N 0.000 description 2
- 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 2
- BLPYXIXXCFVIIF-FXQIFTODSA-N Ser-Cys-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N)CN=C(N)N BLPYXIXXCFVIIF-FXQIFTODSA-N 0.000 description 2
- SQBLRDDJTUJDMV-ACZMJKKPSA-N Ser-Glu-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O SQBLRDDJTUJDMV-ACZMJKKPSA-N 0.000 description 2
- 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 2
- BRGQQXQKPUCUJQ-KBIXCLLPSA-N Ser-Glu-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BRGQQXQKPUCUJQ-KBIXCLLPSA-N 0.000 description 2
- 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 2
- 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 2
- SFTZTYBXIXLRGQ-JBDRJPRFSA-N Ser-Ile-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O SFTZTYBXIXLRGQ-JBDRJPRFSA-N 0.000 description 2
- 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 2
- NNFMANHDYSVNIO-DCAQKATOSA-N Ser-Lys-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NNFMANHDYSVNIO-DCAQKATOSA-N 0.000 description 2
- FLONGDPORFIVQW-XGEHTFHBSA-N Ser-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FLONGDPORFIVQW-XGEHTFHBSA-N 0.000 description 2
- 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 2
- WLJPJRGQRNCIQS-ZLUOBGJFSA-N Ser-Ser-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O WLJPJRGQRNCIQS-ZLUOBGJFSA-N 0.000 description 2
- 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 2
- VVKVHAOOUGNDPJ-SRVKXCTJSA-N Ser-Tyr-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O VVKVHAOOUGNDPJ-SRVKXCTJSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 208000037913 T-cell disorder Diseases 0.000 description 2
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 2
- CEXFELBFVHLYDZ-XGEHTFHBSA-N Thr-Arg-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CEXFELBFVHLYDZ-XGEHTFHBSA-N 0.000 description 2
- 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 2
- WLDUCKSCDRIVLJ-NUMRIWBASA-N Thr-Gln-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O WLDUCKSCDRIVLJ-NUMRIWBASA-N 0.000 description 2
- ZTPXSEUVYNNZRB-CDMKHQONSA-N Thr-Gly-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ZTPXSEUVYNNZRB-CDMKHQONSA-N 0.000 description 2
- YUPVPKZBKCLFLT-QTKMDUPCSA-N Thr-His-Val Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N)O YUPVPKZBKCLFLT-QTKMDUPCSA-N 0.000 description 2
- ADPHPKGWVDHWML-PPCPHDFISA-N Thr-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]([C@@H](C)O)N ADPHPKGWVDHWML-PPCPHDFISA-N 0.000 description 2
- MECLEFZMPPOEAC-VOAKCMCISA-N Thr-Leu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MECLEFZMPPOEAC-VOAKCMCISA-N 0.000 description 2
- GUHLYMZJVXUIPO-RCWTZXSCSA-N Thr-Met-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(O)=O GUHLYMZJVXUIPO-RCWTZXSCSA-N 0.000 description 2
- XIHGJKFSIDTDKV-LYARXQMPSA-N Thr-Phe-Trp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O XIHGJKFSIDTDKV-LYARXQMPSA-N 0.000 description 2
- 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 2
- DEGCBBCMYWNJNA-RHYQMDGZSA-N Thr-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)[C@@H](C)O DEGCBBCMYWNJNA-RHYQMDGZSA-N 0.000 description 2
- IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 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
- 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 2
- 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 2
- 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 2
- HQJOVVWAPQPYDS-ZFWWWQNUSA-N Trp-Gly-Arg Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQJOVVWAPQPYDS-ZFWWWQNUSA-N 0.000 description 2
- KXFYAQUYJKOQMI-QEJZJMRPSA-N Trp-Ser-Gln Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O)=CNC2=C1 KXFYAQUYJKOQMI-QEJZJMRPSA-N 0.000 description 2
- UIRVSEPRMWDVEW-RNXOBYDBSA-N Trp-Tyr-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)N UIRVSEPRMWDVEW-RNXOBYDBSA-N 0.000 description 2
- XKTWZYNTLXITCY-QRTARXTBSA-N Trp-Val-Asn Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)=CNC2=C1 XKTWZYNTLXITCY-QRTARXTBSA-N 0.000 description 2
- 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 2
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 2
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 2
- VCXWRWYFJLXITF-AUTRQRHGSA-N Tyr-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VCXWRWYFJLXITF-AUTRQRHGSA-N 0.000 description 2
- GAYLGYUVTDMLKC-UWJYBYFXSA-N Tyr-Asp-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GAYLGYUVTDMLKC-UWJYBYFXSA-N 0.000 description 2
- CKHQKYHIZCRTAP-SOUVJXGZSA-N Tyr-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O CKHQKYHIZCRTAP-SOUVJXGZSA-N 0.000 description 2
- IMXAAEFAIBRCQF-SIUGBPQLSA-N Tyr-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N IMXAAEFAIBRCQF-SIUGBPQLSA-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
- KCPFDGNYAMKZQP-KBPBESRZSA-N Tyr-Gly-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O KCPFDGNYAMKZQP-KBPBESRZSA-N 0.000 description 2
- 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 2
- XJPXTYLVMUZGNW-IHRRRGAJSA-N Tyr-Pro-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O XJPXTYLVMUZGNW-IHRRRGAJSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- JXGWQYWDUOWQHA-DZKIICNBSA-N Val-Gln-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N JXGWQYWDUOWQHA-DZKIICNBSA-N 0.000 description 2
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- UQMPYVLTQCGRSK-IFFSRLJSSA-N Val-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N)O UQMPYVLTQCGRSK-IFFSRLJSSA-N 0.000 description 2
- JAIZPWVHPQRYOU-ZJDVBMNYSA-N Val-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](C(C)C)N)O JAIZPWVHPQRYOU-ZJDVBMNYSA-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
- AEFJNECXZCODJM-UWVGGRQHSA-N Val-Val-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)NCC([O-])=O AEFJNECXZCODJM-UWVGGRQHSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 229960000548 alemtuzumab Drugs 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 108010004469 allophycocyanin Proteins 0.000 description 2
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 2
- 229960003437 aminoglutethimide Drugs 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- RGHILYZRVFRRNK-UHFFFAOYSA-N anthracene-1,2-dione Chemical class C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 RGHILYZRVFRRNK-UHFFFAOYSA-N 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 108091005948 blue fluorescent proteins Proteins 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 108010060199 cysteinylproline Proteins 0.000 description 2
- 230000002380 cytological effect Effects 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000001066 destructive effect Effects 0.000 description 2
- 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 2
- 238000009826 distribution Methods 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 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 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 102000054766 genetic haplotypes Human genes 0.000 description 2
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 2
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 2
- 108010020688 glycylhistidine Proteins 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000007773 growth pattern Effects 0.000 description 2
- 206010019847 hepatosplenomegaly Diseases 0.000 description 2
- -1 hydroxyurea, methylhydrazine derivatives Chemical class 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000007813 immunodeficiency Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000002602 induced regulatory T cell Anatomy 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000005007 innate immune system Anatomy 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000005024 intraepithelial lymphocyte Anatomy 0.000 description 2
- 108010078274 isoleucylvaline Proteins 0.000 description 2
- 108010053037 kyotorphin Proteins 0.000 description 2
- 108010051673 leucyl-glycyl-phenylalanine Proteins 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 108010009298 lysylglutamic acid Proteins 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 206010029410 night sweats Diseases 0.000 description 2
- 230000036565 night sweats Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 2
- 108010087846 prolyl-prolyl-glycine Proteins 0.000 description 2
- 108010079317 prolyl-tyrosine Proteins 0.000 description 2
- 108010004914 prolylarginine Proteins 0.000 description 2
- 108010090894 prolylleucine Proteins 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 108010054624 red fluorescent protein Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 201000006845 reticulosarcoma Diseases 0.000 description 2
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 238000007480 sanger sequencing Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 108010080629 tryptophan-leucine Proteins 0.000 description 2
- 108010045269 tryptophyltryptophan Proteins 0.000 description 2
- 108010017949 tyrosyl-glycyl-glycine Proteins 0.000 description 2
- 108010051110 tyrosyl-lysine Proteins 0.000 description 2
- 108010077037 tyrosyl-tyrosyl-phenylalanine Proteins 0.000 description 2
- 108010003885 valyl-prolyl-glycyl-glycine Proteins 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- CEHZCZCQHUNAJF-AVGNSLFASA-N (2s)-1-[2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N1[C@H](C(O)=O)CCC1 CEHZCZCQHUNAJF-AVGNSLFASA-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
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- WOJJIRYPFAZEPF-YFKPBYRVSA-N 2-[[(2s)-2-[[2-[(2-azaniumylacetyl)amino]acetyl]amino]propanoyl]amino]acetate Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)CN WOJJIRYPFAZEPF-YFKPBYRVSA-N 0.000 description 1
- IDGZVZJLYFTXSL-UHFFFAOYSA-N 2-[[2-[(2-amino-4-methylpentanoyl)amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound CC(C)CC(N)C(=O)NC(CO)C(=O)NC(C(O)=O)CCCN=C(N)N IDGZVZJLYFTXSL-UHFFFAOYSA-N 0.000 description 1
- QMOQBVOBWVNSNO-UHFFFAOYSA-N 2-[[2-[[2-[(2-azaniumylacetyl)amino]acetyl]amino]acetyl]amino]acetate Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(O)=O QMOQBVOBWVNSNO-UHFFFAOYSA-N 0.000 description 1
- CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 description 1
- 101150023956 ALK gene Proteins 0.000 description 1
- 208000010962 ALK-positive anaplastic large cell lymphoma Diseases 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 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 1
- KQFRUSHJPKXBMB-BHDSKKPTSA-N Ala-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 KQFRUSHJPKXBMB-BHDSKKPTSA-N 0.000 description 1
- DVWVZSJAYIJZFI-FXQIFTODSA-N Ala-Arg-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O DVWVZSJAYIJZFI-FXQIFTODSA-N 0.000 description 1
- FXKNPWNXPQZLES-ZLUOBGJFSA-N Ala-Asn-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O FXKNPWNXPQZLES-ZLUOBGJFSA-N 0.000 description 1
- GSCLWXDNIMNIJE-ZLUOBGJFSA-N Ala-Asp-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O GSCLWXDNIMNIJE-ZLUOBGJFSA-N 0.000 description 1
- 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 1
- WJRXVTCKASUIFF-FXQIFTODSA-N Ala-Cys-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WJRXVTCKASUIFF-FXQIFTODSA-N 0.000 description 1
- LGFCAXJBAZESCF-ACZMJKKPSA-N Ala-Gln-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O LGFCAXJBAZESCF-ACZMJKKPSA-N 0.000 description 1
- PUBLUECXJRHTBK-ACZMJKKPSA-N Ala-Glu-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O PUBLUECXJRHTBK-ACZMJKKPSA-N 0.000 description 1
- 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 1
- VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 1
- BTBUEVAGZCKULD-XPUUQOCRSA-N Ala-Gly-His Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BTBUEVAGZCKULD-XPUUQOCRSA-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
- IVKWMMGFLAMMKJ-XVYDVKMFSA-N Ala-His-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC(=O)N)C(=O)O)N IVKWMMGFLAMMKJ-XVYDVKMFSA-N 0.000 description 1
- NYDBKUNVSALYPX-NAKRPEOUSA-N Ala-Ile-Arg Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NYDBKUNVSALYPX-NAKRPEOUSA-N 0.000 description 1
- AWNAEZICPNGAJK-FXQIFTODSA-N Ala-Met-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(O)=O AWNAEZICPNGAJK-FXQIFTODSA-N 0.000 description 1
- HYIDEIQUCBKIPL-CQDKDKBSSA-N Ala-Phe-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N HYIDEIQUCBKIPL-CQDKDKBSSA-N 0.000 description 1
- RUXQNKVQSKOOBS-JURCDPSOSA-N Ala-Phe-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RUXQNKVQSKOOBS-JURCDPSOSA-N 0.000 description 1
- VQAVBBCZFQAAED-FXQIFTODSA-N Ala-Pro-Asn Chemical compound C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)N)C(=O)O)N VQAVBBCZFQAAED-FXQIFTODSA-N 0.000 description 1
- FFZJHQODAYHGPO-KZVJFYERSA-N Ala-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N FFZJHQODAYHGPO-KZVJFYERSA-N 0.000 description 1
- YHBDGLZYNIARKJ-GUBZILKMSA-N Ala-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N YHBDGLZYNIARKJ-GUBZILKMSA-N 0.000 description 1
- VJVQKGYHIZPSNS-FXQIFTODSA-N Ala-Ser-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N VJVQKGYHIZPSNS-FXQIFTODSA-N 0.000 description 1
- DYXOFPBJBAHWFY-JBDRJPRFSA-N Ala-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N DYXOFPBJBAHWFY-JBDRJPRFSA-N 0.000 description 1
- MMLHRUJLOUSRJX-CIUDSAMLSA-N Ala-Ser-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN MMLHRUJLOUSRJX-CIUDSAMLSA-N 0.000 description 1
- 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 1
- 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 1
- SYIFFFHSXBNPMC-UWJYBYFXSA-N Ala-Ser-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N SYIFFFHSXBNPMC-UWJYBYFXSA-N 0.000 description 1
- VNFSAYFQLXPHPY-CIQUZCHMSA-N Ala-Thr-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNFSAYFQLXPHPY-CIQUZCHMSA-N 0.000 description 1
- SAHQGRZIQVEJPF-JXUBOQSCSA-N Ala-Thr-Lys Chemical compound C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN SAHQGRZIQVEJPF-JXUBOQSCSA-N 0.000 description 1
- KTXKIYXZQFWJKB-VZFHVOOUSA-N Ala-Thr-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O KTXKIYXZQFWJKB-VZFHVOOUSA-N 0.000 description 1
- MTDDMSUUXNQMKK-BPNCWPANSA-N Ala-Tyr-Arg Chemical compound C[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 MTDDMSUUXNQMKK-BPNCWPANSA-N 0.000 description 1
- QRIYOHQJRDHFKF-UWJYBYFXSA-N Ala-Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 QRIYOHQJRDHFKF-UWJYBYFXSA-N 0.000 description 1
- JPOQZCHGOTWRTM-FQPOAREZSA-N Ala-Tyr-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JPOQZCHGOTWRTM-FQPOAREZSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- SGYSTDWPNPKJPP-GUBZILKMSA-N Arg-Ala-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SGYSTDWPNPKJPP-GUBZILKMSA-N 0.000 description 1
- KWKQGHSSNHPGOW-BQBZGAKWSA-N Arg-Ala-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(O)=O KWKQGHSSNHPGOW-BQBZGAKWSA-N 0.000 description 1
- YFWTXMRJJDNTLM-LSJOCFKGSA-N Arg-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N YFWTXMRJJDNTLM-LSJOCFKGSA-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
- 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 1
- XPSGESXVBSQZPL-SRVKXCTJSA-N Arg-Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XPSGESXVBSQZPL-SRVKXCTJSA-N 0.000 description 1
- HJVGMOYJDDXLMI-AVGNSLFASA-N Arg-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CCCNC(N)=N HJVGMOYJDDXLMI-AVGNSLFASA-N 0.000 description 1
- OVVUNXXROOFSIM-SDDRHHMPSA-N Arg-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O OVVUNXXROOFSIM-SDDRHHMPSA-N 0.000 description 1
- XVLLUZMFSAYKJV-GUBZILKMSA-N Arg-Asp-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XVLLUZMFSAYKJV-GUBZILKMSA-N 0.000 description 1
- DXQIQUIQYAGRCC-CIUDSAMLSA-N Arg-Asp-Gln Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)CN=C(N)N DXQIQUIQYAGRCC-CIUDSAMLSA-N 0.000 description 1
- TTXYKSADPSNOIF-IHRRRGAJSA-N Arg-Asp-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O TTXYKSADPSNOIF-IHRRRGAJSA-N 0.000 description 1
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 1
- YSUVMPICYVWRBX-VEVYYDQMSA-N Arg-Asp-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O YSUVMPICYVWRBX-VEVYYDQMSA-N 0.000 description 1
- PNQWAUXQDBIJDY-GUBZILKMSA-N Arg-Glu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNQWAUXQDBIJDY-GUBZILKMSA-N 0.000 description 1
- HQIZDMIGUJOSNI-IUCAKERBSA-N Arg-Gly-Arg Chemical compound N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQIZDMIGUJOSNI-IUCAKERBSA-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
- SYAUZLVLXCDRSH-IUCAKERBSA-N Arg-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N SYAUZLVLXCDRSH-IUCAKERBSA-N 0.000 description 1
- WVNFNPGXYADPPO-BQBZGAKWSA-N Arg-Gly-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O WVNFNPGXYADPPO-BQBZGAKWSA-N 0.000 description 1
- 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 1
- MSILNNHVVMMTHZ-UWVGGRQHSA-N Arg-His-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CN=CN1 MSILNNHVVMMTHZ-UWVGGRQHSA-N 0.000 description 1
- UAOSDDXCTBIPCA-QXEWZRGKSA-N Arg-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UAOSDDXCTBIPCA-QXEWZRGKSA-N 0.000 description 1
- SSZGOKWBHLOCHK-DCAQKATOSA-N Arg-Lys-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N SSZGOKWBHLOCHK-DCAQKATOSA-N 0.000 description 1
- GSUFZRURORXYTM-STQMWFEESA-N Arg-Phe-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 GSUFZRURORXYTM-STQMWFEESA-N 0.000 description 1
- XSPKAHFVDKRGRL-DCAQKATOSA-N Arg-Pro-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XSPKAHFVDKRGRL-DCAQKATOSA-N 0.000 description 1
- YCYXHLZRUSJITQ-SRVKXCTJSA-N Arg-Pro-Pro Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 YCYXHLZRUSJITQ-SRVKXCTJSA-N 0.000 description 1
- KXOPYFNQLVUOAQ-FXQIFTODSA-N Arg-Ser-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KXOPYFNQLVUOAQ-FXQIFTODSA-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
- OGZBJJLRKQZRHL-KJEVXHAQSA-N Arg-Thr-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OGZBJJLRKQZRHL-KJEVXHAQSA-N 0.000 description 1
- PYDIIVKGTBRIEL-SZMVWBNQSA-N Arg-Trp-Pro Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(O)=O PYDIIVKGTBRIEL-SZMVWBNQSA-N 0.000 description 1
- NVPHRWNWTKYIST-BPNCWPANSA-N Arg-Tyr-Ala Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=C(O)C=C1 NVPHRWNWTKYIST-BPNCWPANSA-N 0.000 description 1
- WOZDCBHUGJVJPL-AVGNSLFASA-N Arg-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N WOZDCBHUGJVJPL-AVGNSLFASA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- AKEBUSZTMQLNIX-UWJYBYFXSA-N Asn-Ala-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N AKEBUSZTMQLNIX-UWJYBYFXSA-N 0.000 description 1
- 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 1
- JJGRJMKUOYXZRA-LPEHRKFASA-N Asn-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)N)N)C(=O)O JJGRJMKUOYXZRA-LPEHRKFASA-N 0.000 description 1
- 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 1
- FANGHKQYFPYDNB-UBHSHLNASA-N Asn-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](CC(=O)N)N FANGHKQYFPYDNB-UBHSHLNASA-N 0.000 description 1
- PAXHINASXXXILC-SRVKXCTJSA-N Asn-Asp-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N)O PAXHINASXXXILC-SRVKXCTJSA-N 0.000 description 1
- WPOLSNAQGVHROR-GUBZILKMSA-N Asn-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)N WPOLSNAQGVHROR-GUBZILKMSA-N 0.000 description 1
- JREOBWLIZLXRIS-GUBZILKMSA-N Asn-Glu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JREOBWLIZLXRIS-GUBZILKMSA-N 0.000 description 1
- HYQYLOSCICEYTR-YUMQZZPRSA-N Asn-Gly-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O HYQYLOSCICEYTR-YUMQZZPRSA-N 0.000 description 1
- 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 1
- JQSWHKKUZMTOIH-QWRGUYRKSA-N Asn-Gly-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N JQSWHKKUZMTOIH-QWRGUYRKSA-N 0.000 description 1
- ZTRJUKDEALVRMW-SRVKXCTJSA-N Asn-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](CC(=O)N)N ZTRJUKDEALVRMW-SRVKXCTJSA-N 0.000 description 1
- AITGTTNYKAWKDR-CIUDSAMLSA-N Asn-His-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O AITGTTNYKAWKDR-CIUDSAMLSA-N 0.000 description 1
- JRCASHGTXZYSPW-XIRDDKMYSA-N Asn-His-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC3=CN=CN3)NC(=O)[C@H](CC(=O)N)N JRCASHGTXZYSPW-XIRDDKMYSA-N 0.000 description 1
- NVWJMQNYLYWVNQ-BYULHYEWSA-N Asn-Ile-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O NVWJMQNYLYWVNQ-BYULHYEWSA-N 0.000 description 1
- 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 1
- MYCSPQIARXTUTP-SRVKXCTJSA-N Asn-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(=O)N)N MYCSPQIARXTUTP-SRVKXCTJSA-N 0.000 description 1
- 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 1
- LZLCLRQMUQWUHJ-GUBZILKMSA-N Asn-Lys-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N LZLCLRQMUQWUHJ-GUBZILKMSA-N 0.000 description 1
- VITDJIPIJZAVGC-VEVYYDQMSA-N Asn-Met-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VITDJIPIJZAVGC-VEVYYDQMSA-N 0.000 description 1
- YUUIAUXBNOHFRJ-IHRRRGAJSA-N Asn-Phe-Met Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(O)=O YUUIAUXBNOHFRJ-IHRRRGAJSA-N 0.000 description 1
- YRTOMUMWSTUQAX-FXQIFTODSA-N Asn-Pro-Asp Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O YRTOMUMWSTUQAX-FXQIFTODSA-N 0.000 description 1
- XMHFCUKJRCQXGI-CIUDSAMLSA-N Asn-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O XMHFCUKJRCQXGI-CIUDSAMLSA-N 0.000 description 1
- 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 1
- VLDRQOHCMKCXLY-SRVKXCTJSA-N Asn-Ser-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O VLDRQOHCMKCXLY-SRVKXCTJSA-N 0.000 description 1
- XHTUGJCAEYOZOR-UBHSHLNASA-N Asn-Ser-Trp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O XHTUGJCAEYOZOR-UBHSHLNASA-N 0.000 description 1
- NCXTYSVDWLAQGZ-ZKWXMUAHSA-N Asn-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O NCXTYSVDWLAQGZ-ZKWXMUAHSA-N 0.000 description 1
- 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 1
- HCZQKHSRYHCPSD-IUKAMOBKSA-N Asn-Thr-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HCZQKHSRYHCPSD-IUKAMOBKSA-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
- 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 1
- DAYDURRBMDCCFL-AAEUAGOBSA-N Asn-Trp-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(=O)N)N DAYDURRBMDCCFL-AAEUAGOBSA-N 0.000 description 1
- RDLYUKRPEJERMM-XIRDDKMYSA-N Asn-Trp-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(O)=O RDLYUKRPEJERMM-XIRDDKMYSA-N 0.000 description 1
- CPYHLXSGDBDULY-IHPCNDPISA-N Asn-Trp-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O CPYHLXSGDBDULY-IHPCNDPISA-N 0.000 description 1
- KSZHWTRZPOTIGY-AVGNSLFASA-N Asn-Tyr-Gln Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O KSZHWTRZPOTIGY-AVGNSLFASA-N 0.000 description 1
- QUCCLIXMVPIVOB-BZSNNMDCSA-N Asn-Tyr-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC(=O)N)N QUCCLIXMVPIVOB-BZSNNMDCSA-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
- DPSUVAPLRQDWAO-YDHLFZDLSA-N Asn-Tyr-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(=O)N)N DPSUVAPLRQDWAO-YDHLFZDLSA-N 0.000 description 1
- JNCRAQVYJZGIOW-QSFUFRPTSA-N Asn-Val-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JNCRAQVYJZGIOW-QSFUFRPTSA-N 0.000 description 1
- 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 1
- WQAOZCVOOYUWKG-LSJOCFKGSA-N Asn-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CC(=O)N)N WQAOZCVOOYUWKG-LSJOCFKGSA-N 0.000 description 1
- WSWYMRLTJVKRCE-ZLUOBGJFSA-N Asp-Ala-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O WSWYMRLTJVKRCE-ZLUOBGJFSA-N 0.000 description 1
- PBVLJOIPOGUQQP-CIUDSAMLSA-N Asp-Ala-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O PBVLJOIPOGUQQP-CIUDSAMLSA-N 0.000 description 1
- NECWUSYTYSIFNC-DLOVCJGASA-N Asp-Ala-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 NECWUSYTYSIFNC-DLOVCJGASA-N 0.000 description 1
- VBVKSAFJPVXMFJ-CIUDSAMLSA-N Asp-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N VBVKSAFJPVXMFJ-CIUDSAMLSA-N 0.000 description 1
- XACXDSRQIXRMNS-OLHMAJIHSA-N Asp-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N)O XACXDSRQIXRMNS-OLHMAJIHSA-N 0.000 description 1
- RYEWQKQXRJCHIO-SRVKXCTJSA-N Asp-Asn-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 RYEWQKQXRJCHIO-SRVKXCTJSA-N 0.000 description 1
- FANQWNCPNFEPGZ-WHFBIAKZSA-N Asp-Asp-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O FANQWNCPNFEPGZ-WHFBIAKZSA-N 0.000 description 1
- BFOYULZBKYOKAN-OLHMAJIHSA-N Asp-Asp-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BFOYULZBKYOKAN-OLHMAJIHSA-N 0.000 description 1
- NYQHSUGFEWDWPD-ACZMJKKPSA-N Asp-Gln-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N NYQHSUGFEWDWPD-ACZMJKKPSA-N 0.000 description 1
- RSMIHCFQDCVVBR-CIUDSAMLSA-N Asp-Gln-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N RSMIHCFQDCVVBR-CIUDSAMLSA-N 0.000 description 1
- JRBVWZLHBGYZNY-QEJZJMRPSA-N Asp-Gln-Trp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O JRBVWZLHBGYZNY-QEJZJMRPSA-N 0.000 description 1
- XJQRWGXKUSDEFI-ACZMJKKPSA-N Asp-Glu-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O XJQRWGXKUSDEFI-ACZMJKKPSA-N 0.000 description 1
- YDJVIBMKAMQPPP-LAEOZQHASA-N Asp-Glu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O YDJVIBMKAMQPPP-LAEOZQHASA-N 0.000 description 1
- OMMIEVATLAGRCK-BYPYZUCNSA-N Asp-Gly-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)NCC(O)=O OMMIEVATLAGRCK-BYPYZUCNSA-N 0.000 description 1
- 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
- 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 1
- CRNKLABLTICXDV-GUBZILKMSA-N Asp-His-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N CRNKLABLTICXDV-GUBZILKMSA-N 0.000 description 1
- SWTQDYFZVOJVLL-KKUMJFAQSA-N Asp-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)O)N)O SWTQDYFZVOJVLL-KKUMJFAQSA-N 0.000 description 1
- 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
- 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 1
- UJGRZQYSNYTCAX-SRVKXCTJSA-N Asp-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UJGRZQYSNYTCAX-SRVKXCTJSA-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
- LBOVBQONZJRWPV-YUMQZZPRSA-N Asp-Lys-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O LBOVBQONZJRWPV-YUMQZZPRSA-N 0.000 description 1
- FQHBAQLBIXLWAG-DCAQKATOSA-N Asp-Lys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N FQHBAQLBIXLWAG-DCAQKATOSA-N 0.000 description 1
- YWLDTBBUHZJQHW-KKUMJFAQSA-N Asp-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N YWLDTBBUHZJQHW-KKUMJFAQSA-N 0.000 description 1
- 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 1
- QJHOOKBAHRJPPX-QWRGUYRKSA-N Asp-Phe-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 QJHOOKBAHRJPPX-QWRGUYRKSA-N 0.000 description 1
- HICVMZCGVFKTPM-BQBZGAKWSA-N Asp-Pro-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HICVMZCGVFKTPM-BQBZGAKWSA-N 0.000 description 1
- UAXIKORUDGGIGA-DCAQKATOSA-N Asp-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CCCCN)C(=O)O UAXIKORUDGGIGA-DCAQKATOSA-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
- KGHLGJAXYSVNJP-WHFBIAKZSA-N Asp-Ser-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O KGHLGJAXYSVNJP-WHFBIAKZSA-N 0.000 description 1
- DRCOAZZDQRCGGP-GHCJXIJMSA-N Asp-Ser-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DRCOAZZDQRCGGP-GHCJXIJMSA-N 0.000 description 1
- HRVQDZOWMLFAOD-BIIVOSGPSA-N Asp-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N)C(=O)O HRVQDZOWMLFAOD-BIIVOSGPSA-N 0.000 description 1
- XYPJXLLXNSAWHZ-SRVKXCTJSA-N Asp-Ser-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XYPJXLLXNSAWHZ-SRVKXCTJSA-N 0.000 description 1
- MJJIHRWNWSQTOI-VEVYYDQMSA-N Asp-Thr-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O MJJIHRWNWSQTOI-VEVYYDQMSA-N 0.000 description 1
- JJQGZGOEDSSHTE-FOHZUACHSA-N Asp-Thr-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O JJQGZGOEDSSHTE-FOHZUACHSA-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
- 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 1
- CXEFNHOVIIDHFU-IHPCNDPISA-N Asp-Trp-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CC(=O)O)N CXEFNHOVIIDHFU-IHPCNDPISA-N 0.000 description 1
- 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 1
- GIKOVDMXBAFXDF-NHCYSSNCSA-N Asp-Val-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GIKOVDMXBAFXDF-NHCYSSNCSA-N 0.000 description 1
- JGLWFWXGOINXEA-YDHLFZDLSA-N Asp-Val-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 JGLWFWXGOINXEA-YDHLFZDLSA-N 0.000 description 1
- ZUNMTUPRQMWMHX-LSJOCFKGSA-N Asp-Val-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O ZUNMTUPRQMWMHX-LSJOCFKGSA-N 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 101100136076 Aspergillus oryzae (strain ATCC 42149 / RIB 40) pel1 gene Proteins 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- DUZCMUMEHMNJCX-HAMGIEOISA-N C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1.C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1.C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 DUZCMUMEHMNJCX-HAMGIEOISA-N 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 210000003967 CLP Anatomy 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 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 1
- SFRQEQGPRTVDPO-NRPADANISA-N Cys-Gln-Val Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O SFRQEQGPRTVDPO-NRPADANISA-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
- PGBLJHDDKCVSTC-CIUDSAMLSA-N Cys-Met-Gln Chemical compound CSCC[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O PGBLJHDDKCVSTC-CIUDSAMLSA-N 0.000 description 1
- ZGERHCJBLPQPGV-ACZMJKKPSA-N Cys-Ser-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N ZGERHCJBLPQPGV-ACZMJKKPSA-N 0.000 description 1
- YWEHYKGJWHPGPY-XGEHTFHBSA-N Cys-Thr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N)O YWEHYKGJWHPGPY-XGEHTFHBSA-N 0.000 description 1
- PCRVDEANNSYGTA-IHRRRGAJSA-N Cys-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CS)CC1=CC=C(O)C=C1 PCRVDEANNSYGTA-IHRRRGAJSA-N 0.000 description 1
- 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 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 102100032620 Cytotoxic granule associated RNA binding protein TIA1 Human genes 0.000 description 1
- 101710086368 Cytotoxic granule associated RNA binding protein TIA1 Proteins 0.000 description 1
- 108010090461 DFG peptide Proteins 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- 101150027879 FOXP3 gene Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 1
- REJJNXODKSHOKA-ACZMJKKPSA-N Gln-Ala-Asp Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N REJJNXODKSHOKA-ACZMJKKPSA-N 0.000 description 1
- JSYULGSPLTZDHM-NRPADANISA-N Gln-Ala-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O JSYULGSPLTZDHM-NRPADANISA-N 0.000 description 1
- PGPJSRSLQNXBDT-YUMQZZPRSA-N Gln-Arg-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O PGPJSRSLQNXBDT-YUMQZZPRSA-N 0.000 description 1
- INFBPLSHYFALDE-ACZMJKKPSA-N Gln-Asn-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O INFBPLSHYFALDE-ACZMJKKPSA-N 0.000 description 1
- TWHDOEYLXXQYOZ-FXQIFTODSA-N Gln-Asn-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N TWHDOEYLXXQYOZ-FXQIFTODSA-N 0.000 description 1
- LPYPANUXJGFMGV-FXQIFTODSA-N Gln-Gln-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LPYPANUXJGFMGV-FXQIFTODSA-N 0.000 description 1
- NKCZYEDZTKOFBG-GUBZILKMSA-N Gln-Gln-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NKCZYEDZTKOFBG-GUBZILKMSA-N 0.000 description 1
- CITDWMLWXNUQKD-FXQIFTODSA-N Gln-Gln-Asn Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N CITDWMLWXNUQKD-FXQIFTODSA-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
- 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 1
- LVNILKSSFHCSJZ-IHRRRGAJSA-N Gln-Gln-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LVNILKSSFHCSJZ-IHRRRGAJSA-N 0.000 description 1
- NPTGGVQJYRSMCM-GLLZPBPUSA-N Gln-Gln-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NPTGGVQJYRSMCM-GLLZPBPUSA-N 0.000 description 1
- SNLOOPZHAQDMJG-CIUDSAMLSA-N Gln-Glu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SNLOOPZHAQDMJG-CIUDSAMLSA-N 0.000 description 1
- HSHCEAUPUPJPTE-JYJNAYRXSA-N Gln-Leu-Tyr Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HSHCEAUPUPJPTE-JYJNAYRXSA-N 0.000 description 1
- JRHPEMVLTRADLJ-AVGNSLFASA-N Gln-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N JRHPEMVLTRADLJ-AVGNSLFASA-N 0.000 description 1
- NMYFPKCIGUJMIK-GUBZILKMSA-N Gln-Met-Gln Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N NMYFPKCIGUJMIK-GUBZILKMSA-N 0.000 description 1
- UESYBOXFJWJVSB-AVGNSLFASA-N Gln-Phe-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O UESYBOXFJWJVSB-AVGNSLFASA-N 0.000 description 1
- NPMFDZGLKBNFOO-SRVKXCTJSA-N Gln-Pro-His Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CN=CN1 NPMFDZGLKBNFOO-SRVKXCTJSA-N 0.000 description 1
- XQDGOJPVMSWZSO-SRVKXCTJSA-N Gln-Pro-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)N)N XQDGOJPVMSWZSO-SRVKXCTJSA-N 0.000 description 1
- KUBFPYIMAGXGBT-ACZMJKKPSA-N Gln-Ser-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KUBFPYIMAGXGBT-ACZMJKKPSA-N 0.000 description 1
- KVQOVQVGVKDZNW-GUBZILKMSA-N Gln-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N KVQOVQVGVKDZNW-GUBZILKMSA-N 0.000 description 1
- BYKZWDGMJLNFJY-XKBZYTNZSA-N Gln-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)O BYKZWDGMJLNFJY-XKBZYTNZSA-N 0.000 description 1
- OTQSTOXRUBVWAP-NRPADANISA-N Gln-Ser-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O OTQSTOXRUBVWAP-NRPADANISA-N 0.000 description 1
- PAOHIZNRJNIXQY-XQXXSGGOSA-N Gln-Thr-Ala 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(O)=O PAOHIZNRJNIXQY-XQXXSGGOSA-N 0.000 description 1
- VLOLPWWCNKWRNB-LOKLDPHHSA-N Gln-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O VLOLPWWCNKWRNB-LOKLDPHHSA-N 0.000 description 1
- VXAIXLOYBPMZPT-JBACZVJFSA-N Gln-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](CCC(=O)N)N VXAIXLOYBPMZPT-JBACZVJFSA-N 0.000 description 1
- BJVBMSTUUWGZKX-JYJNAYRXSA-N Gln-Tyr-His Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O BJVBMSTUUWGZKX-JYJNAYRXSA-N 0.000 description 1
- UQKVUFGUSVYJMQ-IRIUXVKKSA-N Gln-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)N)N)O UQKVUFGUSVYJMQ-IRIUXVKKSA-N 0.000 description 1
- 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 1
- MXOODARRORARSU-ACZMJKKPSA-N Glu-Ala-Ser Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)O)N MXOODARRORARSU-ACZMJKKPSA-N 0.000 description 1
- KBKGRMNVKPSQIF-XDTLVQLUSA-N Glu-Ala-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KBKGRMNVKPSQIF-XDTLVQLUSA-N 0.000 description 1
- 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 1
- NLKVNZUFDPWPNL-YUMQZZPRSA-N Glu-Arg-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O NLKVNZUFDPWPNL-YUMQZZPRSA-N 0.000 description 1
- LTUVYLVIZHJCOQ-KKUMJFAQSA-N Glu-Arg-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LTUVYLVIZHJCOQ-KKUMJFAQSA-N 0.000 description 1
- GCYFUZJHAXJKKE-KKUMJFAQSA-N Glu-Arg-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GCYFUZJHAXJKKE-KKUMJFAQSA-N 0.000 description 1
- NTBDVNJIWCKURJ-ACZMJKKPSA-N Glu-Asp-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NTBDVNJIWCKURJ-ACZMJKKPSA-N 0.000 description 1
- XXCDTYBVGMPIOA-FXQIFTODSA-N Glu-Asp-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XXCDTYBVGMPIOA-FXQIFTODSA-N 0.000 description 1
- 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 1
- JVSBYEDSSRZQGV-GUBZILKMSA-N Glu-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O JVSBYEDSSRZQGV-GUBZILKMSA-N 0.000 description 1
- OXEMJGCAJFFREE-FXQIFTODSA-N Glu-Gln-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O OXEMJGCAJFFREE-FXQIFTODSA-N 0.000 description 1
- PXXGVUVQWQGGIG-YUMQZZPRSA-N Glu-Gly-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N PXXGVUVQWQGGIG-YUMQZZPRSA-N 0.000 description 1
- 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 1
- 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 1
- QMOSCLNJVKSHHU-YUMQZZPRSA-N Glu-Met-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O QMOSCLNJVKSHHU-YUMQZZPRSA-N 0.000 description 1
- ITVBKCZZLJUUHI-HTUGSXCWSA-N Glu-Phe-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ITVBKCZZLJUUHI-HTUGSXCWSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- WXONSNSSBYQGNN-AVGNSLFASA-N Glu-Ser-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WXONSNSSBYQGNN-AVGNSLFASA-N 0.000 description 1
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 1
- 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 1
- 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 1
- 108010068370 Glutens Proteins 0.000 description 1
- 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 1
- PHONXOACARQMPM-BQBZGAKWSA-N Gly-Ala-Met Chemical compound [H]NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(O)=O PHONXOACARQMPM-BQBZGAKWSA-N 0.000 description 1
- RQZGFWKQLPJOEQ-YUMQZZPRSA-N Gly-Arg-Gln Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)CN)CN=C(N)N RQZGFWKQLPJOEQ-YUMQZZPRSA-N 0.000 description 1
- JVACNFOPSUPDTK-QWRGUYRKSA-N Gly-Asn-Phe Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JVACNFOPSUPDTK-QWRGUYRKSA-N 0.000 description 1
- XRTDOIOIBMAXCT-NKWVEPMBSA-N Gly-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)CN)C(=O)O XRTDOIOIBMAXCT-NKWVEPMBSA-N 0.000 description 1
- QSTLUOIOYLYLLF-WDSKDSINSA-N Gly-Asp-Glu Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QSTLUOIOYLYLLF-WDSKDSINSA-N 0.000 description 1
- LXXLEUBUOMCAMR-NKWVEPMBSA-N Gly-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)CN)C(=O)O LXXLEUBUOMCAMR-NKWVEPMBSA-N 0.000 description 1
- LCNXZQROPKFGQK-WHFBIAKZSA-N Gly-Asp-Ser Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O LCNXZQROPKFGQK-WHFBIAKZSA-N 0.000 description 1
- PMNHJLASAAWELO-FOHZUACHSA-N Gly-Asp-Thr Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PMNHJLASAAWELO-FOHZUACHSA-N 0.000 description 1
- CQZDZKRHFWJXDF-WDSKDSINSA-N Gly-Gln-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CN CQZDZKRHFWJXDF-WDSKDSINSA-N 0.000 description 1
- BULIVUZUDBHKKZ-WDSKDSINSA-N Gly-Gln-Asn Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O BULIVUZUDBHKKZ-WDSKDSINSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- QITBQGJOXQYMOA-ZETCQYMHSA-N Gly-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CN QITBQGJOXQYMOA-ZETCQYMHSA-N 0.000 description 1
- QPCVIQJVRGXUSA-LURJTMIESA-N Gly-Gly-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)CNC(=O)CN QPCVIQJVRGXUSA-LURJTMIESA-N 0.000 description 1
- VAXIVIPMCTYSHI-YUMQZZPRSA-N Gly-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)CN VAXIVIPMCTYSHI-YUMQZZPRSA-N 0.000 description 1
- SWQALSGKVLYKDT-ZKWXMUAHSA-N Gly-Ile-Ala Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O SWQALSGKVLYKDT-ZKWXMUAHSA-N 0.000 description 1
- SWQALSGKVLYKDT-UHFFFAOYSA-N Gly-Ile-Ala Natural products NCC(=O)NC(C(C)CC)C(=O)NC(C)C(O)=O SWQALSGKVLYKDT-UHFFFAOYSA-N 0.000 description 1
- BHPQOIPBLYJNAW-NGZCFLSTSA-N Gly-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN BHPQOIPBLYJNAW-NGZCFLSTSA-N 0.000 description 1
- XVYKMNXXJXQKME-XEGUGMAKSA-N Gly-Ile-Tyr Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XVYKMNXXJXQKME-XEGUGMAKSA-N 0.000 description 1
- YTSVAIMKVLZUDU-YUMQZZPRSA-N Gly-Leu-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YTSVAIMKVLZUDU-YUMQZZPRSA-N 0.000 description 1
- TWTPDFFBLQEBOE-IUCAKERBSA-N Gly-Leu-Gln Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O TWTPDFFBLQEBOE-IUCAKERBSA-N 0.000 description 1
- LLZXNUUIBOALNY-QWRGUYRKSA-N Gly-Leu-Lys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN LLZXNUUIBOALNY-QWRGUYRKSA-N 0.000 description 1
- JPAACTMBBBGAAR-HOTGVXAUSA-N Gly-Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)CN)CC(C)C)C(O)=O)=CNC2=C1 JPAACTMBBBGAAR-HOTGVXAUSA-N 0.000 description 1
- 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 1
- VEPBEGNDJYANCF-QWRGUYRKSA-N Gly-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN VEPBEGNDJYANCF-QWRGUYRKSA-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
- SSFWXSNOKDZNHY-QXEWZRGKSA-N Gly-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN SSFWXSNOKDZNHY-QXEWZRGKSA-N 0.000 description 1
- OOCFXNOVSLSHAB-IUCAKERBSA-N Gly-Pro-Pro Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OOCFXNOVSLSHAB-IUCAKERBSA-N 0.000 description 1
- YOBGUCWZPXJHTN-BQBZGAKWSA-N Gly-Ser-Arg Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YOBGUCWZPXJHTN-BQBZGAKWSA-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
- 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 1
- 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 1
- FKESCSGWBPUTPN-FOHZUACHSA-N Gly-Thr-Asn Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O FKESCSGWBPUTPN-FOHZUACHSA-N 0.000 description 1
- FFALDIDGPLUDKV-ZDLURKLDSA-N Gly-Thr-Ser Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O FFALDIDGPLUDKV-ZDLURKLDSA-N 0.000 description 1
- WSWWTQYHFCBKBT-DVJZZOLTSA-N Gly-Thr-Trp Chemical compound C[C@@H](O)[C@H](NC(=O)CN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O WSWWTQYHFCBKBT-DVJZZOLTSA-N 0.000 description 1
- 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 1
- RJVZMGQMJOQIAX-GJZGRUSLSA-N Gly-Trp-Met Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCSC)C(O)=O RJVZMGQMJOQIAX-GJZGRUSLSA-N 0.000 description 1
- XBGGUPMXALFZOT-VIFPVBQESA-N Gly-Tyr Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-VIFPVBQESA-N 0.000 description 1
- COZMNNJEGNPDED-HOCLYGCPSA-N Gly-Val-Trp Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O COZMNNJEGNPDED-HOCLYGCPSA-N 0.000 description 1
- IZVICCORZOSGPT-JSGCOSHPSA-N Gly-Val-Tyr Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IZVICCORZOSGPT-JSGCOSHPSA-N 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-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
- LSQHWKPPOFDHHZ-YUMQZZPRSA-N His-Asp-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N LSQHWKPPOFDHHZ-YUMQZZPRSA-N 0.000 description 1
- DVHGLDYMGWTYKW-GUBZILKMSA-N His-Gln-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O DVHGLDYMGWTYKW-GUBZILKMSA-N 0.000 description 1
- FMRKUXFLLPKVPG-JYJNAYRXSA-N His-Gln-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CN=CN2)N)O FMRKUXFLLPKVPG-JYJNAYRXSA-N 0.000 description 1
- FYTCLUIYTYFGPT-YUMQZZPRSA-N His-Gly-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FYTCLUIYTYFGPT-YUMQZZPRSA-N 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- ILUVWFTXAUYOBW-CUJWVEQBSA-N His-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CN=CN1)N)O ILUVWFTXAUYOBW-CUJWVEQBSA-N 0.000 description 1
- FCPSGEVYIVXPPO-QTKMDUPCSA-N His-Thr-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FCPSGEVYIVXPPO-QTKMDUPCSA-N 0.000 description 1
- UPJODPVSKKWGDQ-KLHWPWHYSA-N His-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O UPJODPVSKKWGDQ-KLHWPWHYSA-N 0.000 description 1
- LPBWRHRHEIYAIP-KKUMJFAQSA-N His-Tyr-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O LPBWRHRHEIYAIP-KKUMJFAQSA-N 0.000 description 1
- WSWAUVHXQREQQG-JYJNAYRXSA-N His-Tyr-Gln Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O WSWAUVHXQREQQG-JYJNAYRXSA-N 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 1
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 1
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101001109719 Homo sapiens Nucleophosmin Proteins 0.000 description 1
- 101000714926 Homo sapiens Taste receptor type 2 member 14 Proteins 0.000 description 1
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 1
- 101000766332 Homo sapiens Tribbles homolog 1 Proteins 0.000 description 1
- DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- HDOYNXLPTRQLAD-JBDRJPRFSA-N Ile-Ala-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)O)N HDOYNXLPTRQLAD-JBDRJPRFSA-N 0.000 description 1
- BOTVMTSMOUSDRW-GMOBBJLQSA-N Ile-Arg-Asn Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(O)=O BOTVMTSMOUSDRW-GMOBBJLQSA-N 0.000 description 1
- ASCFJMSGKUIRDU-ZPFDUUQYSA-N Ile-Arg-Gln Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O ASCFJMSGKUIRDU-ZPFDUUQYSA-N 0.000 description 1
- AZEYWPUCOYXFOE-CYDGBPFRSA-N Ile-Arg-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](C(C)C)C(=O)O)N AZEYWPUCOYXFOE-CYDGBPFRSA-N 0.000 description 1
- DCQMJRSOGCYKTR-GHCJXIJMSA-N Ile-Asp-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O DCQMJRSOGCYKTR-GHCJXIJMSA-N 0.000 description 1
- HOLOYAZCIHDQNS-YVNDNENWSA-N Ile-Gln-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N HOLOYAZCIHDQNS-YVNDNENWSA-N 0.000 description 1
- JXMSHKFPDIUYGS-SIUGBPQLSA-N Ile-Glu-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N JXMSHKFPDIUYGS-SIUGBPQLSA-N 0.000 description 1
- IGJWJGIHUFQANP-LAEOZQHASA-N Ile-Gly-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)O)N IGJWJGIHUFQANP-LAEOZQHASA-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
- LWWILHPVAKKLQS-QXEWZRGKSA-N Ile-Gly-Met Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCSC)C(=O)O)N LWWILHPVAKKLQS-QXEWZRGKSA-N 0.000 description 1
- VOBYAKCXGQQFLR-LSJOCFKGSA-N Ile-Gly-Val Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O VOBYAKCXGQQFLR-LSJOCFKGSA-N 0.000 description 1
- DMSVBUWGDLYNLC-IAVJCBSLSA-N Ile-Ile-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 DMSVBUWGDLYNLC-IAVJCBSLSA-N 0.000 description 1
- 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 1
- KLJKJVXDHVUMMZ-KKPKCPPISA-N Ile-Phe-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N KLJKJVXDHVUMMZ-KKPKCPPISA-N 0.000 description 1
- 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 1
- JODPUDMBQBIWCK-GHCJXIJMSA-N Ile-Ser-Asn Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O JODPUDMBQBIWCK-GHCJXIJMSA-N 0.000 description 1
- ZNOBVZFCHNHKHA-KBIXCLLPSA-N Ile-Ser-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZNOBVZFCHNHKHA-KBIXCLLPSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- HJDZMPFEXINXLO-QPHKQPEJSA-N Ile-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N HJDZMPFEXINXLO-QPHKQPEJSA-N 0.000 description 1
- 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 1
- RMJWFINHACYKJI-SIUGBPQLSA-N Ile-Tyr-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N RMJWFINHACYKJI-SIUGBPQLSA-N 0.000 description 1
- DZMWFIRHFFVBHS-ZEWNOJEFSA-N Ile-Tyr-Phe 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=CC=C2)C(=O)O)N DZMWFIRHFFVBHS-ZEWNOJEFSA-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
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102100039897 Interleukin-5 Human genes 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 206010022704 Intestinal T-cell lymphomas Diseases 0.000 description 1
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- CZCSUZMIRKFFFA-CIUDSAMLSA-N Leu-Ala-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O CZCSUZMIRKFFFA-CIUDSAMLSA-N 0.000 description 1
- KWTVLKBOQATPHJ-SRVKXCTJSA-N Leu-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(C)C)N KWTVLKBOQATPHJ-SRVKXCTJSA-N 0.000 description 1
- 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 1
- SUPVSFFZWVOEOI-CQDKDKBSSA-N Leu-Ala-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 SUPVSFFZWVOEOI-CQDKDKBSSA-N 0.000 description 1
- 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 1
- ZURHXHNAEJJRNU-CIUDSAMLSA-N Leu-Asp-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZURHXHNAEJJRNU-CIUDSAMLSA-N 0.000 description 1
- JQSXWJXBASFONF-KKUMJFAQSA-N Leu-Asp-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JQSXWJXBASFONF-KKUMJFAQSA-N 0.000 description 1
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 1
- 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 1
- LOLUPZNNADDTAA-AVGNSLFASA-N Leu-Gln-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LOLUPZNNADDTAA-AVGNSLFASA-N 0.000 description 1
- 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 1
- BABSVXFGKFLIGW-UWVGGRQHSA-N Leu-Gly-Arg Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCNC(N)=N BABSVXFGKFLIGW-UWVGGRQHSA-N 0.000 description 1
- 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 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
- 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 1
- LKXANTUNFMVCNF-IHPCNDPISA-N Leu-His-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O LKXANTUNFMVCNF-IHPCNDPISA-N 0.000 description 1
- SGIIOQQGLUUMDQ-IHRRRGAJSA-N Leu-His-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N SGIIOQQGLUUMDQ-IHRRRGAJSA-N 0.000 description 1
- 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 1
- DSFYPIUSAMSERP-IHRRRGAJSA-N Leu-Leu-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DSFYPIUSAMSERP-IHRRRGAJSA-N 0.000 description 1
- 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 1
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 1
- OVZLLFONXILPDZ-VOAKCMCISA-N Leu-Lys-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OVZLLFONXILPDZ-VOAKCMCISA-N 0.000 description 1
- 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 1
- 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 1
- KWLWZYMNUZJKMZ-IHRRRGAJSA-N Leu-Pro-Leu Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O KWLWZYMNUZJKMZ-IHRRRGAJSA-N 0.000 description 1
- 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 1
- 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 1
- PPGBXYKMUMHFBF-KATARQTJSA-N Leu-Ser-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PPGBXYKMUMHFBF-KATARQTJSA-N 0.000 description 1
- SVBJIZVVYJYGLA-DCAQKATOSA-N Leu-Ser-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O SVBJIZVVYJYGLA-DCAQKATOSA-N 0.000 description 1
- 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 1
- RDFIVFHPOSOXMW-ACRUOGEOSA-N Leu-Tyr-Phe 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](CC1=CC=CC=C1)C(O)=O RDFIVFHPOSOXMW-ACRUOGEOSA-N 0.000 description 1
- BGGTYDNTOYRTTR-MEYUZBJRSA-N Leu-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](CC(C)C)N)O BGGTYDNTOYRTTR-MEYUZBJRSA-N 0.000 description 1
- YIRIDPUGZKHMHT-ACRUOGEOSA-N Leu-Tyr-Tyr 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](CC1=CC=C(O)C=C1)C(O)=O YIRIDPUGZKHMHT-ACRUOGEOSA-N 0.000 description 1
