CN114891126B - 一种靶向fshr和cd3分子的双结合蛋白及其应用 - Google Patents
一种靶向fshr和cd3分子的双结合蛋白及其应用 Download PDFInfo
- Publication number
- CN114891126B CN114891126B CN202210714513.3A CN202210714513A CN114891126B CN 114891126 B CN114891126 B CN 114891126B CN 202210714513 A CN202210714513 A CN 202210714513A CN 114891126 B CN114891126 B CN 114891126B
- Authority
- CN
- China
- Prior art keywords
- fshr
- amino acid
- binding protein
- targeting
- ser
- 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.)
- Active
Links
- 102000014914 Carrier Proteins Human genes 0.000 title claims abstract description 26
- 108091008324 binding proteins Proteins 0.000 title claims abstract description 26
- 230000018883 protein targeting Effects 0.000 title claims abstract description 16
- 102100027627 Follicle-stimulating hormone receptor Human genes 0.000 title claims abstract 20
- 101000862396 Homo sapiens Follicle-stimulating hormone receptor Proteins 0.000 title claims abstract 20
- 150000001413 amino acids Chemical class 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 7
- 102000003864 Human Follicle Stimulating Hormone Human genes 0.000 claims abstract description 5
- 108010082302 Human Follicle Stimulating Hormone Proteins 0.000 claims abstract description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 14
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims description 30
- 102000004169 proteins and genes Human genes 0.000 claims description 28
- 230000009977 dual effect Effects 0.000 claims description 8
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 101150105462 HIS6 gene Proteins 0.000 claims description 2
- 101100395023 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) his-7 gene Proteins 0.000 claims description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 230000002611 ovarian Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 27
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 abstract description 13
- 230000002147 killing effect Effects 0.000 abstract description 9
- 210000004881 tumor cell Anatomy 0.000 abstract description 8
- 206010028980 Neoplasm Diseases 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000008685 targeting Effects 0.000 abstract description 5
- 238000002474 experimental method Methods 0.000 abstract description 2
- 108010060374 FSH Receptors Proteins 0.000 description 33
- 102000018343 Follicle stimulating hormone receptors Human genes 0.000 description 33
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 7
- 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 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 229910021642 ultra pure water Inorganic materials 0.000 description 5
- 239000012498 ultrapure water Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 4
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 description 3
- 108010028230 Trp-Ser- His-Pro-Gln-Phe-Glu-Lys Proteins 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000003208 gene overexpression Methods 0.000 description 3
- UCIYCBSJBQGDGM-LPEHRKFASA-N Ala-Arg-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N UCIYCBSJBQGDGM-LPEHRKFASA-N 0.000 description 2
- 208000002109 Argyria Diseases 0.000 description 2
- KZZYVYWSXMFYEC-DCAQKATOSA-N Cys-Val-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KZZYVYWSXMFYEC-DCAQKATOSA-N 0.000 description 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
- YIFUFYZELCMPJP-YUMQZZPRSA-N Gly-Leu-Cys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(O)=O YIFUFYZELCMPJP-YUMQZZPRSA-N 0.000 description 2
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
- 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 2
- IFMPDNRWZZEZSL-SRVKXCTJSA-N Leu-Leu-Cys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(O)=O IFMPDNRWZZEZSL-SRVKXCTJSA-N 0.000 description 2
- UZVWDRPUTHXQAM-FXQIFTODSA-N Met-Asp-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O UZVWDRPUTHXQAM-FXQIFTODSA-N 0.000 description 2
- BEZJTLKUMFMITF-AVGNSLFASA-N Met-Lys-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CCCNC(N)=N BEZJTLKUMFMITF-AVGNSLFASA-N 0.000 description 2
- 108010079364 N-glycylalanine Proteins 0.000 description 2
- 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 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 2
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 108010004073 cysteinylcysteine Proteins 0.000 description 2
- 108010016616 cysteinylglycine Proteins 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229940028334 follicle stimulating hormone Drugs 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 2
- 108010089804 glycyl-threonine Proteins 0.000 description 2
- 108010087823 glycyltyrosine Proteins 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 2
- 108010003137 tyrosyltyrosine Proteins 0.000 description 2
- IGXNPQWXIRIGBF-KEOOTSPTSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoic acid Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 IGXNPQWXIRIGBF-KEOOTSPTSA-N 0.000 description 1
- WYPUMLRSQMKIJU-BPNCWPANSA-N Ala-Arg-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WYPUMLRSQMKIJU-BPNCWPANSA-N 0.000 description 1
- HXNNRBHASOSVPG-GUBZILKMSA-N Ala-Glu-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O HXNNRBHASOSVPG-GUBZILKMSA-N 0.000 description 1
- FAJIYNONGXEXAI-CQDKDKBSSA-N Ala-His-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 FAJIYNONGXEXAI-CQDKDKBSSA-N 0.000 description 1
- XCZXVTHYGSMQGH-NAKRPEOUSA-N Ala-Ile-Met Chemical compound C[C@H]([NH3+])C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C([O-])=O XCZXVTHYGSMQGH-NAKRPEOUSA-N 0.000 description 1
- 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 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
- 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 1
- 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 1
- 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 1
- XKXAZPSREVUCRT-BPNCWPANSA-N Ala-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=C(O)C=C1 XKXAZPSREVUCRT-BPNCWPANSA-N 0.000 description 1
- DHONNEYAZPNGSG-UBHSHLNASA-N Ala-Val-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 DHONNEYAZPNGSG-UBHSHLNASA-N 0.000 description 1
- 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 1
- OTCJMMRQBVDQRK-DCAQKATOSA-N Arg-Asp-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O OTCJMMRQBVDQRK-DCAQKATOSA-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
- 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 1
- FVBZXNSRIDVYJS-AVGNSLFASA-N Arg-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCN=C(N)N FVBZXNSRIDVYJS-AVGNSLFASA-N 0.000 description 1
- POZKLUIXMHIULG-FDARSICLSA-N Arg-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCCN=C(N)N)N POZKLUIXMHIULG-FDARSICLSA-N 0.000 description 1
- IZSMEUDYADKZTJ-KJEVXHAQSA-N Arg-Tyr-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IZSMEUDYADKZTJ-KJEVXHAQSA-N 0.000 description 1
- QNJIRRVTOXNGMH-GUBZILKMSA-N Asn-Gln-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(N)=O QNJIRRVTOXNGMH-GUBZILKMSA-N 0.000 description 1
- SZNGQSBRHFMZLT-IHRRRGAJSA-N Asn-Pro-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SZNGQSBRHFMZLT-IHRRRGAJSA-N 0.000 description 1
- 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 1
- LGCVSPFCFXWUEY-IHPCNDPISA-N Asn-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N LGCVSPFCFXWUEY-IHPCNDPISA-N 0.000 description 1
- KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 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
- SDDAYZYYUJILPB-UHFFFAOYSA-N Asp-Leu-Val-Tyr Chemical compound OC(=O)CC(N)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 SDDAYZYYUJILPB-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KPSHWSWFPUDEGF-FXQIFTODSA-N Asp-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(O)=O KPSHWSWFPUDEGF-FXQIFTODSA-N 0.000 description 1
- 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 1
- GCACQYDBDHRVGE-LKXGYXEUSA-N Asp-Thr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC(O)=O GCACQYDBDHRVGE-LKXGYXEUSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 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 1
- BLGNLNRBABWDST-CIUDSAMLSA-N Cys-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N BLGNLNRBABWDST-CIUDSAMLSA-N 0.000 description 1
- 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 1
- CMYVIUWVYHOLRD-ZLUOBGJFSA-N Cys-Ser-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O CMYVIUWVYHOLRD-ZLUOBGJFSA-N 0.000 description 1
- JTEGHEWKBCTIAL-IXOXFDKPSA-N Cys-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CS)N)O JTEGHEWKBCTIAL-IXOXFDKPSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- XOKGKOQWADCLFQ-GARJFASQSA-N Gln-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XOKGKOQWADCLFQ-GARJFASQSA-N 0.000 description 1
- 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
- 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 1
- LGIKBBLQVSWUGK-DCAQKATOSA-N Gln-Leu-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGIKBBLQVSWUGK-DCAQKATOSA-N 0.000 description 1
- 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 1
- 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 1
- CVRUVYDNRPSKBM-QEJZJMRPSA-N Gln-Trp-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N CVRUVYDNRPSKBM-QEJZJMRPSA-N 0.000 description 1
- 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 1
- 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 1
- RDPOETHPAQEGDP-ACZMJKKPSA-N Glu-Asp-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O RDPOETHPAQEGDP-ACZMJKKPSA-N 0.000 description 1
- 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 1
- HVYWQYLBVXMXSV-GUBZILKMSA-N Glu-Leu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HVYWQYLBVXMXSV-GUBZILKMSA-N 0.000 description 1
- UJMNFCAHLYKWOZ-DCAQKATOSA-N Glu-Lys-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O UJMNFCAHLYKWOZ-DCAQKATOSA-N 0.000 description 1
- SUIAHERNFYRBDZ-GVXVVHGQSA-N Glu-Lys-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O SUIAHERNFYRBDZ-GVXVVHGQSA-N 0.000 description 1
- LJPIRKICOISLKN-WHFBIAKZSA-N Gly-Ala-Ser Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O LJPIRKICOISLKN-WHFBIAKZSA-N 0.000 description 1
- 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 1
- ZQIMMEYPEXIYBB-IUCAKERBSA-N Gly-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN ZQIMMEYPEXIYBB-IUCAKERBSA-N 0.000 description 1
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 1
- CSMYMGFCEJWALV-WDSKDSINSA-N Gly-Ser-Gln Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O CSMYMGFCEJWALV-WDSKDSINSA-N 0.000 description 1
- 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
- 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 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
- KOYUSMBPJOVSOO-XEGUGMAKSA-N Gly-Tyr-Ile Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KOYUSMBPJOVSOO-XEGUGMAKSA-N 0.000 description 1
- 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 1
- 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 1
- YKUAGFAXQRYUQW-KKUMJFAQSA-N His-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O YKUAGFAXQRYUQW-KKUMJFAQSA-N 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- YKRIXHPEIZUDDY-GMOBBJLQSA-N Ile-Asn-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YKRIXHPEIZUDDY-GMOBBJLQSA-N 0.000 description 1
- 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 1
- LKACSKJPTFSBHR-MNXVOIDGSA-N Ile-Gln-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N LKACSKJPTFSBHR-MNXVOIDGSA-N 0.000 description 1
- UYODHPPSCXBNCS-XUXIUFHCSA-N Ile-Val-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(C)C UYODHPPSCXBNCS-XUXIUFHCSA-N 0.000 description 1
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 1
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- GZRABTMNWJXFMH-UVOCVTCTSA-N Leu-Thr-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZRABTMNWJXFMH-UVOCVTCTSA-N 0.000 description 1
- 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 1
- 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 1
- 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 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
- 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 1
- OJDFAABAHBPVTH-MNXVOIDGSA-N Lys-Ile-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O OJDFAABAHBPVTH-MNXVOIDGSA-N 0.000 description 1
- MYZMQWHPDAYKIE-SRVKXCTJSA-N Lys-Leu-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O MYZMQWHPDAYKIE-SRVKXCTJSA-N 0.000 description 1
- 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 1
- 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 1
- AZOFEHCPMBRNFD-BZSNNMDCSA-N Lys-Phe-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CC=CC=C1 AZOFEHCPMBRNFD-BZSNNMDCSA-N 0.000 description 1
- SBQDRNOLGSYHQA-YUMQZZPRSA-N Lys-Ser-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SBQDRNOLGSYHQA-YUMQZZPRSA-N 0.000 description 1
- 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 1
- TVOOGUNBIWAURO-KATARQTJSA-N Lys-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N)O TVOOGUNBIWAURO-KATARQTJSA-N 0.000 description 1
- QWTGQXGNNMIUCW-BPUTZDHNSA-N Met-Asn-Trp Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O QWTGQXGNNMIUCW-BPUTZDHNSA-N 0.000 description 1
- VOOINLQYUZOREH-SRVKXCTJSA-N Met-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCSC)N VOOINLQYUZOREH-SRVKXCTJSA-N 0.000 description 1
- UYAKZHGIPRCGPF-CIUDSAMLSA-N Met-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)N UYAKZHGIPRCGPF-CIUDSAMLSA-N 0.000 description 1
- CIDICGYKRUTYLE-FXQIFTODSA-N Met-Ser-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O CIDICGYKRUTYLE-FXQIFTODSA-N 0.000 description 1
- 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 1
- 241001465754 Metazoa Species 0.000 description 1
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- 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 1
- BIYWZVCPZIFGPY-QWRGUYRKSA-N Phe-Gly-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CO)C(O)=O BIYWZVCPZIFGPY-QWRGUYRKSA-N 0.000 description 1
- LTAWNJXSRUCFAN-UNQGMJICSA-N Phe-Thr-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LTAWNJXSRUCFAN-UNQGMJICSA-N 0.000 description 1
- FZHBZMDRDASUHN-NAKRPEOUSA-N Pro-Ala-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1)C(O)=O FZHBZMDRDASUHN-NAKRPEOUSA-N 0.000 description 1
- 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 1
- JUJCUYWRJMFJJF-AVGNSLFASA-N Pro-Lys-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1 JUJCUYWRJMFJJF-AVGNSLFASA-N 0.000 description 1
- SPLBRAKYXGOFSO-UNQGMJICSA-N Pro-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H]2CCCN2)O SPLBRAKYXGOFSO-UNQGMJICSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 1
- YPUSXTWURJANKF-KBIXCLLPSA-N Ser-Gln-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O YPUSXTWURJANKF-KBIXCLLPSA-N 0.000 description 1
- 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 1
- UAJAYRMZGNQILN-BQBZGAKWSA-N Ser-Gly-Met Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O UAJAYRMZGNQILN-BQBZGAKWSA-N 0.000 description 1
- 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 1
- 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 1
- 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 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
- 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
- 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
- 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 1
- 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 1
- 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 1
- PYTKULIABVRXSC-BWBBJGPYSA-N Ser-Ser-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PYTKULIABVRXSC-BWBBJGPYSA-N 0.000 description 1
- VGQVAVQWKJLIRM-FXQIFTODSA-N Ser-Ser-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O VGQVAVQWKJLIRM-FXQIFTODSA-N 0.000 description 1
- 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 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
- 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 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 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 1
- MMTOHPRBJKEZHT-BWBBJGPYSA-N Thr-Cys-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O MMTOHPRBJKEZHT-BWBBJGPYSA-N 0.000 description 1
- LIXBDERDAGNVAV-XKBZYTNZSA-N Thr-Gln-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O LIXBDERDAGNVAV-XKBZYTNZSA-N 0.000 description 1
- 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 1
- LHNNQVXITHUCAB-QTKMDUPCSA-N Thr-Met-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O LHNNQVXITHUCAB-QTKMDUPCSA-N 0.000 description 1
- KPNSNVTUVKSBFL-ZJDVBMNYSA-N Thr-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KPNSNVTUVKSBFL-ZJDVBMNYSA-N 0.000 description 1
- 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 1
- MXNAOGFNFNKUPD-JHYOHUSXSA-N Thr-Phe-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MXNAOGFNFNKUPD-JHYOHUSXSA-N 0.000 description 1
- 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 1
- VUXIQSUQQYNLJP-XAVMHZPKSA-N Thr-Ser-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N)O VUXIQSUQQYNLJP-XAVMHZPKSA-N 0.000 description 1
- 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 1
- YRJOLUDFVAUXLI-GSSVUCPTSA-N Thr-Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O YRJOLUDFVAUXLI-GSSVUCPTSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- 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 1
- KIMOCKLJBXHFIN-YLVFBTJISA-N Trp-Ile-Gly Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O)=CNC2=C1 KIMOCKLJBXHFIN-YLVFBTJISA-N 0.000 description 1
- WNZRNOGHEONFMS-PXDAIIFMSA-N Trp-Ile-Tyr Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WNZRNOGHEONFMS-PXDAIIFMSA-N 0.000 description 1
- 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 1
- MBFJIHUHHCJBSN-AVGNSLFASA-N Tyr-Asn-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MBFJIHUHHCJBSN-AVGNSLFASA-N 0.000 description 1
- 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
- MNMYOSZWCKYEDI-JRQIVUDYSA-N Tyr-Asp-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MNMYOSZWCKYEDI-JRQIVUDYSA-N 0.000 description 1
- SMLCYZYQFRTLCO-UWJYBYFXSA-N Tyr-Cys-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O SMLCYZYQFRTLCO-UWJYBYFXSA-N 0.000 description 1
- 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 1
- 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 1
- MQGGXGKQSVEQHR-KKUMJFAQSA-N Tyr-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MQGGXGKQSVEQHR-KKUMJFAQSA-N 0.000 description 1
- ITDWWLTTWRRLCC-KJEVXHAQSA-N Tyr-Thr-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ITDWWLTTWRRLCC-KJEVXHAQSA-N 0.000 description 1
- BIVIUZRBCAUNPW-JRQIVUDYSA-N Tyr-Thr-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O BIVIUZRBCAUNPW-JRQIVUDYSA-N 0.000 description 1
- NUQZCPSZHGIYTA-HKUYNNGSSA-N Tyr-Trp-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N NUQZCPSZHGIYTA-HKUYNNGSSA-N 0.000 description 1
- 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 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
- XBJKAZATRJBDCU-GUBZILKMSA-N Val-Pro-Ala Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O XBJKAZATRJBDCU-GUBZILKMSA-N 0.000 description 1
- 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 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
- 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 1
- RLVTVHSDKHBFQP-ULQDDVLXSA-N Val-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=C(O)C=C1 RLVTVHSDKHBFQP-ULQDDVLXSA-N 0.000 description 1
- 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 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 108010060035 arginylproline Proteins 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 108010068265 aspartyltyrosine Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 108010078144 glutaminyl-glycine Proteins 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 230000002710 gonadal effect Effects 0.000 description 1
- 210000002503 granulosa cell Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 108010092114 histidylphenylalanine Proteins 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 1
- 108010078274 isoleucylvaline Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 108010057952 lysyl-phenylalanyl-lysine Proteins 0.000 description 1
- 108010038320 lysylphenylalanine Proteins 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 108010044292 tryptophyltyrosine Proteins 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K14/575—Hormones
- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- 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
- C07K2317/60—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
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/22—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a Strep-tag
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明公开了一种靶向FSHR和CD3分子的双结合蛋白及其应用，属于生物医药领域。该双结合蛋白包含至少一个靶向CD3的单链抗体和至少一个结合FSHR的氨基酸片段，其中靶向CD3的单链抗体来源于OKT3单克隆抗体重链可变区和轻链可变区通过15个氨基酸短肽连接而成的抗体，结合FSHR的氨基酸片段来源人FSH分子中具有结合FSHR能力的氨基酸片段。本发明的上述双结合蛋白同时结合CD3分子和FSHR分子，通过细胞实验发现其可显著提高PBMC对FSHR阳性的肿瘤细胞系的杀伤能力，为FSHR阳性的相关肿瘤疾病提供候选药物。
Description
技术领域
本发明属于生物医药领域，具体涉及一种靶向FSHR和CD3分子的双结合蛋白及其应用。
背景技术
单克隆抗体因其特异性靶向分子的能力，在肿瘤治疗中已发展成为一种关键和有效的治疗方式。但是，由于肿瘤复杂的疾病发病机制，针对单一靶点的单克隆抗体难以表现出足够的治疗效果。在这一背景下，双特异性抗体应运而生。双特异性抗体拥有两种特异性抗原结合位点，可以同时与靶细胞和功能细胞相互作用，进而促进对靶细胞的杀伤。
单链抗体是由抗体重链的可变区与轻链的可变区在一段肽链的连接下构成的小分子，是具有抗体活性的最小功能结构单位。完整的抗体由两条重链和两条轻链构成，人工改造可使其只表达可变区，通过人工设计的连接肽将抗体重链可变区和轻链可变区连接而成的抗体就称为单链抗体，最简单的双特异性抗体就是把分别来自两个单克隆抗体的不同单链抗体串联起来，就可以起到连接靶细胞和功能细胞(如T细胞)的作用。
CD3靶点是双特异性抗体开发中较早切入的靶点方向，CD3单克隆抗体可与T细胞抗原受体(TCR)结合形成受体复合物激活T细胞，实现T细胞重定向。与单克隆抗体相比，双特异性抗体增加了一个特异性抗原结合位点，因而特异性更强、更能准确靶向肿瘤细胞并降低脱靶毒性，但双特异性抗体药物的开发复杂性更高，技术壁垒更高，对于技术平台和靶点选择的适配性要求更高。
在成年人和动物中，卵泡刺激素受体(FSHR)主要在睾丸支持细胞和卵巢颗粒细胞表面表达，在睾丸和卵巢血管内皮细胞低表达。卵泡刺激素(FSH)通过与睾丸支持细胞和卵巢粒层细胞表面的FSHR结合，在性腺发育过程中发挥重要作用。同时FSHR在多种肿瘤细胞中表达，如卵巢癌、睾丸癌、前列腺癌以及子宫内膜癌等，是肿瘤治疗的一个候选靶点。
发明内容
有鉴于此，本发明借鉴于双特异性抗体的方法提出一种靶向FSHR和CD3分子的双结合蛋白及其应用，获得具有靶向FSHR和CD3分子的双结合蛋白，为FSHR阳性肿瘤的治疗提供候选药物。
为了实现上述发明目的，本发明提供以下技术方案：
本发明提供的一种靶向FSHR和CD3分子的双结合蛋白，包含至少一个靶向CD3的单链抗体和至少一个结合FSHR的氨基酸片段。
作为优选，所述靶向CD3的单链抗体来源于OKT3单克隆抗体重链可变区和轻链可变区通过15个氨基酸短肽连接而成的抗体，其氨基酸序列为QVQLQQSGAELARPGASVKMSCKASGYTFTRYTMHWVKQRPGQGLEWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYCLDYWGQGTTLTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWYQQKSGTSPKRWIYDTSKLASGVPAHFRGSGSGTSYSLTISGMEAEDAATYYCQQWSSNPFTFGSGTKLEINR(SEQ IDNO.1)。
作为优选，所述结合FSHR的氨基酸片段来源人FSH分子的一部分。
作为更优选，所述结合FSHR的氨基酸片段来源于人FSH分子中具有结合FSHR能力的氨基酸片段，其氨基酸序列为YTRDLVYKDPARPKIQKTCTF(SEQ ID NO.2)。
作为优选，所述靶向FSHR和CD3分子的双结合蛋白包含两个蛋白标签，一个蛋白标签Strep II，其氨基酸序列为WSHPQFEK(SEQ ID NO.3)，一个蛋白标签HIS6，其氨基酸序列为HHHHHH(SEQ ID NO.4)，双蛋白标签的设计有利于该结合蛋白的纯化和鉴定。
作为优选，所述靶向FSHR和CD3分子的双结合蛋白的N端含有信号肽序列，其氨基酸序列为MDAMKRGLCCVLLLCGAVFVSA(SEQ ID NO.5)，该结构使该双结合蛋白通过工程细胞分泌表达，便于蛋白生产和纯化。
作为优选，所述靶向FSHR和CD3分子的双结合蛋白的氨基酸序列为MDAMKRGLCCVLLLCGAVFVSAWSHPQFEKQVQLQQSGAELARPGASVKMSCKASGYTFTRYTMHWVKQRPGQGLEWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYCLDYWGQGTTLTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWYQQKSGTSPKRWIYDTSKLASGVPAHFRGSGSGTSYSLTISGMEAEDAATYYCQQWSSNPFTFGSGTKLEINRGGGGSGGGGSGGGGSYTRDLVYKDPARPKIQKTCTFHHHHHH(SEQID NO.6)。
本发明还提供上述靶向FSHR和CD3分子的双结合蛋白在制备治疗与FSHR阳性相关的肿瘤疾病的药物中的应用。
与现有技术相比，本发明提供的靶向FSHR和CD3分子的双结合蛋白同时结合CD3分子和FSHR分子，通过细胞实验发现其可显著提高外周血单个核细胞(PBMC)对FSHR阳性的肿瘤细胞系的杀伤能力，为FSHR阳性的相关肿瘤疾病提供候选药物。
附图说明
图1是实施例中过表达目的蛋白质粒转染293FT荧光图。
图2是实施例中目的蛋白提取纯化后银染结果图。
图3是实施例中PBMC对肿瘤细胞系杀伤检测结果。
具体实施方式
下面结合附图详细说明本发明的技术方案，但本发明的保护范围不限于下述的实施例。
实施例1：目的蛋白表达
(一)根据目的蛋白氨基酸序列设计对应的密码子，优化后的目的基因为atggacgccatgaagcggggcctgtgctgcgtgctgctcctgtgtggcgctgttttcgtgtccgcctggtcccacccccagttcgagaagcaagtgcagctgcagcaaagcggcgccgagctggccagacctggagccagcgtgaagatgagctgcaaggccagcggctacacctttacaagatacacaatgcactgggtcaagcagagacccggccaaggcctggaatggatcggctatatcaaccccagcagaggctacaccaactacaaccagaaattcaaggacaaggccacactgacaacagataagtcttcttccacagcctacatgcagctgagctccctgacaagtgaagatagcgccgtgtactactgcgcacggtactatgacgaccactactgcctggactactggggacagggcaccaccctgaccgtgtccagcggcggaggcggctctggcggaggcggaagcggcggcggcggctcacagatcgtgctgacccagagccctgctatcatgagcgcctctcctggcgagaaagtgacaatgacctgcagcgccagctcttctgtgtcttacatgaactggtaccagcagaagagcggcaccagcccaaagagatggatctacgacaccagcaagctggcttctggcgtgcctgcccacttccggggcagcggcagcggcaccagctatagcctgaccatcagcggcatggaagccgaggatgccgctacatactactgtcagcagtggagcagcaatcctttcaccttcggctctggaaccaagctggagatcaacagaggcggcggaggcagcggcggcggcggaagcggtggaggaggcagctacaccagagatctggtgtacaaagaccccgcccggcctaaaattcagaagacctgtacctttcaccaccatcaccaccactga(SEQ ID NO.7)。
(二)构建目的基因过表达质粒，委托上海吉凯基因医学科技股份有限公司构建质粒和鉴定质粒。
(三)目的蛋白表达与提取纯化
1、将293FT细胞以10000/cm2的密度接种于六孔板。
2、当293FT细胞汇合度达到80％左右，转染目的基因过表达质粒。
3、过夜后更换新鲜细胞培养液。
4、48小时后收集细胞培养上清液，使用His标签蛋白纯化试剂盒提取纯化目的蛋白。
5、使用Bradford蛋白浓度测定试剂盒进行蛋白浓度测定后，SDS-PAGE凝胶电泳，银染显色。
结果如图1和2所示，可以看出以GV658为载体构建的目的基因过表达质粒成功转染293FT细胞，表达并提取纯化了目的蛋白。
实施例2：目的蛋白靶向能力鉴定
1、超纯水、CD3D-CD3E异二聚体蛋白(10ug/mL)和FSHR(10ug/mL)，各取100uL分别包被于96孔板的1个孔位，4℃过夜。
2、去除包被液，用超纯水清洗3遍，各取100uL胎牛血清封闭包被孔位，4℃过夜。
3、去除封闭液，用超纯水清洗3遍，各取实施例1中的目的蛋白(1ug/mL)加入包被孔位中，37℃，1小时。
4、去除上清液，用超纯水清洗5遍，各取100uL稀释2000倍的HRP-Streptavidin加入包被孔位中，37℃，1小时。
5、去除上清液，用超纯水清洗10遍，各取TMB溶液100uL加入包被孔位中，5分钟后测定620nm吸光度值。
HRP-Streptavidin用高纯度的Streptavidin和超纯的HRP交联而成。Streptavidin的中文名为链霉亲和素，可以特异性地与Strep II蛋白标签结合，HRP即辣根过氧化物酶，可以在ELISA时催化TMB产生蓝色。
表1
| 组别 | 对照组(water) | CD3D-CD3E | FSHR |
| 吸光度值 | 0.0524 | 0.0532 | 0.0564 |
从结果可以看出，实施例1中的目的蛋白可以与CD3D-CD3E异二聚体蛋白和FSHR结合，证明实施例1中的目的蛋白可以结合CD3分子和FSHR分子。
实施例3：目的蛋白对FSHR阳性的肿瘤细胞系的杀伤检测
PBMC是T细胞的主要来源，HO8910是FSHR阳性的人卵巢癌细胞系，Hela是FSHR阳性的人宫颈癌细胞系，本实施例选用以上两种细胞系和PBMC作为实验材料，对目的蛋白靶向性诱导T细胞杀伤FSHR阳性肿瘤细胞的作用进行检测。
1、取HO8910细胞和Hela细胞系，按10000/cm2的密度分组接种于96孔板，分别设置对照组和实验组，每组设4个复孔，置于二氧化碳细胞培养箱培养。
2、接种24小时后，对照组和实验组每孔按效靶比1：20添加PBMC，并且实验组每孔添加目的蛋白，使其终浓度为500ng/mL，对照组不添加目的蛋白，置于二氧化碳细胞培养箱培养。
3、添加PBMC 24小时后，对照组和实验组每孔加入CCK-8溶液20ul，37℃孵育1小时。
4、酶标仪检测，在450nm处测得各孔吸光度值。
PBMC对HO8910细胞和Hela细胞的杀伤检测结果如图2和表2所示，其中效靶比为1：20时的吸光度值。
表2
使用SPSS 26.0软件进行方差分析，添加目的蛋白后，PBMC对HO8910细胞的杀伤，P<0.05，差异显著；添加目的蛋白后，PBMC对Hela细胞的杀伤，P<0.01，差异极显著，PBMC对HO8910细胞和Hela细胞的杀伤检测方差分析分别如表3和4所示，证明目的蛋白能显著提高PBMC对FSHR阳性的肿瘤细胞系的杀伤能力。
表3
| 平方和 | 自由度 | 均方 | F | 显著性 | |
| 组间 | 0.149 | 1 | 0.149 | 6.978 | 0.038 |
| 组内 | 0.128 | 6 | 0.021 | - | - |
| 总计 | 0.277 | 7 | - | - | - |
表4
| 平方和 | 自由度 | 均方 | F | 显著性 | |
| 组间 | 0.593 | 1 | 0.593 | 31.090 | 0.001 |
| 组内 | 0.114 | 6 | 0.019 | - | - |
| 总计 | 0.707 | 7 | - | - | - |
以上所述，仅为本发明的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到变化或替换，都应涵盖在本发明的保护范围之内。因此，本发明的保护范围应所述以权利要求的保护范围为准。
序列表
<110> 上海安库生医生物科技有限公司
<120> 一种靶向FSHR和CD3分子的双结合蛋白及其应用
<141> 2022-06-23
<160> 7
<170> SIPOSequenceListing 1.0
<210> 1
<211> 241
<212> PRT
<213> 人工序列()
<400> 1
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr
20 25 30
Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Thr Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Gln Ile Val Leu Thr Gln Ser Pro Ala Ile
130 135 140
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser
145 150 155 160
Ser Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys Ser Gly Thr Ser
165 170 175
Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro
180 185 190
Ala His Phe Arg Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
195 200 205
Ser Gly Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp
210 215 220
Ser Ser Asn Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Asn
225 230 235 240
Arg
<210> 2
<211> 21
<212> PRT
<213> 人工序列()
<400> 2
Tyr Thr Arg Asp Leu Val Tyr Lys Asp Pro Ala Arg Pro Lys Ile Gln
1 5 10 15
Lys Thr Cys Thr Phe
20
<210> 3
<211> 8
<212> PRT
<213> 人工序列()
<400> 3
Trp Ser His Pro Gln Phe Glu Lys
1 5
<210> 4
<211> 6
<212> PRT
<213> 人工序列()
<400> 4
His His His His His His
1 5
<210> 5
<211> 22
<212> PRT
<213> 人工序列()
<400> 5
Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 10 15
Ala Val Phe Val Ser Ala
20
<210> 6
<211> 313
<212> PRT
<213> 人工序列()
<400> 6
Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 10 15
Ala Val Phe Val Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gln Val
20 25 30
Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala Ser Val
35 40 45
Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr Thr Met
50 55 60
His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Tyr
65 70 75 80
Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Asn Gln Lys Phe Lys Asp
85 90 95
Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln
100 105 110
Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg
115 120 125
Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly Thr Thr
130 135 140
Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
145 150 155 160
Gly Gly Gly Ser Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser
165 170 175
Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser
180 185 190
Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys Ser Gly Thr Ser Pro Lys
195 200 205
Arg Trp Ile Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro Ala His
210 215 220
Phe Arg Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Gly
225 230 235 240
Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser
245 250 255
Asn Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Asn Arg Gly
260 265 270
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Tyr Thr
275 280 285
Arg Asp Leu Val Tyr Lys Asp Pro Ala Arg Pro Lys Ile Gln Lys Thr
290 295 300
Cys Thr Phe His His His His His His
305 310
<210> 7
<211> 942
<212> DNA
<213> 人工序列()
<400> 7
atggacgcca tgaagcgggg cctgtgctgc gtgctgctcc tgtgtggcgc tgttttcgtg 60
tccgcctggt cccaccccca gttcgagaag caagtgcagc tgcagcaaag cggcgccgag 120
ctggccagac ctggagccag cgtgaagatg agctgcaagg ccagcggcta cacctttaca 180
agatacacaa tgcactgggt caagcagaga cccggccaag gcctggaatg gatcggctat 240
atcaacccca gcagaggcta caccaactac aaccagaaat tcaaggacaa ggccacactg 300
acaacagata agtcttcttc cacagcctac atgcagctga gctccctgac aagtgaagat 360
agcgccgtgt actactgcgc acggtactat gacgaccact actgcctgga ctactgggga 420
cagggcacca ccctgaccgt gtccagcggc ggaggcggct ctggcggagg cggaagcggc 480
ggcggcggct cacagatcgt gctgacccag agccctgcta tcatgagcgc ctctcctggc 540
gagaaagtga caatgacctg cagcgccagc tcttctgtgt cttacatgaa ctggtaccag 600
cagaagagcg gcaccagccc aaagagatgg atctacgaca ccagcaagct ggcttctggc 660
gtgcctgccc acttccgggg cagcggcagc ggcaccagct atagcctgac catcagcggc 720
atggaagccg aggatgccgc tacatactac tgtcagcagt ggagcagcaa tcctttcacc 780
ttcggctctg gaaccaagct ggagatcaac agaggcggcg gaggcagcgg cggcggcgga 840
agcggtggag gaggcagcta caccagagat ctggtgtaca aagaccccgc ccggcctaaa 900
attcagaaga cctgtacctt tcaccaccat caccaccact ga 942
Claims (5)
1.一种靶向FSHR和CD3分子的双结合蛋白，其特征在于，包含一个靶向CD3的单链抗体和一个结合FSHR的氨基酸片段；
所述靶向CD3的单链抗体来源于OKT3单克隆抗体重链可变区和轻链可变区通过15个氨基酸短肽连接而成的抗体，其氨基酸序列如SEQ ID NO.1所示；
所述结合FSHR的氨基酸片段来源人FSH分子的一部分；
所述结合FSHR的氨基酸片段来源于人FSH分子中具有结合FSHR能力的氨基酸片段，其氨基酸序列如SEQ ID NO.2所示。
2.根据权利要求1所述靶向FSHR和CD3分子的双结合蛋白，其特征在于，所述靶向FSHR和CD3分子的双结合蛋白还包含两个蛋白标签：一个氨基酸序列如SEQ ID NO.3所示的蛋白标签Strep II，一个氨基酸序列如SEQ ID NO.4所示的蛋白标签HIS6。
3.根据权利要求1所述靶向FSHR和CD3分子的双结合蛋白，其特征在于，所述靶向FSHR和CD3分子的双结合蛋白的N端含有信号肽序列，其氨基酸序列如SEQ ID NO.5所示。
4.根据权利要求1至3任一项所述靶向FSHR和CD3分子的双结合蛋白，其特征在于，所述靶向FSHR和CD3分子的双结合蛋白的氨基酸序列如SEQ ID NO.6所示。
5.权利要求1至4任一项所述靶向FSHR和CD3分子的双结合蛋白在制备治疗FSHR阳性的卵巢癌和宫颈癌疾病的药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210714513.3A CN114891126B (zh) | 2022-06-23 | 2022-06-23 | 一种靶向fshr和cd3分子的双结合蛋白及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210714513.3A CN114891126B (zh) | 2022-06-23 | 2022-06-23 | 一种靶向fshr和cd3分子的双结合蛋白及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114891126A CN114891126A (zh) | 2022-08-12 |
| CN114891126B true CN114891126B (zh) | 2023-05-09 |
Family
ID=82728033
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210714513.3A Active CN114891126B (zh) | 2022-06-23 | 2022-06-23 | 一种靶向fshr和cd3分子的双结合蛋白及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114891126B (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108697745A (zh) * | 2015-12-17 | 2018-10-23 | 皮斯奥克斯治疗公司 | 编码抗tcr复合体抗体或片段的b组腺病毒 |
| CN109680003A (zh) * | 2019-01-09 | 2019-04-26 | 上海怡豪生物科技有限公司 | 靶向卵巢癌细胞特异性高表达蛋白fshr的car载体及其构建方法和应用 |
| CN114686436A (zh) * | 2020-12-31 | 2022-07-01 | 复星凯特生物科技有限公司 | 一种靶向fshr和folr1双打靶点car t的制备及应用 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20210340263A1 (en) * | 2018-08-09 | 2021-11-04 | The Wistar Institute | Anti-Follicule Stimulating Hormone Receptor Antibodies |
-
2022
- 2022-06-23 CN CN202210714513.3A patent/CN114891126B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108697745A (zh) * | 2015-12-17 | 2018-10-23 | 皮斯奥克斯治疗公司 | 编码抗tcr复合体抗体或片段的b组腺病毒 |
| CN108697746A (zh) * | 2015-12-17 | 2018-10-23 | 皮斯奥克斯治疗公司 | 编码抗tcr复合体抗体或片段的病毒 |
| CN109680003A (zh) * | 2019-01-09 | 2019-04-26 | 上海怡豪生物科技有限公司 | 靶向卵巢癌细胞特异性高表达蛋白fshr的car载体及其构建方法和应用 |
| CN114686436A (zh) * | 2020-12-31 | 2022-07-01 | 复星凯特生物科技有限公司 | 一种靶向fshr和folr1双打靶点car t的制备及应用 |
Non-Patent Citations (3)
| Title |
|---|
| A mab against surface-expressed FSHR engineered to engage adaptive immunity for ovarian cancer immunotherapy;Devivasha Bordoloi et al;《JCI Insight》;第7卷(第22期);全文 * |
| Anti-angiogenic therapy:albumin-binding proteins could mediate mechanisms underlying the accumulation of small molecule receptor tyrosine kinase inhibitors in normal tissues with potential harmful effects on health;Nicolae Ghinea;《Diseases》;第9卷(第2期);全文 * |
| 卵泡刺激素受体基因与卵巢功能的研究进展;夏良斌;《国外医学计划生育/生殖健康分册》;第26卷(第4期);全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114891126A (zh) | 2022-08-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8343760B2 (en) | p53 activator peptides | |
| CN104507961A (zh) | 抗炎性肽及包含其的组合物 | |
| NO174971B (no) | Fremgangsmåter for bestemmelse av polypetider som er komplementære til peptider eller proteiner som har en aminosyresekvens eller en nukleotidkodende sekvens som er minst delvis kjent | |
| RU2725954C1 (ru) | Пептид, обладающий высокой аффинностью к белку pd-l1, и его применение | |
| CN106866823A (zh) | 一种抗Her2的纳米抗体 | |
| CN112933219B (zh) | 一种dna-多肽可逆共价偶联分子的制备方法及其用途 | |
| Li et al. | Recombinant thymosin beta 4 can promote full-thickness cutaneous wound healing | |
| CN114891126B (zh) | 一种靶向fshr和cd3分子的双结合蛋白及其应用 | |
| Wu et al. | Limnonectins: a new class of antimicrobial peptides from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis) | |
| Kaga et al. | Screening of a novel octamer peptide, CNSCWSKD, that induces caspase-dependent cell death | |
| CN104193828B (zh) | 同时阻断her2和vegfr信号通路的重组融合蛋白 | |
| CN103360497A (zh) | 一种新型抗肿瘤融合蛋白疫苗及其制备方法和应用 | |
| KR101587622B1 (ko) | 상피세포 성장인자 수용체의 세포외 도메인과 결합하는 신규 폴리펩타이드 | |
| CN102391377B (zh) | 一种可诱导和激活癌靶向t细胞的融合蛋白及制备方法及用途 | |
| CN108003239B (zh) | 一种全人源抗egfr单链抗体及其应用 | |
| CN110903402A (zh) | 一种双特异性融合蛋白及其构建方法与应用 | |
| CN115028738A (zh) | 一种Fc融合蛋白双重靶向降解剂及应用 | |
| NO177859B (no) | Fremgangsmåte til produksjon av angiogen faktor | |
| CN107739410B (zh) | CD3单链抗体-iRGD融合蛋白、制备及其作为抗肿瘤药物的应用 | |
| CN108864258A (zh) | 具有抑制肿瘤功能的peg化多肽及其制备方法与应用 | |
| CN108997488B (zh) | 具有抗乳腺癌活性的间斑寇蛛卵粒蛋白质及其制法与应用 | |
| CN113667018A (zh) | 一种可以进入肿瘤细胞内的BR2-抗p21Ras单链抗体融合蛋白及其制备方法 | |
| CN102477096B (zh) | 分子伴侣功能的人肌酸激酶单链抗体 | |
| KR100612673B1 (ko) | 세포도입성 보톡신 융합단백질 | |
| CN109942715A (zh) | 一种靶向治疗肿瘤的重组融合蛋白及其制备方法和应用 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |