CN114949194A - 一种用于治疗SARS-CoV-2病毒感染的多肽制剂 - Google Patents
一种用于治疗SARS-CoV-2病毒感染的多肽制剂 Download PDFInfo
- Publication number
- CN114949194A CN114949194A CN202210368802.2A CN202210368802A CN114949194A CN 114949194 A CN114949194 A CN 114949194A CN 202210368802 A CN202210368802 A CN 202210368802A CN 114949194 A CN114949194 A CN 114949194A
- Authority
- CN
- China
- Prior art keywords
- hla
- ser
- leu
- thr
- ala
- 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.)
- Granted
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 75
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 61
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 60
- 241001678559 COVID-19 virus Species 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 230000009385 viral infection Effects 0.000 title claims abstract description 17
- 150000002148 esters Chemical class 0.000 claims description 6
- 229940002612 prodrug Drugs 0.000 claims description 6
- 239000000651 prodrug Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 241000282414 Homo sapiens Species 0.000 description 48
- 210000004027 cell Anatomy 0.000 description 22
- 102000007079 Peptide Fragments Human genes 0.000 description 14
- 108010033276 Peptide Fragments Proteins 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 10
- 108010036972 HLA-A11 Antigen Proteins 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 150000001413 amino acids Chemical group 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000013473 artificial intelligence Methods 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 108010080347 HLA-A*26 antigen Proteins 0.000 description 6
- 108010041379 HLA-A*30 antigen Proteins 0.000 description 6
- 108010026122 HLA-A*33 antigen Proteins 0.000 description 6
- 108010013476 HLA-A24 Antigen Proteins 0.000 description 6
- 108010018475 HLA-A31 antigen Proteins 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 208000025721 COVID-19 Diseases 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000007969 cellular immunity Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- 241000711573 Coronaviridae Species 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- YUOXLJYVSZYPBJ-CIUDSAMLSA-N Asn-Pro-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O YUOXLJYVSZYPBJ-CIUDSAMLSA-N 0.000 description 2
- 108010041986 DNA Vaccines Proteins 0.000 description 2
- 229940021995 DNA vaccine Drugs 0.000 description 2
- ZRLUISBDKUWAIZ-CIUDSAMLSA-N Leu-Ala-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O ZRLUISBDKUWAIZ-CIUDSAMLSA-N 0.000 description 2
- KKXDHFKZWKLYGB-GUBZILKMSA-N Leu-Asn-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKXDHFKZWKLYGB-GUBZILKMSA-N 0.000 description 2
- BIZNDKMFQHDOIE-KKUMJFAQSA-N Leu-Phe-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=CC=C1 BIZNDKMFQHDOIE-KKUMJFAQSA-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
- JYVCOTWSRGFABJ-DCAQKATOSA-N Lys-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCCN)N JYVCOTWSRGFABJ-DCAQKATOSA-N 0.000 description 2
- 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 2
- 101710085938 Matrix protein Proteins 0.000 description 2
- 101710127721 Membrane protein Proteins 0.000 description 2
- 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 2
- DWGFLKQSGRUQTI-IHRRRGAJSA-N Pro-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1 DWGFLKQSGRUQTI-IHRRRGAJSA-N 0.000 description 2
- 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 2
- 208000037847 SARS-CoV-2-infection Diseases 0.000 description 2
- IDQFQFVEWMWRQQ-DLOVCJGASA-N Ser-Ala-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O IDQFQFVEWMWRQQ-DLOVCJGASA-N 0.000 description 2
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 2
- 108010008038 Synthetic Vaccines Proteins 0.000 description 2
- TZKPNGDGUVREEB-FOHZUACHSA-N Thr-Asn-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O TZKPNGDGUVREEB-FOHZUACHSA-N 0.000 description 2
- MPKPIWFFDWVJGC-IRIUXVKKSA-N Tyr-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O MPKPIWFFDWVJGC-IRIUXVKKSA-N 0.000 description 2
- TYFLVOUZHQUBGM-IHRRRGAJSA-N Tyr-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 TYFLVOUZHQUBGM-IHRRRGAJSA-N 0.000 description 2
- 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 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
- 108010044940 alanylglutamine Proteins 0.000 description 2
- 108010087924 alanylproline Proteins 0.000 description 2
- 230000010100 anticoagulation Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 108010089804 glycyl-threonine Proteins 0.000 description 2
- 238000012165 high-throughput sequencing Methods 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229940031551 inactivated vaccine Drugs 0.000 description 2
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 108700021021 mRNA Vaccine Proteins 0.000 description 2
- 229940126582 mRNA vaccine Drugs 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229940126583 recombinant protein vaccine Drugs 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 108010051110 tyrosyl-lysine Proteins 0.000 description 2
- 229940126580 vector vaccine Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NTUPOKHATNSWCY-PMPSAXMXSA-N (2s)-2-[[(2s)-1-[(2r)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=CC=C1 NTUPOKHATNSWCY-PMPSAXMXSA-N 0.000 description 1
- YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 1
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 1
- 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 1
- ZODMADSIQZZBSQ-FXQIFTODSA-N Ala-Gln-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZODMADSIQZZBSQ-FXQIFTODSA-N 0.000 description 1
- YIGLXQRFQVWFEY-NRPADANISA-N Ala-Gln-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O YIGLXQRFQVWFEY-NRPADANISA-N 0.000 description 1
- NJPMYXWVWQWCSR-ACZMJKKPSA-N Ala-Glu-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NJPMYXWVWQWCSR-ACZMJKKPSA-N 0.000 description 1
- QHASENCZLDHBGX-ONGXEEELSA-N Ala-Gly-Phe Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QHASENCZLDHBGX-ONGXEEELSA-N 0.000 description 1
- OKIKVSXTXVVFDV-MMWGEVLESA-N Ala-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N OKIKVSXTXVVFDV-MMWGEVLESA-N 0.000 description 1
- AJBVYEYZVYPFCF-CIUDSAMLSA-N Ala-Lys-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O AJBVYEYZVYPFCF-CIUDSAMLSA-N 0.000 description 1
- DHBKYZYFEXXUAK-ONGXEEELSA-N Ala-Phe-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 DHBKYZYFEXXUAK-ONGXEEELSA-N 0.000 description 1
- PEEYDECOOVQKRZ-DLOVCJGASA-N Ala-Ser-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PEEYDECOOVQKRZ-DLOVCJGASA-N 0.000 description 1
- 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
- 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
- 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
- AOAKQKVICDWCLB-UWJYBYFXSA-N Ala-Tyr-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N AOAKQKVICDWCLB-UWJYBYFXSA-N 0.000 description 1
- XAXMJQUMRJAFCH-CQDKDKBSSA-N Ala-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 XAXMJQUMRJAFCH-CQDKDKBSSA-N 0.000 description 1
- MUGAESARFRGOTQ-IGNZVWTISA-N Ala-Tyr-Tyr Chemical compound 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 MUGAESARFRGOTQ-IGNZVWTISA-N 0.000 description 1
- ZATRYQNPUHGXCU-DTWKUNHWSA-N Arg-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ZATRYQNPUHGXCU-DTWKUNHWSA-N 0.000 description 1
- JQHASVQBAKRJKD-GUBZILKMSA-N Arg-Ser-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N JQHASVQBAKRJKD-GUBZILKMSA-N 0.000 description 1
- 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 1
- MOGMYRUNTKYZFB-UNQGMJICSA-N Arg-Thr-Phe 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=CC=C1 MOGMYRUNTKYZFB-UNQGMJICSA-N 0.000 description 1
- LLQIAIUAKGNOSE-NHCYSSNCSA-N Arg-Val-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N LLQIAIUAKGNOSE-NHCYSSNCSA-N 0.000 description 1
- YNSCBOUZTAGIGO-ZLUOBGJFSA-N Asn-Asn-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N)C(=O)N YNSCBOUZTAGIGO-ZLUOBGJFSA-N 0.000 description 1
- XSGBIBGAMKTHMY-WHFBIAKZSA-N Asn-Asp-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O XSGBIBGAMKTHMY-WHFBIAKZSA-N 0.000 description 1
- ZWASIOHRQWRWAS-UGYAYLCHSA-N Asn-Asp-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZWASIOHRQWRWAS-UGYAYLCHSA-N 0.000 description 1
- ZDOQDYFZNGASEY-BIIVOSGPSA-N Asn-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N)C(=O)O ZDOQDYFZNGASEY-BIIVOSGPSA-N 0.000 description 1
- CZIXHXIJJZLYRJ-SRVKXCTJSA-N Asn-Cys-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CZIXHXIJJZLYRJ-SRVKXCTJSA-N 0.000 description 1
- XVAPVJNJGLWGCS-ACZMJKKPSA-N Asn-Glu-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N XVAPVJNJGLWGCS-ACZMJKKPSA-N 0.000 description 1
- DMLSCRJBWUEALP-LAEOZQHASA-N Asn-Glu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O DMLSCRJBWUEALP-LAEOZQHASA-N 0.000 description 1
- RAQMSGVCGSJKCL-FOHZUACHSA-N Asn-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(N)=O RAQMSGVCGSJKCL-FOHZUACHSA-N 0.000 description 1
- SUEIIIFUBHDCCS-PBCZWWQYSA-N Asn-His-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SUEIIIFUBHDCCS-PBCZWWQYSA-N 0.000 description 1
- NLRJGXZWTKXRHP-DCAQKATOSA-N Asn-Leu-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NLRJGXZWTKXRHP-DCAQKATOSA-N 0.000 description 1
- ZMUQQMGITUJQTI-CIUDSAMLSA-N Asn-Leu-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O ZMUQQMGITUJQTI-CIUDSAMLSA-N 0.000 description 1
- FODVBOKTYKYRFJ-CIUDSAMLSA-N Asn-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N FODVBOKTYKYRFJ-CIUDSAMLSA-N 0.000 description 1
- RTFWCVDISAMGEQ-SRVKXCTJSA-N Asn-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N RTFWCVDISAMGEQ-SRVKXCTJSA-N 0.000 description 1
- BKFXFUPYETWGGA-XVSYOHENSA-N Asn-Phe-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BKFXFUPYETWGGA-XVSYOHENSA-N 0.000 description 1
- NPZJLGMWMDNQDD-GHCJXIJMSA-N Asn-Ser-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NPZJLGMWMDNQDD-GHCJXIJMSA-N 0.000 description 1
- 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 1
- QUMKPKWYDVMGNT-NUMRIWBASA-N Asn-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QUMKPKWYDVMGNT-NUMRIWBASA-N 0.000 description 1
- 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 1
- XOQYDFCQPWAMSA-KKHAAJSZSA-N Asn-Val-Thr 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)O)C(O)=O XOQYDFCQPWAMSA-KKHAAJSZSA-N 0.000 description 1
- ICZWAZVKLACMKR-CIUDSAMLSA-N Asp-His-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CN=CN1 ICZWAZVKLACMKR-CIUDSAMLSA-N 0.000 description 1
- XLILXFRAKOYEJX-GUBZILKMSA-N Asp-Leu-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O XLILXFRAKOYEJX-GUBZILKMSA-N 0.000 description 1
- 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 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940022962 COVID-19 vaccine Drugs 0.000 description 1
- UYYZZJXUVIZTMH-AVGNSLFASA-N Cys-Glu-Phe Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O UYYZZJXUVIZTMH-AVGNSLFASA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 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 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
- XEYMBRRKIFYQMF-GUBZILKMSA-N Gln-Asp-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O XEYMBRRKIFYQMF-GUBZILKMSA-N 0.000 description 1
- 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 1
- MAGNEQBFSBREJL-DCAQKATOSA-N Gln-Glu-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N MAGNEQBFSBREJL-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
- HDUDGCZEOZEFOA-KBIXCLLPSA-N Gln-Ile-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HDUDGCZEOZEFOA-KBIXCLLPSA-N 0.000 description 1
- VZRAXPGTUNDIDK-GUBZILKMSA-N Gln-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N VZRAXPGTUNDIDK-GUBZILKMSA-N 0.000 description 1
- ZBKUIQNCRIYVGH-SDDRHHMPSA-N Gln-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZBKUIQNCRIYVGH-SDDRHHMPSA-N 0.000 description 1
- HPCOBEHVEHWREJ-DCAQKATOSA-N Gln-Lys-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HPCOBEHVEHWREJ-DCAQKATOSA-N 0.000 description 1
- JNVGVECJCOZHCN-DRZSPHRISA-N Gln-Phe-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O JNVGVECJCOZHCN-DRZSPHRISA-N 0.000 description 1
- DSRVQBZAMPGEKU-AVGNSLFASA-N Gln-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)N)N DSRVQBZAMPGEKU-AVGNSLFASA-N 0.000 description 1
- HMIXCETWRYDVMO-GUBZILKMSA-N Gln-Pro-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O HMIXCETWRYDVMO-GUBZILKMSA-N 0.000 description 1
- MQJDLNRXBOELJW-KKUMJFAQSA-N Gln-Pro-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O MQJDLNRXBOELJW-KKUMJFAQSA-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
- LPIKVBWNNVFHCQ-GUBZILKMSA-N Gln-Ser-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O LPIKVBWNNVFHCQ-GUBZILKMSA-N 0.000 description 1
- 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 1
- XKPACHRGOWQHFH-IRIUXVKKSA-N Gln-Thr-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XKPACHRGOWQHFH-IRIUXVKKSA-N 0.000 description 1
- HLRLXVPRJJITSK-IFFSRLJSSA-N Gln-Thr-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HLRLXVPRJJITSK-IFFSRLJSSA-N 0.000 description 1
- 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
- FKGNJUCQKXQNRA-NRPADANISA-N Glu-Cys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O FKGNJUCQKXQNRA-NRPADANISA-N 0.000 description 1
- KRGZZKWSBGPLKL-IUCAKERBSA-N Glu-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N KRGZZKWSBGPLKL-IUCAKERBSA-N 0.000 description 1
- ZWQVYZXPYSYPJD-RYUDHWBXSA-N Glu-Gly-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZWQVYZXPYSYPJD-RYUDHWBXSA-N 0.000 description 1
- HILMIYALTUQTRC-XVKPBYJWSA-N Glu-Gly-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HILMIYALTUQTRC-XVKPBYJWSA-N 0.000 description 1
- PJBVXVBTTFZPHJ-GUBZILKMSA-N Glu-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)O)N PJBVXVBTTFZPHJ-GUBZILKMSA-N 0.000 description 1
- OCJRHJZKGGSPRW-IUCAKERBSA-N Glu-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O OCJRHJZKGGSPRW-IUCAKERBSA-N 0.000 description 1
- RBXSZQRSEGYDFG-GUBZILKMSA-N Glu-Lys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O RBXSZQRSEGYDFG-GUBZILKMSA-N 0.000 description 1
- KXTAGESXNQEZKB-DZKIICNBSA-N Glu-Phe-Val Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=CC=C1 KXTAGESXNQEZKB-DZKIICNBSA-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
- 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 1
- FVGOGEGGQLNZGH-DZKIICNBSA-N Glu-Val-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FVGOGEGGQLNZGH-DZKIICNBSA-N 0.000 description 1
- WGYHAAXZWPEBDQ-IFFSRLJSSA-N Glu-Val-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGYHAAXZWPEBDQ-IFFSRLJSSA-N 0.000 description 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
- OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 description 1
- LURCIJSJAKFCRO-QWRGUYRKSA-N Gly-Asn-Tyr Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LURCIJSJAKFCRO-QWRGUYRKSA-N 0.000 description 1
- SUDUYJOBLHQAMI-WHFBIAKZSA-N Gly-Asp-Cys Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(O)=O SUDUYJOBLHQAMI-WHFBIAKZSA-N 0.000 description 1
- XLFHCWHXKSFVIB-BQBZGAKWSA-N Gly-Gln-Gln Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O XLFHCWHXKSFVIB-BQBZGAKWSA-N 0.000 description 1
- LHYJCVCQPWRMKZ-WEDXCCLWSA-N Gly-Leu-Thr Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LHYJCVCQPWRMKZ-WEDXCCLWSA-N 0.000 description 1
- PCPOYRCAHPJXII-UWVGGRQHSA-N Gly-Lys-Met Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(O)=O PCPOYRCAHPJXII-UWVGGRQHSA-N 0.000 description 1
- SJLKKOZFHSJJAW-YUMQZZPRSA-N Gly-Met-Glu Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)CN SJLKKOZFHSJJAW-YUMQZZPRSA-N 0.000 description 1
- OMOZPGCHVWOXHN-BQBZGAKWSA-N Gly-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)CN OMOZPGCHVWOXHN-BQBZGAKWSA-N 0.000 description 1
- YYXJFBMCOUSYSF-RYUDHWBXSA-N Gly-Phe-Gln Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O YYXJFBMCOUSYSF-RYUDHWBXSA-N 0.000 description 1
- 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 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
- 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
- JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 1
- HUFUVTYGPOUCBN-MBLNEYKQSA-N Gly-Thr-Ile Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HUFUVTYGPOUCBN-MBLNEYKQSA-N 0.000 description 1
- SBVMXEZQJVUARN-XPUUQOCRSA-N Gly-Val-Ser Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O SBVMXEZQJVUARN-XPUUQOCRSA-N 0.000 description 1
- NTXIJPDAHXSHNL-ONGXEEELSA-N His-Gly-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O NTXIJPDAHXSHNL-ONGXEEELSA-N 0.000 description 1
- VTZYMXGGXOFBMX-DJFWLOJKSA-N His-Ile-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O VTZYMXGGXOFBMX-DJFWLOJKSA-N 0.000 description 1
- KECFCPNPPYCGBL-PMVMPFDFSA-N His-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](CC4=CN=CN4)N KECFCPNPPYCGBL-PMVMPFDFSA-N 0.000 description 1
- PBJOQLUVSGXRSW-YTQUADARSA-N His-Trp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CC4=CN=CN4)N)C(=O)O PBJOQLUVSGXRSW-YTQUADARSA-N 0.000 description 1
- GBMSSORHVHAYLU-QTKMDUPCSA-N His-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC1=CN=CN1)N)O GBMSSORHVHAYLU-QTKMDUPCSA-N 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- VSZALHITQINTGC-GHCJXIJMSA-N Ile-Ala-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)O)N VSZALHITQINTGC-GHCJXIJMSA-N 0.000 description 1
- TZCGZYWNIDZZMR-NAKRPEOUSA-N Ile-Arg-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](C)C(=O)O)N TZCGZYWNIDZZMR-NAKRPEOUSA-N 0.000 description 1
- TZCGZYWNIDZZMR-UHFFFAOYSA-N Ile-Arg-Ala Natural products CCC(C)C(N)C(=O)NC(C(=O)NC(C)C(O)=O)CCCN=C(N)N TZCGZYWNIDZZMR-UHFFFAOYSA-N 0.000 description 1
- UMYZBHKAVTXWIW-GMOBBJLQSA-N Ile-Asp-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UMYZBHKAVTXWIW-GMOBBJLQSA-N 0.000 description 1
- NKRJALPCDNXULF-BYULHYEWSA-N Ile-Asp-Gly Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O NKRJALPCDNXULF-BYULHYEWSA-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
- APDIECQNNDGFPD-PYJNHQTQSA-N Ile-His-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N APDIECQNNDGFPD-PYJNHQTQSA-N 0.000 description 1
- PNTWNAXGBOZMBO-MNXVOIDGSA-N Ile-Lys-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N PNTWNAXGBOZMBO-MNXVOIDGSA-N 0.000 description 1
- UDBPXJNOEWDBDF-XUXIUFHCSA-N Ile-Lys-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)O)N UDBPXJNOEWDBDF-XUXIUFHCSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 1
- RCFDOSNHHZGBOY-UHFFFAOYSA-N L-isoleucyl-L-alanine Natural products CCC(C)C(N)C(=O)NC(C)C(O)=O RCFDOSNHHZGBOY-UHFFFAOYSA-N 0.000 description 1
- KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-N 0.000 description 1
- 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 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
- 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 1
- 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 1
- APFJUBGRZGMQFF-QWRGUYRKSA-N Leu-Gly-Lys Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN APFJUBGRZGMQFF-QWRGUYRKSA-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
- LIINDKYIGYTDLG-PPCPHDFISA-N Leu-Ile-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LIINDKYIGYTDLG-PPCPHDFISA-N 0.000 description 1
- JNDYEOUZBLOVOF-AVGNSLFASA-N Leu-Leu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JNDYEOUZBLOVOF-AVGNSLFASA-N 0.000 description 1
- LXKNSJLSGPNHSK-KKUMJFAQSA-N Leu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N LXKNSJLSGPNHSK-KKUMJFAQSA-N 0.000 description 1
- VCHVSKNMTXWIIP-SRVKXCTJSA-N Leu-Lys-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O VCHVSKNMTXWIIP-SRVKXCTJSA-N 0.000 description 1
- WXZOHBVPVKABQN-DCAQKATOSA-N Leu-Met-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)O)N WXZOHBVPVKABQN-DCAQKATOSA-N 0.000 description 1
- XXXXOVFBXRERQL-ULQDDVLXSA-N Leu-Pro-Phe Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XXXXOVFBXRERQL-ULQDDVLXSA-N 0.000 description 1
- IDGZVZJLYFTXSL-DCAQKATOSA-N Leu-Ser-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IDGZVZJLYFTXSL-DCAQKATOSA-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
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 1
- VHNOAIFVYUQOOY-XUXIUFHCSA-N Lys-Arg-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VHNOAIFVYUQOOY-XUXIUFHCSA-N 0.000 description 1
- 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 1
- IWWMPCPLFXFBAF-SRVKXCTJSA-N Lys-Asp-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O IWWMPCPLFXFBAF-SRVKXCTJSA-N 0.000 description 1
- XFBBBRDEQIPGNR-KATARQTJSA-N Lys-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N)O XFBBBRDEQIPGNR-KATARQTJSA-N 0.000 description 1
- YVMQJGWLHRWMDF-MNXVOIDGSA-N Lys-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N YVMQJGWLHRWMDF-MNXVOIDGSA-N 0.000 description 1
- LPAJOCKCPRZEAG-MNXVOIDGSA-N Lys-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCCCN LPAJOCKCPRZEAG-MNXVOIDGSA-N 0.000 description 1
- DTUZCYRNEJDKSR-NHCYSSNCSA-N Lys-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN DTUZCYRNEJDKSR-NHCYSSNCSA-N 0.000 description 1
- PBLLTSKBTAHDNA-KBPBESRZSA-N Lys-Gly-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PBLLTSKBTAHDNA-KBPBESRZSA-N 0.000 description 1
- NJNRBRKHOWSGMN-SRVKXCTJSA-N Lys-Leu-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O NJNRBRKHOWSGMN-SRVKXCTJSA-N 0.000 description 1
- YPLVCBKEPJPBDQ-MELADBBJSA-N Lys-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N YPLVCBKEPJPBDQ-MELADBBJSA-N 0.000 description 1
- WBSCNDJQPKSPII-KKUMJFAQSA-N Lys-Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O WBSCNDJQPKSPII-KKUMJFAQSA-N 0.000 description 1
- ATNKHRAIZCMCCN-BZSNNMDCSA-N Lys-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N ATNKHRAIZCMCCN-BZSNNMDCSA-N 0.000 description 1
- LMMBAXJRYSXCOQ-ACRUOGEOSA-N Lys-Tyr-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O LMMBAXJRYSXCOQ-ACRUOGEOSA-N 0.000 description 1
- 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 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- BJEYSVHMGIJORT-NHCYSSNCSA-N Phe-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 BJEYSVHMGIJORT-NHCYSSNCSA-N 0.000 description 1
- WMGVYPPIMZPWPN-SRVKXCTJSA-N Phe-Asp-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N WMGVYPPIMZPWPN-SRVKXCTJSA-N 0.000 description 1
- PSBJZLMFFTULDX-IXOXFDKPSA-N Phe-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=CC=C1)N)O PSBJZLMFFTULDX-IXOXFDKPSA-N 0.000 description 1
- VJLLEKDQJSMHRU-STQMWFEESA-N Phe-Gly-Met Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O VJLLEKDQJSMHRU-STQMWFEESA-N 0.000 description 1
- SMFGCTXUBWEPKM-KBPBESRZSA-N Phe-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 SMFGCTXUBWEPKM-KBPBESRZSA-N 0.000 description 1
- OSBADCBXAMSPQD-YESZJQIVSA-N Phe-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N OSBADCBXAMSPQD-YESZJQIVSA-N 0.000 description 1
- RMKGXGPQIPLTFC-KKUMJFAQSA-N Phe-Lys-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O RMKGXGPQIPLTFC-KKUMJFAQSA-N 0.000 description 1
- CJAHQEZWDZNSJO-KKUMJFAQSA-N Phe-Lys-Cys Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CS)C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 CJAHQEZWDZNSJO-KKUMJFAQSA-N 0.000 description 1
- WLYPRKLMRIYGPP-JYJNAYRXSA-N Phe-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 WLYPRKLMRIYGPP-JYJNAYRXSA-N 0.000 description 1
- GPLWGAYGROGDEN-BZSNNMDCSA-N Phe-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GPLWGAYGROGDEN-BZSNNMDCSA-N 0.000 description 1
- WWPAHTZOWURIMR-ULQDDVLXSA-N Phe-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 WWPAHTZOWURIMR-ULQDDVLXSA-N 0.000 description 1
- IAOZOFPONWDXNT-IXOXFDKPSA-N Phe-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IAOZOFPONWDXNT-IXOXFDKPSA-N 0.000 description 1
- MSSXKZBDKZAHCX-UNQGMJICSA-N Phe-Thr-Val 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(C)C)C(O)=O MSSXKZBDKZAHCX-UNQGMJICSA-N 0.000 description 1
- 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 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
- VWXGFAIZUQBBBG-UWVGGRQHSA-N Pro-His-Gly Chemical compound C([C@@H](C(=O)NCC(=O)[O-])NC(=O)[C@H]1[NH2+]CCC1)C1=CN=CN1 VWXGFAIZUQBBBG-UWVGGRQHSA-N 0.000 description 1
- LXLFEIHKWGHJJB-XUXIUFHCSA-N Pro-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 LXLFEIHKWGHJJB-XUXIUFHCSA-N 0.000 description 1
- VGVCNKSUVSZEIE-IHRRRGAJSA-N Pro-Phe-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O VGVCNKSUVSZEIE-IHRRRGAJSA-N 0.000 description 1
- MLKVIVZCFYRTIR-KKUMJFAQSA-N Pro-Phe-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O MLKVIVZCFYRTIR-KKUMJFAQSA-N 0.000 description 1
- 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 1
- IURWWZYKYPEANQ-HJGDQZAQSA-N Pro-Thr-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O IURWWZYKYPEANQ-HJGDQZAQSA-N 0.000 description 1
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 1
- MWMKFWJYRRGXOR-ZLUOBGJFSA-N Ser-Ala-Asn Chemical compound N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)CC(N)=O)C)CO MWMKFWJYRRGXOR-ZLUOBGJFSA-N 0.000 description 1
- 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
- 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 1
- KYKKKSWGEPFUMR-NAKRPEOUSA-N Ser-Arg-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KYKKKSWGEPFUMR-NAKRPEOUSA-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
- UCXDHBORXLVBNC-ZLUOBGJFSA-N Ser-Asn-Cys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(O)=O UCXDHBORXLVBNC-ZLUOBGJFSA-N 0.000 description 1
- KAAPNMOKUUPKOE-SRVKXCTJSA-N Ser-Asn-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KAAPNMOKUUPKOE-SRVKXCTJSA-N 0.000 description 1
- GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 1
- WSTIOCFMWXNOCX-YUMQZZPRSA-N Ser-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N WSTIOCFMWXNOCX-YUMQZZPRSA-N 0.000 description 1
- HEUVHBXOVZONPU-BJDJZHNGSA-N Ser-Leu-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HEUVHBXOVZONPU-BJDJZHNGSA-N 0.000 description 1
- KZPRPBLHYMZIMH-MXAVVETBSA-N Ser-Phe-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KZPRPBLHYMZIMH-MXAVVETBSA-N 0.000 description 1
- NUEHQDHDLDXCRU-GUBZILKMSA-N Ser-Pro-Arg Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NUEHQDHDLDXCRU-GUBZILKMSA-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
- SQHKXWODKJDZRC-LKXGYXEUSA-N Ser-Thr-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O SQHKXWODKJDZRC-LKXGYXEUSA-N 0.000 description 1
- PMTWIUBUQRGCSB-FXQIFTODSA-N Ser-Val-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O PMTWIUBUQRGCSB-FXQIFTODSA-N 0.000 description 1
- CTONFVDJYCAMQM-IUKAMOBKSA-N Thr-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H]([C@@H](C)O)N CTONFVDJYCAMQM-IUKAMOBKSA-N 0.000 description 1
- QILPDQCTQZDHFM-HJGDQZAQSA-N Thr-Gln-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QILPDQCTQZDHFM-HJGDQZAQSA-N 0.000 description 1
- ONNSECRQFSTMCC-XKBZYTNZSA-N Thr-Glu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O ONNSECRQFSTMCC-XKBZYTNZSA-N 0.000 description 1
- IMULJHHGAUZZFE-MBLNEYKQSA-N Thr-Gly-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IMULJHHGAUZZFE-MBLNEYKQSA-N 0.000 description 1
- MPUMPERGHHJGRP-WEDXCCLWSA-N Thr-Gly-Lys Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N)O MPUMPERGHHJGRP-WEDXCCLWSA-N 0.000 description 1
- MSIYNSBKKVMGFO-BHNWBGBOSA-N Thr-Gly-Pro Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N1CCC[C@@H]1C(=O)O)N)O MSIYNSBKKVMGFO-BHNWBGBOSA-N 0.000 description 1
- NCXVJIQMWSGRHY-KXNHARMFSA-N Thr-Leu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O NCXVJIQMWSGRHY-KXNHARMFSA-N 0.000 description 1
- 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
- MGJLBZFUXUGMML-VOAKCMCISA-N Thr-Lys-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MGJLBZFUXUGMML-VOAKCMCISA-N 0.000 description 1
- NZRUWPIYECBYRK-HTUGSXCWSA-N Thr-Phe-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O NZRUWPIYECBYRK-HTUGSXCWSA-N 0.000 description 1
- JMBRNXUOLJFURW-BEAPCOKYSA-N Thr-Phe-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N)O JMBRNXUOLJFURW-BEAPCOKYSA-N 0.000 description 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
- GVMXJJAJLIEASL-ZJDVBMNYSA-N Thr-Pro-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O GVMXJJAJLIEASL-ZJDVBMNYSA-N 0.000 description 1
- PRTHQBSMXILLPC-XGEHTFHBSA-N Thr-Ser-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PRTHQBSMXILLPC-XGEHTFHBSA-N 0.000 description 1
- NLWDSYKZUPRMBJ-IEGACIPQSA-N Thr-Trp-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O NLWDSYKZUPRMBJ-IEGACIPQSA-N 0.000 description 1
- LVRFMARKDGGZMX-IZPVPAKOSA-N Thr-Tyr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CC1=CC=C(O)C=C1 LVRFMARKDGGZMX-IZPVPAKOSA-N 0.000 description 1
- KVEWWQRTAVMOFT-KJEVXHAQSA-N Thr-Tyr-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O KVEWWQRTAVMOFT-KJEVXHAQSA-N 0.000 description 1
- OGOYMQWIWHGTGH-KZVJFYERSA-N Thr-Val-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O OGOYMQWIWHGTGH-KZVJFYERSA-N 0.000 description 1
- KPMIQCXJDVKWKO-IFFSRLJSSA-N Thr-Val-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KPMIQCXJDVKWKO-IFFSRLJSSA-N 0.000 description 1
- ICNFHVUVCNWUAB-SZMVWBNQSA-N Trp-Arg-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N ICNFHVUVCNWUAB-SZMVWBNQSA-N 0.000 description 1
- VUMCLPHXCBIJJB-PMVMPFDFSA-N Trp-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)N VUMCLPHXCBIJJB-PMVMPFDFSA-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
- 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 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- IELISNUVHBKYBX-XDTLVQLUSA-N Tyr-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 IELISNUVHBKYBX-XDTLVQLUSA-N 0.000 description 1
- KDGFPPHLXCEQRN-STECZYCISA-N Tyr-Arg-Ile 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@@H](C)CC)C(O)=O KDGFPPHLXCEQRN-STECZYCISA-N 0.000 description 1
- NSTPFWRAIDTNGH-BZSNNMDCSA-N Tyr-Asn-Tyr 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=C(O)C=C1)C(O)=O NSTPFWRAIDTNGH-BZSNNMDCSA-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
- SINRIKQYQJRGDQ-MEYUZBJRSA-N Tyr-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SINRIKQYQJRGDQ-MEYUZBJRSA-N 0.000 description 1
- PSALWJCUIAQKFW-ACRUOGEOSA-N Tyr-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N PSALWJCUIAQKFW-ACRUOGEOSA-N 0.000 description 1
- RWOKVQUCENPXGE-IHRRRGAJSA-N Tyr-Ser-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RWOKVQUCENPXGE-IHRRRGAJSA-N 0.000 description 1
- SOAUMCDLIUGXJJ-SRVKXCTJSA-N Tyr-Ser-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O SOAUMCDLIUGXJJ-SRVKXCTJSA-N 0.000 description 1
- NHOVZGFNTGMYMI-KKUMJFAQSA-N Tyr-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NHOVZGFNTGMYMI-KKUMJFAQSA-N 0.000 description 1
- 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 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
- HZDQUVQEVVYDDA-ACRUOGEOSA-N Tyr-Tyr-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HZDQUVQEVVYDDA-ACRUOGEOSA-N 0.000 description 1
- QVYFTFIBKCDHIE-ACRUOGEOSA-N Tyr-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCCN)C(=O)O)N)O QVYFTFIBKCDHIE-ACRUOGEOSA-N 0.000 description 1
- OBKOPLHSRDATFO-XHSDSOJGSA-N Tyr-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OBKOPLHSRDATFO-XHSDSOJGSA-N 0.000 description 1
- RVGVIWNHABGIFH-IHRRRGAJSA-N Tyr-Val-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O RVGVIWNHABGIFH-IHRRRGAJSA-N 0.000 description 1
- FZSPNKUFROZBSG-ZKWXMUAHSA-N Val-Ala-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O FZSPNKUFROZBSG-ZKWXMUAHSA-N 0.000 description 1
- RUCNAYOMFXRIKJ-DCAQKATOSA-N Val-Ala-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN RUCNAYOMFXRIKJ-DCAQKATOSA-N 0.000 description 1
- FPCIBLUVDNXPJO-XPUUQOCRSA-N Val-Cys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O FPCIBLUVDNXPJO-XPUUQOCRSA-N 0.000 description 1
- 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 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
- WBAJDGWKRIHOAC-GVXVVHGQSA-N Val-Lys-Gln Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O WBAJDGWKRIHOAC-GVXVVHGQSA-N 0.000 description 1
- UZFNHAXYMICTBU-DZKIICNBSA-N Val-Phe-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N UZFNHAXYMICTBU-DZKIICNBSA-N 0.000 description 1
- HJSLDXZAZGFPDK-ULQDDVLXSA-N Val-Phe-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C(C)C)N HJSLDXZAZGFPDK-ULQDDVLXSA-N 0.000 description 1
- PGBMPFKFKXYROZ-UFYCRDLUSA-N Val-Tyr-Phe Chemical compound CC(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 PGBMPFKFKXYROZ-UFYCRDLUSA-N 0.000 description 1
- DFQZDQPLWBSFEJ-LSJOCFKGSA-N Val-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)O)N DFQZDQPLWBSFEJ-LSJOCFKGSA-N 0.000 description 1
- XNLUVJPMPAZHCY-JYJNAYRXSA-N Val-Val-Phe Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 XNLUVJPMPAZHCY-JYJNAYRXSA-N 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
- 108010013835 arginine glutamate Proteins 0.000 description 1
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 1
- 108010018691 arginyl-threonyl-arginine Proteins 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 108010069495 cysteinyltyrosine Proteins 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 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 1
- 238000001035 drying Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 108010057083 glutamyl-aspartyl-leucine Proteins 0.000 description 1
- 108010073628 glutamyl-valyl-phenylalanine Proteins 0.000 description 1
- 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 1
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 108010047926 leucyl-lysyl-tyrosine Proteins 0.000 description 1
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000036281 parasite infection Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 108010089198 phenylalanyl-prolyl-arginine Proteins 0.000 description 1
- 108010018625 phenylalanylarginine Proteins 0.000 description 1
- 108010073101 phenylalanylleucine Proteins 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010004914 prolylarginine Proteins 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 108010007375 seryl-seryl-seryl-arginine Proteins 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
- 239000012224 working solution Substances 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
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明公开了一种用于治疗SARS‑CoV‑2病毒感染的多肽制剂,一种用于治疗SARS‑CoV‑2病毒感染的多肽制剂,所述的多肽制剂包含如SEQ ID NO.1‑SEQ ID NO.47所示的多肽。本发明的优点为:安全性好、合成方便。
Description
技术领域
本发明涉及免疫学和生物医药领域,具体地说是一种用于治疗SARS-CoV-2病毒感染的多肽制剂。
背景技术
多肽疫苗是按照病原体抗原基因中已知或预测的某段抗原表位的氨基酸序列,通过化学合成技术制备的肽段混合物。多肽疫苗具有抗病毒、抗肿瘤、抗细菌、抗寄生虫感染功能。由于多肽疫苗价廉、安全、特异性强、容易保存和应用的优点,越来越受到重视。
目前全球研发的SARS-CoV-2疫苗主要包括减毒活疫苗、灭活疫苗、病毒载体疫苗、重组蛋白疫苗、多肽疫苗、DNA疫苗、mRNA疫苗等,上述疫苗均可激活体液免疫产生中和性抗体,但是减毒活疫苗、灭活疫苗、病毒载体疫苗、重组蛋白疫苗、DNA疫苗、mRNA疫苗均无法清除已被病毒感染的细胞。而多肽疫苗可特异性激活T细胞免疫,清除已被病毒感染的细胞,另外,多肽疫苗还具有可快速合成,开发与制备周期较短,可预防、可治疗等优点,因此,本发明提出了一种用于治疗SARS-CoV-2病毒感染的多肽制剂。
发明内容
本发明之目的是弥补上述之不足,向社会公开安全性好、合成方便的一种用于治疗SARS-CoV-2病毒感染的多肽制剂。
本发明的技术方案是这样实现的:
一种用于治疗SARS-CoV-2病毒感染的多肽制剂,所述的多肽制剂包含如SEQ IDNO.1-SEQ ID NO.47所示的多肽,所述的多肽对应为M97-115、M103-121、M166-184、M193-211、N99-117、N160-178、N176-194、N217-235、N235-253、N261-279、N300-318、N311-329、N320-338、N356-374、S52-70、S73-91、S84-102、S128-146、S164-182、S188-206、S264-282、S297-315、S307-325、S356-374、S365-383、S412-430、S484-502、S524-542、S545-563、S630-648、S701-719、S752-770、S777-795、S816-834、S822-840、S864-882、S951-969、S971-989、S978-996、S995-1013、S1015-1033、S1054-1072、S1055-1073、S1089-1107、S1142-1160、S1180-1198以及S1187-1205。
一种用于治疗SARS-CoV-2病毒感染的多肽制剂的应用,应用在药学上可接受的盐或酯或前药,所述的盐或酯或前药包含如SEQ ID NO.1-SEQ ID NO.47所示的多肽。
本发明多肽制剂的开发主要包括以下几个步骤:
步骤一、多肽预测的人工智能算法的优化:
基于人工智能算法和公共数据库中HLA肽段结合数据优化HLA亲和力肽段预测工具。
步骤二、利用人工智能算法预测并筛选对T细胞高亲和力的抗原肽段:
使用SARS-CoV-2病毒的S、E、N、M蛋白序列预测与I类HLA进行亲和力预测,基于肽段与HLA亲和力、肽段的水溶性、免疫原性等指标筛选与HLA结合IC50低于500nM、水溶性强、免疫原性强9氨基酸(9-mer)肽段。最终筛选出47条9氨基酸(9-mer)肽段,在肽段两端延长5个氨基酸,得到对应的19氨基酸(19-mer)肽段用于后续实验。
步骤三、利用化学合成法合成多肽:
利用化学合成法合成预测的SARS-CoV-2特异性多肽,每条肽段包含19个氨基酸,共47条肽段。
步骤四、收集新冠病毒感染康复者的全血,分离PBMC(peripheral bloodmononuclear cells):
在某医院收集COVID-19康复患者的临床信息与全血样本,全血取于绿色抗凝管中,每个个体收集全血16ml,并于6小时内分离PBMC用于实验或-80℃冻存。
步骤五、HLA分型测序:
提取康复者全血DNA,基于高通量测序技术进行HLA分型鉴定。
步骤六、体外免疫系统激活实验验证HLA分型对应的多肽激活T细胞免疫的有效性:
PBMC细胞与合成的肽段疫苗共培养,采用酶联免疫斑点(Enzyme-linkedimmunospot,ELISpot)方法检测激活的T细胞IFN-γ分泌水平,在体外实验验证多肽的有效性。
本发明与现有技术相比的优点是:
本发明提出一种用于治疗SARS-CoV-2病毒感染的多肽制剂,该多肽是基于人工智能算法预测的SARS-CoV-2特异性抗原肽,具有安全性好,合成速度快的优点。利用多肽刺激HLA-A*02:01、HLA-A*02:07、HLA-A*11:01、HLA-A*11:02、HLA-A*24:02、HLA-A*26:01、HLA-A*30:01、HLA-A*31:01、HLA-A*32:01、HLA-A*33:03分型的SARS-CoV-2感染康复者血液PBMC细胞,均能够检测到T细胞的强烈应答反应。该多肽制剂非常适用目前临床HLA-A*02:01、HLA-A*02:07、HLA-A*03:01、HLA-A*11:01、HLA-A*11:02、HLA-A*24:02、HLA-A*26:01、HLA-A*30:01、HLA-A*31:01、HLA-A*32:01、HLA-A*33:03分型患者的SARS-CoV-2感染的治疗。
附图说明
图1是本发明多肽制剂的研发流程图;
图2是本发明多肽制剂实验结果图;
图3是本发明多肽制剂实验结果统计图。
具体实施方式
下面结合附图进一步详细描述本发明:
一种用于治疗SARS-CoV-2病毒感染的多肽制剂,所述的多肽制剂包含如SEQ IDNO.1-SEQ ID NO.47所示的多肽,所述的多肽对应为M97-115、M103-121、M166-184、M193-211、N99-117、N160-178、N176-194、N217-235、N235-253、N261-279、N300-318、N311-329、N320-338、N356-374、S52-70、S73-91、S84-102、S128-146、S164-182、S188-206、S264-282、S297-315、S307-325、S356-374、S365-383、S412-430、S484-502、S524-542、S545-563、S630-648、S701-719、S752-770、S777-795、S816-834、S822-840、S864-882、S951-969、S971-989、S978-996、S995-1013、S1015-1033、S1054-1072、S1055-1073、S1089-1107、S1142-1160、S1180-1198以及S1187-1205。
一种用于治疗SARS-CoV-2病毒感染的多肽制剂的应用,应用在药学上可接受的盐或酯或前药,所述的盐或酯或前药包含如SEQ ID NO.1-SEQ ID NO.47所示的多肽。
本发明提出一种用于治疗SARS-CoV-2病毒感染的多肽制剂,该多肽是基于人工智能算法预测的SARS-CoV-2特异性抗原肽,具有安全性好,合成速度快的优点。利用多肽刺激HLA-A*02:01、HLA-A*02:07、HLA-A*11:01、HLA-A*11:02、HLA-A*24:02、HLA-A*26:01、HLA-A*30:01、HLA-A*31:01、HLA-A*32:01、HLA-A*33:03分型的SARS-CoV-2感染康复者血液PBMC细胞,均能够检测到T细胞的强烈应答反应。该多肽制剂非常适用目前临床HLA-A*02:01、HLA-A*02:07、HLA-A*03:01、HLA-A*11:01、HLA-A*11:02、HLA-A*24:02、HLA-A*26:01、HLA-A*30:01、HLA-A*31:01、HLA-A*32:01、HLA-A*33:03分型患者的SARS-CoV-2感染的治疗。
本发明基于人工智能算法预测并筛选与HLA高亲和力的SARS-CoV-2病毒特异性抗原肽,在体外进行化学合成后用于刺激人体免疫细胞,激活SARS-CoV-2特异性的细胞免疫。下面通过实验证明本发明多肽制剂在治疗SARS-CoV-2病毒感染上有效性。
如图1所示,本发明多肽制剂的开发过程以下几个步骤:
步骤一、人工智能算法的优化:
构建前馈单层人工神经网络,设定23个参数值作为算法的评分向量。23评分向量输入值均为0.05,另外肽段水溶性、和正常人类蛋白差异等均作为输入层的参数。输入数据集主要使用IEBD数据库和文献提供的质谱数据,并通过已经验证过的数据集验证模型。
步骤二、预测多肽:
通过构建的模型,输入SARS-CoV-2病毒的S、E、N、M蛋白序列和HLA序列信息可以获取与该HLA分型的高亲和力多肽序列,我们挑选排名前0.5%的多肽作为候选肽段。根据多肽与HLA亲和力、肽段的水溶性、免疫原性等指标筛选出与HLA结合IC50低于500nM、水溶性强、免疫原性强的肽段。最终筛选出47条9氨基酸(9-mer)肽段,并得到对应的延长后的19氨基酸(19-mer)肽段。
47条免疫肽段如下:
步骤三、合成多肽:
利用化学合成法合成预测的SARS-CoV-2特异性多肽,分别为M97-115、M103-121、M166-184、M193-211、N99-117、N160-178、N176-194、N217-235、N235-253、N261-279、N300-318、N311-329、N320-338、N356-374、S52-70、S73-91、S84-102、S128-146、S164-182、S188-206、S264-282、S297-315、S307-325、S356-374、S365-383、S412-430、S484-502、S524-542、S545-563、S630-648、S701-719、S752-770、S777-795、S816-834、S822-840、S864-882、S951-969、S971-989、S978-996、S995-1013、S1015-1033、S1054-1072、S1055-1073、S1089-1107、S1142-1160、S1180-1198、S1187-1205,每种肽段纯度>95%,共合成5mg肽段。取1mg溶于100μl无菌水中,制成母液,接着取一部分母液使用无菌水进行稀释,配制成工作液为200μg/ml。
步骤四、收集新冠病毒感染康复者的全血,分离PBMC(peripheral bloodmononuclear cells):
在某医院收集COVID-19康复患者血液于绿色抗凝管中,每个个体收集血液16ml,并于6小时内分离PBMC用于实验或-80°冻存。首先将血液转移到干净的50ml离心管中,2000rpm,20℃离心10分钟;收集上层血清,-80℃冻存;向SepMateTM-50管底部加入Ficoll-Paque Premium 1.077溶液,再向沉淀物中加入等体积的PBS,稀释血样并轻轻混合保持试管垂直,将稀释后的样品沿管壁加入SepMateTM-50管中,,1200xg离心15min;然后将上层溶液离心并转移到一个新的50ml无菌离心管中,用PBS清洗沉淀物,共清洗2次;使用红细胞裂解液裂解细胞3分钟;最后用细胞冻存液悬浮细胞,被储存在液氮中,以便将来用于检测或直接用培养基悬浮用于检测。
步骤五、HLA分型鉴定:
使用Ex-DNA全血基因组核酸提取试剂盒和NP968全自动核酸提取仪进行全血DNA的提取。按照说明书要求设置仪器自动化提取程序,DNA提取完成后转移干净无核酸酶离心管中,-20℃保存。利用全血DNA,HiSeq X10等二代测序平台进行高通量测序鉴定HLA分型。本实验涉及的17名康复者HLA分型包括HLA-A*02:01、HLA-A*02:07、HLA-A*11:01、HLA-A*11:02、HLA-A*24:02、HLA-A*26:01、HLA-A*30:01、HLA-A*31:01、HLA-A*32:01、HLA-A*33:03。
步骤六、体外免疫系统激活实验验证HLA分型对应的多肽激活T细胞免疫的有效性:
a)细胞复苏并计数:从液氮中取出冻存PBMC细胞,于37℃水浴快速解冻。完全解冻后,台盼蓝染色计数活细胞数量。
b)细胞培养:按每孔5*10^6个细胞铺于24孔板。加入IL-2(工作浓度20U/ml)、IL-7(工作浓度20ng/ml)、合成的所有肽段(工作浓度2μg/ml),于37℃(含5%CO2)细胞培养箱培养10天。培养期间每三天半换液。
c)收细胞:培养10天后收取细胞。将细胞转移到离心管中,使用1*PBS清洗细胞3次,以去除培养液中的IFN-γ。使用1640培养液(含10%FBS)重悬细胞,并计数。
d)准备ELISpot板:配置35%乙醇,每孔加入35%乙醇孵育1min。无菌H2O洗涤5遍。每孔加100μl包被抗体(工作浓度15μg/ml),4-8℃过夜孵育。
e)孵育细胞:用无菌1*PBS洗板5次。每孔加1640培养液(含10%FBS),置于室温孵育至少30min。弃上清,加入细胞悬浮液,每孔细胞数2×10^4-2.5×10^5。
f)加入刺激物共培养:不含诱导物-H2O(阴性对照组):加入无菌H2O 2μl;PHA刺激(阳性对照组):每孔加入10μl PHA(工作浓度2.5ug/ml);肽段刺激(实验组):每孔加入47条肽段混合肽池1μl(All pep.Pool:M97-115、M103-121、M166-184、M193-211、N99-117、N160-178、N176-194、N217-235、N235-253、N261-279、N300-318、N311-329、N320-338、N356-374、S52-70、S73-91、S84-102、S128-146、S164-182、S188-206、S264-282、S297-315、S307-325、S356-374、S365-383、S412-430、S484-502、S524-542、S545-563、S630-648、S701-719、S752-770、S777-795、S816-834、S822-840、S864-882、S951-969、S971-989、S978-996、S995-1013、S1015-1033、S1054-1072、S1055-1073、S1089-1107、S1142-1160、S1180-1198、S1187-1205,工作浓度2μg/ml)。把板置于37℃培养箱(5%CO2),培养12-48小时。
g)显色:吸走细胞,用无菌1*PBS洗板5次。每孔加100μl检测抗体(工作浓度1μg/ml),室温孵育2h。用无菌1*PBS洗板5次。每孔加100μl Streptavidin-HRP,室温孵育1h。用无菌1*PBS洗板5次。每孔加入显色剂,室温避光孵育5-10min。
h)终止:加入无菌H2O终止。吸走上清,无菌H2O清洗3遍,晾干板,解剖镜下检测并统计斑点数。
i)结果分析:本实验收集17名COVID-19康复者的外周血分离PBMC,利用预测的多肽池进行体外刺激实验。结果发现,HLA分型为HLA-A*02:01、HLA-A*02:07、HLA-A*03:01、HLA-A*11:01、HLA-A*11:02、HLA-A*24:02、HLA-A*26:01、HLA-A*30:01、HLA-A*31:01、HLA-A*32:01、HLA-A*33:03的康复者经多肽池刺激可产生强烈的T细胞反应,且具有统计学意义(如图2和图3所示,图2中Pos.con.为阳性对照结果;All pep.pool为47条肽段共刺激结果;Neg.con.为阴性对照结果;三位野生型新冠病毒感染康复者P01、P02和P03;两位Delta型新冠病毒感染康复者P04和P05)。该肽池可显著引起患者体内的SARS-CoV-2特异性T细胞反应,可用于SARS-CoV-2病毒感染的治疗。
本发明的最佳实施例已被阐明,由本领域普通技术人员做出的各种变化或改型都不会脱离本发明的范围。
序列表
<110> 国科宁波生命与健康产业研究院
<120> 一种用于治疗SARS-CoV-2病毒感染的多肽制剂
<160> 47
<170> SIPOSequenceListing 1.0
<210> 1
<211> 19
<212> PRT
<213> Homo sapiens
<400> 1
Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser Phe
1 5 10 15
Asn Pro Glu
<210> 2
<211> 19
<212> PRT
<213> Homo sapiens
<400> 2
Phe Ala Arg Thr Arg Ser Met Trp Ser Phe Asn Pro Glu Thr Asn Ile
1 5 10 15
Leu Leu Asn
<210> 3
<211> 19
<212> PRT
<213> Homo sapiens
<400> 3
Lys Glu Ile Thr Val Ala Thr Ser Arg Thr Leu Ser Tyr Tyr Lys Leu
1 5 10 15
Gly Ala Ser
<210> 4
<211> 19
<212> PRT
<213> Homo sapiens
<400> 4
Phe Ala Ala Tyr Ser Arg Tyr Arg Ile Gly Asn Tyr Lys Leu Asn Thr
1 5 10 15
Asp His Ser
<210> 5
<211> 19
<212> PRT
<213> Homo sapiens
<400> 5
Gly Lys Met Lys Asp Leu Ser Pro Arg Trp Tyr Phe Tyr Tyr Leu Gly
1 5 10 15
Thr Gly Pro
<210> 6
<211> 19
<212> PRT
<213> Homo sapiens
<400> 6
Gln Leu Pro Gln Gly Thr Thr Leu Pro Lys Gly Phe Tyr Ala Glu Gly
1 5 10 15
Ser Arg Gly
<210> 7
<211> 19
<212> PRT
<213> Homo sapiens
<400> 7
Ser Arg Gly Gly Ser Gln Ala Ser Ser Arg Ser Ser Ser Arg Ser Arg
1 5 10 15
Asn Ser Ser
<210> 8
<211> 19
<212> PRT
<213> Homo sapiens
<400> 8
Ala Ala Leu Ala Leu Leu Leu Leu Asp Arg Leu Asn Gln Leu Glu Ser
1 5 10 15
Lys Met Ser
<210> 9
<211> 19
<212> PRT
<213> Homo sapiens
<400> 9
Ser Gly Lys Gly Gln Gln Gln Gln Gly Gln Thr Val Thr Lys Lys Ser
1 5 10 15
Ala Ala Glu
<210> 10
<211> 19
<212> PRT
<213> Homo sapiens
<400> 10
Lys Arg Thr Ala Thr Lys Ala Tyr Asn Val Thr Gln Ala Phe Gly Arg
1 5 10 15
Arg Gly Pro
<210> 11
<211> 19
<212> PRT
<213> Homo sapiens
<400> 11
His Trp Pro Gln Ile Ala Gln Phe Ala Pro Ser Ala Ser Ala Phe Phe
1 5 10 15
Gly Met Ser
<210> 12
<211> 19
<212> PRT
<213> Homo sapiens
<400> 12
Pro Ser Ala Ser Ala Phe Phe Gly Met Ser Arg Ile Gly Met Glu Val
1 5 10 15
Thr Pro Ser
<210> 13
<211> 19
<212> PRT
<213> Homo sapiens
<400> 13
Ile Gly Met Glu Val Thr Pro Ser Gly Thr Trp Leu Thr Tyr Thr Gly
1 5 10 15
Ala Ile Lys
<210> 14
<211> 19
<212> PRT
<213> Homo sapiens
<400> 14
His Ile Asp Ala Tyr Lys Thr Phe Pro Pro Thr Glu Pro Lys Lys Asp
1 5 10 15
Lys Lys Lys
<210> 15
<211> 19
<212> PRT
<213> Homo sapiens
<400> 15
Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala
1 5 10 15
Ile His Val
<210> 16
<211> 19
<212> PRT
<213> Homo sapiens
<400> 16
Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp
1 5 10 15
Gly Val Tyr
<210> 17
<211> 19
<212> PRT
<213> Homo sapiens
<400> 17
Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn
1 5 10 15
Ile Ile Arg
<210> 18
<211> 19
<212> PRT
<213> Homo sapiens
<400> 18
Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val
1 5 10 15
Tyr Tyr His
<210> 19
<211> 19
<212> PRT
<213> Homo sapiens
<400> 19
Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu
1 5 10 15
Glu Gly Lys
<210> 20
<211> 19
<212> PRT
<213> Homo sapiens
<400> 20
Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile
1 5 10 15
Tyr Ser Lys
<210> 21
<211> 19
<212> PRT
<213> Homo sapiens
<400> 21
Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr
1 5 10 15
Asn Glu Asn
<210> 22
<211> 19
<212> PRT
<213> Homo sapiens
<400> 22
Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile
1 5 10 15
Tyr Gln Thr
<210> 23
<211> 19
<212> PRT
<213> Homo sapiens
<400> 23
Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro
1 5 10 15
Thr Glu Ser
<210> 24
<211> 19
<212> PRT
<213> Homo sapiens
<400> 24
Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser
1 5 10 15
Ala Ser Phe
<210> 25
<211> 19
<212> PRT
<213> Homo sapiens
<400> 25
Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr
1 5 10 15
Gly Val Ser
<210> 26
<211> 19
<212> PRT
<213> Homo sapiens
<400> 26
Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp
1 5 10 15
Asp Phe Thr
<210> 27
<211> 19
<212> PRT
<213> Homo sapiens
<400> 27
Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro
1 5 10 15
Thr Asn Gly
<210> 28
<211> 19
<212> PRT
<213> Homo sapiens
<400> 28
Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val
1 5 10 15
Asn Phe Asn
<210> 29
<211> 19
<212> PRT
<213> Homo sapiens
<400> 29
Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu
1 5 10 15
Pro Phe Gln
<210> 30
<211> 19
<212> PRT
<213> Homo sapiens
<400> 30
Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr
1 5 10 15
Arg Ala Gly
<210> 31
<211> 19
<212> PRT
<213> Homo sapiens
<400> 31
Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr
1 5 10 15
Asn Phe Thr
<210> 32
<211> 19
<212> PRT
<213> Homo sapiens
<400> 32
Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu
1 5 10 15
Thr Gly Ile
<210> 33
<211> 19
<212> PRT
<213> Homo sapiens
<400> 33
Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro
1 5 10 15
Pro Ile Lys
<210> 34
<211> 19
<212> PRT
<213> Homo sapiens
<400> 34
Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala
1 5 10 15
Gly Phe Ile
<210> 35
<211> 19
<212> PRT
<213> Homo sapiens
<400> 35
Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr
1 5 10 15
Gly Asp Cys
<210> 36
<211> 19
<212> PRT
<213> Homo sapiens
<400> 36
Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala
1 5 10 15
Gly Thr Ile
<210> 37
<211> 19
<212> PRT
<213> Homo sapiens
<400> 37
Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu
1 5 10 15
Ser Ser Asn
<210> 38
<211> 19
<212> PRT
<213> Homo sapiens
<400> 38
Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys
1 5 10 15
Val Glu Ala
<210> 39
<211> 19
<212> PRT
<213> Homo sapiens
<400> 39
Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile
1 5 10 15
Asp Arg Leu
<210> 40
<211> 19
<212> PRT
<213> Homo sapiens
<400> 40
Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln
1 5 10 15
Gln Leu Ile
<210> 41
<211> 19
<212> PRT
<213> Homo sapiens
<400> 41
Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser
1 5 10 15
Glu Cys Val
<210> 42
<211> 19
<212> PRT
<213> Homo sapiens
<400> 42
Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro
1 5 10 15
Ala Gln Glu
<210> 43
<211> 19
<212> PRT
<213> Homo sapiens
<400> 43
Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala
1 5 10 15
Gln Glu Lys
<210> 44
<211> 19
<212> PRT
<213> Homo sapiens
<400> 44
Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val
1 5 10 15
Thr Gln Arg
<210> 45
<211> 19
<212> PRT
<213> Homo sapiens
<400> 45
Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys
1 5 10 15
Asn His Thr
<210> 46
<211> 19
<212> PRT
<213> Homo sapiens
<400> 46
Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu
1 5 10 15
Ser Leu Ile
<210> 47
<211> 19
<212> PRT
<213> Homo sapiens
<400> 47
Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu
1 5 10 15
Leu Gly Lys
Claims (2)
1.一种用于治疗SARS-CoV-2病毒感染的多肽制剂,其特征是:所述的多肽制剂包含如SEQ ID NO.1- SEQ ID NO.47所示的多肽,所述的多肽对应为M97-115、M103-121、M166-184、M193-211、N99-117、N160-178、N176-194、N217-235、N235-253、N261-279、N300-318、N311-329、N320-338、N356-374、S52-70、S73-91、S84-102、S128-146、S164-182、S188-206、S264-282、S297-315、S307-325、S356-374、S365-383、S412-430、S484-502、S524-542、S545-563、S630-648、S701-719、S752-770、S777-795、S816-834、S822-840、S864-882、S951-969、S971-989、S978-996、S995-1013、S1015-1033、S1054-1072、S1055-1073、S1089-1107、S1142-1160、S1180-1198以及S1187-1205。
2.根据权利要求1所述的一种用于治疗SARS-CoV-2病毒感染的多肽制剂的应用,其特征是:应用在药学上可接受的盐或酯或前药,所述的盐或酯或前药包含如SEQ ID NO.1-SEQ ID NO.47所示的多肽。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210368802.2A CN114949194B (zh) | 2022-04-08 | 2022-04-08 | 一种用于治疗SARS-CoV-2病毒感染的多肽制剂 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210368802.2A CN114949194B (zh) | 2022-04-08 | 2022-04-08 | 一种用于治疗SARS-CoV-2病毒感染的多肽制剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114949194A true CN114949194A (zh) | 2022-08-30 |
CN114949194B CN114949194B (zh) | 2023-11-28 |
Family
ID=82977004
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210368802.2A Active CN114949194B (zh) | 2022-04-08 | 2022-04-08 | 一种用于治疗SARS-CoV-2病毒感染的多肽制剂 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114949194B (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11040340B1 (en) * | 2020-08-19 | 2021-06-22 | Timothy S. Moore | Collection system and device for reducing clinical false positives and negatives in the detection of SARS-CoV-2 |
WO2021211552A1 (en) * | 2020-04-14 | 2021-10-21 | Ut-Battelle, Llc | Compositions and methods for drug delivery and treating viral infections |
CN113717258A (zh) * | 2021-09-03 | 2021-11-30 | 郑州安图生物工程股份有限公司 | 一种SARS-CoV-2感染细胞免疫检测的抗原多肽组合物及其应用、试剂盒 |
WO2022010813A2 (en) * | 2020-07-06 | 2022-01-13 | Rutgers, The State University Of New Jersey | Enhancing immune responses through targeted antigen expression |
WO2022031790A1 (en) * | 2020-08-05 | 2022-02-10 | The Cleveland Clinic Foundation | Multi-epitope vaccine |
WO2022039126A1 (ja) * | 2020-08-17 | 2022-02-24 | ブライトパス・バイオ株式会社 | SARS-CoV-2予防抗原ペプチドおよびその使用 |
WO2022049595A1 (en) * | 2020-09-01 | 2022-03-10 | Helmholtz Zentrum für Infektionsforschung GmbH | Multi-patch vaccines and immunogenic compositions, methods of production and uses thereof |
-
2022
- 2022-04-08 CN CN202210368802.2A patent/CN114949194B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021211552A1 (en) * | 2020-04-14 | 2021-10-21 | Ut-Battelle, Llc | Compositions and methods for drug delivery and treating viral infections |
WO2022010813A2 (en) * | 2020-07-06 | 2022-01-13 | Rutgers, The State University Of New Jersey | Enhancing immune responses through targeted antigen expression |
WO2022031790A1 (en) * | 2020-08-05 | 2022-02-10 | The Cleveland Clinic Foundation | Multi-epitope vaccine |
WO2022039126A1 (ja) * | 2020-08-17 | 2022-02-24 | ブライトパス・バイオ株式会社 | SARS-CoV-2予防抗原ペプチドおよびその使用 |
US11040340B1 (en) * | 2020-08-19 | 2021-06-22 | Timothy S. Moore | Collection system and device for reducing clinical false positives and negatives in the detection of SARS-CoV-2 |
WO2022049595A1 (en) * | 2020-09-01 | 2022-03-10 | Helmholtz Zentrum für Infektionsforschung GmbH | Multi-patch vaccines and immunogenic compositions, methods of production and uses thereof |
CN113717258A (zh) * | 2021-09-03 | 2021-11-30 | 郑州安图生物工程股份有限公司 | 一种SARS-CoV-2感染细胞免疫检测的抗原多肽组合物及其应用、试剂盒 |
Non-Patent Citations (5)
Title |
---|
CARTER等: "Preliminary Immunogenicity of a Pan-COVID-19 T Cell Vaccine in HLA-A*02:01 Mice", 《BIORXIV》, pages 2 * |
GE LIU等: "Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and Their Augmentation by Compact Peptide Sets", 《CELL SYSTEMS》, pages 2102 - 107 * |
OBERMAIR等: "High resolution profiling of MHC-II peptide presentation capacity, by Mammalian Epitope Display, reveals SARS-CoV-2 targets for CD4 T cells and mechanisms of immune-escape", 《BIORXIV》, pages 21 * |
OLIVEIRA等: "Immunoinformatic Analysis of SARS-CoV-2 Nucleocapsid Protein and Identification of COVID-19 Vaccine Targets", 《FRONTIERS IN IMMUNOLOGY》, pages 3 * |
SRIVASTAVA等: "Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch vaccines, designed by reverse epitomics approach, show potential to cover large ethnically distributed human population worldwide", 《JOURNAL OF BIOMOLECULAR STRUCTURE AND DYNAMICS》, pages 2376 * |
Also Published As
Publication number | Publication date |
---|---|
CN114949194B (zh) | 2023-11-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN112028978B (zh) | 新冠病毒特异性cd8+t细胞表位肽及其应用 | |
CN111450244B (zh) | 一种防治冠状病毒感染的细胞组合及其应用 | |
CN110627895B (zh) | 肺癌特异性tcr及其分析技术和应用 | |
CN111330002A (zh) | 靶向冠状病毒的通用dc细胞疫苗及其制备方法和应用 | |
CN113801208B (zh) | 一种新型冠状病毒的t细胞免疫检测方法 | |
CN113528549B (zh) | 编码新型冠状病毒b.1.351突变株抗原的dna分子、dna疫苗及应用 | |
CN116496383A (zh) | 原发性肝癌相关抗原的胸腺依赖性淋巴细胞抗原表位肽及其应用 | |
CN114949194B (zh) | 一种用于治疗SARS-CoV-2病毒感染的多肽制剂 | |
CN114907452B (zh) | 一种用于治疗SARS-CoV-2病毒感染的M蛋白多肽 | |
CN114907453B (zh) | 一种用于治疗SARS-CoV-2病毒感染的S蛋白多肽 | |
CN114907454A (zh) | 一种用于治疗SARS-CoV-2病毒感染的N蛋白多肽 | |
CN114832099B (zh) | 一种用于治疗SARS-CoV-2变异毒株感染的多肽制剂 | |
CN113248577B (zh) | 一种以腺病毒为载体的冠状病毒疫苗及其制备方法 | |
CN111533795A (zh) | Hla-a2限制性膀胱癌肿瘤新抗原肽序列及其应用 | |
CN115991733A (zh) | 一种alv-j mhc-b21限制性表位肽及其应用 | |
CN105693828A (zh) | 一种新的eb病毒ebna1表位肽及其在ebv相关疾病的诊断、治疗和预防中的用途 | |
CN113423724B (zh) | Ebv表位高亲和力t细胞受体 | |
CN113528546A (zh) | 编码新型冠状病毒p.1突变株抗原的dna分子、dna疫苗及应用 | |
CN114573667B (zh) | SARS-CoV-2病毒B.1.1.529突变株DNA疫苗及应用 | |
WO2023051611A1 (zh) | SARS-CoV-2特异性多肽及其应用 | |
CN113249331B (zh) | 负载Tax抗原的DC细胞、CTL细胞及其制备方法和应用 | |
CN109957581A (zh) | 特异性高表达棕榈酰化缺失mtdh的mda-mb-231细胞株及构建方法 | |
CN113234129B (zh) | Hla-e限制性htnv结构蛋白特异性cd8+t细胞表位肽及其聚合物和应用 | |
CN113862286B (zh) | 编码sars-cov-2病毒c.37突变株抗原的dna分子、dna疫苗及应用 | |
CN109172818B (zh) | 一种蛋白牛痘疫苗及其效力检测方法 |
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 |