- FMFNIDICDKEMOE-XUXIUFHCSA-N Leu-Val-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FMFNIDICDKEMOE-XUXIUFHCSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- YNNPKXBBRZVIRX-IHRRRGAJSA-N Lys-Arg-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O YNNPKXBBRZVIRX-IHRRRGAJSA-N 0.000 description 1
- NQCJGQHHYZNUDK-DCAQKATOSA-N Lys-Arg-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CCCN=C(N)N NQCJGQHHYZNUDK-DCAQKATOSA-N 0.000 description 1
- 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 1
- NCTDKZKNBDZDOL-GARJFASQSA-N Lys-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N)C(=O)O NCTDKZKNBDZDOL-GARJFASQSA-N 0.000 description 1
- 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 1
- 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 1
- YEIYAQQKADPIBJ-GARJFASQSA-N Lys-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)N)C(=O)O YEIYAQQKADPIBJ-GARJFASQSA-N 0.000 description 1
- IRRZDAIFYHNIIN-JYJNAYRXSA-N Lys-Gln-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IRRZDAIFYHNIIN-JYJNAYRXSA-N 0.000 description 1
- ITWQLSZTLBKWJM-YUMQZZPRSA-N Lys-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCCN ITWQLSZTLBKWJM-YUMQZZPRSA-N 0.000 description 1
- 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 1
- UETQMSASAVBGJY-QWRGUYRKSA-N Lys-Gly-His Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CNC=N1 UETQMSASAVBGJY-QWRGUYRKSA-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
- URGPVYGVWLIRGT-DCAQKATOSA-N Lys-Met-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O URGPVYGVWLIRGT-DCAQKATOSA-N 0.000 description 1
- LUAJJLPHUXPQLH-KKUMJFAQSA-N Lys-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](CCCCN)N LUAJJLPHUXPQLH-KKUMJFAQSA-N 0.000 description 1
- NQSFIPWBPXNJII-PMVMPFDFSA-N Lys-Phe-Trp Chemical compound C([C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=CC=C1 NQSFIPWBPXNJII-PMVMPFDFSA-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
- 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 1
- MEQLGHAMAUPOSJ-DCAQKATOSA-N Lys-Ser-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O MEQLGHAMAUPOSJ-DCAQKATOSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- NROQVSYLPRLJIP-PMVMPFDFSA-N Lys-Trp-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NROQVSYLPRLJIP-PMVMPFDFSA-N 0.000 description 1
- RQILLQOQXLZTCK-KBPBESRZSA-N Lys-Tyr-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O RQILLQOQXLZTCK-KBPBESRZSA-N 0.000 description 1
- RIPJMCFGQHGHNP-RHYQMDGZSA-N Lys-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)N)O RIPJMCFGQHGHNP-RHYQMDGZSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- ONGCSGVHCSAATF-CIUDSAMLSA-N Met-Ala-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O ONGCSGVHCSAATF-CIUDSAMLSA-N 0.000 description 1
- PJWDQHNOJIBMRY-JYJNAYRXSA-N Met-Arg-Tyr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PJWDQHNOJIBMRY-JYJNAYRXSA-N 0.000 description 1
- DBOMZJOESVYERT-GUBZILKMSA-N Met-Asn-Met Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCSC)C(=O)O)N DBOMZJOESVYERT-GUBZILKMSA-N 0.000 description 1
- RZJOHSFAEZBWLK-CIUDSAMLSA-N Met-Gln-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N RZJOHSFAEZBWLK-CIUDSAMLSA-N 0.000 description 1
- FYRUJIJAUPHUNB-IUCAKERBSA-N Met-Gly-Arg Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCNC(N)=N FYRUJIJAUPHUNB-IUCAKERBSA-N 0.000 description 1
- XDGFFEZAZHRZFR-RHYQMDGZSA-N Met-Leu-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XDGFFEZAZHRZFR-RHYQMDGZSA-N 0.000 description 1
- NDJSSFWDYDUQID-YTWAJWBKSA-N Met-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCSC)N)O NDJSSFWDYDUQID-YTWAJWBKSA-N 0.000 description 1
- IIHMNTBFPMRJCN-RCWTZXSCSA-N Met-Val-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IIHMNTBFPMRJCN-RCWTZXSCSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102400000047 Minor histocompatibility antigen HA-1 Human genes 0.000 description 1
- 101800003181 Minor histocompatibility antigen HA-1 Proteins 0.000 description 1
- 206010028124 Mucosal ulceration Diseases 0.000 description 1
- 101000798132 Mus musculus Taste receptor type 2 member 116 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- WYBVBIHNJWOLCJ-UHFFFAOYSA-N N-L-arginyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCCN=C(N)N WYBVBIHNJWOLCJ-UHFFFAOYSA-N 0.000 description 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- 108010087066 N2-tryptophyllysine Proteins 0.000 description 1
- 206010028698 Nail dystrophy Diseases 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 102100022678 Nucleophosmin Human genes 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010056995 Perforin Proteins 0.000 description 1
- 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 1
- MDHZEOMXGNBSIL-DLOVCJGASA-N Phe-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N MDHZEOMXGNBSIL-DLOVCJGASA-N 0.000 description 1
- UHRNIXJAGGLKHP-DLOVCJGASA-N Phe-Ala-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O UHRNIXJAGGLKHP-DLOVCJGASA-N 0.000 description 1
- 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 1
- QCHNRQQVLJYDSI-DLOVCJGASA-N Phe-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 QCHNRQQVLJYDSI-DLOVCJGASA-N 0.000 description 1
- DJPXNKUDJKGQEE-BZSNNMDCSA-N Phe-Asp-Phe Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O DJPXNKUDJKGQEE-BZSNNMDCSA-N 0.000 description 1
- OJUMUUXGSXUZJZ-SRVKXCTJSA-N Phe-Asp-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O OJUMUUXGSXUZJZ-SRVKXCTJSA-N 0.000 description 1
- WFDAEEUZPZSMOG-SRVKXCTJSA-N Phe-Cys-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O WFDAEEUZPZSMOG-SRVKXCTJSA-N 0.000 description 1
- 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 1
- 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 1
- ZLGQEBCCANLYRA-RYUDHWBXSA-N Phe-Gly-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O ZLGQEBCCANLYRA-RYUDHWBXSA-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
- AAERWTUHZKLDLC-IHRRRGAJSA-N Phe-Pro-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O AAERWTUHZKLDLC-IHRRRGAJSA-N 0.000 description 1
- MMJJFXWMCMJMQA-STQMWFEESA-N Phe-Pro-Gly Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)C1=CC=CC=C1 MMJJFXWMCMJMQA-STQMWFEESA-N 0.000 description 1
- WEDZFLRYSIDIRX-IHRRRGAJSA-N Phe-Ser-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=CC=C1 WEDZFLRYSIDIRX-IHRRRGAJSA-N 0.000 description 1
- 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 1
- JXQVYPWVGUOIDV-MXAVVETBSA-N Phe-Ser-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JXQVYPWVGUOIDV-MXAVVETBSA-N 0.000 description 1
- 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 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000101040 Pityriasis Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108010039918 Polylysine Chemical group 0.000 description 1
- VXCHGLYSIOOZIS-GUBZILKMSA-N Pro-Ala-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 VXCHGLYSIOOZIS-GUBZILKMSA-N 0.000 description 1
- 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 1
- SSSFPISOZOLQNP-GUBZILKMSA-N Pro-Arg-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O SSSFPISOZOLQNP-GUBZILKMSA-N 0.000 description 1
- BNBBNGZZKQUWCD-IUCAKERBSA-N Pro-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H]1CCCN1 BNBBNGZZKQUWCD-IUCAKERBSA-N 0.000 description 1
- KIGGUSRFHJCIEJ-DCAQKATOSA-N Pro-Asp-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O KIGGUSRFHJCIEJ-DCAQKATOSA-N 0.000 description 1
- UPJGUQPLYWTISV-GUBZILKMSA-N Pro-Gln-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UPJGUQPLYWTISV-GUBZILKMSA-N 0.000 description 1
- HJSCRFZVGXAGNG-SRVKXCTJSA-N Pro-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1 HJSCRFZVGXAGNG-SRVKXCTJSA-N 0.000 description 1
- PULPZRAHVFBVTO-DCAQKATOSA-N Pro-Glu-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PULPZRAHVFBVTO-DCAQKATOSA-N 0.000 description 1
- PTLOFJZJADCNCD-DCAQKATOSA-N Pro-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1 PTLOFJZJADCNCD-DCAQKATOSA-N 0.000 description 1
- 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 1
- HAEGAELAYWSUNC-WPRPVWTQSA-N Pro-Gly-Val Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HAEGAELAYWSUNC-WPRPVWTQSA-N 0.000 description 1
- BWCZJGJKOFUUCN-ZPFDUUQYSA-N Pro-Ile-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O BWCZJGJKOFUUCN-ZPFDUUQYSA-N 0.000 description 1
- 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 1
- YXHYJEPDKSYPSQ-AVGNSLFASA-N Pro-Leu-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 YXHYJEPDKSYPSQ-AVGNSLFASA-N 0.000 description 1
- RUDOLGWDSKQQFF-DCAQKATOSA-N Pro-Leu-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O RUDOLGWDSKQQFF-DCAQKATOSA-N 0.000 description 1
- FKYKZHOKDOPHSA-DCAQKATOSA-N Pro-Leu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FKYKZHOKDOPHSA-DCAQKATOSA-N 0.000 description 1
- 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 1
- 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 1
- AJBQTGZIZQXBLT-STQMWFEESA-N Pro-Phe-Gly Chemical compound C([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 AJBQTGZIZQXBLT-STQMWFEESA-N 0.000 description 1
- FHZJRBVMLGOHBX-GUBZILKMSA-N Pro-Pro-Asp Chemical compound OC(=O)C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1)C(O)=O FHZJRBVMLGOHBX-GUBZILKMSA-N 0.000 description 1
- FYKUEXMZYFIZKA-DCAQKATOSA-N Pro-Pro-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O FYKUEXMZYFIZKA-DCAQKATOSA-N 0.000 description 1
- 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 1
- 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 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
- 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 1
- POQFNPILEQEODH-FXQIFTODSA-N Pro-Ser-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O POQFNPILEQEODH-FXQIFTODSA-N 0.000 description 1
- 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 1
- 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 1
- JDJMFMVVJHLWDP-UNQGMJICSA-N Pro-Thr-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JDJMFMVVJHLWDP-UNQGMJICSA-N 0.000 description 1
- DLZBBDSPTJBOOD-BPNCWPANSA-N Pro-Tyr-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O DLZBBDSPTJBOOD-BPNCWPANSA-N 0.000 description 1
- DYJTXTCEXMCPBF-UFYCRDLUSA-N Pro-Tyr-Phe Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O DYJTXTCEXMCPBF-UFYCRDLUSA-N 0.000 description 1
- QDDJNKWPTJHROJ-UFYCRDLUSA-N Pro-Tyr-Tyr Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H]1NCCC1)C1=CC=C(O)C=C1 QDDJNKWPTJHROJ-UFYCRDLUSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 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 1
- 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 1
- WTWGOQRNRFHFQD-JBDRJPRFSA-N Ser-Ala-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WTWGOQRNRFHFQD-JBDRJPRFSA-N 0.000 description 1
- BRKHVZNDAOMAHX-BIIVOSGPSA-N Ser-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N BRKHVZNDAOMAHX-BIIVOSGPSA-N 0.000 description 1
- PZZJMBYSYAKYPK-UWJYBYFXSA-N Ser-Ala-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O PZZJMBYSYAKYPK-UWJYBYFXSA-N 0.000 description 1
- FCRMLGJMPXCAHD-FXQIFTODSA-N Ser-Arg-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O FCRMLGJMPXCAHD-FXQIFTODSA-N 0.000 description 1
- 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 1
- XVAUJOAYHWWNQF-ZLUOBGJFSA-N Ser-Asn-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O XVAUJOAYHWWNQF-ZLUOBGJFSA-N 0.000 description 1
- OBXVZEAMXFSGPU-FXQIFTODSA-N Ser-Asn-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)N)CN=C(N)N OBXVZEAMXFSGPU-FXQIFTODSA-N 0.000 description 1
- OOKCGAYXSNJBGQ-ZLUOBGJFSA-N Ser-Asn-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O OOKCGAYXSNJBGQ-ZLUOBGJFSA-N 0.000 description 1
- 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 1
- RDFQNDHEHVSONI-ZLUOBGJFSA-N Ser-Asn-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O RDFQNDHEHVSONI-ZLUOBGJFSA-N 0.000 description 1
- HEQPKICPPDOSIN-SRVKXCTJSA-N Ser-Asp-Tyr Chemical compound OC[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 HEQPKICPPDOSIN-SRVKXCTJSA-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
- 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 1
- RNMRYWZYFHHOEV-CIUDSAMLSA-N Ser-Gln-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RNMRYWZYFHHOEV-CIUDSAMLSA-N 0.000 description 1
- 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 1
- BQWCDDAISCPDQV-XHNCKOQMSA-N Ser-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N)C(=O)O BQWCDDAISCPDQV-XHNCKOQMSA-N 0.000 description 1
- LALNXSXEYFUUDD-GUBZILKMSA-N Ser-Glu-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LALNXSXEYFUUDD-GUBZILKMSA-N 0.000 description 1
- AEGUWTFAQQWVLC-BQBZGAKWSA-N Ser-Gly-Arg Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O AEGUWTFAQQWVLC-BQBZGAKWSA-N 0.000 description 1
- MUARUIBTKQJKFY-WHFBIAKZSA-N Ser-Gly-Asp Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MUARUIBTKQJKFY-WHFBIAKZSA-N 0.000 description 1
- IOVHBRCQOGWAQH-ZKWXMUAHSA-N Ser-Gly-Ile Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IOVHBRCQOGWAQH-ZKWXMUAHSA-N 0.000 description 1
- 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 1
- CXBFHZLODKPIJY-AAEUAGOBSA-N Ser-Gly-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N CXBFHZLODKPIJY-AAEUAGOBSA-N 0.000 description 1
- 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 1
- CJINPXGSKSZQNE-KBIXCLLPSA-N Ser-Ile-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O CJINPXGSKSZQNE-KBIXCLLPSA-N 0.000 description 1
- DOSZISJPMCYEHT-NAKRPEOUSA-N Ser-Ile-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O DOSZISJPMCYEHT-NAKRPEOUSA-N 0.000 description 1
- 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 1
- 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 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
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- 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 1
- QJKPECIAWNNKIT-KKUMJFAQSA-N Ser-Lys-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QJKPECIAWNNKIT-KKUMJFAQSA-N 0.000 description 1
- JAWGSPUJAXYXJA-IHRRRGAJSA-N Ser-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)N)CC1=CC=CC=C1 JAWGSPUJAXYXJA-IHRRRGAJSA-N 0.000 description 1
- UGTZYIPOBYXWRW-SRVKXCTJSA-N Ser-Phe-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O UGTZYIPOBYXWRW-SRVKXCTJSA-N 0.000 description 1
- XKFJENWJGHMDLI-QWRGUYRKSA-N Ser-Phe-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O XKFJENWJGHMDLI-QWRGUYRKSA-N 0.000 description 1
- JLKWJWPDXPKKHI-FXQIFTODSA-N Ser-Pro-Asn Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CC(=O)N)C(=O)O JLKWJWPDXPKKHI-FXQIFTODSA-N 0.000 description 1
- 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 1
- RHAPJNVNWDBFQI-BQBZGAKWSA-N Ser-Pro-Gly Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O RHAPJNVNWDBFQI-BQBZGAKWSA-N 0.000 description 1
- FKYWFUYPVKLJLP-DCAQKATOSA-N Ser-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FKYWFUYPVKLJLP-DCAQKATOSA-N 0.000 description 1
- 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 1
- KQNDIKOYWZTZIX-FXQIFTODSA-N Ser-Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQNDIKOYWZTZIX-FXQIFTODSA-N 0.000 description 1
- FZXOPYUEQGDGMS-ACZMJKKPSA-N Ser-Ser-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O FZXOPYUEQGDGMS-ACZMJKKPSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- VLMIUSLQONKLDV-HEIBUPTGSA-N Ser-Thr-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VLMIUSLQONKLDV-HEIBUPTGSA-N 0.000 description 1
- BDMWLJLPPUCLNV-XGEHTFHBSA-N Ser-Thr-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BDMWLJLPPUCLNV-XGEHTFHBSA-N 0.000 description 1
- ZWSZBWAFDZRBNM-UBHSHLNASA-N Ser-Trp-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O ZWSZBWAFDZRBNM-UBHSHLNASA-N 0.000 description 1
- RTXKJFWHEBTABY-IHPCNDPISA-N Ser-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](CO)N RTXKJFWHEBTABY-IHPCNDPISA-N 0.000 description 1
- PIQRHJQWEPWFJG-UWJYBYFXSA-N Ser-Tyr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O PIQRHJQWEPWFJG-UWJYBYFXSA-N 0.000 description 1
- QYBRQMLZDDJBSW-AVGNSLFASA-N Ser-Tyr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYBRQMLZDDJBSW-AVGNSLFASA-N 0.000 description 1
- HXPNJVLVHKABMJ-KKUMJFAQSA-N Ser-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CO)N)O HXPNJVLVHKABMJ-KKUMJFAQSA-N 0.000 description 1
- UBTNVMGPMYDYIU-HJPIBITLSA-N Ser-Tyr-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UBTNVMGPMYDYIU-HJPIBITLSA-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
- HKHCTNFKZXAMIF-KKUMJFAQSA-N Ser-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CC1=CC=C(O)C=C1 HKHCTNFKZXAMIF-KKUMJFAQSA-N 0.000 description 1
- YXGCIEUDOHILKR-IHRRRGAJSA-N Ser-Tyr-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CO)N YXGCIEUDOHILKR-IHRRRGAJSA-N 0.000 description 1
- 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 1
- OSFZCEQJLWCIBG-BZSNNMDCSA-N Ser-Tyr-Tyr Chemical compound [H]N[C@@H](CO)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 OSFZCEQJLWCIBG-BZSNNMDCSA-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
- 206010058679 Skin oedema Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 210000003592 T-IEL Anatomy 0.000 description 1
- 206010042970 T-cell chronic lymphocytic leukaemia Diseases 0.000 description 1
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- DFTCYYILCSQGIZ-GCJQMDKQSA-N Thr-Ala-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O DFTCYYILCSQGIZ-GCJQMDKQSA-N 0.000 description 1
- 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 1
- CAJFZCICSVBOJK-SHGPDSBTSA-N Thr-Ala-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAJFZCICSVBOJK-SHGPDSBTSA-N 0.000 description 1
- JMZKMSTYXHFYAK-VEVYYDQMSA-N Thr-Arg-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O JMZKMSTYXHFYAK-VEVYYDQMSA-N 0.000 description 1
- NAXBBCLCEOTAIG-RHYQMDGZSA-N Thr-Arg-Lys Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O NAXBBCLCEOTAIG-RHYQMDGZSA-N 0.000 description 1
- UTCFSBBXPWKLTG-XKBZYTNZSA-N Thr-Cys-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O UTCFSBBXPWKLTG-XKBZYTNZSA-N 0.000 description 1
- 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 1
- FHDLKMFZKRUQCE-HJGDQZAQSA-N Thr-Glu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHDLKMFZKRUQCE-HJGDQZAQSA-N 0.000 description 1
- LGNBRHZANHMZHK-NUMRIWBASA-N Thr-Glu-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O LGNBRHZANHMZHK-NUMRIWBASA-N 0.000 description 1
- SLUWOCTZVGMURC-BFHQHQDPSA-N Thr-Gly-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O SLUWOCTZVGMURC-BFHQHQDPSA-N 0.000 description 1
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 1
- JQAWYCUUFIMTHE-WLTAIBSBSA-N Thr-Gly-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JQAWYCUUFIMTHE-WLTAIBSBSA-N 0.000 description 1
- UDNVOQMPQBEITB-MEYUZBJRSA-N Thr-His-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O UDNVOQMPQBEITB-MEYUZBJRSA-N 0.000 description 1
- XOWKUMFHEZLKLT-CIQUZCHMSA-N Thr-Ile-Ala 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)C(O)=O XOWKUMFHEZLKLT-CIQUZCHMSA-N 0.000 description 1
- 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 1
- 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 1
- TZJSEJOXAIWOST-RHYQMDGZSA-N Thr-Lys-Arg Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N TZJSEJOXAIWOST-RHYQMDGZSA-N 0.000 description 1
- ZSPQUTWLWGWTPS-HJGDQZAQSA-N Thr-Lys-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZSPQUTWLWGWTPS-HJGDQZAQSA-N 0.000 description 1
- WTMPKZWHRCMMMT-KZVJFYERSA-N Thr-Pro-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WTMPKZWHRCMMMT-KZVJFYERSA-N 0.000 description 1
- MUAFDCVOHYAFNG-RCWTZXSCSA-N Thr-Pro-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MUAFDCVOHYAFNG-RCWTZXSCSA-N 0.000 description 1
- MXDOAJQRJBMGMO-FJXKBIBVSA-N Thr-Pro-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O MXDOAJQRJBMGMO-FJXKBIBVSA-N 0.000 description 1
- VTMGKRABARCZAX-OSUNSFLBSA-N Thr-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)[C@@H](C)O VTMGKRABARCZAX-OSUNSFLBSA-N 0.000 description 1
- KERCOYANYUPLHJ-XGEHTFHBSA-N Thr-Pro-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O KERCOYANYUPLHJ-XGEHTFHBSA-N 0.000 description 1
- DOBIBIXIHJKVJF-XKBZYTNZSA-N Thr-Ser-Gln Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O DOBIBIXIHJKVJF-XKBZYTNZSA-N 0.000 description 1
- 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 1
- WKGAAMOJPMBBMC-IXOXFDKPSA-N Thr-Ser-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O WKGAAMOJPMBBMC-IXOXFDKPSA-N 0.000 description 1
- ZMYCLHFLHRVOEA-HEIBUPTGSA-N Thr-Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ZMYCLHFLHRVOEA-HEIBUPTGSA-N 0.000 description 1
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 1
- 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 1
- BZTSQFWJNJYZSX-JRQIVUDYSA-N Thr-Tyr-Asp 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(O)=O)C(O)=O BZTSQFWJNJYZSX-JRQIVUDYSA-N 0.000 description 1
- PELIQFPESHBTMA-WLTAIBSBSA-N Thr-Tyr-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 PELIQFPESHBTMA-WLTAIBSBSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- 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 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 102100026387 Tribbles homolog 1 Human genes 0.000 description 1
- 241000703392 Tribec virus Species 0.000 description 1
- HYLNRGXEQACDKG-NYVOZVTQSA-N Trp-Asn-Trp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HYLNRGXEQACDKG-NYVOZVTQSA-N 0.000 description 1
- LTLBNCDNXQCOLB-UBHSHLNASA-N Trp-Asp-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 LTLBNCDNXQCOLB-UBHSHLNASA-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
- 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 1
- IJRXQJVGFBSKIV-ZFWWWQNUSA-N Trp-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC1=CNC2=CC=CC=C21)N IJRXQJVGFBSKIV-ZFWWWQNUSA-N 0.000 description 1
- NOFFAYIYPAUNRM-HKUYNNGSSA-N Trp-Gly-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC2=CNC3=CC=CC=C32)N NOFFAYIYPAUNRM-HKUYNNGSSA-N 0.000 description 1
- GQHAIUPYZPTADF-FDARSICLSA-N Trp-Ile-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 GQHAIUPYZPTADF-FDARSICLSA-N 0.000 description 1
- CXPJPTFWKXNDKV-NUTKFTJISA-N Trp-Leu-Ala Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 CXPJPTFWKXNDKV-NUTKFTJISA-N 0.000 description 1
- YVXIAOOYAKBAAI-SZMVWBNQSA-N Trp-Leu-Gln Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)=CNC2=C1 YVXIAOOYAKBAAI-SZMVWBNQSA-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
- SUEGAFMNTXXNLR-WFBYXXMGSA-N Trp-Ser-Ala Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O SUEGAFMNTXXNLR-WFBYXXMGSA-N 0.000 description 1
- 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 1
- GBEAUNVBIMLWIB-IHPCNDPISA-N Trp-Ser-Phe Chemical compound C([C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=CC=C1 GBEAUNVBIMLWIB-IHPCNDPISA-N 0.000 description 1
- GEGYPBOPIGNZIF-CWRNSKLLSA-N Trp-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)O GEGYPBOPIGNZIF-CWRNSKLLSA-N 0.000 description 1
- 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 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- DLZKEQQWXODGGZ-KWQFWETISA-N Tyr-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DLZKEQQWXODGGZ-KWQFWETISA-N 0.000 description 1
- XGEUYEOEZYFHRL-KKXDTOCCSA-N Tyr-Ala-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 XGEUYEOEZYFHRL-KKXDTOCCSA-N 0.000 description 1
- OOEUVMFKKZYSRX-LEWSCRJBSA-N Tyr-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OOEUVMFKKZYSRX-LEWSCRJBSA-N 0.000 description 1
- MICSYKFECRFCTJ-IHRRRGAJSA-N Tyr-Arg-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O MICSYKFECRFCTJ-IHRRRGAJSA-N 0.000 description 1
- XHALUUQSNXSPLP-UFYCRDLUSA-N Tyr-Arg-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 XHALUUQSNXSPLP-UFYCRDLUSA-N 0.000 description 1
- IIJWXEUNETVJPV-IHRRRGAJSA-N Tyr-Arg-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N)O IIJWXEUNETVJPV-IHRRRGAJSA-N 0.000 description 1
- 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 1
- AYPAIRCDLARHLM-KKUMJFAQSA-N Tyr-Asn-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N)O AYPAIRCDLARHLM-KKUMJFAQSA-N 0.000 description 1
- 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 1
- 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 1
- VFJIWSJKZJTQII-SRVKXCTJSA-N Tyr-Asp-Ser 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](CO)C(O)=O VFJIWSJKZJTQII-SRVKXCTJSA-N 0.000 description 1
- UABYBEBXFFNCIR-YDHLFZDLSA-N Tyr-Asp-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UABYBEBXFFNCIR-YDHLFZDLSA-N 0.000 description 1
- ZAGPDPNPWYPEIR-SRVKXCTJSA-N Tyr-Cys-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O ZAGPDPNPWYPEIR-SRVKXCTJSA-N 0.000 description 1
- RYSNTWVRSLCAJZ-RYUDHWBXSA-N Tyr-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RYSNTWVRSLCAJZ-RYUDHWBXSA-N 0.000 description 1
- HVHJYXDXRIWELT-RYUDHWBXSA-N Tyr-Glu-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O HVHJYXDXRIWELT-RYUDHWBXSA-N 0.000 description 1
- UNUZEBFXGWVAOP-DZKIICNBSA-N Tyr-Glu-Val 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](C(C)C)C(O)=O UNUZEBFXGWVAOP-DZKIICNBSA-N 0.000 description 1
- NOOMDULIORCDNF-IRXDYDNUSA-N Tyr-Gly-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NOOMDULIORCDNF-IRXDYDNUSA-N 0.000 description 1
- AZGZDDNKFFUDEH-QWRGUYRKSA-N Tyr-Gly-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AZGZDDNKFFUDEH-QWRGUYRKSA-N 0.000 description 1
- ADECJAKCRKPSOR-ULQDDVLXSA-N Tyr-His-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O ADECJAKCRKPSOR-ULQDDVLXSA-N 0.000 description 1
- CVXURBLRELTJKO-BWAGICSOSA-N Tyr-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)O CVXURBLRELTJKO-BWAGICSOSA-N 0.000 description 1
- BSCBBPKDVOZICB-KKUMJFAQSA-N Tyr-Leu-Asp 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(O)=O)C(O)=O BSCBBPKDVOZICB-KKUMJFAQSA-N 0.000 description 1
- 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 1
- DWAMXBFJNZIHMC-KBPBESRZSA-N Tyr-Leu-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O DWAMXBFJNZIHMC-KBPBESRZSA-N 0.000 description 1
- JAGGEZACYAAMIL-CQDKDKBSSA-N Tyr-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=C(C=C1)O)N JAGGEZACYAAMIL-CQDKDKBSSA-N 0.000 description 1
- OGPKMBOPMDTEDM-IHRRRGAJSA-N Tyr-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N OGPKMBOPMDTEDM-IHRRRGAJSA-N 0.000 description 1
- OKDNSNWJEXAMSU-IRXDYDNUSA-N Tyr-Phe-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(O)=O)C1=CC=C(O)C=C1 OKDNSNWJEXAMSU-IRXDYDNUSA-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
- MDXLPNRXCFOBTL-BZSNNMDCSA-N Tyr-Ser-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MDXLPNRXCFOBTL-BZSNNMDCSA-N 0.000 description 1
- 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 1
- GZWPQZDVTBZVEP-BZSNNMDCSA-N Tyr-Tyr-Asn 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](CC(N)=O)C(O)=O GZWPQZDVTBZVEP-BZSNNMDCSA-N 0.000 description 1
- AFWXOGHZEKARFH-ACRUOGEOSA-N Tyr-Tyr-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=C(O)C=C1 AFWXOGHZEKARFH-ACRUOGEOSA-N 0.000 description 1
- TYGHOWWWMTWVKM-HJOGWXRNSA-N Tyr-Tyr-Phe 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=CC=1)C(O)=O)C1=CC=C(O)C=C1 TYGHOWWWMTWVKM-HJOGWXRNSA-N 0.000 description 1
- KLOZTPOXVVRVAQ-DZKIICNBSA-N Tyr-Val-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 KLOZTPOXVVRVAQ-DZKIICNBSA-N 0.000 description 1
- NVJCMGGZHOJNBU-UFYCRDLUSA-N Tyr-Val-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N NVJCMGGZHOJNBU-UFYCRDLUSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 description 1
- JFAWZADYPRMRCO-UBHSHLNASA-N Val-Ala-Phe Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JFAWZADYPRMRCO-UBHSHLNASA-N 0.000 description 1
- COYSIHFOCOMGCF-WPRPVWTQSA-N Val-Arg-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-WPRPVWTQSA-N 0.000 description 1
- COYSIHFOCOMGCF-UHFFFAOYSA-N Val-Arg-Gly Natural products CC(C)C(N)C(=O)NC(C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-UHFFFAOYSA-N 0.000 description 1
- PAPWZOJOLKZEFR-AVGNSLFASA-N Val-Arg-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N PAPWZOJOLKZEFR-AVGNSLFASA-N 0.000 description 1
- VMRFIKXKOFNMHW-GUBZILKMSA-N Val-Arg-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N VMRFIKXKOFNMHW-GUBZILKMSA-N 0.000 description 1
- XLDYBRXERHITNH-QSFUFRPTSA-N Val-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)C(C)C XLDYBRXERHITNH-QSFUFRPTSA-N 0.000 description 1
- 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 1
- XGJLNBNZNMVJRS-NRPADANISA-N Val-Glu-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O XGJLNBNZNMVJRS-NRPADANISA-N 0.000 description 1
- VVZDBPBZHLQPPB-XVKPBYJWSA-N Val-Glu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VVZDBPBZHLQPPB-XVKPBYJWSA-N 0.000 description 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
- PMXBARDFIAPBGK-DZKIICNBSA-N Val-Glu-Tyr Chemical compound CC(C)[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 PMXBARDFIAPBGK-DZKIICNBSA-N 0.000 description 1
- 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 1
- WFENBJPLZMPVAX-XVKPBYJWSA-N Val-Gly-Glu Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O WFENBJPLZMPVAX-XVKPBYJWSA-N 0.000 description 1
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 1
- 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 1
- FEFZWCSXEMVSPO-LSJOCFKGSA-N Val-His-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](C)C(O)=O FEFZWCSXEMVSPO-LSJOCFKGSA-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
- BZWUSZGQOILYEU-STECZYCISA-N Val-Ile-Tyr Chemical compound CC(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 BZWUSZGQOILYEU-STECZYCISA-N 0.000 description 1
- 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 1
- 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 1
- UEPLNXPLHJUYPT-AVGNSLFASA-N Val-Met-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(O)=O UEPLNXPLHJUYPT-AVGNSLFASA-N 0.000 description 1
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 1
- 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 1
- 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 1
- YQYFYUSYEDNLSD-YEPSODPASA-N Val-Thr-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O YQYFYUSYEDNLSD-YEPSODPASA-N 0.000 description 1
- DVLWZWNAQUBZBC-ZNSHCXBVSA-N Val-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N)O DVLWZWNAQUBZBC-ZNSHCXBVSA-N 0.000 description 1
- LNWSJGJCLFUNTN-ZOBUZTSGSA-N Val-Trp-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(=O)N)C(=O)O)N LNWSJGJCLFUNTN-ZOBUZTSGSA-N 0.000 description 1
- PFMSJVIPEZMKSC-DZKIICNBSA-N Val-Tyr-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N PFMSJVIPEZMKSC-DZKIICNBSA-N 0.000 description 1
- 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 1
- ZNGPROMGGGFOAA-JYJNAYRXSA-N Val-Tyr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=C(O)C=C1 ZNGPROMGGGFOAA-JYJNAYRXSA-N 0.000 description 1
- JSOXWWFKRJKTMT-WOPDTQHZSA-N Val-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N JSOXWWFKRJKTMT-WOPDTQHZSA-N 0.000 description 1
- 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 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- GYUDLEOKVQWEHB-UHFFFAOYSA-N acridine Chemical group C1=CC=CC2=CC3=CC=CC=C3N=C21.C1=CC=CC2=CC3=CC=CC=C3N=C21 GYUDLEOKVQWEHB-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000012082 adaptor molecule Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- 108010011559 alanylphenylalanine Proteins 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 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 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 108010013835 arginine glutamate Proteins 0.000 description 1
- 108010029539 arginyl-prolyl-proline Proteins 0.000 description 1
- 108010018691 arginyl-threonyl-arginine Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 108010036533 arginylvaline Proteins 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 108010036999 aspartyl-alanyl-histidyl-lysine Proteins 0.000 description 1
- 108010093581 aspartyl-proline Proteins 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 238000010378 bimolecular fluorescence complementation Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000000749 co-immunoprecipitation Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 108010016616 cysteinylglycine Proteins 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000005202 decontamination Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 229940046085 endocrine therapy drug gonadotropin releasing hormone analogues Drugs 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 229960001751 fluoxymesterone Drugs 0.000 description 1
- YLRFCQOZQXIBAB-RBZZARIASA-N fluoxymesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C[C@@H]2O YLRFCQOZQXIBAB-RBZZARIASA-N 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000001280 germinal center Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- HPAIKDPJURGQLN-UHFFFAOYSA-N glycyl-L-histidyl-L-phenylalanine Natural products C=1C=CC=CC=1CC(C(O)=O)NC(=O)C(NC(=O)CN)CC1=CN=CN1 HPAIKDPJURGQLN-UHFFFAOYSA-N 0.000 description 1
- 108010062266 glycyl-glycyl-argininal Proteins 0.000 description 1
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 1
- 108010008671 glycyl-tryptophyl-methionine Proteins 0.000 description 1
- 108010048994 glycyl-tyrosyl-alanine Proteins 0.000 description 1
- 108010084389 glycyltryptophan Proteins 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical class C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229950000801 hydroxyprogesterone caproate Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003903 intestinal lesions Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 108010060857 isoleucyl-valyl-tyrosine Proteins 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 108010034529 leucyl-lysine Proteins 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 201000001268 lymphoproliferative syndrome Diseases 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 210000001806 memory b lymphocyte Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 108010005942 methionylglycine Proteins 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 229960000350 mitotane Drugs 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 108091005763 multidomain proteins Proteins 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003956 nonsteroidal anti androgen Substances 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 238000002161 passivation Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 101150040383 pel2 gene Proteins 0.000 description 1
- 101150050446 pelB gene Proteins 0.000 description 1
- 239000000863 peptide conjugate Substances 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 108010024607 phenylalanylalanine Proteins 0.000 description 1
- 108010083476 phenylalanyltryptophan Proteins 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 206010035114 pityriasis rosea Diseases 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000656 polylysine Chemical group 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000014660 primary cutaneous lymphoma Diseases 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108010025826 prolyl-leucyl-arginine Proteins 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 108010015796 prolylisoleucine Proteins 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000001823 pruritic effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 108010091078 rigin Proteins 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 1
- 108010071207 serylmethionine Proteins 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010381 tandem affinity purification Methods 0.000 description 1
- 229960001712 testosterone propionate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 108010058119 tryptophyl-glycyl-glycine Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 108010035534 tyrosyl-leucyl-alanine Proteins 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
Images
Classifications
-
- 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
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- 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
- A61K39/464411—Immunoglobulin superfamily
-
- 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
- A61K39/464838—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—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
- C07K16/2809—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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57426—Specifically defined cancers leukemia
-
- 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
- A61K2239/48—Blood cells, e.g. leukemia or lymphoma
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- 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
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N2333/7051—T-cell receptor (TcR)-CD3 complex
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Virology (AREA)
Abstract
本公开涉及嵌合抗原受体(CAR),其包含选择性结合TCR beta恒定区1(TRBC1)或TRBC2的抗原结合域;细胞;包含此类CAR的此类T细胞;以及此类细胞用于受试者中T细胞淋巴瘤或白血病的治疗的用途。
Description
本申请是基于申请日为2015年3月5日,最早优先权日为2014年3月5日,申请号为201580011306.X,发明名称为:“具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR)”的专利申请的分案申请。
发明领域
本发明涉及在T细胞淋巴瘤或白血病的治疗中有用的细胞和试剂。
发明背景
淋巴样恶性肿瘤在很大程度上可以分为来源于T细胞或B细胞的那些。T细胞恶性肿瘤是临床上和生物学上异质性的病症组,总共包括10-20%的非霍奇金(Hodgkin)淋巴瘤和20%的急性白血病。最普遍的经鉴定的病理亚型是外周T细胞淋巴瘤,非特指型(peripheral T-cell lymphoma,not otherwise specified)(PTCL-NOS);血管免疫母细胞T细胞淋巴瘤(angio-immunoblastic T-cell lymphoma,AITL)和间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)。在所有急性淋巴母细胞白血病(ALL)中,约20%是T细胞表型的。
与例如B细胞恶性肿瘤相比,这些状况通常表现为侵袭性的,其中估算的5年存活率为仅30%。在T细胞淋巴瘤的情况下,它们与高比例的呈现播散性疾病(disseminateddisease)的患者,不利的国际预后指标(International Prognostic Indicator)(IPI)评分和结外(extra-nodal)疾病的盛行相关。单独化疗通常不是有效的,且少于30%的患者使用目前的治疗得到治愈。
此外,不像B细胞恶性肿瘤,其中免疫疗法例如抗CD20单克隆抗体利妥昔单抗(rituximab)具有显著改善的结果,目前不存在同等有效的,最低限度毒性的免疫疗法可用于T细胞恶性肿瘤的治疗。开发用于T细胞病症的免疫疗法的重大困难是克隆性和正常T细胞的标志物表达的相当多的重叠,其中没有单个抗原明确地能够鉴定克隆性(恶性)细胞。
当靶向全B细胞抗原以治疗B细胞恶性肿瘤时存在相同的问题。然而,在这种情况下,对B细胞区室的伴随的耗竭导致相对轻微的免疫抑制,这是易于被大多数患者忍受的。此外,在导致特别是正常B细胞区室的长期耗竭的疗法中,其丧失可以在很大程度上通过施用汇集的免疫球蛋白来消除。当靶向T细胞恶性肿瘤时,情况完全不同。这里,T细胞区室的伴随耗竭导致严重的免疫抑制和严重的毒性。此外,不存在令人满意的方法来减轻T细胞区室的丧失。
毒性部分通过治疗性单克隆抗体阿仑单抗(Alemtuzumab)的临床效果所揭示。该试剂裂解表达CD52的细胞并在T细胞恶性肿瘤中具有一些效力。该试剂的效用被深切的细胞免疫缺陷大大限制,很大程度上由于T细胞的耗竭,伴随着升高的感染风险。
因此,对于不与以上缺点相关的,用于T细胞恶性肿瘤的靶向治疗的新方法存在需要。
附图简述
图1:αβT细胞受体/CD3复合物的示意图。T细胞受体由6种不同的蛋白链形成,其必须在内质网中组装以表达在细胞表面上。CD3复合物的四种蛋白(CD3ζ,CD3γ,CD3ε和CD3δ)覆盖(sheath)T细胞受体(TCR)。该TCR给所述复合物注入对特定抗原的特异性并由两条链组成:TCRα和TCRβ。每条TCR链具有膜远端的可变组分和膜近端的恒定组分。几乎所有的T细胞淋巴瘤和许多T细胞白血病表达TCR/CD3复合物。
图2:T细胞受体重排期间T细胞受体β-恒定区(TRBC)-1和TRBC-2的分隔(segregation)。每条TCR beta链从特定beta可变(V),多样性(D),连接(J)和恒定(TRBC)区域的基因组重组形成。人基因组含有两个非常相似且功能上等同的TRBC基因座,称作TRBC1和TRBC2。在TCR基因重排期间,J-区与TRBC1或TRBC2重组。该重排是永久性的。T细胞在它们的表面上表达单个TCR的许多拷贝,因此每个T细胞将表达TCR,其β-链恒定区由TRBC1或TRBV2编码。
图3:人TRBC1和TRBC2在氨基酸水平的比对。由TRBC1和TRBC2编码的TCRβ恒定链仅通过4个氨基酸差异而不同:TRBC位置3处的K/N;TRBC位置4处的N/K;TRBC位置36处的F/Y;TRBC位置135处的V/E。
图4:明确证明JOVI-1抗体结合TRBC1而不结合TRBC2。细胞的遗传工程用于明确证明JOVI-1单克隆抗体识别TCRβ恒定链的TRBC1变体。生成了三-顺反子逆转录病毒基因盒(tri-cistronic retroviral cassette)。这编码人TCR的TCRα和TCRβ链两者,所述人TCR识别次要组织相容性抗原HA1,以及截短的人CD34作为方便的标志物基因。天然地,HA1 TCR是TRBC2。生成了第二逆转录病毒基因盒,除了TCRβ恒定区中的4个残基以外其与第一个相同,所述TCRβ恒定区中的4个残基(其区分TRBC1与TRBC2)改变为由TRBC1编码的那些。使用任一载体转导Jurkat T细胞,其的TCRα和TCRβ链两者都被敲除。这些细胞使用全-TCR/CD3抗体或单克隆JOVI-1与针对CD34的抗体联合染色,并在流式细胞仪中分析。上排揭示了使用全-TCR/CD3抗体对CD34(转导的标志物)的染色,下排揭示了使用JOVI-1对CD34的染色。转导的细胞表现出相似的TCR/CD3染色,但仅TRBC1+ve细胞使用JOVI-1染色。因此,JOVI-1对TRBC1是特异性的且进一步使用抗体区分TRBC1和2的TCR是可能的。
图5:JOVI-1mAb通过识别TRBC的残基3和4区分TRBC1与TRBC2。为了精确地确定JOVI-1如何区分TRBC1与TRBC2,突变上文详细描述的HA1 TCR TRBC2构建体以制备两种TRBC1/2杂交体。生成了另外的变体使得仅TCRβ恒定区的残基3和4从TRBC2的那些改变为TRBC1中存在的那些。制成了进一步的变体,其中仅残基36从TRBC2中存在的改变为TRBC1。使用这些新的构建体转导TCR敲除的Jurkat T细胞。图4中描述的初始的TRBC2和TRBC1转导的Jurkat用作对照。Jurkat T细胞使用JOVI-1染色并使用流式细胞仪分析。将JOVI-1的染色重叠在非转导的TCR敲除的Jurkat T细胞的染色上。JOVI-1染色表达TRBC1 TCR而不是TRBC2 TCR的Jurkat。JOVI-1染色其中仅TRBC残基3和4是TRBC1的那些残基的TRBC1/2杂交体。JOVI-1不染色其中仅TRBC残基36是TRBC1的残基的Jurkat T细胞。
图6:TRBC1的正常供体T细胞表达的例子。正常供体外周血单核细胞使用针对CD3、CD4、CD8的抗体和JOVI-1染色并通过流式细胞术分析。CD4+和CD8+T细胞群体示于上组。对该群体的每一个设门和前向散射(forward scatter)对JOVI-1染色分别示于Y和X轴。这些数据表明CD8+和CD4+区室两者都含有TRBC1+ve和–ve的细胞。这是来自一个供体的代表性数据。
图7:几个正常供体中的TRBC1+T细胞。对十个正常供体采血且外周血单核细胞如上文图4中所述的染色。CD4和CD8区室两者中TRBC1 T细胞的比例的汇总数据连同中位数和范围一起示于柱状图。所有的供体具有TRBC1+和TRBC1-区室。TRBC1+细胞的中位数%=36%。
图8:T细胞恶性肿瘤衍生的细胞系使用JOVI-1染色。已经从T细胞恶性肿瘤衍生了几个细胞系。这些细胞系中的许多仍然表达TCR。我们选择了Jurkats(T细胞白血病细胞系),HPB-ALL(另一种T细胞白血病细胞系)和HD-Mar-2(T细胞淋巴瘤细胞系)用于研究。通过使用全-TCR/CD3抗体染色这些细胞,我们能够证明所有的三种表达TCR(左组,染色重叠在同种型对照染色上)。接着,通过使用JOVI-1染色,我们能够确认这些T细胞系是TRBC1阴性或阳性的。仅Jurkats细胞(TRBC1+)而不是HPB-ALL或HD-Mar-2(TRBC2+)被JOVI-1染色,支持TRBC1或2的排他性表达。
图9:使用JOVI-1mAb对TRBC-1T细胞的选择性杀伤。将野生型Jurkat T细胞(CD34-,TRBC1+)与使用和CD34标志物基因共表达的TRBC2转导的TCRαβ敲除Jurkat T细胞(CD34+TRBC2+)混合。将这些细胞与单独JOVI-1孵育或与JOVI-1和补体孵育1小时。洗涤细胞并对CD34,膜联蛋白V和7-AAD染色。通过流式细胞术分析细胞。以下示出的是活的群体中CD34表达,如通过膜联蛋白-V阴性和7-AAD暗群体所确定的。(a)单独JOVI-1;(b)JOVI-1和补体。观察到了对TRBC1 T细胞(CD34-)的选择性杀伤。
图10:多克隆埃巴病毒(EBV)特异性T细胞可以分为两个大约相等的TRBC1/2群体。使用良好建立的方法,发明人选择性扩增了来自正常供体的外周血的EBV特异性T细胞。随后的品系具有高度选择性针对自体EBV感染的B细胞(auto LCLs),和针对异体EBV感染的T细胞(allo LCLs)无活性,和无非特异性NK活性(如通过针对K562细胞测试所测量的)。此类品系是供体的EBV免疫力的代表。(b)当使用JOVI-1染色时,这些T细胞对于TRBC1和TRBC2大约相等分型。
图11:JOVI-1VH和VL的注解序列。高变区加下划线和加粗。
图12:证明外周T细胞淋巴瘤是TRBC限制的,但正常的循环T细胞不是。从具有循环T细胞淋巴瘤细胞的患者抽取了外周血T细胞。分离了外周血单核细胞并使用包括CD5、TCR和JOVI-1的抗体组染色。通过CD5表达强度,可以在流动上区分正常和恶性T细胞。CD5明亮(正常T细胞)具有大约相等的TRBC1和2群体。CD5中等和暗淡群体(肿瘤)都是TRBC2阳性的。如果该患者具有TRBC2导向的疗法,那么该淋巴瘤将被根除,而他们的T细胞的大约一半将被放过。
图13:证明来源于JOVI-1的VH和VL是正确的且它们能够折叠为单链可变片段。原始的杂交瘤上清,重组JOVI-1抗体和从转导的293T细胞生成的scFv-Fc用于染色一些细胞系:Jurkat TCR敲除,野生型Jurkats,使用TRBC1 TCR转导的Jurkat TCR敲除,所述TRBC1TCR在共表达eBFP2的载体中;使用TRBD2 TCR转导的Jurkat TCR敲除,所述TRBD2 TCR在共表达eBFP2的载体中。通过流式细胞术分析染色。重组抗体和scFv两者都结合表达TRBC2的细胞。
图14:不同形式的基于JOVI-1的CAR。CARs通常包含结合域,间隔区,跨膜域和胞内信号传导域。在本研究中生成了CAR,其包含JOVI-1;来源于CD8茎部,人IgG1的铰链-CH2-CH3域(具有去除FcR结合的突变)的间隔区;或来源于人IgG1的间隔区。
图15:基于JOVI-1的CAR的功能。使用上述不同的CAR转导正常供体外周血T细胞。也使用CD19特异性CAR转导T细胞作为对照。接着,这些T细胞使用以下靶细胞攻击:Jurkats-TCR敲除和Jurkats野生型以及Raji细胞(CD19+B细胞淋巴瘤系)。示出了针对不同靶标的效应物的铬释放数据。JOVI-1CAR T细胞杀伤Jurkats但不杀伤Raji细胞或具有TCR敲除的Jurkats。
图16:JOVI-1CAR T细胞培养物的自净化(Self-Purging)。由于T细胞包含大约相等数量的TRBC1或TRBC2阳性的T细胞,可能的是在引入CAR后,培养物的一定量的“相残(fratricide)”或自净化可以发生。证明了情况就是这样。在该例子中,CAR T细胞在转导后染色并通过流式细胞术分析。比较假转导的与转导的,可以观察到该T细胞群体失去了TRBC1阳性T细胞。
图17:调查T细胞大颗粒白血病(T-LGL)的克隆性-患者A
图18:调查T细胞大颗粒白血病(T-LGL)的克隆性-患者B
图19:调查T细胞大颗粒白血病(T-LGL)的克隆性-患者C
图20:调查多克隆T细胞淋巴瘤(PCTL)的克隆性-患者D
图21:TRBC肽噬菌体选择策略。A)在直接或间接固定化到表面上的TRBC肽上的两轮固相噬菌体展示选择。B)在生物素化的TRBC肽上的三轮溶液相噬菌体展示选择。
图22:来自TRBC肽噬菌体展示选择的多克隆噬菌体输出的分析。使用多克隆噬菌体的TRF结合测定,所述多克隆噬菌体来自在直接固定化为BSA/OA缀合物的TRBC肽上进行的固相选择(A),在固定化于链霉亲合素/中性亲合素(neutravidin)的TRBC肽上的固相选择(B)和来自溶液相选择(C)。
图23:pSANG10-3F载体的示意图。将编码单链抗体(scFv)的基因克隆在T7启动子和pelB引导序列(用于周质转位)下游的NcoI/NotI。该载体还含有C末端六组氨酸标签(His6)用于纯化和三FLAG标签检测。
图24:TRBC1和TRBC2特异性结合物的初级筛选。来自TRBC1(A)和TRBC2(B)选择的94个scFvs对生物素化的TRBC1和TRBC2(0.5μg/ml)的结合,所述TRBC1和TRBC2固定化于中性亲合素(10μg/ml)包被的NuncMaxisorpTM96孔板上。使用缀合有铕的抗FLAG抗体检测scFv对固定化的肽的结合。
图25:来自使用TRBC1肽免疫的兔#13174的多克隆抗体血清针对TRBC1和TRBC2肽的结合。(A)第三次免疫后(B)第三次免疫和TRBC1特异性抗体的纯化后。
图26:来自使用TRBC2肽免疫的兔#17363的多克隆抗体血清针对TRBC1和TRBC2肽的结合。(A)第三次免疫后(B)第三次免疫和TRBC2特异性抗体的纯化后。
图27:来自使用TRBC2肽免疫的兔#17364的多克隆抗体血清针对TRBC1和TRBC2肽的结合。(A)第三次免疫后(B)第三次免疫和TRBC2特异性抗体的纯化后。
发明简述
本发明人已经设计了方法,其中在受试者中耗竭恶性T细胞而不影响健康T细胞的显著比例是可能的。具体地,他们已经开发了TRBC1和TRBC2特异性嵌合抗原受体(CAR),用于T细胞恶性肿瘤的治疗中的用途。
因此,在第一个方面中,本发明提供嵌合抗原受体(CAR),其包含选择性结合TCRbeta恒定区1(TRBC1)或TRBC2的抗原结合域。
在本发明的第一个方面的第一个实施方案中,提供选择性结合TRBC1的CAR。在这一实施方案中,CAR可以包含抗原结合域,其具有包含以下互补决定区(CDR)的可变重链(VH)和可变轻链(VL):
VH CDR1:SEQ ID No.7;
VH CDR2:SEQ ID No.8;
VH CDR3:SEQ ID No.9;
VL CDR1:SEQ ID No.10;
VL CDR2:SEQ ID No.11;和
VL CDR3:SEQ ID No.12
CAR可以包含抗原结合域,其包含具有如SEQ ID No.1所示序列的可变重链(VH)和具有如SEQ ID No.2所示序列的可变轻链(VL)。
CAR可以包含抗原结合域,其包含具有如SEQ ID No.3所示的氨基酸序列的scFv。
CAR可以包含选自SEQ ID No.33、34和35的氨基酸序列。
CAR可以包含来自表1中列出的那些的VH CDR3和/或VL CDR3。
CAR可以包含抗体或其功能片段,其包含:
(1)重链CDR3和/或轻链CDR3;
(ii)重链CDR1、CDR2和CDR3和/或轻链CDR1、CDR2和CDR3;或
(iii)可变重链(VH)和/或可变轻链(VL);来自如SEQ ID No.13至22所示的scFvs的一个。
在本发明的第一个方面的第二个实施方案中,提供选择性结合TRBC2的CAR。
与此实施方案相关,CAR可以包含来自表2中列出的那些的VH CDR3和/或VL CDR3。
CAR可以包含抗体或其功能片段,其包含:
(i)重链CDR和/或所述轻链CDR3;
(ii)重链CDR1、CDR2和CDR3和/或轻链CDR1、CDR2和CDR3;或
(iii)可变重链(VH)和/或可变轻链(VL);来自如SEQ ID No.23至32所示的scFvs的一个。
在第二个方面,本发明提供编码根据本发明的第一个方面的CAR的核酸序列。
在第三个方面,提供载体,其包含根据本发明的第二个方面的核酸序列。
在第四个方面,提供细胞,其包含根据本发明的第一个方面的CAR。细胞可以是细胞溶解性免疫细胞,例如T细胞或天然杀伤(NK)细胞。
在第五个方面,提供用于制备根据本发明的第四个方面的细胞的方法,其包括使用根据本发明的第二个方面的核酸序列或根据本发明的第三个方面的载体转导或转染细胞的步骤。
在第六个方面,提供根据本发明的第四个方面的细胞,用于在用于治疗受试者中T细胞淋巴瘤或白血病的方法中的用途,所述方法包括以下步骤
将包含TCRB1或TCRB2选择性CAR的细胞施用至受试者,以引起恶性T细胞连同与恶性T细胞表达相同TRBC的正常T细胞的选择性耗竭,而不引起表达恶性T细胞不表达的TRBC的正常T细胞的耗竭。
方法还可以包括调查来自受试者的恶性T细胞的TCR beta恒定区(TCRB)的步骤,以确定其是否表达TRBC1或TRBC2。
还提供用于治疗受试者中T细胞淋巴瘤或白血病的方法,其包括向所述受试者施用TCRB1或TCRB2选择性试剂的步骤,其中所述试剂导致恶性T细胞连同与恶性T细胞表达相同TRBC的正常T细胞的选择性耗竭,而不引起表达恶性T细胞不表达的TRBC的正常T细胞的耗竭。
在本发明的这一方面的第一个实施方案中,试剂是TCRB1选择性试剂。在本发明的这一方面的第二个实施方案中,试剂是TRBC2选择性试剂。
方法还可以包括在施用步骤前调查恶性T细胞的TCR beta恒定区(TRBC),以确定其是否表达TRBC1或TRBC2的步骤。
试剂可以是耗竭性(depleting)单克隆抗体或其片段。试剂可以是缀合的抗体,其可以包含化疗实体。
试剂可以是双特异性T细胞结合剂(engager)。试剂可以是表达嵌合抗原受体(CAR)的T细胞。CAR可以包含选择下组的氨基酸序列:SEQ ID No.33,34和35。
试剂可以包含JOVI-1抗体或其功能片段。
试剂可以包含具有包含以下互补决定区(CDR)的可变重链(VH)和可变轻链(VL)的抗体或其功能片段:
VH CDR1:SEQ ID No.7;
VH CDR2:SEQ ID No.8;
VH CDR3:SEQ ID No.9;
VL CDR1:SEQ ID No.10;
VL CDR2:SEQ ID No.11;和
VL CDR3:SEQ ID No.12
试剂可以包含抗体或其功能片段,其包含具有如SEQ ID No.1所示的氨基酸序列的可变重链(VH)和具有如SEQ ID No.2所示的氨基酸序列的可变轻链(VL)。
试剂可以包含具有如SEQ ID No.3所示的氨基酸序列的scFv。试剂可以作为药物组合物提供。
T细胞淋巴瘤或白血病可以选自外周T细胞淋巴瘤,非特指型(PTCL-NOS);血管免疫母细胞T细胞淋巴瘤(AITL),间变性大细胞淋巴瘤(ALCL),肠病相关的T细胞淋巴瘤(EATL),肝脾T细胞淋巴瘤(HSTL),结外NK/T细胞淋巴瘤鼻型,皮肤T细胞淋巴瘤,原发性皮肤ALCL,T细胞幼淋巴细胞白血病和T细胞急性淋巴母细胞白血病。
本发明还提供试剂,用于根据此类方法治疗T细胞淋巴瘤或白血病中的用途。
本发明还提供试剂盒,包含用于如上文所定义的用途的试剂。
本发明还提供了试剂在制备用于根据上述方法治疗T细胞淋巴瘤或白血病的药物中的用途。
本发明还提供用于诊断受试者中T细胞淋巴瘤或白血病的方法,其包括确定样品中呈TRBC1或TRBC2阳性的总T细胞的百分比的步骤。
TRBC1或TRBC2阳性T细胞的百分比大于约80%指示T细胞淋巴瘤或白血病的存在。
样品可以是外周血样品或活组织检查(biopsy)。
结合总T细胞的试剂可以结合CD3。
本发明包括以下实施方案。
实施方案1.嵌合抗原受体(CAR),其包含选择性结合TCR beta恒定区1(TRBC1)或TRBC2的抗原结合域。
实施方案2.根据实施方案1的CAR,其选择性结合TRBC1。
实施方案3.根据实施方案2的CAR,其中所述抗原结合域具有可变重链(VH)和可变轻链(VL),其包含以下互补决定区(CDR):
VH CDR1:SEQ ID No.7;
VH CDR2:SEQ ID No.8;
VH CDR3:SEQ ID No.9;
VL CDR1:SEQ ID No.10;
VL CDR2:SEQ ID No.11;和
VL CDR3:SEQ ID No.12。
实施方案4.根据实施方案2的CAR,其中所述抗原结合域包含具有如SEQ ID No.1所示的序列的可变重链(VH)和具有如SEQ ID No.2所示的序列的可变轻链(VL)。
实施方案5.根据实施方案2的CAR,其中所述抗原结合域包含具有如SEQ ID No.3所示的氨基酸序列的scFv。
实施方案6.根据实施方案2的CAR,其包含选自SEQ ID No.4、5和6的氨基酸序列。
实施方案7.根据实施方案1的CAR,其选择性结合TRBC2。
实施方案8.编码根据前述实施方案任一项的CAR的核酸序列。
实施方案9.包含根据实施方案8的核酸序列的载体。
实施方案10.包含根据实施方案1至7任一项的CAR的细胞。
实施方案11.根据实施方案10的T细胞。
实施方案12.用于制备根据实施方案10或11的细胞的方法,其包括使用根据实施方案8的核酸序列或根据实施方案9的载体转导或转染细胞的步骤。
实施方案13.根据实施方案10或11的细胞,用于在治疗受试者中T细胞淋巴瘤或白血病的方法中的用途,所述方法包括以下步骤:
将包含TCRB1或TCRB2选择性CAR的细胞施用至所述受试者,以引起恶性T细胞以及与所述恶性T细胞表达相同TRBC的正常T细胞的选择性耗竭,但不引起表达所述恶性T细胞不表达的TRBC的正常T细胞的耗竭。
实施方案14.根据实施方案13的用途的细胞,其中所述方法还包括调查来自所述受试者的恶性T细胞的TCR beta恒定区(TCRB)以确定其是否表达TRBC1或TRBC2的步骤。
实施方案15.根据实施方案13或14的用途的细胞,其中所述T细胞淋巴瘤或白血病选自外周T细胞淋巴瘤,非特指型(PTCL-NOS);血管免疫母细胞T细胞淋巴瘤(AITL),间变性大细胞淋巴瘤(ALCL),肠病相关的T细胞淋巴瘤(EATL),肝脾T细胞淋巴瘤(HSTL),结外NK/T细胞淋巴瘤鼻型,皮肤T细胞淋巴瘤,原发性皮肤ALCL,T细胞幼淋巴细胞白血病和T细胞急性淋巴母细胞白血病。
实施方案16.用于诊断受试者中T细胞淋巴瘤或白血病的方法,其包括确定分离自所述受试者的样品中呈TRBC1或TRBC2阳性的总T细胞的百分比的步骤。
实施方案17.根据实施方案16的方法,其中TRBC1或TRBC2阳性T细胞的百分比大于约80%指示T细胞淋巴瘤或白血病的存在。
实施方案18.根据实施方案16或17的方法,其中所述样品是外周血样品或活组织检查。
实施方案19.根据实施方案16至18任一项的方法,其中使用结合CD3的试剂在所述样品中鉴定或从所述样品分离总T细胞。
发明详述
本发明提供选择性结合TRBC1或TRBC2的试剂,如嵌合抗原受体(CARs)。此类试剂在用于治疗受试者中的T细胞淋巴瘤或白血病的方法中是有用的。T细胞恶性肿瘤是克隆性的,因此它们表达TRBC1或TRBC2。通过施用TCRB1或TCRB2选择性试剂至受试者,试剂引起恶性T细胞连同与恶性T细胞表达相同TRBC的正常T细胞的选择性耗竭,而不引起表达恶性T细胞不表达的TRBC的正常T细胞的耗竭。
TCRβ恒定区(TRBC)
T细胞受体(TCR)在T淋巴细胞的表面上表达,并负责识别结合至主要组织相容性复合物(MHC)分子的抗原。当TCR结合抗原肽和MHC(肽/MHC)时,T淋巴细胞通过一系列生物化学事件活化,所述生物化学事件由相关的酶,共受体,特化的衔接头(adaptor)分子,和活化或释放的转录因子介导。
TCR是二硫键连接的膜锚定异二聚体,通常由高度可变的alpha(α)和beta(β)链组成,作为与不变的CD3链分子的复合物的一部分表达。表达该受体的T细胞称为α:β(或αβ)T细胞(~95%总T细胞)。少数T细胞表达替换受体,由可变gamma(γ)和deta(δ)链形成,并称作γδT细胞(~5%总T细胞)。
每条α和β链由两个胞外域组成:可变(V)和恒定(C)区,两者都是形成反向平行的β-片层的免疫球蛋白超家族(IgSF)域的。恒定区与细胞膜靠近,接着是跨膜区和短胞质尾部,而可变区结合肽/MHC复合物(见图1)。TCR的恒定区由短的连接序列组成,其中半胱氨酸形成二硫键,其形成两条链之间的连接。
TCRα-链和β-链两者的可变域具有三个超变或互补决定区(CDRs)。β-链的可变区还可以具有另外的超变区域(HV4),然而,这通常不接触抗原并因此认为不是CDR。
TCR还可以包含多达五个不变链γ、δ、ε(统称为CD3)和ζ。在抗原被αβ或γδ识别后,CD3和ζ亚基通过特定的胞质域介导TCR信号传导,所述胞质域与第二信使和衔接头分子相互作用。TCR复合物的细胞表面表达之前是亚基的成对(pair-wise)组装,其中TCRα和β以及CD3γ和δ的跨膜和胞外域两者都发挥作用。
因此,TCR通常由CD3复合物和TCRα和β链组成,其继而由可变和恒定区组成(图1)。
提供TCRβ-恒定区(TRBC)的基因座(Chr7:q34)在进化史中已经复制以产生两个几乎相同且功能等同的基因:TRBC1和TRBC2(图2),其差异仅在于各自产生的成熟蛋白中的4个氨基酸(图3)。每个TCR将以互相排斥的方式包含TRBC1或TRBC2,而因此,每个αβT细胞将以互相排斥的方式表达TRBC1或TRBC2。
本发明人已经确定了,尽管TRBC1和TRBC2的序列之间的相似性,区分它们是可能的。本发明人也已经确定了可以在细胞(例如T细胞)表面上原位区分TRBC1和TRBC2的氨基酸序列。
恶性细胞
术语“恶性”用于本文根据其标准含义指代细胞,其生长不是自我限制的,可以能够侵入临近组织并可以能够扩散到远端组织。因而,术语“恶性T细胞”用于本文指代在淋巴瘤或白血病的情况下克隆扩增的T细胞。
本发明的方法涉及确定恶性T细胞的TRBC。这可以使用本领域已知的方法进行。例如,可以通过PCR,western印迹,流式细胞术,或荧光显微术方法确定。
一旦已经确定了恶性T细胞表达的TRBC,将适合的TRBC1或TRBC2选择性试剂施用至受试者。“适合的TRBC选择性试剂”表示在恶性T细胞确定为表达TRBC1的情况下,施用TRBC1选择性试剂,而在恶性T细胞确定为表达TRBC2的情况下,施用TRBC2选择性试剂。
选择性试剂
选择性试剂以互相排斥的方式结合TRBC1或TRBC2。
如上文所述,每个αβT细胞表达TCR,其包含TRBC1或TRBC2。在克隆T细胞病症如T细胞淋巴瘤或白血病中,来源于相同克隆的恶性T细胞将全部表达TRBC1或TRBC2。
因此,本方法包括施用TRBC1或TRBC2选择性试剂至受试者的步骤,其中试剂导致恶性T细胞连同与恶性T细胞表达相同TRBC的正常T细胞的选择性耗竭,而不引起与恶性T细胞相比表达另一种TRBC的正常T细胞的显著耗竭。
因为TRBC选择性试剂不引起与恶性T细胞相比表达另一种TRBC的正常T细胞的显著耗竭,其不引起整个T细胞区室的耗竭。一定比例的患者T细胞区室的保留(即不表达与恶性T细胞相同TRBC的T细胞)导致降低的毒性和减低的细胞和体液免疫缺陷,从而降低感染的风险。
根据本发明的方法,TRBC1选择性试剂的施用可以导致5,10,20,50,75,90,95或99%耗竭,即表达TRBC1的T细胞数量的减少。
根据本发明的方法,TRBC2选择性试剂的施用可以导致5,10,20,50,75,90,95或99%耗竭,即表达TRBC2的T细胞数量的减少。
TRBC1选择性试剂可以以TRBC2的大至少2倍,4倍,5倍,7倍或10倍的亲和力结合TRBC1。相似地,TRBC2选择性试剂可以以TRBC1的大至少2倍,4倍,5倍,7倍或10倍的亲和力结合TRBC2。
TRBC1选择性试剂引起细胞群体中比表达TRBC2的细胞更大比例的表达TRBC1的T细胞的耗竭。例如,表达TRBC1的T细胞比表达TRBC2的细胞的耗竭的比率可以为至少60%:40%,70%:30%,80%:20%,90%:10%或95%:5%。相似地,TRBC2选择性试剂引起细胞群体中比表达TRBC2的细胞更大比例的表达TRBC1的T细胞的耗竭。例如,表达TRBC2的T细胞比表达TRBC1的细胞的耗竭的比率可以为至少60%:40%,70%:30%,80%:20%,90%:10%或95%:5%。
使用本发明的方法,受试者中的恶性T细胞被耗竭,而不影响相当大比例的健康T细胞。通过“相当大比例”表示的是为了维持受试者中T细胞的功能,足够比例的与恶性T细胞表达不同TRBC的T细胞存活。试剂可以导致表达另一种TCRB的T细胞群体的少于20%,15%,10%或5%的耗竭。
选择性试剂可以是对于TRBC1或TRBC2是选择性的,因为其区分如下列出的残基:
(i)TRBC位置3处N与K;
(ii)TRBC位置3处K与N;
(iii)TRBC位置4处K与N;
(iv)TRBC位置4处N与K;
(v)TRBC位置36处F与Y;
(vi)TRBC位置36处Y与F;
(vii)TRBC位置135处V与E;和/或
(viii)TRBC位置135处E与V。
选择性试剂可以区分上述差异的任意差异组合。
抗体
本发明的方法中使用的试剂可以是耗竭性单克隆抗体(mAb)或其功能片段,或抗体模拟物(antibody mimetic)。
术语“耗竭性抗体”以其常规意义使用,涉及结合靶T细胞上存在的抗原并介导靶T细胞的死亡的抗体。因此,施用耗竭性抗体至受试者导致受试者中表达靶抗原的细胞的数量降低/减少。
如本文所用的,“抗体”表示具有抗原结合位点的多肽,所述抗原结合位点包括至少一个互补决定区CDR。抗体可以包含3个CDR并具有与域抗体(dAb)等同的抗原结合位点。抗体可以包含6个CDR,并具有与经典抗体分子等同的抗原结合位点。多肽的剩余部分可以是任意序列,其提供用于抗原结合位点的适合支架,并以对于其结合抗原适合的方式展示它。抗体可以是整个免疫球蛋白分子或其部分,例如Fab,F(ab)’2,Fv,单链Fv(ScFv)片段或纳米抗体。抗体可以是双功能抗体。抗体可以是非人的,嵌合的,人源化的或全人的。
因此,抗体可以是任意功能片段,其保留了全长抗体的抗原特异性。
TRBC1选择性抗体
用于本发明的方法中的试剂可以包含抗体或其功能片段,所述抗体或功能片段具有可变重链(VH)和可变轻链(VL),其包含一个或多个以下互补决定区(CDR):
VH CDR1:GYTFTGY(SEQ ID No.7);
VH CDR2:NPYNDD(SEQ ID No.8);
VH CDR3:GAGYNFDGAYRFFDF(SEQ ID No.9);
VL CDR1:RSSQRLVHSNGNTYLH(SEQ ID No.10);
VL CDR2:RVSNRFP(SEQ ID No.11);和
VL CDR3:SQSTHVPYT(SEQ ID No.12)
相比于如SEQ ID No.7至12给出的序列,一个或多个CDR每个独立地可以包含或不包含一个或多个氨基酸突变(例如,取代),只要所得的抗体保留了选择性结合TRBC1的能力。
研究已经表明CDR L3和H3普遍地负责与抗原的高能量相互作用,因此抗体或其功能性片段可以包含如上文所述的VH CDR3和/或VL CDR3。
使用噬菌体展示,已经鉴定了几个另外的抗体结合域,其对于结合TRBC1相对于结合TRBC2是高度选择性的,如实施例12中所描述的。
试剂可以包含抗体或其功能性片段,所述抗体或其功能性片段具有可变重链(VH)和/或可变轻链(VL),其包含表1中示出的一个或多个互补决定区(CDR3)。
表1
在试剂是域抗体的情况下,其可以包含3个CDR,即VH CDR1-CD3R或VL CDR1-CDR3。
试剂可以包含抗体或其功能部分,其包含具有如SEQ ID No.1所示的氨基酸序列的可变重链(VH)和具有如SEQ ID No.2所示的氨基酸序列的可变轻链(VL)。
SEQ_ID_1 Jovi-1 VH
EVRLQQSGPDLIKPGASVKMSCKASGYTFTGYVMHWVKQRPGQGLEWIGFINPYNDDIQSNERFRGKATLTSDKSSTTAYMELSSLTSEDSAVYYCARGAGYNFDGAYRFFDFWGQGTTLTVSS
SEQ_ID_2 Jovi-1 VL
DVVMTQSPLSLPVSLGDQASISCRSSQRLVHSNGNTYLHWYLQKPGQSPKLLIYRVSNRFPGVPDRFSGSGSGTDFTLKISRVEAEDLGIYFCSQSTHVPYTFGGGTKLEIKR
试剂可以包含具有如SEQ ID No.3所示的氨基酸序列的scFv。
SEQ_ID_3 Jovi-1scFv
EVRLQQSGPDLIKPGASVKMSCKASGYTFTGYVMHWVKQRPGQGLEWIGFINPYNDDIQSNERFRGKATLTSDKSSTTAYMELSSLTSEDSAVYYCARGAGYNFDGAYRFFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDVVMTQSPLSLPVSLGDQASISCRSSQRLVHSNGNTYLHWYLQKPGQSPKLLIYRVSNRFPGVPDRFSGSGSGTDFTLKISRVEAEDLGIYFCSQSTHVPYTFGGGTKLEIKR
或者,试剂可以包含抗体或其功能片段,其包含:
(i)重链CDR3和/或轻链CDR3;
(ii)重链CDR1、CDR2和CDR3和/或轻链CDR1、CDR2和CDR3;或
(iii)可变重链(VH)和/或可变轻链(VL);
来自如SEQ ID No.13至22所示的scFvs的一个。
在如SEQ ID No.13-22所示的序列中,序列的VH和VL部分加粗示出,且重链和轻链的CDR1和CDR2序列下划线标出。VH和VL的CDR3序列在表1中给出。
SEQ ID No.13_(CP_01_E09)
SEQ ID No.14(CP_01_D12)
SEQ ID No.15(CP_01_D10)
SEQ ID No.16(CP_01_C08)
SEQ ID No.17(CP_01_C11)
SEQ ID No.18(CP_01_F03)
SEQ ID No.19(CP_01_E07)
SEQ ID No.20(CP_01_D03)
SEQ ID No.21(CP_01_F06)
SEQ ID No.22(CP_01_F02)
TRBC2-特异性
使用噬菌体展示,已经鉴定了几个抗体结合域,其对于结合TRBC2相对于结合TRBC1是高度选择性的,如实施例12中所描述的。
试剂可以包含抗体或其功能性片段,所述抗体或其功能性片段具有可变重链(VH)和/或可变轻链(VL),其包含表2中示出的一个或多个互补决定区(CDR3s)。
表2
试剂可以包含抗体或其功能片段,其包含:
(i)重链CDR3和/或轻链CDR3;
(ii)重链CDR1、CDR2和CDR3和/或轻链CDR1、CDR2和CDR3;或
(iii)可变重链(VH)和/或可变轻链(VL);
来自如SEQ ID No.23-32所示的scFvs的一个。
在如SEQ ID No.23-32所示的序列中,序列的VH和VL部分加粗示出,且重链和轻链的CDR1和CDR2序列下划线标出。VH和VL的CDR3序列在表2中给出。
SEQ ID No.23(CP_03_E05)
SEQ ID No.24(CP_03_D05)
SEQ ID No.25(CP_03_H06)
SEQ ID No.26(CP_03_C12)
SEQ ID No.27(CP_03_G02)
SEQ ID No.28(CP_03_D04)
SEQ ID No.29(CP_03_F10)
SEQ ID No.30(CP_03_G09)
SEQ ID No.31(CP_03_F09)
SEQ ID No.32(CP_03_D09)
以上氨基酸序列的变体也可以用于本发明,只要所得的抗体结合TRBC1或TRBC2且不显著交叉反应。典型地,此类变体与上文指定序列的一个具有高度序列同一性。
用于比较的序列的比对方法是本领域中公知的。
NCBI Basic Local Alignment Search Tool(BLAST)从几个来源可用,包括National Center for Biotechnology Information(NCBI,Bethesda,Md.)和互联网,用于与序列分析程序blastp,blastn,blastx,tblastn和tblastx相关使用。如何使用该程序确定序列同一性的说明可以在互联网上的NCBI网站上获得。
VL或VH域或scFv的变体通常具有与如SEQ ID No.1-3,13-32所给出的序列至少约75%,例如至少约80%,90%,95%,96%,97%,98%或99%的序列同一性。
典型地,相比于原始氨基酸或核酸序列,变体可以含有一个或多个保守氨基酸取代。保守取代是不实质上影响或降低抗体结合TRBC1或TRBC2的亲和力的那些取代。例如,特异性结合TRBC1或TRBC2的人抗体相比于如SEQ ID No.1-3或13-32所给出的任何序列,可以在VH或VL之任一或两者中包括多达1个,多达2个,多达5个,多达10个,或多达15个的保守取代并保留对TRBC1或TRBC2的特异性结合。
可以通过保守取代的方式交换的功能上相似的氨基酸对于本领域的普通技术人员是公知的。以下六组是认为对于彼此是保守取代的氨基酸的例子:1)丙氨酸(A),丝氨酸(S),苏氨酸(T);2)天冬氨酸(D),谷氨酸(E);3)天冬酰胺(N),谷氨酰胺(Q);4)精氨酸(R),赖氨酸(K);5)异亮氨酸(I),亮氨酸(L),甲硫氨酸(M),缬氨酸(V)和6)苯丙氨酸(F),酪氨酸(Y),色氨酸(W)。
抗体的制备
可以使用标准的实验室技术进行抗体的制备。可以从动物血清获得抗体,或者,在单克隆抗体或其片段的情况下,在细胞培养物中产生。可以使用重组DNA技术根据建立的程序在细菌或哺乳动物细胞培养物中产生抗体。
用于单克隆抗体的产生的方法是本领域中公知的。简单的说,通常通过将骨髓瘤细胞与来自已经使用期望的抗原免疫的小鼠或兔的脾细胞融合来制备单克隆抗体。本文中,期望的抗原是TRBC1或TRBC2肽,或包含TRBC1或TRBC2的TCRβ链。
或者,可以通过以重组的方式组合VH和VL链的文库,在免疫系统之外制备抗体和相关的分子,特别是scFv。可以使用如实施例12所述的噬菌体展示技术构建和筛选此类文库。
鉴定TRBC1/TRBC2选择性抗体
可以使用本领域中标准的方法鉴定对于TRBC1或TRBC2选择性的抗体。用于确定抗体的结合特异性的方法包括但不限于,ELISA,western印迹,免疫组织化学,流式细胞术,共振能量转移(FRET),噬菌体展示文库,酵母双杂交筛选,共免疫沉淀,双分子荧光互补和串联亲和纯化。
为了鉴定对于TRBC1或TRBC2选择性的抗体,评估了抗体对TRBC1和TRBC2每一个的结合。典型地,这是通过确定抗体分别对每一个TRBC的结合来评估。抗体选择性结合TRBC1或TRBC2而不显著结合另一种TRBC。
抗体模拟物
或者,试剂可以是不来源于或基于免疫球蛋白的分子。已经发展了一些“抗体模拟物”设计的重复蛋白(DRPs)以开发非抗体多肽的结合能力。
重复蛋白如锚蛋白(ankyrin)或富含亮氨酸的重复蛋白是独特的结合分子,不像抗体,其发生于细胞内和细胞外。它们独特的模块架构特征重复结构单元(重复),其堆叠在一起以形成延长的重复域,展现出可变的和模块靶标结合表面。基于这一模块性,可以产生具有高度多样化的结合特异性的多肽的组合文库。DARPins(设计的锚蛋白重复蛋白)是基于该技术的抗体模拟物的一个例子。
对于Anticalins,结合特异性来源于脂质运载蛋白(lipocalins),即实施与化学敏感性或不溶性化合物的生理运输和储存相关的一批体内功能的蛋白家族。脂质运载蛋白具有强的(robust)内在结构,包括高度保守的β-桶,其支持所述蛋白一个末端处的四个环。用于进入结合口袋的这些环和该分子的这部分中的构象差异负责不同脂质运载蛋白之间的结合特异性的变化。
Avimers从人细胞外受体域的大家族进化,通过体外外显子改组(exonshuffling)和噬菌体展示,产生具有结合和抑制特性的多结构域蛋白。
Versabodies是具有>15%的半胱氨酸的3-5kDa的小蛋白,其形成高二硫键密度支架,替代大多数蛋白中存在的疏水核心。大量疏水性氨基酸,包括疏水核心被少量二硫化物的替换导致较小的,更亲水的,对蛋白酶和热更抗性的,并具有较低密度T细胞表位的蛋白。这些特性的所有四种导致具有大大降低的免疫原性的蛋白。它们也可以在大肠杆菌中制备,并是高度可溶和稳定的。
缀合物
抗体或模拟物可以是抗体或模拟物和另一种试剂或抗体的缀合物,例如缀合物可以是可检测实体或化疗实体。
可检测实体可以是荧光部分,例如荧光肽。“荧光肽”指代多肽,其在激发后,发射可检测波长的光。荧光蛋白的例子包括但不限于,异硫氰酸荧光素(FITC),藻红蛋白(PE),别藻蓝蛋白(APC),绿色荧光蛋白(GFP),增强的绿色荧光蛋白,红色荧光蛋白(RFP),蓝色荧光蛋白(BFP)和mCherry。
与可检测实体缀合的选择性TRBC1或TRBC2试剂可以用于确定恶性T细胞的TRBC。
化疗实体如用于本文指代对细胞破坏性的实体,也就是降低细胞的生存力的实体。该化疗试剂可以是细胞毒性药物。考虑的化疗试剂包括但不限于,烷化剂,亚硝基脲,乙烯亚胺/甲基三聚氰胺,烷基磺酸盐,抗代谢物,嘧啶类似物,表鬼臼毒素(epipodophylotoxins),酶例如L-天冬酰胺酶;生物反应调节剂,如干扰素α,IL-2,G-CSF和GM-CSF;铂配位络合物,如顺铂和卡铂,蒽二酮(anthracenediones),取代脲例如羟基脲,甲基肼衍生物包括N-甲基肼(MIH)和甲基苄肼,肾上腺皮质抑制剂,如米托坦(o,p'-DDD)和氨鲁米特;激素和拮抗剂,包括肾上腺皮质类固醇拮抗剂例如强的松(prednisone)和等同物,地塞米松和氨鲁米特;孕激素例如己酸羟孕酮,醋酸甲羟孕酮和醋酸甲地孕酮;雌激素例如己烯雌酚(diethylstilbestrol)和炔雌醇等同物;抗雌激素如他莫昔芬(tamoxifen);雄激素包括丙酸睾酮和氟甲睾酮/等同物;抗雄激素如氟他胺,促性腺激素释放激素类似物和亮丙瑞林(leuprolide);和非类固醇抗雄激素,如氟他胺(flutamide)。
缀合有化疗实体的TRBC选择性试剂使得能够将化疗实体靶向递送至表达TRBC1或TRBC2的细胞。
双特异性T细胞结合剂
已经开发了极其多种基于具有两个抗体样结合域的基本概念的分子。
双特异性T细胞结合分子是一类已经开发的双特异性抗体类分子,主要用于抗癌症药物的用途。它们将宿主的免疫系统,更具体地T细胞的细胞毒性活性,引导针对靶细胞如癌细胞。在这些分子中,一个结合域通过CD3受体结合T细胞,而另一个结合靶细胞如肿瘤细胞(通过肿瘤特异性分子)。由于双特异性分子结合靶细胞和T细胞两者,其将靶细胞带到与T细胞临近,使得T细胞能够发挥其效果,例如,对癌细胞的细胞毒性效果。T细胞:双特异性Ab:癌细胞复合物的形成诱导T细胞中的信号传导,引起例如细胞毒性介导物的释放。理想地,试剂在靶细胞的存在下仅诱导期望的信号传导,引起选择性杀伤。
已经以一些不同的形式开发了双特异性T细胞结合分子,但是最普遍的一个是由不同抗体的两个单链可变片段(scFv)组成的融合物。这些有时称为BiTEs(双特异性T细胞结合剂)。
本发明的方法中使用的试剂可以是双特异性分子,其选择性识别TRBC1或TRBC2,并能够活化T细胞。例如,试剂可以是BiTE。方法中使用的试剂可以包含:
(i)结合TRBC1或TRBC2的第一结构域;和
(ii)能够活化T细胞的第二结构域。
双特异性分子可以包含信号肽以帮助其产生。信号肽可以引起双特异性分子被宿主细胞分泌,使得可以从宿主细胞的上清收获双特异性分子。
信号肽可以在分子的氨基末端。双特异性分子可以具有以下通式:信号肽-第一结构域-第二结构域。
双特异性分子可以包含间隔序列以连接第一结构域与第二结构域并在空间上分开两个结构域。
间隔序列可以例如包含IgG1铰链或CD8茎部。接头可以可选包括备选接头序列,其具有与IgG1铰链或CD8茎部相似的长度和/或结构域间隔特性。
双特异性分子可以包含JOVI-1,或其功能性片段,如上文所定义的。
嵌合抗原受体(CAR)
嵌合抗原受体(CAR),也称为嵌合T细胞受体,人工T细胞受体和嵌合免疫受体,是工程化的受体,其将任意特异性嫁接到免疫效应细胞上。在经典的CAR中,将单克隆抗体的特异性嫁接到T细胞上。可以使用例如逆转录病毒载体将编码CAR的核酸转移到T细胞中。以这种方式,可以产生大量癌症特异性的T细胞用于过继细胞转移。该方法的I期临床研究表现出效力。
CAR的靶抗原结合域通常经由间隔区和跨膜域融合至胞内域,其包含细胞内T细胞信号传导域,或与细胞内T细胞信号传导域相关联。当CAR结合靶抗原时,这导致活化信号传输至它在上面表达的T细胞。
本发明的方法中使用的试剂可以是CAR,其选择性识别TRBC1或TRBC2。试剂可以是表达选择性识别TRBC1或TRBC2的CAR的T细胞。
CAR还可以包含跨越膜的跨膜域。其可以包含疏水alpha螺旋。跨膜域可以来源于CD28,其给予良好的受体稳定性。
胞内域是CAR参与信号传输的部分。胞内域包含细胞内T细胞信号传导域,或与细胞内T细胞信号传导域相关联。在抗原识别后,受体簇集且信号传输至细胞。最普遍使用的T细胞信号传导组分是CD3-zeta的,其含有3个ITAM。在抗原结合后,这将活化信号传输至T细胞。CD3-zeta可以不提供完全有能力的活化信号,可以需要另外的共刺激信号。例如,嵌合CD28和OX40可以与CD3-Zeta一起使用以传输增殖/存活信号,或所有三种可以一起使用。
CAR的胞内域可以包含CD28胞内域和OX40和CD3-Zeta胞内域。
CAR可以包含信号肽,使得当CAR表达在细胞如T细胞内时,初生蛋白被引导至内质网和随后到细胞表面,在那里其被表达。
CAR可以包含间隔序列以连接TRBC结合域与跨膜域并在空间上将TRBC结合域从胞内域分开。柔性间隔区允许TRBC结合域在不同的方向定向,以实现TRBC结合。
间隔序列可以例如包含IgG1 Fc区,IgG1铰链或CD8茎部,或其组合。接头可以可选包含备选接头序列,其具有与IgG1 Fc区,IgG1铰链或CD8茎部相似的长度和/或结构域间隔特性。
发现包含基于IgG1铰链或CD8茎部的间隔区的CAR表现出针对Jurkat细胞最好的表现(图15)。因此,间隔区可以包含IgG1铰链或CD8茎部,或具有与IgG1铰链或CD8茎部相似的长度和/或结构域间隔特性的间隔区。
可以改变人IgG1间隔区以去除Fc结合基序。
CAR可以包含JOVI-1抗体,或其功能片段,如上文定义的。
CAR可以包含选自下组的氨基酸序列:SEQ ID No.33、34和35。
>SEQ_ID_33具有CD8茎部间隔区的JOVI-1CAR
METDTLLLWVLLVWIPGSTGEVRLQQSGPDLIKPGASVKMSCKASGYTFTGYVMHWVKQRPGQGLEWIGFINPYNDDIQSNERFRGKATLTSDKSSTTAYMELSSLTSEDSAVYYCARGAGYNFDGAYRFFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDVVMTQSPLSLPVSLGDQASISCRSSQRLVHSNGNTYLHWYLQKPGQSPKLLIYRVSNRFPGVPDRFSGSGSGTDFTLKISRVEAEDLGIYFCSQSTHVPYTFGGGTKLEIKRSDPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKIRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
>SEQ_ID_34具有H-CH2-CH3 pvaa间隔区的JOVI-1CAR
METDTLLLWVLLVWIPGSTGEVRLQQSGPDLIKPGASVKMSCKASGYTFTGYVMHWVKQRPGQGLEWIGFINPYNDDIQSNERFRGKATLTSDKSSTTAYMELSSLTSEDSAVYYCARGAGYNFDGAYRFFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDVVMTQSPLSLPVSLGDQASISCRSSQRLVHSNGNTYLHWYLQKPGQSPKLLIYRVSNRFPGVPDRFSGSGSGTDFTLKISRVEAEDLGIYFCSQSTHVPYTFGGGTKLEIKRSDPAEPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKKDPKFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKIRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
>SEQ_ID_35具有IgG1铰链间隔区的JOVI-1CAR
METDTLLLWVLLVWIPGSTGEVRLQQSGPDLIKPGASVKMSCKASGYTFTGYVMHWVKQRPGQGLEWIGFINPYNDDIQSNERFRGKATLTSDKSSTTAYMELSSLTSEDSAVYYCARGAGYNFDGAYRFFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDVVMTQSPLSLPVSLGDQASISCRSSQRLVHSNGNTYLHWYLQKPGQSPKLLIYRVSNRFPGVPDRFSGSGSGTDFTLKISRVEAEDLGIYFCSQSTHVPYTFGGGTKLEIKRSDPAEPKSPDKTHTCPPCPKDPKFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKIRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
在上文给出的CAR序列中,6个CDR的一个或多个各种独立地可以包含或不包含与SEQ ID No.7至12给出的序列相比一个或多个氨基酸突变(例如,取代),只要所得的CAR保留了结合TRBC1的能力。
以上氨基酸序列的变体也可以用于本发明中,只要所得的CAR结合TRBC1或TRBC2且不显著地交叉反应。典型地,此类变体与SEQ ID No.33,34或35给出的序列的一个具有高度的序列同一性。
CAR的变体通常具有与如SEQ ID No.33,34或35给出的序列的一个至少约75%,例如至少约80%,90%,95%,96%,97%,98%或99%的序列同一性。
核酸
本发明进一步提供编码本发明的第一个方面的试剂,如BiTE或CAR的核酸。
核酸序列可以编码包含如SEQ ID No.33,34或35所述的氨基酸序列的一个的CAR。
如本文所使用的,术语“多核苷酸”,“核苷酸”和“核酸”旨在是彼此同义的。
本领域的技术人员将理解由于遗传密码的简并性,许多不同的多核苷酸和核酸可以编码相同的多肽。另外,本领域的技术人员应当理解使用常规技术,可以制备核苷酸取代,其不影响由此处所述的多核苷酸编码的多肽序列,以反映多肽将在其中表达的任意特定宿主生物中的密码子选择。
根据本发明的核酸可以包括DNA或RNA。它们可以是单链的或双链的。它们也可以是在它们之中包括合成的或修饰的核苷酸的多核苷酸。对寡核苷酸的一些不同类型的修饰是本领域已知的。这些包括膦酸甲酯和硫代磷酸酯骨架,在分子的3’和/或5’末端的吖啶(acridine)或聚赖氨酸链的添加。为了如本文所述的用途的目的,应当理解可以通过本领域可用的任意方法修饰多核苷酸。为了提高感兴趣的多核苷酸的体内活性或寿命可以进行此类修饰。
术语“变体”、“同源物”或“衍生物”关于核苷酸序列包括来自序列或对序列的一个(或多个)核酸的任意取代,变异,修饰,置换,缺失或添加。
载体
本发明还提供载体,或载体的试剂盒,其包括本发明的一个或多个核酸序列。此类载体可以用于将核酸序列引入宿主细胞中,使得其表达根据本发明的第一个方面的CAR。
载体可以是例如质粒或病毒载体,如逆转录病毒载体或慢病毒载体,或基于转座子的载体或合成的mRNA。
载体可以能够转染或转导T细胞或NK细胞。
细胞
本发明还涉及包含根据本发明的第一个方面的CAR的细胞,如免疫细胞。
细胞可以包含本发明的核酸或载体。
细胞可以是T细胞或天然杀伤(NK)细胞。
T细胞可以是T细胞或T淋巴细胞,其是细胞介导的免疫中发挥中心作用的淋巴细胞类型。通过细胞表面上的T细胞受体(TCR)的存在,可以将它们与其它淋巴细胞,如B细胞和天然杀伤细胞(NK细胞)区分。存在多种类型的T细胞,如下文总结的。
辅助T辅助细胞(TH细胞)在免疫过程中协助其它白细胞,包括B细胞成熟成为浆细胞和记忆B细胞,和细胞毒性T细胞和巨噬细胞的活化。TH细胞在它们的表面上表达CD4。当抗原提呈细胞(APCs)表面上的MHC II类分子将肽抗原呈递至TH细胞时,它们变得活化。这些细胞可以分化成几个亚型的一种,包括TH1,TH2,TH3,TH17,Th9,或TFH,其分泌不同的细胞因子以促进不同类型的免疫应答。
细胞毒性T细胞(TC细胞,或CTL)破坏病毒感染的细胞和肿瘤细胞,并也牵连在移植排斥中。CTL在它们表面上表达CD8。这些细胞通过结合与MHC I类联合的抗原识别它们的靶标,所述MHC I类存在于所有有核细胞的表面上。通过由调节T细胞分泌的IL-10,腺苷和其它分子,CD8+细胞可以失活为无变应性状态,其防止自身免疫性疾病,如实验性自身免疫性脑脊髓炎。
记忆T细胞是抗原特异性T细胞的亚组,所述抗原特异性T细胞在感染已经消退后长期保持。一旦再暴露于它们的关联(cognate)抗原,其快速扩增为大量的效应T细胞,从而给免疫系统提供针对过去感染的“记忆”。记忆T细胞包括三个亚型:中央记忆T细胞(TCM细胞)和两类效应记忆T细胞(TEM细胞和TEMRA细胞)。记忆细胞可以是CD4+或CD8+。记忆T细胞通常表达细胞表面蛋白CD45RO。
调节T细胞(Treg细胞),以前称为抑制T细胞,对于免疫耐受的维持是重要的。它们主要的作用是关闭T细胞介导的免疫朝向免疫反应的结束和抑制逃脱胸腺中的阴性选择过程的自身反应T细胞。
已经描述了两类主要的CD4+Treg细胞:天然发生的Treg细胞和适应Treg细胞。
天然发生的Treg细胞(也称为CD4+CD25+FoxP3+Treg细胞)在胸腺中产生,并已经与形成中的T细胞和已经使用TSLP活化的髓样(CD11c+)以及浆细胞样(CD123+)树突细胞两者之间的相互作用相连。可以通过称为FoxP3的细胞内分子的存在,将天然发生的Treg细胞与其它T细胞区分。FOXP3基因的突变可以阻止调节性T细胞的发育,导致致命的自身免疫病IPEX。
适应Treg细胞(也称为Tr1细胞或Th3细胞)可以在正常免疫应答期间起源。
细胞可以是天然杀伤细胞(或NK细胞)。NK细胞形成固有免疫系统的一部分。NK细胞以不依赖MHC的方式提供对来自病毒感染细胞的固有信号的快速应答。
NK细胞(属于固有淋巴样细胞组)定义为大颗粒淋巴细胞(LGL)并构成第三种细胞,其与产生B和T淋巴细胞的共同淋巴样前体细胞区分。已知NK细胞在骨髓、淋巴结、脾、扁桃体和胸腺中分化并成熟,然后它们在那里进入循环。
本发明的CAR细胞可以是上述任意细胞类型。
可以离体从患者自身的外周血(第一方),或在来自供体外周血的造血干细胞移植物的背景(第二方)中,或来自无关联供体的外周血(第三方)创建表达根据本发明的第一个方面的CAR的T或NK细胞。
或者,表达根据本发明的第一个方面的CAR的T或NK细胞可以来源于可诱导祖细胞或胚胎祖细胞离体分化为T或NK细胞。或者,可以使用保留了其溶解功能并可以起治疗剂作用的永生化的T细胞系。
在所有这些实施方案中,通过许多方法的一种引入编码CAR的DNA或RNA生成CAR细胞,所述方法包括使用病毒载体转导,使用DNA或RNA转染。
本发明的CAR细胞可以是来自受试者的离体T或NK细胞。T或NK细胞可以来自外周血单核细胞(PBMC)样品。在使用编码根据本发明的第一个方面的CAR的核酸转导之前,可以活化和/或扩增T或NK细胞,例如通过使用抗CD3单克隆抗体处理。
本发明的T或NK细胞可以通过以下制成:
(i)从受试者或以上列出的其它来源分离含有T或NK细胞的样品;和
(ii)使用编码本发明的CAR的核酸序列转导或转染T或NK细胞。
接着,可以纯化T或NK细胞,例如基于抗原结合多肽的抗原结合域的表达选择。
本发明还提供试剂盒,其包括包含根据本发明的第一个方面的CAR的T或NK细胞。
药物组合物
本发明还涉及含有多个表达本发明第一个方面的CAR的细胞的药物组合物。药物组合物可以另外包含药学上可接受的载体,稀释剂或赋形剂。药物组合物可以任选地包含一种或多种另外的药学上活性的多肽和/或化合物。此类配制剂可以是例如为适用于静脉内输注的形式。
T细胞淋巴瘤和/或白血病
本发明涉及用于治疗T细胞淋巴瘤和/或白血病的试剂,细胞和方法。
用于治疗T细胞淋巴瘤和/或白血病的方法涉及试剂的治疗用途。本文中可以将试剂施用至患有存在的T细胞淋巴瘤和/或白血病疾病的受试者,以减轻,降低或改善与疾病相关的至少一种症状和/或减慢,降低或阻断疾病的进展。
本发明的方法可以用于与表达T细胞受体(TCR)的细胞的克隆性扩增相关的任意淋巴瘤和/或白血病,所述T细胞受体包含β恒定区。因而,本发明涉及用于治疗涉及恶性T细胞的疾病的方法,所述恶性T细胞表达包含TRBC的TCR。
本发明的方法可以用于治疗T细胞淋巴瘤,其中恶性T细胞表达包含TRBC的TCR。“淋巴瘤”用于本文根据其标准含义指代通常在淋巴结中发展,但也可以影响脾,骨髓,血液和其它器官的癌症。淋巴瘤通常表现为淋巴样细胞的实体瘤。与淋巴瘤相关的原发性症状是淋巴结病,但继发性(B)症状可以包括发热,盗汗,消瘦,食欲不振,乏力,呼吸窘迫和瘙痒。
本发明的方法可以用于治疗T细胞白血病,其中恶性T细胞表达包含TRBC的TCR。“白血病”用于本文根据其标准含义指代血液或骨髓的癌症。
以下是可以通过本发明的方法治疗的疾病的说明性的,非穷举列表。
外周T细胞淋巴瘤
外周T细胞淋巴瘤是相对不常见的淋巴瘤,并占所有非霍奇金淋巴瘤(NHL)的少于10%。然而,它们与侵袭性的临床过程相关,且大多数T细胞淋巴瘤的原因和精确的细胞起源仍然没有很好的定义。
淋巴瘤通常首先表现为颈部,腋下或腹股沟的肿大。另外的肿大可以发生在其它淋巴结定位的地方例如在脾中。一般来说,扩大的淋巴结可以侵犯血管,神经或胃部的空间,分别导致肿胀的手臂和腿,导致刺痛和麻木,以及导致饱的感觉。淋巴瘤症状还包括非特异性症状例如发热,寒战,不明原因的体重减轻,盗汗,嗜睡和瘙痒。
WHO分类利用形态学和免疫表型特征连同临床方面以及在一些情况下遗传学来划定外周T细胞淋巴瘤的预后和治疗上有意义的分类(Swerdlow等;WHO classification oftumours of haematopoietic and lymphoid tissues.4th ed.;Lyon:IARC Press;2008)。赘生性T细胞的解剖定位部分平行于它们所提议的正常细胞的对应物和功能,因此T细胞淋巴瘤与淋巴结和外周血相关。该方法允许更好的理解一些T细胞淋巴瘤的临床表现,包括它们的细胞分布,形态学的一些方面和甚至相关的临床发现。
最普遍的T细胞淋巴瘤是外周T细胞淋巴瘤,非特指型(PTCL-NOS),包括总体的25%,接着是血管免疫母细胞T细胞淋巴瘤(AITL)(18.5%)。
外周T细胞淋巴瘤,非特指型(PTCL-NOS)
PTCL-NOS构成所有外周T细胞淋巴瘤和NK/T细胞淋巴瘤的超过25%且是最常见的亚型。其通过排除诊断确定,不对应在目前WHO 2008中列出的任意特定成熟T细胞淋巴瘤实体。因此其类似于弥散性大B细胞淋巴瘤,非特指型(DLBCL-NOS)。
大多数患者是成年人,其中中位数年龄为60且男性比女性比率2:1。大部分的病例是结(nodal)起源的,然而,结外表现发生于约13%的患者中,最常见涉及皮肤和胃肠道。
该细胞学范围非常广,范围从多形的到单形的。已经描述了三种形态学上定义的变体,包括淋巴上皮样(Lennert)变体,T-区变体和滤泡变体。PTCL的淋巴上皮样变体含有丰富的背景上皮样组织细胞且通常是CD8阳性的。其已经与较好的预后相关。PTCL-NOS的滤泡变体正在成为潜在的独特临床病理学实体。
大部分PTCL-NOS具有成熟的T细胞表型且大多数病例是CD4阳性的。75%的病例表现出至少一种全T细胞标志物(CD3,CD2,CD5或CD7)的可变缺失,其中CD7和CD5是经常下调的。可以表达CD30和罕见地CD15,其中CD15是不利的预后特征。尽管不常见,CD56的表达也具有负面的预后影响。另外的不利病理预后诊断因素包括基于KI-67表达的大于25%的增殖速率,和大于70%的转化细胞的存在。这些淋巴瘤的免疫表型分析提供很少的对它们生物学的了解。
血管免疫母细胞T细胞淋巴瘤(AITL)
AITL是系统性疾病,特征在于涉及淋巴结的多形性浸润,突出的高内皮静脉(HEV)和滤泡状树突细胞(FDC)网状组织的血管周围扩张。认为AITL是来源于滤泡辅助型(TFH)αβT细胞的从头(de-novo)T细胞淋巴瘤,通常发现于生发中心。
在外周T细胞淋巴瘤和NK/T细胞淋巴瘤中,AITL是第二常见的实体,构成病例的约18.5%。其在中年至老年成人中发生,其中中位数年龄为65岁龄,并在男性和女性中约相等的发病率。临床上,患者通常具有晚期阶段疾病,具有全身性淋巴结病,肝脾肿大和突出的全身症状。通常存在皮疹及关联的瘙痒。通常存在与自身免疫现象有关的多克隆高球蛋白血症。
AITL中描述了三种不同的形态学模式。AITL的早期病变(模式I)通常表现出保守的架构,具有特征性增生性滤泡。赘生性增殖定位于滤泡的外围。在模式II中,结节构架部分被消除,保留少数的退化滤泡。被膜下淋巴窦得到保留甚至扩张。副皮质区含有树枝状的HEV且存在B细胞滤泡外的FDC增殖。赘生性细胞为小至中等大小,具有最小的细胞学异型性(cytologic atypia)。它们通常具有清澈到暗淡的细胞质,并可以表现出不同的T细胞膜。多形性炎症背景通常是明显的。
尽管AITL是T细胞恶性肿瘤,但存在B细胞和浆细胞的特征性扩增,其可能反映了赘生性细胞作为TFH细胞的功能。EBC阴性和EBV阳性B细胞两者都存在。偶尔,非典型的B细胞可以在形态学上和免疫表型上类似霍奇金/里德-斯特恩伯格样细胞,有时导致与该实体的诊断混淆。AITL中的B细胞增殖可以是广泛的,且一些患者形成了次级EBV阳性的弥散性大B细胞淋巴瘤(DLBCL)或更罕见地EBV阴性的B细胞肿瘤,通常伴随浆细胞分化。
AITL的赘生性CD4阳性T细胞表现出CD10和CD279(PD-1)的强表达和CXCL13阳性。通过对HEV的粘附,B细胞活化,浆细胞分化和FDC网状组织的扩张,CXCL13引起增加的B细胞向淋巴结募集,这些都有助于AITL的形态学和临床特征。滤泡周围的肿瘤细胞中强烈的PD-1表达在区分AITL模式I与反应性滤泡及副皮质增生中是特别有用的。
PTCL-NOS的滤泡变体是具有TFH表型的另一种实体。与AITL对比,其不具有突出的HEV或FDC网状组织的滤泡外扩张。赘生性细胞可以形成滤泡内聚集,模拟B细胞滤泡淋巴瘤,而且还可以具有滤泡间生长模式或涉及扩增的外套层(mantle zone)。临床上,PTCL-NOS的滤泡变体与AITL不同,因为患者更经常表现为部分淋巴结受累的早期疾病且可以缺乏与AITL相关的全身症状。
渐变性大细胞淋巴瘤(ANAPLASTIC LARGE CELL LYMPHOMA,ALCL)
ALCL可以细分为ALCL-“渐变性淋巴瘤激酶”(ALK)+或ALCL-ALK-。
ALCL-ALK+是外周T细胞淋巴瘤中被最好地定义的实体之一,特征性的“标志细胞”携带马蹄铁形核并表达ALK和CD30。其占所有外周T细胞和NK细胞淋巴瘤的约7%并在生命的第一个三十年中最常见。患者通常表现为淋巴结病,但结外部位(皮肤,骨,软组织,肺,肝)的累及和B症状是普遍的。
ALCL,ALK+表现出广泛的形态学范围,其中描述了5种不同的模式,但是所有的变体含有一些标志细胞。标志细胞具有怪异的马蹄铁或肾形核,和突出的核周嗜曙红高尔基区。肿瘤细胞以黏着的模式生长,具有窦受累的偏好。在小细胞变体中,较小的肿瘤细胞占主导地位,而在淋巴组织细胞变体中丰富的组织细胞掩蔽了肿瘤细胞的存在,所述肿瘤细胞中许多是小的。
通过定义,所有的病例表现出ALK和CD30阳性,其中在较小的肿瘤细胞中表达通常较弱。通常存在全T细胞标志物的缺失,其中75%的病例缺乏CD3的表面表达。
ALK表达是由染色体2p23上的ALK基因向许多配对基因之一重排组成的特征性复发性遗传改变的结果,导致嵌合蛋白的表达。最常见的配对基因,在75%的病例中发生,是染色体5q35上的核仁磷酸蛋白(NPM1),导致t(2;5)(p23;q35)。在不同的转位变体中,ALK的细胞分布可以根据配对基因而变化。
ALCL-ALK-在2008WHO分类中被纳入临时类别。其定义为CD30阳性T细胞淋巴瘤,其形态学上不能与具有黏着生长模式的ALCL-ALK+区分,并存在标志细胞,但缺少ALK蛋白表达。
与ALCL-ALK+(其在儿童和年轻人中更常见)不同,患者通常是年龄在40和65之间的成年人。ALCL-ALK-可以涉及淋巴结和结外组织两者,但后者比ALCL-ALK+中较不常见。通过具有典型“标志”特征的粘着性赘生性细胞的层,ALCL-ALK-的大多数病例表现出淋巴结架构的消失。与ALCL-ALK+不同,没有识别小细胞形态学变体。
不像其ALK+对应物,ALCL-ALK-表现出更大的对表面T细胞标志物表达的保留,而细胞毒性标志物和上皮膜抗原(EMA)的表达较不可能。ALCL-ALK-和ALCL-ALK+中的基因表达标签(signature)和复发性染色体不平衡不同,确认了它们是分子水平和遗传水平的不同实体。
ALCL-ALK-在临床上与ALCL-ALK+和PTCL-NOS两者不同,其中在这三种不同的实体中预后存在显著差异。ALCL-ALK-的5年总体存活报道为49%,其不像ALCL-ALK+(为70%)一样好,但同时比PTCL-NOS(32%)明显更好。
肠病相关的T细胞淋巴瘤(EATL)
EATL是侵袭性的赘生物,认为其来源于肠的上皮内T细胞。2008WHO分类中认证了两种形态学上,免疫组织化学和遗传学上不同类型的EATL:I型(代表了大多数的EATL)和II型(构成10-20%的病例)。
I型EATL通常与明显的或临床上无症状的麸质敏感性肠病相关,且在北欧出身的患者中由于该群体中腹腔疾病的高发病率而更常见。
最常见地,EATL的病变存在于空肠或回肠(90%的病例),其中罕见表现在十二指肠,结肠,胃,或胃肠道外的区域中。肠病变通常是多病灶的,伴有黏膜性溃疡。EATL的临床过程是侵袭性的,其中大多数患者在1年内死于疾病或疾病的并发症。
EATL I型的细胞学谱是广泛的,且一些病例可以含有渐变性(anaplastic)细胞。存在多形性炎症背景,其可以在某些病例中掩盖赘生性组分。肿瘤临近区域中的肠黏膜通常表现出腹腔疾病的特征,具有绒毛的钝化和上皮内淋巴细胞数量(IEL)的增加,其可以代表损伤前体细胞。
通过免疫组织化学,赘生性细胞通常是CD3+CD4-CD8-CD7+CD5-CD56-βF1+,并含有细胞毒性颗粒相关蛋白(TIA-1,粒酶B,穿孔蛋白)。CD30部分表达在几乎所有的病例中。CD103,其是黏膜归巢受体,可以在EATL中表达。
II型EATL,也称为单型CD56+肠T细胞淋巴瘤,定义为由小和中等大小单型T细胞组成的肠肿瘤,所述T细胞表达CD8和CD56两者。通常存在肿瘤在黏膜内的横向扩散,而没有炎性背景。大多数病例表达γδTCR,然而存在与αβTCR相关的病例。
II型EATL具有更比I型EATL更多的世界广泛分布,并通常在亚裔或西班牙裔人群中看到,其中腹腔病是罕见的。在欧洲血统EATL的个体中,II代表了肠T细胞淋巴瘤的约20%,在病例的至少一个亚群中具有腹腔病的历史。临床过程是侵袭性的。
肝脾T细胞淋巴瘤(HSTL)
HSTL是一种侵袭性系统赘生物,通常来源于内在免疫系统的γδ细胞毒性T细胞,然而,在罕见的病例中其也可以来源于αβT细胞。它是最罕见的T细胞淋巴瘤的一种,并通常以较强的男性主导性影响青少年和青年(中位数年龄,35岁)。
结外NK/T细胞淋巴瘤鼻型
结外NK/T细胞淋巴瘤鼻型是侵袭性的疾病,通常具有破坏性的中线病变和坏死。大多数病例是NK细胞衍生的,但一些病例来源于细胞毒性T细胞。其普遍地与埃巴病毒(EBV)相关。
皮肤T细胞淋巴瘤
本发明的方法也可以用于治疗皮肤T细胞淋巴瘤。
皮肤T细胞淋巴瘤(CTCL)特征在于恶性T细胞向皮肤的迁移,其导致出现各种损伤。这些损伤随着疾病的进展改变形状,通常开始于表现为疹,并且最终形成斑和肿瘤,之后转移至身体的其它部位。
皮肤T细胞淋巴瘤包括以下说明性的,非穷举列表中提到的那些:蕈样肉芽肿病(mycosis fungoides),佩吉特样网状细胞增多症(pagetoid reticulosis),塞扎里综合症(Sézary syndrome),肉芽肿性皮肤松弛(granulomatous slack skin),淋巴瘤样丘疹病(lymphomatoid papulosis),慢性苔癣样糠疹(pityriasislichenoideschronica),CD30+皮肤T细胞淋巴瘤,继发性皮肤CD30+大细胞淋巴瘤,非蕈样肉芽肿CD30-皮肤大T细胞淋巴瘤,多形性T细胞淋巴瘤(pleomorphic T-cell lymphoma),伦纳特淋巴瘤(Lennertlymphoma),皮下T细胞淋巴瘤和血管中心性淋巴瘤(angiocentric lymphoma)。
CTCL的征兆和症状根据特定的疾病不同,其中两种最常见的类型是蕈样肉芽肿病和塞扎里综合症。典型的蕈样肉芽肿病分为三个阶段:
斑点(Patch)(萎缩性或非萎缩性):非特异性皮炎,下躯干和臀部上的斑点;最小/没有瘙痒;
斑块(Plaque):强烈的瘙痒斑块,淋巴结病;和
肿瘤:容易发生溃疡。
塞扎里综合症由红皮病和白血病定义。征兆和症状包括皮肤水肿,淋巴结病,手掌和/或足底角化过度,脱发,指甲营养不良,睑外翻(ectropion)和肝脾肿大。
在所有的原发性皮肤淋巴瘤中,65%是T细胞类型的。最常见的免疫表型是CD4阳性。对于这些疾病没有共同的病理生理学,因为术语皮肤T细胞淋巴瘤包含了极其多种的病症。
皮肤T细胞淋巴瘤(即蕈样肉芽肿病)的形成的主要病因机制尚未阐明。蕈样肉芽肿病之前可以有T细胞介导的慢性炎性皮肤疾病,其可以偶尔发展为致命的淋巴瘤。
原发性皮肤ALCL(C-ALCL)
C-ALCL通常不能通过形态学与ALC-ALK-区分。其定义为具有渐变性,多形性,或免疫母细胞形态的大细胞的皮肤肿瘤,其中多于75%的细胞表达CD30。与淋巴瘤样丘疹病(LyP)一起,C-ALCL属于原发性皮肤CD30阳性T细胞淋巴增生性病症的范围,其以组包括蕈样肉芽肿病之后第二普遍的皮肤T细胞淋巴增生的组。
免疫组织化学染色概况与ALCL-ALK-相当相似,其中较大比例的病例对于细胞毒性标志物染色呈阳性。至少75%的肿瘤细胞应当是CD30阳性的。也可以表达CD15,且当淋巴结受累发生时,与典型霍奇金淋巴瘤的区分可以是困难的。ALCL-ALK+的罕见病例可以表现为局部的皮肤病变,并可以类似C-ALCL。
T细胞急性淋巴母细胞白血病
T细胞急性淋巴母细胞白血病(T-ALL)分别占所有儿童和成人群体的ALL的约15%和25%。患者通常具有高白细胞计数并且可以表现为脏器肿大,特别是纵隔扩大和CNS受累。
本发明的方法可以用于治疗T-ALL,其与表达包含TRBC的TCR的恶性T细胞相关。
T细胞幼淋巴细胞白血病
T细胞幼淋巴细胞白血病(T-cell-prolymphocytic leukemia,T-PLL)是具有侵袭行为的成熟T细胞白血病,并对于血液,骨髓,淋巴结,肝,脾和皮肤受累具有偏好。T-PLL主要影响超过30岁的成人。其它名字包括T细胞慢性淋巴细胞白血病,“多瘤(knobby)”型T细胞白血病,和T-幼淋巴细胞白血病/T细胞淋巴细胞白血病。
在外周血中,T-PLL由中等大小的淋巴细胞组成,具有单个核和嗜碱性胞质,偶尔具有泡或突出。核通常是圆形到椭圆形形状,其中偶尔患者具有更不规则核轮廓的细胞,所述核轮廓与塞扎里综合症中看到的脑状核形相似。小细胞变体构成所有T-PLL病例的20%,而塞扎里细胞样(脑状)变体在5%的病例中见到。
T-PLL具有成熟(胸腺后)T淋巴细胞的免疫表现,且赘生性细胞通常对于全T抗原CD2,CD3和CD7阳性并对于TdT和CD1a阴性。免疫表型CD4+/CD8-存在于60%的病例中,CD4+/CD8+免疫表型存在于25%,而CD4-/CD8+免疫表型存在于15%的病例中。
药物组合物
本发明的方法可以包括施用药物组合物形式的试剂的步骤。
试剂可以与药学上可接受的载体,稀释剂,赋形剂或佐剂一起施用。药学载体,赋形剂或稀释剂的选择可以关于预定的施用途径和标准的医药实践选择。作为载体,赋形剂或稀释剂(在载体,赋形剂或稀释剂外),药物组合物可以包括任意适合的结合剂,润滑剂,悬浮剂,包被剂,增溶剂,和其它载体试剂。
施用
试剂的施用可以使用多种途径的任一种完成,所述途径使得活性成分生物可利用。例如,可以通过口服和肠胃外途径,腹膜内,静脉内,皮下,经皮,肌肉内,经由局部递送例如通过导管或支架实现试剂的施用。
典型地,内科医生将确定对于个体受试者最适合的实际剂量,并它将随着具体患者的年龄,体重和反应而变化。试剂是使得其足以降低或耗竭表达TRBC1或TRBC2的克隆性T细胞的数量。
用途
本发明还提供试剂,用于根据第一个方面的方法治疗T细胞淋巴瘤中的用途。试剂可以是上文定义的任意试剂。
本发明还涉及如上文定义的试剂在制备用于根据第一个方面的方法治疗T细胞淋巴瘤的药物中的用途。
试剂盒
本发明进一步提供包含如上文所定义的试剂的试剂盒,用于根据第一个方面的方法治疗T细胞淋巴瘤中的用途。
试剂盒还可以包含适合用于确定恶性T细胞的TRBC的试剂。例如,试剂盒可以包含对于TRBC1或TRBC2特异性的PCR引物或抗体。
用于确定T细胞淋巴瘤和/或白血病的方法
本发明进一步涉及用于确定受试者中T细胞淋巴瘤或白血病的方法,其包括确定来自受试者的样品中TRBC1或TRBC2阳性的T细胞比例的步骤。
T细胞淋巴瘤涉及个体恶性T细胞的克隆性扩增。因此,可以通过确定来源于患者的样品中TRBC1或TRBC2 T细胞的比例鉴定受试者中T细胞淋巴瘤的存在。
样品可以是外周血样品,淋巴样品或直接取自肿瘤的样品,例如活组织检查样品。
TRBC1或TRBC2阳性的总T细胞的比例(其指示T细胞淋巴瘤或白血病的存在)可以是例如细胞总群体的80,85,90,95,98或99%。
方法可以涉及通过活组织检查或样品中T细胞的不同群体确定浸润。本文中,样品中T细胞总群体的80,85,90,95,98或99%是TRBC1或TRBC2的情况下,指示T细胞淋巴瘤或白血病的存在。
可以通过确定样品中表达CD3,CD4,CD8和/或CD45的细胞的数量,确定样品中的总T细胞。也可以使用这些标志物的组合。
可以使用本领域已知的方法确定样品中表达TRBC1或TRBC2的总T细胞的比例,例如流式细胞术,免疫组织化学或荧光显微术。
本发明将通过实施例的方式进一步描述,其是为了起到帮助本领域的普通技术人员实施本发明,而不意图以任何方式限制本发明的范围。
实施例
实施例1-区分表达TRBC1和TRBC2的细胞
JOVI抗体先前已经由Viney等人公开(Hybridoma;1992;11(6);701-713)且是商品化的(Abcam,ab5465)。本发明人确定了JOVI-1能够基于TRBC1或TRBC2的特异性表达区分细胞。
本发明人生成了提供TCR的完全可变和恒定区的两种质粒载体,其差异仅在于TRBC1或TRBC2的表达。这些质粒用于通过293T-细胞的瞬时转染生成逆转录病毒上清。该上清用于稳定转导Jurkats TCR敲除T细胞(在TCR beta链基因座处具有突变的T-ALL细胞系,所述突变阻止该链的表达,从而整个表面TCR/CD3复合物的表达)。这导致除了TRBC1或TRBC2的表达外相同的细胞系的生成。这些细胞系的染色揭示表面TCR/CD3复合物的充分表达,且仅表达TRBC1的细胞使用JOVI-1抗体染色(图4)。
实施例2-正常供体CD4+和CD8+ T细胞含有不同的TRBC1阳性和TRBC-1阴性群体
发明人在正常供体的原代人T细胞上测试了JOVI-1抗体。这些分析揭示了所有的供体具有一定比例的表达TRBC1的CD4+和CD8+T细胞两者和一定比例的不表达TRBC1的每种。约20-50%的正常CD4+和CD8+T细胞是TRBC1+ve(图6和7)。
实施例3-表达TCR的克隆性T细胞系是TRBC1阳性或阴性的
细胞系来源于患者中原始克隆性肿瘤群体。表达TCR的T细胞系的染色揭示T细胞表达TRBC1或TRBC2,确定了这作为克隆性的标志物。在测试的三种T细胞系中,Jurkats细胞(已知为TRBC1+)而不是HPB-ALL或HD-Mar-2(已知为TRBC2+)细胞被JOVI-1染色,支持TRBC1或2的排他性表达(图8)。
实施例4-患有T幼淋巴细胞白血病的患者中的原代克隆性T细胞是TRBC1阳性或阴性的
一致地,从患有T幼淋巴细胞白血病(T-PLL)的患者的外周血提取的克隆性T细胞是TRBC1阳性或TRBC1阴性。
实施例5-对于TCBC1独特的残基的突变效果
生成了编码除了TCRβ链恒定区中的杂交TRBC1/2突变外相同的TCR的质粒载体。分析表明,JOVI-1识别TCRβ恒定链位置3和4处的残基的差异,表明这些残基对于抗体识别是可接近的,且可能是生成区分TRBC1与TRBC2或TRBC2与TRBC1的试剂的最好靶点(图5)。
实施例6-对表达TRBC1而不是TRBC2 TCR的T细胞的特异性溶解
将野生型Jurkat T细胞(CD34-,TRBC1+)与使用和CD34标志物基因共表达的TRBC2转导的TCRαβ敲除Jurkat T细胞(CD34+TRBC2+)混合。将这些细胞与JOVI-1单独孵育,或与JOVI1和补体孵育1小时。洗涤细胞并对于CD34,膜联蛋白V和7-AAD染色。通过流式细胞术分析细胞。
如通过膜联蛋白-V阴性和71AAD暗淡群体限定的活群体中CD34表达示于图9中。观察到了对TRBC1 T细胞(CD34-)的选择性杀伤(图9)。
野生型Jurkat T细胞是天然TRBC1+且不表达截短的CD34标志物基因。如上文所述,本发明人通过使用逆转录病毒载体转导TCRαβ敲除的Jurkat T细胞衍生TRBC2+Jurkat系,所述逆转录病毒载体编码TRBC2 TCR以及截短的CD34标志物基因。然后将这些T细胞混合在一起。接着,本发明人将该T细胞与JOVI-1单独或与JOVI1和补体孵育1小时。便利地,本发明人可以通过CD34标志物基因的染色区分TRBC1和2群体,并从而避免无法检测TRBC1TCR(由于长时间暴露于抗TCR mAb的TCR内化)。洗涤细胞并对于CD34,膜联蛋白V和7-AAD染色。通过流式细胞术分析细胞。通过在活细胞(即,膜联蛋白V阴性和7-AAD暗淡的细胞)上设门,本发明人可以确定在补体的存在下,TRBC1 T细胞被JOVI-1选择性杀伤(图9)。
实施例7-多克隆埃巴病毒(EBV)特异性T细胞可以分为两个大约相等的TRBC1/2群体
从正常血液供体取出外周血T细胞。分离了单核细胞且大多数的细胞冷藏保存。使用EBV的实验室株(B95-8)感染少量细胞。几周里,永生化的EBV感染的细胞系,称为成淋巴细胞样细胞系(LCL)出现。此类细胞系已知呈递大量不同的EBV抗原。将先前冷藏保存的单核细胞解冻并在IL2的存在下重复地使用该LCL系每周刺激持续4周。该过程从外周血单核群体选择性扩增EBV特异性T细胞。还已知此类过程导致多克隆系,其中>90%的T细胞为EBV特异性并代表了供体的EBV免疫系统。通过表现出高程度杀伤自体LCL而非异体LCL或K562细胞,检查了该系的特异性(图10a)。接着使用JOVI-1染色该细胞系并表明含有TRBC1和TRBC2 T细胞的大致相等混合物(图10b)。
因此,如果施用耗竭TRBC1或TRBC2区室的治疗剂,那么将保留足够的EBV免疫力。由于EBV免疫力认为是免疫应答的模式系统,假设合理假定对其它病原体的免疫力将得到同等保留。
实施例8-循环外周T细胞淋巴瘤的JOVI-1染色
假说是T细胞淋巴瘤(为克隆性的)将表达TRBC1或TRBC2 T细胞受体,而多克隆的正常T细胞将包含T细胞的群体,所述T细胞为具有TRBC1或TRBC2的那些的混合物。为了证明这个,获得了来自患者的T细胞淋巴瘤的血液样品,所述患者的淋巴瘤为外周血中循环的。分离了外周血单核细胞并使用一组抗体染色,其包括CD5和JOVI1。首先鉴定了总T细胞群体(其含有淋巴瘤和正常T细胞两者)。该群体由具有正常(明亮)CD5表达的T细胞和具有中等/暗淡CD5表达的T细胞组成。前者代表了正常T细胞,而后者代表了淋巴瘤。接着,调查了JOVI-1结合且结果示于图12中。
CD5中等和暗淡群体(肿瘤)都为TRBC2阳性。
实施例9-阐明JOVI-1的VH/VL序列
使用5’RACE用与小鼠IgG CH1的恒定区和小鼠kappa的恒定区退火的引物,我们从杂交瘤JOVI-1分离了单个功能性VH序列和单个功能性VL序列。VH和VL的序列分别为SEQ ID1和2(见上文)。VH和VL注释的序列示于图11中。
将这些VH和VL序列分别与小鼠IgG重链和kappa轻链以符合读码框的方式克隆回去。另外,将VH和VL融合以形成单链可变片段(scFv),将这融合到小鼠IgG2a的铰链-CH2-CH3区以创建scFv-Fv。scFv的氨基酸序列在发明详述中作为SEQ ID No.3给出。通过转染到293T细胞中,生成了重组抗体和重组scFv-Fc。与来自杂交瘤的JOVI-1一起,对以下细胞进行了染色:具有TCR敲除的Jurkats;野生型Jurkats;使用与eBFP2共表达的TRBC1转导的Jurkat TCR敲除和使用与eBFP2共表达的TRBC2转导的Jurkat TCR敲除。来源于JOVI的重组抗体和scFv-Fc两者都结合TRBC2,确认了我们鉴定了正确的VH/VL,且JOVI-1VH/VL可以折叠为scFv。该结合数据示于图13中。
实施例10-基于JOVI-1的CAR的功能
将JOVI-1scFv克隆到CAR形式中。为了阐明哪种间隔区长度将产生最优的基于JOVI-1的CAR,使用人Fc间隔区,人CD8茎部间隔区或来源于IgG1铰链的间隔区生成了第三代CAR(图4)。使用这些CAR转导来自正常供体的原代人T细胞并比较对Jurkats和TRC敲除的Jurkats的杀伤。具有JOVI-1scFv的CAR(其具有IgG1铰链间隔区或CD8茎部间隔区)杀伤Jurkats而不杀伤TCR敲除的Jurkats(图5),证明了预期的特异性。由于使用CAR转导的正常供体T细胞应当具有TRB1/2T细胞的混合物,预期该培养物将“自净化(self-purge)”。事实上,观察到了这点。图6中示出了CAR T细胞培养物的JOVI-1染色,其成为100%TRBC2阴性的。
材料和方法
证明JOVI-1的特异性
生成了三顺反子逆转录病毒盒(cassette),其编码良好表征的人TCR以及便利的标志物基因。使用从头基因合成从重叠的寡核苷酸生成了TCRα和β链的编码序列。将这些链以符合读码框的方式与口蹄疫2A肽连接以允许共表达。通过PCR从cDNA克隆截短的CD34标志物基因并使用内部核糖体进入序列(IRES)与TCR共表达。将该盒引入逆转录病毒载体中。通过重叠PCR,使用引入所需突变的引物,通过剪接生成了该构建体的变体。通过Sanger测序确认了构建体的准确性(veracity)。Jurkat 76系是良好表征的Jurkat T细胞系衍生物,其具有TCRα和β链两者敲除。使用标准技术用以上逆转录病毒载体转导该Jurkat系。
Jurkats,外周血T细胞和细胞系的染色和分析
从ECACC获得了Jurkats并如上文详细描述的那样工程化改造。其它T细胞系也从ECACC获得。外周血通过静脉穿刺从正常供体抽取。血液经蔗聚糖处理(ficolled)以分离单核细胞。细胞使用JOVI-1以及识别所有TCR和CD3的商品化单克隆抗体染色。在工程化T细胞的情况下,细胞使用识别CD34的抗体染色。在外周血单核细胞的情况下,细胞使用识别CD4和CD8的抗体染色。购买的抗体与适合的荧光团缀合,使得使用流式细胞仪分析细胞同时可以获得独立的荧光信号。
证明对TRBC1 T细胞的特异性溶解
将野生型Jurkat T细胞(TRBC1-TCR)和具有引入的TRBC2 TCR的Jurkat T细胞TCRKO以1:1的比率混合在一起。接着,在补体的存在或不存在下将Jurkat的该混合物与1ug/ml的JOVI-1单克隆抗体孵育。四小时后,细胞使用膜联蛋白-V和7AAD和CD34染色。便利地,标志物基因CD34可以区分野生型(TRBC1)和转基因(TRBC2)Jurkats。通过流式细胞术分析细胞群体。通过在流式细胞事件上设门选择性研究活细胞,所述事件为对于膜联蛋白-V呈阴性和对于7AAD呈暗淡。以这种方式,研究了转基因(TRBC2)对野生型(TRBC1)T细胞的存活。
实施例11-调查T细胞淋巴增殖性病症的克隆性
测试了四位患者:三位患有T细胞大颗粒淋巴细胞淋巴增殖性病症(T-LGL);和一位患有外周T细胞淋巴瘤(PCTL)以确认恶性细胞一致为TRBC1阳性或阴性。
从患有T淋巴细胞增生性病症的患者收集了全血或骨髓。通过蔗聚糖(Ficoll)梯度离心分离获得外周血单核细胞。新鲜获得的PBMC形成团块(pelleted)并使用适合的预缀合抗体染色20分钟。接着,洗涤细胞并在磷酸盐缓冲盐水中重悬用于在BD LSR FortessaII上立即流式细胞分析。通过FSc/SSc特性和未能摄取死细胞区分染料鉴定活淋巴细胞。通过使用抗TCR alpha/beta抗体染色鉴定T细胞。基于通过临床实验室分析先前鉴定的免疫表型,对每个样品使用适合的细胞表面染剂鉴定肿瘤和正常T细胞群体。
结果示于图18至21。
在患者A(T-LGL,图18)中,正常T细胞为CD7明亮且含有混合的CD4/CD8细胞,和TRBC1或TRBC1-细胞的混合群体。相比之下,恶性细胞为CD7-或CD7暗淡,一致为CD8+CD4-,且一致为TRBC1-。
在患者B(T-LGL,图19)中,通过CD4-,CD8+,CD7+CD57+鉴定恶性细胞,且为克隆性的TRBC1-(高亮的小图)。正常CD4+CD8-和CD4-CD8+T细胞含有TRBC1+和TRBC1-群体。
在患者C(T-LGL,图20)中,正常CD4+和CD8+T-细胞群体为30-40%TRBC1+。通过CD4-,CD8+,CD7+CD57+鉴定恶性细胞并为克隆性的TRBC1+(高亮的小图,注意84%的细胞为TRBC1-,剩下的16%似乎是污染性“正常”T细胞)。正常CD4+CD8-和CD4-CD8+T细胞含有TRBC1+和TRBC1-群体。
在患者D(PTCL-NOS,图21)中,骨髓中的恶性细胞,基于FSC高CD5暗淡CD4暗淡鉴定,一致为TRBC1+,而CD4+CD8-和CD4-CD8+T细胞含有TRBC1+和TRBC1-群体两者。
实施例12-使用噬菌体展示生成区分T细胞受体β链恒定域的两种同种型的单克隆人抗体
为了生成区分TRBC2和TRBC1的抗体,合成了覆盖两种TRBC同种型之间差异区域的肽片段。在TRBC2和TRBC1之间的四个氨基酸差异中,发现两个在恒定域的起点。合成了代表这些区域的肽(见以下)并用于抗体生成。
TRBC2 VLEDLKNVFPPEVAV(SEQ ID No.36)
TRBC1 VLEDLNKVFPPEVAV(SEQ ID No.37)
以生物素化的,非生物素化的,和半胱氨酸修饰的形式(通过添加C末端半胱氨酸)制备了这些肽。接着,根据制备商推荐的条件,将TRBC1和TRBC2的半胱氨酸修饰形式缀合到经修饰的牛血清白蛋白(Imm-Link BSA,Innova 462-001)或卵白蛋白(Imm-LinkOvalbumin,Innova 461-001)。
结果
抗体噬菌体展示选择
如(Schofield等人,2007Genome Biol 8,R254)所描述的,构建了人噬菌体展示文库并进行了噬菌体选择。为了从抗体文库鉴定TRBC1和TRBC2特异性抗体,进行了多轮噬菌体展示选择。平行使用了两种噬菌体选择策略,以最大化生成一大组特异性结合物的机会。这些策略称为固相和溶液相选择(图21)。在固相选择中,允许噬菌体抗体结合至固定化在固体表面上的靶抗原(Schofield等人,2007,如上文)。在溶液相选择中,噬菌体抗体结合溶液中的生物素化的抗原,然后通过链霉亲合素或中性亲合素包被的顺磁珠捕获噬菌体抗体-抗原复合物。在固相选择策略中,采用了两种不同的固定化或抗原呈现方法。使用第一种方法,通过直接吸附将缀合有牛血清白蛋白(BSA)或卵白蛋白(OA)的TRBC肽固定化到MaxisorpTM免疫管上。使用第二种方法,将生物素化的TRBC肽间接固定化到用链霉亲合素或中性亲合素预包被的MaxisorpTM免疫管上。
为了选择对于期望的肽特异性的抗体,所有的选择在过量的相反肽的存在下进行。例如,所有的TRBC1选择在10倍摩尔过量的非生物素化的TRBC2的存在下进行。该方法称为“去选择(deselection)”且预期其耗竭识别两种TRBC肽上共享的表位的抗体,因为这些优先结合溶液中过量的TRBC2。为了避免富集结合载体蛋白(BSA或OA)或固定化配对物(来自Thermo fisher scientific的链霉亲合素或中性亲合素),组合采用两种策略。
第一种策略是在选择的轮数之间切换缀合或固定化的配对物。对于直接固定化的肽,第一轮选择在BSA-肽上进行而对于第2轮使用OA-肽缀合物。相似地,对于第1轮将生物素化的TRBC肽固定化在链霉亲合素上,而中性亲合素用于第二轮的固定化。
第二种策略是通过在第1轮中进行“去选择”以耗竭对缀合/固定化配对物的任意结合物的噬菌体库。对于直接固定化的肽,通过在溶液中10倍摩尔过量的游离BSA存在下进行噬菌体-肽结合步骤进行“去选择”。在固定化于链霉亲合素上的生物素化的肽的情况下,将噬菌体文库与链霉亲合素包被的顺磁珠预孵育。在向抗原管添加噬菌体之前去除珠,从而限制链霉亲合素结合物进入选择中。使用的不同选择条件总结于图21中。对于选择条件的详细信息见表3。
使用肽或支持蛋白的各自呈现在ELISA中测试了从第2轮选择输出制备的多克隆噬菌体。这包括直接固定化为BSA或OA缀合物的TRBC肽,或间接固定化在链霉亲合素或中性亲合素上的生物素化的肽。包括的对照蛋白为链霉亲合素,中性亲合素,BSA和不相关的抗原。使用小鼠抗M13抗体(GE healthcare),接着是用铕标记的抗小鼠Fc抗体(PerkinElmers),使用时间分辨荧光检测噬菌体结合(图22)。该结果证明了多克隆噬菌体群体对相应TRBC肽的优先结合(如与相反TRBC肽比较)。例如,从TRBC1选择制备的多克隆噬菌体表现出对TRBC1比TRBC2明显更高的结合信号,且反之亦然。对固定化或缀合配对物以及不相关的抗原存在限制的结合或无结合。
单链抗体(scFv)亚克隆和单克隆筛选
将来自第2轮和第3轮选择输出的scFv群体亚克隆到pSANG10-3F表达载体中并转化到大肠杆菌BL21(DE3)细胞中。将1128个个体转化子(564个克隆/TRBC肽)挑取到12x 96孔培养板中(94个克隆/板)并使用自诱导培养基诱导抗体表达。对过夜诱导后分泌到培养基上清中的重组单克隆抗体测试对固定化于中性亲合素包被的NuncMaxisorpTM96孔板上的生物素化TRBC1和TRBC2的结合。在从TRBC1选择筛选的564个克隆中,255个克隆发现对于TRBC1特异性(对于TRBC1为>10000TRF单位而对于TRBC2为<1000TRF单位)。从TRBC2选择筛选的564个克隆鉴定了138个TRBC2特异性结合物(对于TRBC2为>10000TRF单位而对于TRBC1为<2000TRF单位)。图24示出了从对TRBC1(图24A)或TRBC2(图24B)选择产生的来自单个96孔板的代表性结合概况。使用不同选择条件生成的特异性结合物的细节总结于表5中。
从TRBC1和TRBC2选择分别挑取了142个和138个特异性结合物用于序列分析和进一步表征。通过Sanger测序使用terminator v3.1循环测序试剂盒(Lifetechnologies)生成了cherry挑取(cherry-picked)克隆的序列。分析了DNA序列以确定蛋白序列并鉴定了VH和VL域的CDR。对VH和VL CDR3区的分析鉴定了74个独特的TRBC1和42个独特的TRBC2克隆(其中独特定义为VH CDR3和VL CDR3序列的任意组合)。TRBC1-特异性克隆和它们的VH CDR3和VL CDR3序列总结于以上表1中。TRBC2-特异性克隆和它们的VH CDR3和VL CDR3序列总结于以上表2中。
表3A.固相TRBC选择的细节
表3B.溶液相TRBC选择的细节
表4:选择输出数量
表5:单克隆筛选的细节
实施例13-通过兔的肽免疫的TRBC多克隆抗体产生
为了生成区分TRBC2和TRBC1的抗体,合成了覆盖两种TRBC同种型之间差异的主要区域的2种肽并用于兔的免疫。使用了以下肽序列:
TRBC1:VLEDLNKVFPPEVAVC(SEQ ID No.38)
TRBC2:VLEDLKNVFPPEVAVC(SEQ ID No.39)
合成了15mg的TRBC1和TRBC2肽。通过肽上存在的C末端半胱氨酸将钥孔虫戚血兰素(Keyhole Lympet Hemocyanin)缀合至TRBC1和TRBC2肽。对于每种肽,使用KLH缀合的TRBC1或TRBC2肽免疫2只New England兔共三次。在第三次免疫后,处死兔并取血,并收集血清用于纯化。将从兔获得的粗制血清通过偶联了用于免疫的肽的交联珠琼脂树脂柱,以收集对于肽的共有片段和TRBC同种型特异性表位特异性的抗体。然后进一步纯化初步纯化的上清,通过具有固定化的备选肽的柱,以去除对于肽的共有片段特异性的抗体。
ELISA设置
包被试剂:A:肽TRBC1
B:肽TRBC2
包被浓度:4ug/ml,100μl/孔
包被缓冲液:磷酸盐缓冲水,pH7.4
二抗:过氧化物酶缀合的抗兔IgG(H&L)(山羊)抗体
结果示于图25和26中。通过该方法制备包含TRBC1或TRBC2特异性抗体的多克隆血清是可能的。
序列表
<110> UCL商务有限公司
<120> 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR)
<130> P0007CNB
<150> GB 1403905.1
<151> 2014-03-05
<150> GB 1416908.0
<151> 2014-09-25
<160> 272
<170> PatentIn version 3.5
<210> 1
<211> 124
<212> PRT
<213> 人工序列
<220>
<223> 可变重链 (VH) Jovi-1 VH
<400> 1
Glu Val Arg Leu Gln Gln Ser Gly Pro Asp Leu Ile Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr
20 25 30
Val Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Phe Ile Asn Pro Tyr Asn Asp Asp Ile Gln Ser Asn Glu Arg Phe
50 55 60
Arg Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ala Gly Tyr Asn Phe Asp Gly Ala Tyr Arg Phe Phe Asp
100 105 110
Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
115 120
<210> 2
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 可变轻链 (VL) Jovi-1 VL
<400> 2
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Arg Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Arg Val Ser Asn Arg Phe Pro Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Ile Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 3
<211> 252
<212> PRT
<213> 人工序列
<220>
<223> Jovi-1 scFv
<400> 3
Glu Val Arg Leu Gln Gln Ser Gly Pro Asp Leu Ile Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr
20 25 30
Val Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Phe Ile Asn Pro Tyr Asn Asp Asp Ile Gln Ser Asn Glu Arg Phe
50 55 60
Arg Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ala Gly Tyr Asn Phe Asp Gly Ala Tyr Arg Phe Phe Asp
100 105 110
Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr
130 135 140
Gln Ser Pro Leu Ser Leu Pro Val Ser Leu Gly Asp Gln Ala Ser Ile
145 150 155 160
Ser Cys Arg Ser Ser Gln Arg Leu Val His Ser Asn Gly Asn Thr Tyr
165 170 175
Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile
180 185 190
Tyr Arg Val Ser Asn Arg Phe Pro Gly Val Pro Asp Arg Phe Ser Gly
195 200 205
Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala
210 215 220
Glu Asp Leu Gly Ile Tyr Phe Cys Ser Gln Ser Thr His Val Pro Tyr
225 230 235 240
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
245 250
<210> 4
<400> 4
000
<210> 5
<400> 5
000
<210> 6
<400> 6
000
<210> 7
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 互补决定区 (CDR) 可变重链
(VH) CDR1
<400> 7
Gly Tyr Thr Phe Thr Gly Tyr
1 5
<210> 8
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> VH CDR2
<400> 8
Asn Pro Tyr Asn Asp Asp
1 5
<210> 9
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> VH CDR3
<400> 9
Gly Ala Gly Tyr Asn Phe Asp Gly Ala Tyr Arg Phe Phe Asp Phe
1 5 10 15
<210> 10
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 可变轻链 (VL) CDR1
<400> 10
Arg Ser Ser Gln Arg Leu Val His Ser Asn Gly Asn Thr Tyr Leu His
1 5 10 15
<210> 11
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> VL CDR2
<400> 11
Arg Val Ser Asn Arg Phe Pro
1 5
<210> 12
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> VL CDR3
<400> 12
Ser Gln Ser Thr His Val Pro Tyr Thr
1 5
<210> 13
<211> 247
<212> PRT
<213> 人工序列
<220>
<223> 单连可变片段 (scFv) CP_01_E09
<400> 13
Gln Val Gln Leu Val 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
Ala 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 Arg Ala His Asn Ser Ser Ser Trp Ser Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Ser
130 135 140
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala
145 150 155 160
Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
165 170 175
Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu Glu Thr Gly
180 185 190
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe
195 200 205
Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln
210 215 220
Gln Tyr Asp Asn Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp
225 230 235 240
Ile Lys Arg Thr Ala Ala Ala
245
<210> 14
<211> 246
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_D12
<400> 14
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
Ala 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 Gly Gly Asp Thr Tyr Gly Phe Leu Asp Asn Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Thr
130 135 140
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
145 150 155 160
Gln Ser Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys
165 170 175
Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val
180 185 190
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
195 200 205
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
210 215 220
Phe Asn Ala Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
225 230 235 240
Lys Arg Thr Ala Ala Ala
245
<210> 15
<211> 246
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_D10
<400> 15
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu 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
Ala 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 Ser 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 Gly Gly Gly Ser Phe Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
130 135 140
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
145 150 155 160
Gln Ser Ile Ser Arg Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys
165 170 175
Ala Pro Asn Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val
180 185 190
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
195 200 205
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
210 215 220
Tyr Asn Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
225 230 235 240
Lys Arg Thr Ala Ala Ala
245
<210> 16
<211> 246
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_C08
<400> 16
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Ala 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
Ala 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 Ser Gly Tyr Ser Ser Ser Trp Tyr Leu Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
130 135 140
Val Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser
145 150 155 160
Gln Asp Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys
165 170 175
Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val
180 185 190
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr
195 200 205
Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln
210 215 220
Tyr Asp Asn Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
225 230 235 240
Lys Arg Thr Ala Ala Ala
245
<210> 17
<211> 245
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_C11
<400> 17
Gln Val Gln Leu Val Glu 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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ser Gly Gly Ala Gly Trp Asn Trp Gly Gln Gly Thr Met Val Thr
100 105 110
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
115 120 125
Ala Ser Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu Ser Pro
130 135 140
Gly Lys Thr Ala Thr Ile Ser Cys Thr Arg Ser Ser Gly Ser Ile Ala
145 150 155 160
Ser Asn Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ala Pro Thr
165 170 175
Thr Val Ile Tyr Glu Asp Asn Gln Arg Pro Phe Gly Val Pro Asp Arg
180 185 190
Phe Ser Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile
195 200 205
Ser Gly Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser His
210 215 220
Asp Ser Ser Asn Val Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu
225 230 235 240
Gly Gln Pro Ala Ala
245
<210> 18
<211> 247
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_F03
<220>
<221> misc_feature
<222> (101)..(101)
<223> Xaa 可以是任意自然发生的氨基酸
<400> 18
Glu Val Gln Leu Val 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
Ala 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 Arg Gly Tyr Xaa Ala Ser Ser Trp Ser Gln Gly Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Ser
130 135 140
Ser Leu Ser Ala Ser Val Arg Asp Arg Val Thr Ile Thr Cys Gln Ala
145 150 155 160
Ser Gln Asp Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
165 170 175
Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu Glu Thr Gly
180 185 190
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe
195 200 205
Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln
210 215 220
Gln Tyr Asp Asn Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu
225 230 235 240
Ile Lys Arg Thr Ala Ala Ala
245
<210> 19
<211> 251
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_E07
<400> 19
Gln Val Gln Leu Val 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 Leu Gly Gly Ser Gly Gly Ala Phe Asp Ile Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ala Ser Asp Ile Val Met Thr Gln Thr Pro His
130 135 140
Ser Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser
145 150 155 160
Ser Gln Ser Leu Leu Tyr Ser Asp Gly Lys Thr Tyr Leu Tyr Trp Tyr
165 170 175
Leu Gln Lys Pro Gly Gln Pro Pro Gln Leu Leu Ile Tyr Glu Val Ser
180 185 190
Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly
195 200 205
Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly
210 215 220
Val Tyr Tyr Cys Met Gln Ser Ile Gln Leu Tyr Thr Phe Gly Gln Gly
225 230 235 240
Thr Lys Val Asp Ile Lys Arg Thr Ala Ala Ala
245 250
<210> 20
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_D03
<400> 20
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro 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 Arg Asn Lys Gln Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Ala Ser Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser
130 135 140
Leu Ala Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
145 150 155 160
Val Gly Ser Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro
165 170 175
Ser Leu Leu Ile Tyr Asp Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala
180 185 190
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
195 200 205
Ser Leu Gln Ser Glu Asp Ile Ala Val Tyr Tyr Cys Gln Gln Tyr His
210 215 220
Arg Trp Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
225 230 235 240
Thr Ala Ala Ala
<210> 21
<211> 249
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_F06
<400> 21
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 Asp Gly Ala Met Arg Tyr Trp Gly Gln Gly Thr Met Val
100 105 110
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val
130 135 140
Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val
145 150 155 160
Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys
165 170 175
Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu
180 185 190
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
195 200 205
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
210 215 220
Cys Gln Gln Tyr Tyr Asp Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys
225 230 235 240
Val Asp Ile Lys Arg Thr Ala Ala Ala
245
<210> 22
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_01_F02
<400> 22
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Pro Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala 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 Arg Ala Gly Tyr Ser Tyr Ala Asp Tyr Trp Gly Gln Gly Thr Met
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser
130 135 140
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly
145 150 155 160
Ile Arg Asn Asp Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro
165 170 175
Lys Arg Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser
180 185 190
Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser
195 200 205
Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln His Asn
210 215 220
Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Arg
225 230 235 240
Thr Ala Ala Ala
<210> 23
<211> 249
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_E05
<400> 23
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Ser 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 Arg Thr Arg Ser Ser Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ala Ser Asn Phe Met Leu Thr Gln Pro His Ser Val Ser
130 135 140
Glu Ser Pro Gly Lys Thr Val Thr Ile Ser Cys Thr Arg Ser Ser Gly
145 150 155 160
Ser Ile Ala Ser Lys Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser
165 170 175
Ser Pro Thr Thr Val Ile Tyr Glu Asp Asn Gln Arg Pro Ser Gly Val
180 185 190
Pro Asp Arg Phe Ser Gly Ser Ile Asp Thr Ser Ser Asn Ser Ala Ser
195 200 205
Leu Thr Ile Ser Gly Leu Arg Thr Glu Asp Glu Ala Asp Tyr Tyr Cys
210 215 220
His Ser Tyr Asp Ser Asn Asn His Ser Val Phe Gly Gly Gly Thr Lys
225 230 235 240
Val Thr Val Leu Gly Gln Pro Ala Ala
245
<210> 24
<211> 246
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_D05
<400> 24
Gln Val Gln Leu Val Glu 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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ser Pro Arg Gly Arg Gly Ser Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ala Ser Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val
130 135 140
Ser Val Ser Pro Gly Gln Thr Ala Thr Ile Ser Cys Ser Gly Asp Gln
145 150 155 160
Leu Gly Gly Lys Tyr Gly His Trp Tyr Gln Lys Lys Pro Gly Gln Ser
165 170 175
Pro Val Leu Val Leu Tyr Gln Asp Arg Lys Arg Pro Ala Gly Ile Pro
180 185 190
Glu Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ile Thr Leu Thr Ile
195 200 205
Ser Gly Thr Gln Ala Val Asp Glu Ala Asp Tyr Tyr Cys Gln Ala Trp
210 215 220
Asp Thr Asn Leu Gly Gly Val Phe Gly Gly Gly Thr Lys Val Thr Val
225 230 235 240
Leu Gly Gln Pro Ala Ala
245
<210> 25
<211> 249
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_H06
<400> 25
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr
20 25 30
Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val
50 55 60
Glu Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ala Arg Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr Met
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Ala Ser Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu
130 135 140
Ser Pro Gly Lys Thr Val Thr Ile Ser Cys Thr Arg Ser Ser Gly Ser
145 150 155 160
Ile Ala Ser Asn Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ser
165 170 175
Pro Thr Thr Val Ile Tyr Glu Asp Asn Gln Arg Pro Ser Gly Val Pro
180 185 190
Asp Arg Phe Ser Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu
195 200 205
Thr Ile Ser Gly Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Gln
210 215 220
Ser Phe Asp Ala Asp Asn Leu His Val Val Phe Gly Gly Gly Thr Lys
225 230 235 240
Leu Thr Val Leu Gly Gln Pro Ala Ala
245
<210> 26
<211> 248
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_C12
<400> 26
Glu 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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile 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 Asp Thr Gly Pro Ile Asp Tyr Trp Gly Gln Gly Thr Met Val
100 105 110
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ala Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val
130 135 140
Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu
145 150 155 160
Leu His Ser Asp Gly Lys Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro
165 170 175
Gly Gln Pro Pro Gln Leu Leu Val Tyr Glu Val Ser Asn Arg Phe Ser
180 185 190
Gly Val Pro Asp Lys Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
195 200 205
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys
210 215 220
Met Gln Gly Ile Gln Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val
225 230 235 240
Asp Ile Lys Arg Thr Ala Ala Ala
245
<210> 27
<211> 249
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_G02
<400> 27
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Ile 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 Gly Val Trp Asn Ser Gly Ser Tyr Leu Gly Phe Asp Tyr 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 Ala 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 Asp Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys
165 170 175
Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln
180 185 190
Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
195 200 205
Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr
210 215 220
Cys Gln Gln Ser Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys
225 230 235 240
Leu Glu Ile Lys Arg Thr Ala Ala Ala
245
<210> 28
<211> 251
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_D04
<400> 28
Glu Val Gln Leu Val 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
Ala 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 Arg Gly Gly Phe Thr Val Pro Gly Gly Ala Phe Asp Ile Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Ala Ser Asn Phe Met Leu Thr Gln Pro His
130 135 140
Ser Val Ser Asp Ser Pro Gly Lys Thr Val Thr Ile Ser Cys Thr Arg
145 150 155 160
Ser Ser Gly Arg Ile Gly Ser Asn Phe Val Gln Trp Tyr Gln Gln Arg
165 170 175
Pro Gly Ser Ser Pro Thr Thr Val Ile Tyr Glu Asp Asp Gln Arg Pro
180 185 190
Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Ile Asp Ser Ser Ser Asn
195 200 205
Ser Ala Ser Leu Thr Ile Ser Gly Leu Thr Thr Ala Asp Glu Ala Gly
210 215 220
Tyr Tyr Cys Gln Ser Tyr Asp Ala Ser Asn Val Ile Phe Gly Gly Gly
225 230 235 240
Thr Lys Leu Thr Val Leu Gly Gln Pro Ala Ala
245 250
<210> 29
<211> 247
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_F10
<400> 29
Glu Val Gln Leu Val Glu 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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile 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 Phe Gly Glu Arg Tyr Ala Phe Asp Ile Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ala Ser Gln Ser Glu Leu Thr Gln Pro Pro Ser Ala Ser
130 135 140
Gly Ser Pro Gly Gln Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Thr
145 150 155 160
Asp Val Gly Ala Phe His Phe Val Ser Trp Tyr Gln His Thr Pro Gly
165 170 175
Lys Ala Pro Lys Leu Leu Ile Ser Glu Val Arg Lys Arg Ala Ser Gly
180 185 190
Val Pro Asp Arg Phe Ser Gly Ser Arg Ser Gly Asn Thr Ala Ser Leu
195 200 205
Thr Val Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Phe Cys Ser
210 215 220
Ala Tyr Thr Gly Ser Asn Tyr Val Phe Gly Ser Gly Thr Lys Leu Thr
225 230 235 240
Val Leu Gly Gln Pro Ala Ala
245
<210> 30
<211> 252
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_G09
<400> 30
Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn
20 25 30
Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu
35 40 45
Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Asn Asp Tyr Ala
50 55 60
Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Ser Lys Asn
65 70 75 80
Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Ala Arg Asp Gln Trp Leu Ala Asn Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Ser Tyr Glu
130 135 140
Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln Thr Ala Arg
145 150 155 160
Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Asn Val His Trp Tyr
165 170 175
Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Arg Asp Asn
180 185 190
Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly
195 200 205
Asn Thr Ala Thr Leu Thr Ile Ser Lys Ala Gln Ala Gly Asp Glu Ala
210 215 220
Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Ser Trp Val Phe Gly Gly
225 230 235 240
Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Ala Ala
245 250
<210> 31
<211> 252
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_F09
<400> 31
Gln Met 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 Ala Ser Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ser Asn Arg Gly Gly Ser Tyr Lys Ser Val Gly Met Asp Val Trp
100 105 110
Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Gly Ser Gly Gly Gly Ala Ser Asn Phe Met Leu Thr Gln Pro
130 135 140
Gln Ser Val Ser Glu Ser Pro Gly Lys Thr Val Thr Ile Ser Cys Thr
145 150 155 160
Arg Ser Ser Gly Asn Phe Ala Ser Lys Tyr Val Gln Trp Tyr Gln Gln
165 170 175
Arg Pro Gly Ser Ser Pro Thr Thr Val Ile Tyr Glu Asn Tyr Gln Arg
180 185 190
Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ile Asp Ser Ser Ser
195 200 205
Asn Ser Ala Thr Leu Thr Ile Ser Gly Leu Lys Thr Glu Asp Glu Ala
210 215 220
Asp Tyr Tyr Cys Gln Ser Tyr Asp Glu Val Ser Val Val Phe Gly Gly
225 230 235 240
Gly Thr Gln Leu Thr Val Leu Gly Gln Pro Ala Ala
245 250
<210> 32
<211> 249
<212> PRT
<213> 人工序列
<220>
<223> scFv CP_03_D09
<400> 32
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Glu Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asn Thr Ser Ile 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 Val Ser Ser Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ala Ser Asn Phe Met Leu Thr Gln Pro Leu Ser Val Ser
130 135 140
Glu Ser Pro Gly Lys Thr Val Thr Ile Ser Cys Thr Arg Ser Ser Gly
145 150 155 160
Ser Ile Ala Ser Asn Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser
165 170 175
Ala Pro Thr Thr Val Ile Tyr Glu Asp Asn Gln Arg Pro Ser Gly Val
180 185 190
Pro Asp Arg Phe Ser Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser
195 200 205
Leu Thr Ile Ser Gly Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys
210 215 220
Gln Ser Tyr Asn Ser Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys
225 230 235 240
Val Thr Val Leu Gly Gln Pro Ala Ala
245
<210> 33
<211> 537
<212> PRT
<213> 人工序列
<220>
<223> 嵌合抗原受体 (CAR), 具有CD8茎部间隔区的JOVI-1 CAR
<400> 33
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Val Trp Ile Pro
1 5 10 15
Gly Ser Thr Gly Glu Val Arg Leu Gln Gln Ser Gly Pro Asp Leu Ile
20 25 30
Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr
35 40 45
Phe Thr Gly Tyr Val Met His Trp Val Lys Gln Arg Pro Gly Gln Gly
50 55 60
Leu Glu Trp Ile Gly Phe Ile Asn Pro Tyr Asn Asp Asp Ile Gln Ser
65 70 75 80
Asn Glu Arg Phe Arg Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser
85 90 95
Thr Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala
100 105 110
Val Tyr Tyr Cys Ala Arg Gly Ala Gly Tyr Asn Phe Asp Gly Ala Tyr
115 120 125
Arg Phe Phe Asp Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
130 135 140
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
145 150 155 160
Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Ser Leu Gly Asp
165 170 175
Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Arg Leu Val His Ser Asn
180 185 190
Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro
195 200 205
Lys Leu Leu Ile Tyr Arg Val Ser Asn Arg Phe Pro Gly Val Pro Asp
210 215 220
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser
225 230 235 240
Arg Val Glu Ala Glu Asp Leu Gly Ile Tyr Phe Cys Ser Gln Ser Thr
245 250 255
His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
260 265 270
Ser Asp Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro
275 280 285
Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro
290 295 300
Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp
305 310 315 320
Ile Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser
325 330 335
Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg
340 345 350
Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro
355 360 365
Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe
370 375 380
Ala Ala Tyr Arg Ser Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys
385 390 395 400
Pro Pro Gly Gly Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala
405 410 415
Asp Ala His Ser Thr Leu Ala Lys Ile Arg Val Lys Phe Ser Arg Ser
420 425 430
Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu
435 440 445
Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg
450 455 460
Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln
465 470 475 480
Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr
485 490 495
Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp
500 505 510
Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala
515 520 525
Leu His Met Gln Ala Leu Pro Pro Arg
530 535
<210> 34
<211> 727
<212> PRT
<213> 人工序列
<220>
<223> 具有H-CH2-CH3pvaa间隔区的JOVI-1 CAR
<400> 34
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Val Trp Ile Pro
1 5 10 15
Gly Ser Thr Gly Glu Val Arg Leu Gln Gln Ser Gly Pro Asp Leu Ile
20 25 30
Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr
35 40 45
Phe Thr Gly Tyr Val Met His Trp Val Lys Gln Arg Pro Gly Gln Gly
50 55 60
Leu Glu Trp Ile Gly Phe Ile Asn Pro Tyr Asn Asp Asp Ile Gln Ser
65 70 75 80
Asn Glu Arg Phe Arg Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser
85 90 95
Thr Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala
100 105 110
Val Tyr Tyr Cys Ala Arg Gly Ala Gly Tyr Asn Phe Asp Gly Ala Tyr
115 120 125
Arg Phe Phe Asp Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
130 135 140
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
145 150 155 160
Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Ser Leu Gly Asp
165 170 175
Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Arg Leu Val His Ser Asn
180 185 190
Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro
195 200 205
Lys Leu Leu Ile Tyr Arg Val Ser Asn Arg Phe Pro Gly Val Pro Asp
210 215 220
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser
225 230 235 240
Arg Val Glu Ala Glu Asp Leu Gly Ile Tyr Phe Cys Ser Gln Ser Thr
245 250 255
His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
260 265 270
Ser Asp Pro Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr Cys Pro
275 280 285
Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro
290 295 300
Pro Lys Pro Lys Asp Thr Leu Met Ile Ala Arg Thr Pro Glu Val Thr
305 310 315 320
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
325 330 335
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
340 345 350
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
355 360 365
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
370 375 380
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
385 390 395 400
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
405 410 415
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
420 425 430
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
435 440 445
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
450 455 460
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
465 470 475 480
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
485 490 495
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Lys Asp Pro Lys Phe
500 505 510
Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu
515 520 525
Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Ser Arg
530 535 540
Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro
545 550 555 560
Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala
565 570 575
Tyr Arg Ser Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys Pro Pro
580 585 590
Gly Gly Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala Asp Ala
595 600 605
His Ser Thr Leu Ala Lys Ile Arg Val Lys Phe Ser Arg Ser Ala Asp
610 615 620
Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn
625 630 635 640
Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg
645 650 655
Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly
660 665 670
Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu
675 680 685
Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu
690 695 700
Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His
705 710 715 720
Met Gln Ala Leu Pro Pro Arg
725
<210> 35
<211> 511
<212> PRT
<213> 人工序列
<220>
<223> 具有IgG1铰链间隔区的JOVI-1 CAR
<400> 35
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Val Trp Ile Pro
1 5 10 15
Gly Ser Thr Gly Glu Val Arg Leu Gln Gln Ser Gly Pro Asp Leu Ile
20 25 30
Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr
35 40 45
Phe Thr Gly Tyr Val Met His Trp Val Lys Gln Arg Pro Gly Gln Gly
50 55 60
Leu Glu Trp Ile Gly Phe Ile Asn Pro Tyr Asn Asp Asp Ile Gln Ser
65 70 75 80
Asn Glu Arg Phe Arg Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser
85 90 95
Thr Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala
100 105 110
Val Tyr Tyr Cys Ala Arg Gly Ala Gly Tyr Asn Phe Asp Gly Ala Tyr
115 120 125
Arg Phe Phe Asp Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
130 135 140
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
145 150 155 160
Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Ser Leu Gly Asp
165 170 175
Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Arg Leu Val His Ser Asn
180 185 190
Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro
195 200 205
Lys Leu Leu Ile Tyr Arg Val Ser Asn Arg Phe Pro Gly Val Pro Asp
210 215 220
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser
225 230 235 240
Arg Val Glu Ala Glu Asp Leu Gly Ile Tyr Phe Cys Ser Gln Ser Thr
245 250 255
His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
260 265 270
Ser Asp Pro Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr Cys Pro
275 280 285
Pro Cys Pro Lys Asp Pro Lys Phe Trp Val Leu Val Val Val Gly Gly
290 295 300
Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe
305 310 315 320
Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn
325 330 335
Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr
340 345 350
Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser Arg Asp Gln Arg Leu
355 360 365
Pro Pro Asp Ala His Lys Pro Pro Gly Gly Gly Ser Phe Arg Thr Pro
370 375 380
Ile Gln Glu Glu Gln Ala Asp Ala His Ser Thr Leu Ala Lys Ile Arg
385 390 395 400
Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln
405 410 415
Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp
420 425 430
Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro
435 440 445
Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp
450 455 460
Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg
465 470 475 480
Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr
485 490 495
Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg
500 505 510
<210> 36
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 对于TRBC2的合成肽
<400> 36
Val Leu Glu Asp Leu Lys Asn Val Phe Pro Pro Glu Val Ala Val
1 5 10 15
<210> 37
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 对于TRBC1的合成肽
<400> 37
Val Leu Glu Asp Leu Asn Lys Val Phe Pro Pro Glu Val Ala Val
1 5 10 15
<210> 38
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 对于TRBC1的合成肽
<400> 38
Val Leu Glu Asp Leu Asn Lys Val Phe Pro Pro Glu Val Ala Val Cys
1 5 10 15
<210> 39
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 对于TRBC2的合成肽
<400> 39
Val Leu Glu Asp Leu Lys Asn Val Phe Pro Pro Glu Val Ala Val Cys
1 5 10 15
<210> 40
<211> 175
<212> PRT
<213> 人类
<400> 40
Asp Leu Asn Lys Val Phe Pro Pro Glu Val Ala Val Phe Glu Pro Ser
1 5 10 15
Glu Ala Glu Ile Ser His Thr Gln Lys Ala Thr Leu Val Cys Leu Ala
20 25 30
Thr Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly
35 40 45
Lys Glu Val His Ser Gly Val Ser Thr Asp Pro Gln Pro Leu Lys Glu
50 55 60
Gln Pro Ala Leu Asn Asp Ser Arg Tyr Cys Leu Ser Ser Arg Leu Arg
65 70 75 80
Val Ser Ala Thr Phe Trp Gln Asn Pro Arg Asn His Phe Arg Cys Gln
85 90 95
Val Gln Phe Tyr Gly Leu Ser Glu Asn Asp Glu Trp Thr Gln Asp Arg
100 105 110
Ala Lys Pro Val Thr Gln Ile Val Ser Ala Glu Ala Trp Gly Arg Ala
115 120 125
Asp Cys Gly Phe Thr Ser Val Ser Tyr Gln Gln Gly Val Leu Ser Ala
130 135 140
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
145 150 155 160
Leu Val Ser Ala Leu Val Leu Met Ala Met Val Lys Arg Lys Asp
165 170 175
<210> 41
<211> 175
<212> PRT
<213> 人类
<400> 41
Asp Leu Lys Asn Val Phe Pro Pro Glu Val Ala Val Phe Glu Pro Ser
1 5 10 15
Glu Ala Glu Ile Ser His Thr Gln Lys Ala Thr Leu Val Cys Leu Ala
20 25 30
Thr Gly Phe Tyr Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly
35 40 45
Lys Glu Val His Ser Gly Val Ser Thr Asp Pro Gln Pro Leu Lys Glu
50 55 60
Gln Pro Ala Leu Asn Asp Ser Arg Tyr Cys Leu Ser Ser Arg Leu Arg
65 70 75 80
Val Ser Ala Thr Phe Trp Gln Asn Pro Arg Asn His Phe Arg Cys Gln
85 90 95
Val Gln Phe Tyr Gly Leu Ser Glu Asn Asp Glu Trp Thr Gln Asp Arg
100 105 110
Ala Lys Pro Val Thr Gln Ile Val Ser Ala Glu Ala Trp Gly Arg Ala
115 120 125
Asp Cys Gly Phe Thr Ser Glu Ser Tyr Gln Gln Gly Val Leu Ser Ala
130 135 140
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
145 150 155 160
Leu Val Ser Ala Leu Val Leu Met Ala Met Val Lys Arg Lys Asp
165 170 175
<210> 42
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_E09
<400> 42
Ala His Asn Ser Ser Ser Trp Ser Phe
1 5
<210> 43
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D12
<400> 43
Gly Gly Asp Thr Tyr Gly Phe Leu
1 5
<210> 44
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D10
<400> 44
Gly Gly Gly Ser Phe Gly Ala Phe
1 5
<210> 45
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_C08
<400> 45
Gly Tyr Ser Ser Ser Trp Tyr Leu
1 5
<210> 46
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_C11
<400> 46
Gly Gly Ala Gly
1
<210> 47
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F03
<220>
<221> misc_feature
<222> (3)..(3)
<223> Xaa 可以是任意自然发生的氨基酸
<400> 47
Gly Tyr Xaa Ala Ser Ser Trp Ser Gln
1 5
<210> 48
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_E07
<400> 48
Asp Leu Gly Gly Ser Gly Gly Ala Phe
1 5
<210> 49
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D03
<400> 49
Asn Lys Gln Tyr Gly Met
1 5
<210> 50
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F06
<400> 50
Asp Asp Gly Ala Met
1 5
<210> 51
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F02
<400> 51
Ala Gly Tyr Ser Tyr Ala
1 5
<210> 52
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_C03
<400> 52
Gly Gly Arg Tyr Ser Ser Asn Tyr Phe
1 5
<210> 53
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_D10
<400> 53
Val Gly Glu Gly Ser Ala Met
1 5
<210> 54
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_B01
<400> 54
Val Ser Ser His Tyr Asp Ser Ser Gly Tyr Tyr Ala Gly Gly Phe
1 5 10 15
<210> 55
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_D02
<400> 55
Gly Arg Asp Ser Ser Ser Trp Ser Pro
1 5
<210> 56
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A02
<400> 56
Val Thr Thr Tyr Ser Gly Leu Asp Phe
1 5
<210> 57
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_D04
<400> 57
Lys Gly Ala Val Val Val Pro Gly Ala Leu
1 5 10
<210> 58
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_E10
<400> 58
Asn Ser Leu Tyr Gly Gly Asn Ser Ala
1 5
<210> 59
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_H08
<400> 59
Asp Gly Gly Gly Gly Arg Phe
1 5
<210> 60
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F11
<400> 60
Gly Gly Gly Ala Leu Gly Arg Gly Met
1 5
<210> 61
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F09
<400> 61
Leu Leu Arg Ser Gly Gly Gln Ser Tyr Ala Phe
1 5 10
<210> 62
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_D05
<400> 62
Gly Tyr Ser Ser Ser Trp Ser Phe
1 5
<210> 63
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A09
<400> 63
Ala Gly Ser Ser Gly Trp Thr Leu
1 5
<210> 64
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_D03
<400> 64
Asp Lys Gly Trp Gly Phe
1 5
<210> 65
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_C11
<400> 65
Leu Gly Val Val Arg Gly Val Met Lys Gly Phe
1 5 10
<210> 66
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_H10
<400> 66
Ser Ser Tyr Ser Ser Ser Trp Gly Met
1 5
<210> 67
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_C04
<400> 67
Ala Asn Ser Trp Ser Ala Gly Gly Met
1 5
<210> 68
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G03
<400> 68
Glu Arg Gly Arg Gly Tyr Ser Tyr Met
1 5
<210> 69
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G06
<400> 69
Val Ala Arg Gly Ile His Asp Ala Phe
1 5
<210> 70
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D06
<400> 70
Arg His Gly Met
1
<210> 71
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_B03
<400> 71
Phe Asp Ser Ser Gly Tyr Tyr Tyr
1 5
<210> 72
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A12
<400> 72
Asp Leu Val Thr Thr Gly Ala Phe
1 5
<210> 73
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_H03
<400> 73
Ala Ile Arg Val Ser Gly Thr Pro Glu Asn Gly Phe
1 5 10
<210> 74
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G08
<400> 74
Val Arg Ile Thr His Gly Met
1 5
<210> 75
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_A06
<400> 75
Gly Lys Leu Ala Phe
1 5
<210> 76
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A04
<400> 76
Asn Gly Asp Ser Ser Gly Tyr His Thr Ser Pro Asn Trp Tyr Phe
1 5 10 15
<210> 77
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_E08
<400> 77
Val Ser Thr Asp Ser Ser Ser Met
1 5
<210> 78
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_A08
<400> 78
Thr Ser Gln Asp Pro Gly Ala Phe
1 5
<210> 79
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D01
<400> 79
Ala Glu Ser Gly Val Tyr Ser Ser Asn Gly Met
1 5 10
<210> 80
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A07
<400> 80
Val Asp Arg Val Arg Ser Gly Met
1 5
<210> 81
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_B08
<400> 81
Ile Gly Gln Tyr Cys Ser Ser Thr Ser Cys Tyr Met
1 5 10
<210> 82
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D09
<400> 82
Asp Leu Gly Gly Ser Gly Gly Ala Phe
1 5
<210> 83
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G07
<400> 83
Asp Ser Asp Ala Gly Tyr Phe
1 5
<210> 84
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_A05
<400> 84
Ala Ser Ile Val Ala Ser Gly Ala Phe
1 5
<210> 85
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A08
<400> 85
Ala Gly Gly Ser Asn Ala Phe
1 5
<210> 86
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_D07
<400> 86
Val Ser Thr Asp Ser Tyr Gly Arg Gln Asn Trp Phe
1 5 10
<210> 87
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_C04
<400> 87
Gln Tyr Thr Ser Gly Arg Leu Ala Tyr Tyr Tyr His Tyr Met
1 5 10
<210> 88
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_A07
<400> 88
Gly Ile Arg Gly Ala Phe
1 5
<210> 89
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_H02
<400> 89
Val Gly Tyr Ser Thr Thr Gln Leu
1 5
<210> 90
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F10
<400> 90
Met Ala Gly Ser Tyr Tyr Ala Phe
1 5
<210> 91
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_C10
<400> 91
Val Gly Asp Tyr Tyr Asp Ser Ser Gly Tyr Leu Asp Trp Tyr Phe
1 5 10 15
<210> 92
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_B05
<400> 92
Gly Ser Asp Thr Thr Ser Phe Val Ser
1 5
<210> 93
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G04
<400> 93
Ala Gly His Tyr Tyr Tyr Tyr Met
1 5
<210> 94
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F08
<400> 94
Val Thr Gly Tyr Pro Asp Tyr Tyr Asp Ser Ser Gly Phe
1 5 10
<210> 95
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G05
<400> 95
Val Glu Gly Gly Pro Pro Tyr Tyr Phe
1 5
<210> 96
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A03
<400> 96
Asn Gly Leu Asp Asn Tyr Gly Met
1 5
<210> 97
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_B09
<400> 97
Leu Gly Thr Thr Lys Arg Ala Phe
1 5
<210> 98
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_A10
<400> 98
Val Tyr Val Asp His Glu Gly Met
1 5
<210> 99
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_H04
<400> 99
Trp Ser Gly Ser Gly Phe
1 5
<210> 100
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_B04
<400> 100
Asp Phe Gly Trp Gly Gly Ala Phe
1 5
<210> 101
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A05
<400> 101
Val Val Gly Gly Thr Gln His
1 5
<210> 102
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_F07
<400> 102
Asn Trp Leu Leu Tyr Tyr Gly Asp Pro Gln Gln Asn Ala Phe
1 5 10
<210> 103
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_H01
<400> 103
Leu Tyr Phe Asp Trp Phe Ala Asp Ser Gln Asn Ala Phe
1 5 10
<210> 104
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G10
<400> 104
Val Gly Tyr Gln Pro Leu Leu Tyr Ala Asp Tyr Tyr Phe
1 5 10
<210> 105
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G11
<400> 105
Gly Ala Met Gly Leu
1 5
<210> 106
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G01
<400> 106
Val Tyr Tyr Leu Ser Gly Val His Ala Phe
1 5 10
<210> 107
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_A12
<400> 107
Thr Glu Arg Trp Leu Gln Phe
1 5
<210> 108
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_H05
<400> 108
Asn Gly Asp Tyr Ala Phe
1 5
<210> 109
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_B07
<400> 109
Ala Ser Arg Tyr Ser Gly Ser Tyr His Phe
1 5 10
<210> 110
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_G09
<400> 110
His Gly Ser Gln Gly Gly Phe
1 5
<210> 111
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_C02
<400> 111
Val Gly Tyr Met Gly Gly Met
1 5
<210> 112
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D05
<400> 112
Asn Thr Pro Gly Ile Ala Ala Ala Gly Pro
1 5 10
<210> 113
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_01_D08
<400> 113
Val Gly Thr Thr Thr Val Thr Ser Phe
1 5
<210> 114
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_A11
<400> 114
Val Gly Gly Pro Leu Asn Asp Ala Phe
1 5
<210> 115
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_D08
<400> 115
His Ser Ser Gly Gly Ala Phe
1 5
<210> 116
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_E09
<400> 116
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 117
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D12
<400> 117
Gln Gln Phe Asn Ala Tyr Pro
1 5
<210> 118
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D10
<400> 118
Gln Gln Tyr Asn Ser Tyr Pro
1 5
<210> 119
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_C08
<400> 119
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 120
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_C11
<400> 120
Gln Ser His Asp Ser Ser Asn
1 5
<210> 121
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F03
<400> 121
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 122
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_E07
<400> 122
Met Gln Ser Ile Gln Leu
1 5
<210> 123
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D03
<400> 123
Gln Gln Tyr His Arg Trp Pro
1 5
<210> 124
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F06
<400> 124
Gln Gln Tyr Tyr Asp Ser Pro
1 5
<210> 125
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F02
<400> 125
Leu Gln His Asn Ser Tyr Pro
1 5
<210> 126
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_C03
<400> 126
Gln Gln Tyr Phe Gly Thr
1 5
<210> 127
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_D10
<400> 127
Gln Gln Tyr Asn Asp Trp Pro
1 5
<210> 128
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_B01
<400> 128
Gln Ser Phe Asp Thr Asn Ser Leu
1 5
<210> 129
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_D02
<400> 129
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 130
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A02
<400> 130
Ser Ser Tyr Thr Ser Ser Ser Thr
1 5
<210> 131
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_D04
<400> 131
Gln Gln Tyr Asn Ser Tyr Pro
1 5
<210> 132
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_E10
<400> 132
Gln Gln Thr Phe Thr Thr Pro
1 5
<210> 133
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_H08
<400> 133
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 134
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F11
<400> 134
Gln Ser Tyr Asp Thr Asn Asn
1 5
<210> 135
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F09
<400> 135
Gln Gln Ser Tyr Ser Thr Pro
1 5
<210> 136
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_D05
<400> 136
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 137
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A09
<400> 137
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 138
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_D03
<400> 138
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 139
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_C11
<400> 139
Gln Ser Tyr Asp Ser Ser Asn
1 5
<210> 140
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_H10
<400> 140
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 141
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_C04
<400> 141
Gln Gln Tyr Asp Asp Leu Pro
1 5
<210> 142
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G03
<400> 142
Met Gln Arg Ile Glu Phe Pro
1 5
<210> 143
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G06
<400> 143
Gln Ser Tyr Asp Asn Thr Arg His
1 5
<210> 144
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D06
<400> 144
Gln Ser Tyr Asp Ser Ser Asn
1 5
<210> 145
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_B03
<400> 145
Gln Ser Tyr Asp Ser Ser Asn
1 5
<210> 146
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A12
<400> 146
Gln Gln His Asn Asp Trp Pro
1 5
<210> 147
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_H03
<400> 147
Gln Ser Tyr His Ser Ser Asn Leu
1 5
<210> 148
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G08
<400> 148
Met Gln Ala Thr His Phe Pro
1 5
<210> 149
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_A06
<400> 149
Gln Gln Tyr Tyr Ser Thr Pro
1 5
<210> 150
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A04
<400> 150
Gln Ser Tyr Asp Asp Ser Asn Tyr
1 5
<210> 151
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_E08
<400> 151
Ser Ser Tyr Ala Gly Ser Asn Thr Leu
1 5
<210> 152
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_A08
<400> 152
Gln Gln Ala Asn Ser Phe Pro
1 5
<210> 153
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D01
<400> 153
Gln Ser Tyr Asp Ser Ser Ile
1 5
<210> 154
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A07
<400> 154
Gln Ser Tyr Asp Ser Ile His
1 5
<210> 155
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_B08
<400> 155
Gln Ser Tyr Asp Ser Ser Thr His
1 5
<210> 156
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D09
<400> 156
Gln Gln Tyr Asp Asn Leu Pro
1 5
<210> 157
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G07
<400> 157
Gln Ser Phe Thr Ser Ser Thr Leu
1 5
<210> 158
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_A05
<400> 158
Gln Gln Tyr Asn Lys Trp Pro
1 5
<210> 159
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A08
<400> 159
Gln Ser Tyr Asp Asp Ser Asn Tyr
1 5
<210> 160
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_D07
<400> 160
Gln Ser Tyr Asp Ser Ser Asn His
1 5
<210> 161
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_C04
<400> 161
Gln Gln Ser Tyr Ser Thr Pro
1 5
<210> 162
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_A07
<400> 162
Asn Ser Arg Asp Ser Ser Gly Asn Pro Asn
1 5 10
<210> 163
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_H02
<400> 163
Gln Ser Tyr Asp Ser Ser Asn Leu
1 5
<210> 164
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F10
<400> 164
Gln Ser Tyr Asp Ser Ser Asn His
1 5
<210> 165
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_C10
<400> 165
Ala Val Trp Asp Asp Arg Leu Asn Gly
1 5
<210> 166
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_B05
<400> 166
Gln Gln Tyr Asp Ser Tyr Ser
1 5
<210> 167
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G04
<400> 167
Gln Ser Ala Asp Ser Ser Gly Thr Asn
1 5
<210> 168
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F08
<400> 168
Gln Ser Tyr Asp Ser Ser Asn His
1 5
<210> 169
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G05
<400> 169
Gln Ser Tyr Asp Thr Arg Asn Gln
1 5
<210> 170
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A03
<400> 170
Gln Gln Tyr Tyr Ser Thr Pro
1 5
<210> 171
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_B09
<400> 171
Gln Gln Ser Tyr Ser Thr
1 5
<210> 172
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_A10
<400> 172
Ala Ala Trp Asp Asp Ser Leu Phe
1 5
<210> 173
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_H04
<400> 173
Met Gln Arg Ile Glu Phe Pro
1 5
<210> 174
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_B04
<400> 174
Gln Gln Tyr Tyr Asn Thr Pro
1 5
<210> 175
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A05
<400> 175
Gln Ser Tyr Asp Ser Ser Ile
1 5
<210> 176
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_F07
<400> 176
Gln Ser Tyr Asp Ser Thr Asn Leu
1 5
<210> 177
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_H01
<400> 177
Gln Gln Ser Tyr Ser Thr Pro
1 5
<210> 178
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G10
<400> 178
Asn Ser Arg Asp Ser Ser Gly Asn His
1 5
<210> 179
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G11
<400> 179
Gln Gln Ser Tyr Ser Thr Pro
1 5
<210> 180
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G01
<220>
<221> misc_feature
<222> (9)..(9)
<223> Xaa 可以是任意自然发生的氨基酸
<400> 180
Asp Ser Arg Asp Thr Arg Val Asn Xaa
1 5
<210> 181
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_A12
<400> 181
Gln Gln Tyr Asp Asn Leu
1 5
<210> 182
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_H05
<400> 182
Met Gln Ala Leu Gln Thr Pro
1 5
<210> 183
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_B07
<400> 183
Gln Ser Tyr Asp Ser Ser Asn
1 5
<210> 184
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_G09
<400> 184
Ser Ser Tyr Thr Ser Ser Ser Thr
1 5
<210> 185
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_C02
<400> 185
Met Gln Ala Leu Gln Thr Pro Pro
1 5
<210> 186
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D05
<400> 186
Gln Ser Tyr Asp Ser Thr Asn His
1 5
<210> 187
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_01_D08
<400> 187
Gln Ser Tyr Asp Ser Ala Asn Leu
1 5
<210> 188
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_A11
<400> 188
Gln Ser Phe Asp Glu Asn Ile Ser
1 5
<210> 189
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_D08
<400> 189
His Gln Ser Ala Thr Ser Pro
1 5
<210> 190
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_E05
<400> 190
Thr Arg Ser Ser Gly Ala Phe
1 5
<210> 191
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_D05
<400> 191
Pro Arg Gly Arg Gly Ser Ala Phe
1 5
<210> 192
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_H06
<400> 192
Ala Arg Val Gly Gly Met
1 5
<210> 193
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_C12
<400> 193
Asp Thr Gly Pro Ile
1 5
<210> 194
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_G02
<400> 194
Gly Val Trp Asn Ser Gly Ser Tyr Leu Gly Phe
1 5 10
<210> 195
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_D04
<400> 195
Gly Gly Phe Thr Val Pro Gly Gly Ala Phe
1 5 10
<210> 196
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_F10
<400> 196
Phe Gly Glu Arg Tyr Ala Phe
1 5
<210> 197
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_G09
<400> 197
Asp Gln Trp Leu Ala Asn Tyr Tyr Tyr Tyr Gly Met
1 5 10
<210> 198
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_F09
<400> 198
Asn Arg Gly Gly Ser Tyr Lys Ser Val Gly Met
1 5 10
<210> 199
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_D09
<400> 199
Val Ser Ser Tyr Tyr Gly Met
1 5
<210> 200
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_F02
<400> 200
Ala Pro Ala Ser Ser Ala His
1 5
<210> 201
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_02_E03
<400> 201
Gln Arg Gly Tyr Tyr Tyr Gly Met
1 5
<210> 202
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_H07
<400> 202
Ser Ser Val Ala Ala Gly Ala Phe
1 5
<210> 203
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_C02
<400> 203
Leu Ser Gly Arg Gly Leu Gly Phe
1 5
<210> 204
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_E09
<400> 204
Asp His Tyr Phe
1
<210> 205
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_D08
<400> 205
Ser Gly Arg Arg Val Thr Ala Ile
1 5
<210> 206
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_E11
<400> 206
Met Gly Arg Tyr Ser Ser Ser Trp
1 5
<210> 207
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_B05
<400> 207
His Ser Arg Phe Gly Pro Ala Phe
1 5
<210> 208
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_H02
<400> 208
Asp Arg Glu Ala Phe
1 5
<210> 209
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_D02
<400> 209
Leu Arg Gly Arg Tyr Ser Tyr Gly Tyr Ser Asp Ala Phe
1 5 10
<210> 210
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_E01
<400> 210
Leu Leu Asn Ala Val Thr Tyr Ala Phe
1 5
<210> 211
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_C11
<400> 211
Ile Gly Val Ile Gly Gly Phe
1 5
<210> 212
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_B12
<400> 212
Ile Glu Tyr Ser Ser Ser Ser Pro Tyr Phe
1 5 10
<210> 213
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_E03
<400> 213
Asp Leu Leu Pro Thr Thr Val Thr Thr Thr Gly Ala Phe
1 5 10
<210> 214
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_F01
<400> 214
Asp Ser Gly Ser Tyr Ser
1 5
<210> 215
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_C01
<400> 215
Ala Ser Tyr Pro Tyr Tyr Tyr Tyr Tyr Tyr Gly Met
1 5 10
<210> 216
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_G07
<400> 216
Ala Leu Gly His Phe
1 5
<210> 217
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_E02
<400> 217
Phe Thr Thr Gly Ser Ala Leu
1 5
<210> 218
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_C07
<400> 218
Asp Ala Ser Gly Tyr
1 5
<210> 219
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_H04
<400> 219
Asp Leu Gly Thr Tyr Tyr Tyr Gly Ser Gly Asp
1 5 10
<210> 220
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_E06
<400> 220
Val Gly Glu Leu Leu Gly Ala Phe
1 5
<210> 221
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_E05
<400> 221
His Ser Tyr Asp Ser Asn Asn His
1 5
<210> 222
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_G11
<400> 222
His Ser Gly Val Gly Gly Leu Ala Phe
1 5
<210> 223
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_G01
<400> 223
Gly Gly Ser Ile Ala Ala Ala Leu Ala Phe
1 5 10
<210> 224
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_H01
<400> 224
Val Glu Tyr Ser Arg Asn Gly Met
1 5
<210> 225
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_F11
<400> 225
Gly Arg Tyr Asn
1
<210> 226
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_C06
<400> 226
Leu Asp Tyr Tyr Tyr Gly Met
1 5
<210> 227
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_D03
<400> 227
Gly Gly Leu Ser Ser Ala Phe
1 5
<210> 228
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_G05
<400> 228
Tyr Gly Gly Gly Leu
1 5
<210> 229
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_G12
<400> 229
Pro Asp His Leu Thr Val Phe
1 5
<210> 230
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_C10
<400> 230
Val Gly Tyr Tyr Gly Met
1 5
<210> 231
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 重链CD3克隆CP_03_F04
<400> 231
Tyr Glu Gly Tyr Ala Gly Phe
1 5
<210> 232
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_D05
<400> 232
Gln Ala Trp Asp Thr Asn Leu Gly
1 5
<210> 233
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_H06
<400> 233
Gln Ser Phe Asp Ala Asp Asn Leu His
1 5
<210> 234
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_C12
<400> 234
Met Gln Gly Ile Gln Leu Pro
1 5
<210> 235
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_G02
<400> 235
Gln Gln Ser Tyr Ser Thr Pro
1 5
<210> 236
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_D04
<400> 236
Gln Ser Tyr Asp Ala Ser Asn
1 5
<210> 237
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_F10
<400> 237
Ser Ala Tyr Thr Gly Ser Asn
1 5
<210> 238
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_G09
<400> 238
Gln Val Trp Asp Ser Asn Ser
1 5
<210> 239
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_F09
<400> 239
Gln Ser Tyr Asp Glu Val Ser
1 5
<210> 240
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_D09
<400> 240
Gln Ser Tyr Asn Ser Ser Asn His
1 5
<210> 241
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_F02
<400> 241
Gln Ser Tyr Asp Ser Ser His
1 5
<210> 242
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_02_E03
<400> 242
Gln Gln Ser Arg Ser Thr Pro
1 5
<210> 243
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_H07
<400> 243
Ser Ser Tyr Thr Ser Ser Ser Thr
1 5
<210> 244
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_C02
<400> 244
Ser Ser Tyr Ala Gly Ser Ser Asn Leu
1 5
<210> 245
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_E09
<400> 245
Asn Ser Tyr Thr Arg Ser Ser Thr
1 5
<210> 246
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_D08
<400> 246
Gln Ser Tyr Asp Asp Thr Asn
1 5
<210> 247
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_E11
<400> 247
Gln Ala Trp Asp Thr Asn Ile Gly
1 5
<210> 248
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_B05
<400> 248
Ser Ser Tyr Ala Gly Ser Asn Asn
1 5
<210> 249
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_H02
<400> 249
Gln Ala Trp Asp Thr Asn Ile Gly
1 5
<210> 250
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_D02
<400> 250
Ser Ser Tyr Ala Gly Ser Ser Thr
1 5
<210> 251
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_E01
<400> 251
Asn Ser Arg Asp Ser Ser Gly Phe
1 5
<210> 252
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_C11
<400> 252
Ser Ser Tyr Thr Ser Ser Ser
1 5
<210> 253
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_B12
<400> 253
Gln Ser Tyr Asp Ser Asn Asn Arg
1 5
<210> 254
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_E03
<400> 254
Ser Ser Arg Asp Ser Ser Gly Asn His
1 5
<210> 255
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_F01
<400> 255
Gln Ala Trp Asp Thr Asn Ile Gly
1 5
<210> 256
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_C01
<400> 256
Gln Val Trp Asp Ser Ser Thr Ala Asn
1 5
<210> 257
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_G07
<400> 257
Gln Ser Tyr Asp Ser Ser Asn His His
1 5
<210> 258
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_E02
<400> 258
Ser Ser Tyr Ala Gly Asn Ser Asn
1 5
<210> 259
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_C07
<400> 259
Gln Ala Trp Asp Thr Asn Ile Gly
1 5
<210> 260
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_H04
<400> 260
Gly Thr Trp Asp Ser Ser Leu Ser Ala Gly
1 5 10
<210> 261
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_E06
<400> 261
Ser Ser Leu Asp Ser Asn Asp Asn His
1 5
<210> 262
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_H03
<400> 262
Ala Ala Trp Asp Asp Ser Leu Asn Gly
1 5
<210> 263
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_G11
<400> 263
Ser Ser Tyr Ala Gly Ser Ser Thr
1 5
<210> 264
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_G01
<400> 264
His Gln Tyr Asp Val Tyr Pro
1 5
<210> 265
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_H01
<400> 265
Asn Ser Arg Asp Ser Ser Gly Asn His
1 5
<210> 266
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_F11
<400> 266
Gln Ser Tyr Asp Ser Ser Asn
1 5
<210> 267
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_C06
<400> 267
Gln Ser Tyr Asp Ser Ser Asn
1 5
<210> 268
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_D03
<400> 268
Gln Ser Tyr Asp Ser Ser Asn
1 5
<210> 269
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_G05
<400> 269
Ser Ser Tyr Ala Gly Ser Tyr Thr
1 5
<210> 270
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_G12
<400> 270
Ser Ser Tyr Thr Pro Ser Ser
1 5
<210> 271
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_C10
<400> 271
Gln Ala Trp Asp Thr Asn Ile Gly
1 5
<210> 272
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 轻链CD3克隆CP_03_F04
<400> 272
Gln Ala Trp Asp Thr Asn Ile Gly
1 5
Claims (18)
1.双特异性T细胞结合剂,其包含:
a)选择性结合TCR beta恒定区1(TRBC1)或TRBC2的第一结构域;和
b)能够活化T细胞的第二结构域。
2.根据权利要求1的双特异性T细胞结合剂,其中所述第一结构域和第二结构域是单链可变片段(scFv)。
3.根据权利要求1或2中任一项的双特异性T细胞结合剂,其中所述第一结构域选择性结合TRBC1。
4.根据权利要求3的双特异性T细胞结合剂,其中所述第一结构域具有可变重链(VH)和可变轻链(VL),所述VH和VL包含以下互补决定区(CDR):
VH CDR1:SEQ ID No.7;
VH CDR2:SEQ ID No.8;
VH CDR3:SEQ ID No.9;
VL CDR1:SEQ ID No.10;
VL CDR2:SEQ ID No.11;和
VL CDR3:SEQ ID No.12。
5.根据权利要求3的双特异性T细胞结合剂,其中所述第一结构域包含具有如SEQ IDNo.1所示的序列的可变重链(VH)和具有如SEQ ID No.2所示的序列的可变轻链(VL)。
6.根据权利要求3的双特异性T细胞结合剂,其中所述第一结构域包含具有如SEQ IDNo.3所示的序列的scFv。
7.根据权利要求1或2中任一项的双特异性T细胞结合剂,其中所述第一结构域选择性结合TRBC2。
8.核酸,其编码根据权利要求1至7中任一项的双特异性T细胞结合剂。
9.载体,其包含根据权利要求8的核酸。
10.根据权利要求1至7中任一项的双特异性T细胞结合剂在制备用于治疗受试者中T细胞淋巴瘤或白血病的药物中的用途,其包括以下步骤:
将所述双特异性T细胞结合剂施用至所述受试者,以引起恶性T细胞以及与所述恶性T细胞表达相同TRBC的正常T细胞的选择性耗竭,但不引起表达所述恶性T细胞不表达的TRBC的正常T细胞的耗竭。
11.根据权利要求10的用途,其进一步包括调查来自所述受试者的恶性T细胞的TCRbeta恒定区(TCRB)以确定其表达TRBC1还是TRBC2的步骤。
12.根据权利要求11或12中任一项的用途,其中所述T细胞淋巴瘤或白血病选自外周T细胞淋巴瘤,非特指型(PTCL-NOS);血管免疫母细胞T细胞淋巴瘤(AITL),间变性大细胞淋巴瘤(ALCL),肠病相关的T细胞淋巴瘤(EATL),肝脾T细胞淋巴瘤(HSTL),结外NK/T细胞淋巴瘤鼻型,皮肤T细胞淋巴瘤,原发性皮肤ALCL,T细胞幼淋巴细胞白血病和T细胞急性淋巴母细胞白血病。
13.药物组合物,其包含根据权利要求1至7中任一项的双特异性T细胞结合剂和药学上可接受的载体、稀释剂、赋形剂或佐剂。
14.选择适合的疗法以治疗患有T细胞淋巴瘤或白血病的受试者的方法,所述方法包括:
i)确定从所述受试者分离的样品中恶性T细胞表达TRBC1还是TRBC2;和
ii)基于所述恶性T细胞的TRBC1或TRBC2表达选择根据权利要求10至12中任一项使用的双特异性T细胞结合剂。
15.选择患有T细胞淋巴瘤或白血病的受试者以接受疗法的方法,所述疗法基于根据权利要求10至12中任一项使用的双特异性T细胞结合剂,所述方法包括:
i)确定从所述受试者分离的样品中恶性T细胞表达TRBC1还是TRBC2;和
ii)基于所述恶性T细胞的TRBC1或TRBC2表达选择所述受试者以接受根据权利要求10至12中任一项使用的双特异性T细胞结合剂的疗法。
16.缀合的抗体,其选择性结合TRBC1或TRBC2。
17.鉴定对于TRBC1或TRBC2选择性的抗体的方法,所述方法包括:
确定抗体对TRBC1和TRBC2每一个的结合;和
鉴定选择性结合TRBC1或TRBC2而不显著结合另一种TRBC的抗体。
18.抗体模拟物,其选择性结合TRBC1或TRBC2。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB201403905A GB201403905D0 (en) | 2014-03-05 | 2014-03-05 | Method |
GB1403905.1 | 2014-03-05 | ||
GB1416908.0 | 2014-09-25 | ||
GB201416908A GB201416908D0 (en) | 2014-09-25 | 2014-09-25 | Method |
CN201580011306.XA CN106068276B (zh) | 2014-03-05 | 2015-03-05 | 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201580011306.XA Division CN106068276B (zh) | 2014-03-05 | 2015-03-05 | 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) |
Publications (1)
Publication Number | Publication Date |
---|---|
CN112094353A true CN112094353A (zh) | 2020-12-18 |
Family
ID=52649058
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010858243.4A Pending CN112094347A (zh) | 2014-03-05 | 2015-03-05 | 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) |
CN202010859460.5A Pending CN112094353A (zh) | 2014-03-05 | 2015-03-05 | 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) |
CN201580011306.XA Active CN106068276B (zh) | 2014-03-05 | 2015-03-05 | 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010858243.4A Pending CN112094347A (zh) | 2014-03-05 | 2015-03-05 | 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201580011306.XA Active CN106068276B (zh) | 2014-03-05 | 2015-03-05 | 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR) |
Country Status (23)
Country | Link |
---|---|
US (2) | US20170066827A1 (zh) |
EP (2) | EP3241561A1 (zh) |
JP (4) | JP6767872B2 (zh) |
KR (3) | KR102088082B1 (zh) |
CN (3) | CN112094347A (zh) |
AU (3) | AU2015225944B2 (zh) |
BR (1) | BR112016020304B1 (zh) |
CA (1) | CA2940564C (zh) |
CL (4) | CL2016002195A1 (zh) |
CU (1) | CU24475B1 (zh) |
DK (1) | DK3125934T3 (zh) |
ES (1) | ES2758173T3 (zh) |
HU (1) | HUE047641T2 (zh) |
IL (3) | IL278878B (zh) |
MX (3) | MX2016010856A (zh) |
MY (1) | MY173567A (zh) |
PE (2) | PE20211887A1 (zh) |
PH (2) | PH12016501646A1 (zh) |
PL (1) | PL3125934T3 (zh) |
PT (1) | PT3125934T (zh) |
RU (3) | RU2021101502A (zh) |
SG (3) | SG10201906460PA (zh) |
WO (1) | WO2015132598A1 (zh) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11885806B2 (en) | 2014-03-05 | 2024-01-30 | Autolus Limited | Method for depleting malignant T-cells |
US11385233B2 (en) | 2015-03-05 | 2022-07-12 | Autolus Limited | Methods of depleting malignant T-cells |
GB201403972D0 (en) | 2014-03-06 | 2014-04-23 | Ucl Business Plc | Chimeric antigen receptor |
WO2016051205A1 (en) * | 2014-10-03 | 2016-04-07 | Isis Innovation Limited | Analysis of t-cell monotypia |
CA2937157A1 (en) * | 2016-07-25 | 2018-01-25 | Ucl Business Plc | Protein-based t-cell receptor knockdown |
AU2018219887A1 (en) | 2017-02-08 | 2019-08-22 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
AU2018220736A1 (en) | 2017-02-20 | 2019-09-05 | Dragonfly Therapeutics, Inc. | Proteins binding HER2, NKG2D and CD16 |
TWI704158B (zh) * | 2017-04-04 | 2020-09-11 | 瑞士商赫孚孟拉羅股份公司 | 能夠特異性結合至cd40及fap之新穎雙特異性抗原結合分子 |
GB201709203D0 (en) | 2017-06-09 | 2017-07-26 | Autolus Ltd | Antigen-binding domain |
US20210130775A1 (en) * | 2017-08-02 | 2021-05-06 | Autolus Limited | Cells expressing a chimeric antigen receptor or engineered tcr and comprising a nucleotide sequence which is selectively expressed |
RU2020111554A (ru) * | 2017-08-23 | 2021-09-23 | Драгонфлай Терапьютикс, Инк. | Белки, связывающие nkg2d, cd16 и опухолеассоциированный антиген |
EP3684399A1 (en) * | 2017-12-29 | 2020-07-29 | Cellectis | Method for improving production of car t cells |
WO2019129850A1 (en) * | 2017-12-29 | 2019-07-04 | Cellectis | Off-the-shelf engineered cells for therapy |
GB201800298D0 (en) * | 2018-01-09 | 2018-02-21 | Autolus Ltd | Method |
WO2019143961A2 (en) * | 2018-01-19 | 2019-07-25 | The Trustees Of The University Of Pennsylvania | Compositions and methods for targeting gamma delta t cells with chimeric antigen receptors |
MX2020008336A (es) | 2018-02-08 | 2020-09-21 | Dragonfly Therapeutics Inc | Dominios variables de anticuerpos que se dirigen al receptor nkg2d. |
US20210283180A1 (en) * | 2018-07-06 | 2021-09-16 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Car t cell therapy to target t cell specific cancers |
WO2020018708A1 (en) * | 2018-07-18 | 2020-01-23 | The General Hospital Corporation | Compositions and methods for treatment of t cell malignancies |
GB201812650D0 (en) | 2018-08-03 | 2018-09-19 | Autolus Ltd | Molecular assessment of TRBC usage |
GB201817172D0 (en) | 2018-10-22 | 2018-12-05 | Autolus Ltd | Antibody |
GB201817822D0 (en) * | 2018-10-31 | 2018-12-19 | Autolus Ltd | Binding domain |
KR20210121136A (ko) * | 2019-01-29 | 2021-10-07 | 상하이 지아오통 유니버시티 | 키메라 항원 수용체 및 그 용용 |
SG11202109061YA (en) * | 2019-02-21 | 2021-09-29 | Marengo Therapeutics Inc | Multifunctional molecules that bind to t cell related cancer cells and uses thereof |
CN110317266A (zh) * | 2019-07-17 | 2019-10-11 | 东北农业大学 | 三种scFv抗体、其编码基因及其在制备治疗或预防O型口蹄疫病制剂中的应用 |
EP4121518A1 (en) * | 2020-03-16 | 2023-01-25 | Marengo Therapeutics, Inc. | Engineered cell compositions and methods of use thereof |
GB202004263D0 (en) | 2020-03-24 | 2020-05-06 | Autolus Ltd | Antibody conjugate |
GB202005216D0 (en) | 2020-04-08 | 2020-05-20 | Autolus Ltd | Cell |
WO2021205175A1 (en) | 2020-04-09 | 2021-10-14 | Autolus Limited | Molecule |
GB202101491D0 (en) | 2021-02-03 | 2021-03-17 | Autolus Ltd | Molecule |
CA3180321A1 (en) * | 2020-04-24 | 2021-10-28 | Marengo Therapeutics, Inc. | Multifunctional molecules that bind to t cell related cancer cells and uses thereof |
CN111537735A (zh) * | 2020-05-15 | 2020-08-14 | 江西赛基生物技术有限公司 | 抗体检测试剂盒以及在免疫分析方面的应用 |
CN111549044B (zh) * | 2020-07-13 | 2020-10-23 | 北京市肿瘤防治研究所 | 靶向trbc1 car-t细胞的制备方法与应用 |
US20230287345A1 (en) * | 2020-08-18 | 2023-09-14 | Medigene Immunotherapies Gmbh | ENRICHMENT OF T CELLS USING AN ANTI-Cß ANTIBODY |
WO2022047046A1 (en) * | 2020-08-26 | 2022-03-03 | Marengo Therapeutics, Inc. | Methods of detecting trbc1 or trbc2 |
US20220267415A1 (en) * | 2021-02-17 | 2022-08-25 | The Board Of Regents Of The University Of Texas System | Multimeric sars-cov-2 binding molecules and uses thereof |
US20240124608A1 (en) | 2021-02-17 | 2024-04-18 | The Johns Hopkins University | Methods and materials for treating clonal t cell expansions |
GB202112923D0 (en) * | 2021-09-10 | 2021-10-27 | Ucl Business Ltd | Binding domain |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR930701620A (ko) * | 1990-08-09 | 1993-06-12 | 프레드릭 에이. 란길레 | 재조합 dna 백터를 이용하여 인체 t-세포 리셉터 성분에 대한 단일 클론성 항체의 제조방법 |
US6790604B1 (en) * | 1998-05-12 | 2004-09-14 | Stefan A. Cohen | Methods for identifying or diagnosing carcinoma cells with metastatic potential based on the measurement of lymphoid genes or their products in carcinoma cells |
US20070274998A1 (en) * | 2002-04-29 | 2007-11-29 | Genpatzz Pharmacogentetics Ag | Novel Bispecific Molecules For Use In Therapy And Diagnosis |
RU2355703C2 (ru) * | 2002-10-09 | 2009-05-20 | Медиджен Лимитед | Одноцепочечные рекомбинантные т-клеточные рецепторы |
GB0304068D0 (en) * | 2003-02-22 | 2003-03-26 | Avidex Ltd | Substances |
US7741045B2 (en) * | 2006-11-16 | 2010-06-22 | General Electric Company | Sequential analysis of biological samples |
WO2009151628A2 (en) * | 2008-06-12 | 2009-12-17 | Gov't Of The Usa, As Represented By The Secretary, Department Of Health Human Services | Monitoring tcr-b to determine hiv therapy and disease progression |
WO2010027797A1 (en) * | 2008-08-26 | 2010-03-11 | Macrogenics Inc. | T-cell receptor antibodies and methods of use thereof |
DK2519543T3 (en) * | 2009-12-29 | 2016-09-26 | Emergent Product Dev Seattle | HETERODIMER BINDING PROTEINS AND USE THEREOF |
JP6000507B2 (ja) * | 2010-09-30 | 2016-09-28 | パナソニックヘルスケアホールディングス株式会社 | 診療情報登録装置 |
EP3305798A1 (en) * | 2010-12-09 | 2018-04-11 | The Trustees of The University of Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
US10391126B2 (en) * | 2011-11-18 | 2019-08-27 | Board Of Regents, The University Of Texas System | CAR+ T cells genetically modified to eliminate expression of T-cell receptor and/or HLA |
ES2962571T3 (es) * | 2012-05-25 | 2024-03-19 | Cellectis | Métodos para modificar células T alogénicas y resistentes a la inmunosupresión para inmunoterapia |
US10443100B2 (en) * | 2014-05-22 | 2019-10-15 | The Scripps Research Institute | Gene expression profiles associated with sub-clinical kidney transplant rejection |
WO2016044745A1 (en) * | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
CN115537396A (zh) * | 2015-03-27 | 2022-12-30 | 哈佛学院校长同事会 | 经过修饰的t细胞及其制备和使用方法 |
-
2015
- 2015-03-05 CN CN202010858243.4A patent/CN112094347A/zh active Pending
- 2015-03-05 ES ES15709319T patent/ES2758173T3/es active Active
- 2015-03-05 US US15/123,287 patent/US20170066827A1/en not_active Abandoned
- 2015-03-05 PE PE2021000759A patent/PE20211887A1/es unknown
- 2015-03-05 HU HUE15709319A patent/HUE047641T2/hu unknown
- 2015-03-05 SG SG10201906460PA patent/SG10201906460PA/en unknown
- 2015-03-05 SG SG11201606583VA patent/SG11201606583VA/en unknown
- 2015-03-05 KR KR1020167027423A patent/KR102088082B1/ko active IP Right Grant
- 2015-03-05 EP EP17172755.5A patent/EP3241561A1/en active Pending
- 2015-03-05 CN CN202010859460.5A patent/CN112094353A/zh active Pending
- 2015-03-05 PL PL15709319T patent/PL3125934T3/pl unknown
- 2015-03-05 PE PE2016001548A patent/PE20170125A1/es unknown
- 2015-03-05 BR BR112016020304-6A patent/BR112016020304B1/pt active IP Right Grant
- 2015-03-05 RU RU2021101502A patent/RU2021101502A/ru unknown
- 2015-03-05 AU AU2015225944A patent/AU2015225944B2/en active Active
- 2015-03-05 DK DK15709319.6T patent/DK3125934T3/da active
- 2015-03-05 SG SG10201906461SA patent/SG10201906461SA/en unknown
- 2015-03-05 JP JP2016554603A patent/JP6767872B2/ja active Active
- 2015-03-05 CA CA2940564A patent/CA2940564C/en active Active
- 2015-03-05 IL IL278878A patent/IL278878B/en unknown
- 2015-03-05 EP EP15709319.6A patent/EP3125934B1/en active Active
- 2015-03-05 WO PCT/GB2015/050643 patent/WO2015132598A1/en active Application Filing
- 2015-03-05 KR KR1020207006445A patent/KR102235202B1/ko active IP Right Grant
- 2015-03-05 KR KR1020207006444A patent/KR102235201B1/ko active IP Right Grant
- 2015-03-05 PT PT157093196T patent/PT3125934T/pt unknown
- 2015-03-05 CU CU2016000129A patent/CU24475B1/es unknown
- 2015-03-05 MY MYPI2016703188A patent/MY173567A/en unknown
- 2015-03-05 MX MX2016010856A patent/MX2016010856A/es active IP Right Grant
- 2015-03-05 RU RU2018140694A patent/RU2018140694A/ru unknown
- 2015-03-05 RU RU2016138421A patent/RU2744046C2/ru active
- 2015-03-05 CN CN201580011306.XA patent/CN106068276B/zh active Active
-
2016
- 2016-08-04 IL IL247110A patent/IL247110A0/en active IP Right Grant
- 2016-08-17 PH PH12016501646A patent/PH12016501646A1/en unknown
- 2016-08-19 MX MX2019013845A patent/MX2019013845A/es unknown
- 2016-08-19 MX MX2019013846A patent/MX2019013846A/es unknown
- 2016-09-01 CL CL2016002195A patent/CL2016002195A1/es unknown
-
2017
- 2017-05-26 US US15/606,480 patent/US20170334998A1/en not_active Abandoned
- 2017-05-31 JP JP2017107689A patent/JP6767931B2/ja active Active
-
2018
- 2018-10-30 CL CL2018003096A patent/CL2018003096A1/es unknown
-
2019
- 2019-06-07 CL CL2019001567A patent/CL2019001567A1/es unknown
- 2019-06-07 CL CL2019001568A patent/CL2019001568A1/es unknown
- 2019-07-09 AU AU2019204921A patent/AU2019204921C1/en active Active
- 2019-07-09 AU AU2019204925A patent/AU2019204925B2/en active Active
-
2020
- 2020-03-25 JP JP2020054667A patent/JP7149304B2/ja active Active
- 2020-04-01 PH PH12020550203A patent/PH12020550203A1/en unknown
- 2020-11-22 IL IL278879A patent/IL278879A/en unknown
-
2021
- 2021-09-15 JP JP2021150189A patent/JP2021184773A/ja not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
JOANNE L. VINEY: "Generation of Monoclonal Antibodies Against a Human T Cell Receptor ß Chain Expressed in Transgenic Mice", HYBRIDOMA, vol. 11, no. 6, pages 701, XP002062863 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2019204921B2 (en) | Chimeric Antigen Receptor (CAR) with Antigen Binding Domains to the T Cell Receptor Beta Constant Region. | |
US11385233B2 (en) | Methods of depleting malignant T-cells | |
US11885806B2 (en) | Method for depleting malignant T-cells | |
JP2024074907A (ja) | T細胞受容体ベータ定常領域に対する抗原結合ドメインを有するキメラ抗原抗体(car) | |
NZ761844B2 (en) | Conjugated antibody with antigen binding domains to the t cell receptor beta constant region | |
NZ761848B2 (en) | Bispecific t-cell engager with antigen binding domains to the t cell receptor beta constant domain | |
NZ723307B2 (en) | Chimeric antigen receptor (car) with antigen binding domains to the t cell receptor beta constant region |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |