EP0932684A2 - Mutationen in der genomischen 3'promoterregion und im polymerasegen, die für die attenuierung von viren der ordnung mononegavirales verantwortlich sind - Google Patents
Mutationen in der genomischen 3'promoterregion und im polymerasegen, die für die attenuierung von viren der ordnung mononegavirales verantwortlich sindInfo
- Publication number
- EP0932684A2 EP0932684A2 EP97942613A EP97942613A EP0932684A2 EP 0932684 A2 EP0932684 A2 EP 0932684A2 EP 97942613 A EP97942613 A EP 97942613A EP 97942613 A EP97942613 A EP 97942613A EP 0932684 A2 EP0932684 A2 EP 0932684A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- leu
- ser
- val
- virus
- arg
- 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.)
- Withdrawn
Links
- 241000700605 Viruses Species 0.000 title claims abstract description 190
- 108700039691 Genetic Promoter Regions Proteins 0.000 title claims abstract description 44
- 241000711513 Mononegavirales Species 0.000 title claims abstract description 21
- 206010064571 Gene mutation Diseases 0.000 title description 2
- 229960005486 vaccine Drugs 0.000 claims abstract description 134
- 230000035772 mutation Effects 0.000 claims abstract description 87
- 230000002238 attenuated effect Effects 0.000 claims abstract description 42
- 241001493065 dsRNA viruses Species 0.000 claims abstract description 21
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 claims abstract description 19
- 230000003053 immunization Effects 0.000 claims abstract description 10
- 239000002773 nucleotide Substances 0.000 claims description 152
- 125000003729 nucleotide group Chemical group 0.000 claims description 149
- 108090000623 proteins and genes Proteins 0.000 claims description 128
- 241000712079 Measles morbillivirus Species 0.000 claims description 86
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 82
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 79
- 102000004169 proteins and genes Human genes 0.000 claims description 69
- 235000001014 amino acid Nutrition 0.000 claims description 67
- 235000018102 proteins Nutrition 0.000 claims description 67
- 229940024606 amino acid Drugs 0.000 claims description 65
- 150000001413 amino acids Chemical class 0.000 claims description 65
- 230000035897 transcription Effects 0.000 claims description 54
- 238000013518 transcription Methods 0.000 claims description 54
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 46
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 38
- 230000010076 replication Effects 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 35
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 30
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 29
- 102000039446 nucleic acids Human genes 0.000 claims description 27
- 108020004707 nucleic acids Proteins 0.000 claims description 27
- 150000007523 nucleic acids Chemical class 0.000 claims description 27
- 108010062796 arginyllysine Proteins 0.000 claims description 25
- 210000004027 cell Anatomy 0.000 claims description 25
- 208000015181 infectious disease Diseases 0.000 claims description 25
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 24
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 14
- 239000004473 Threonine Substances 0.000 claims description 14
- 239000004475 Arginine Substances 0.000 claims description 13
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- 239000013598 vector Substances 0.000 claims description 13
- 210000003501 vero cell Anatomy 0.000 claims description 13
- 241000711902 Pneumovirus Species 0.000 claims description 12
- 230000002458 infectious effect Effects 0.000 claims description 11
- 241000711502 Paramyxovirinae Species 0.000 claims description 9
- 235000004279 alanine Nutrition 0.000 claims description 9
- 239000013604 expression vector Substances 0.000 claims description 9
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 8
- 230000014509 gene expression Effects 0.000 claims description 8
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 7
- 239000004472 Lysine Substances 0.000 claims description 7
- 241000711504 Paramyxoviridae Species 0.000 claims description 7
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 7
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 6
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 6
- 238000003780 insertion Methods 0.000 claims description 6
- 230000037431 insertion Effects 0.000 claims description 6
- 229960000310 isoleucine Drugs 0.000 claims description 6
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 6
- 241000711920 Human orthopneumovirus Species 0.000 claims description 5
- 241000711904 Pneumoviridae Species 0.000 claims description 5
- 235000003704 aspartic acid Nutrition 0.000 claims description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 5
- 230000000295 complement effect Effects 0.000 claims description 5
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 4
- 241000711950 Filoviridae Species 0.000 claims description 4
- 229960001230 asparagine Drugs 0.000 claims description 4
- 235000009582 asparagine Nutrition 0.000 claims description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- 241000712045 Morbillivirus Species 0.000 claims description 3
- 241000711931 Rhabdoviridae Species 0.000 claims description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- XIFDBACLRPLVEQ-BXRBKJIMSA-N (2s)-2-aminobutanedioic acid;(2s)-2,4-diamino-4-oxobutanoic acid Chemical compound OC(=O)[C@@H](N)CC(N)=O.OC(=O)[C@@H](N)CC(O)=O XIFDBACLRPLVEQ-BXRBKJIMSA-N 0.000 claims description 2
- 230000004186 co-expression Effects 0.000 claims description 2
- 230000001605 fetal effect Effects 0.000 claims description 2
- GTHSCFHWXDWOPL-JAIWQFPISA-N (2s,3r)-2-amino-3-hydroxybutanoic acid;(2s,3s)-2-amino-3-methylpentanoic acid Chemical compound C[C@@H](O)[C@H](N)C(O)=O.CC[C@H](C)[C@H](N)C(O)=O GTHSCFHWXDWOPL-JAIWQFPISA-N 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 210000005265 lung cell Anatomy 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 53
- 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 41
- 230000003612 virological effect Effects 0.000 description 40
- 241000880493 Leptailurus serval Species 0.000 description 39
- 101150062031 L gene Proteins 0.000 description 36
- 108020004999 messenger RNA Proteins 0.000 description 36
- NKBQZKVMKJJDLX-SRVKXCTJSA-N Arg-Glu-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NKBQZKVMKJJDLX-SRVKXCTJSA-N 0.000 description 31
- 230000008859 change Effects 0.000 description 31
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 31
- 108010061238 threonyl-glycine Proteins 0.000 description 31
- 108010050848 glycylleucine Proteins 0.000 description 30
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 28
- 201000005505 Measles Diseases 0.000 description 27
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 description 26
- 108010077245 asparaginyl-proline Proteins 0.000 description 25
- DJIMLSXHXKWADV-CIUDSAMLSA-N Asn-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(N)=O DJIMLSXHXKWADV-CIUDSAMLSA-N 0.000 description 23
- 108010081551 glycylphenylalanine Proteins 0.000 description 22
- 108010034529 leucyl-lysine Proteins 0.000 description 22
- 108010003700 lysyl aspartic acid Proteins 0.000 description 22
- 108010025306 histidylleucine Proteins 0.000 description 21
- KPYAOIVPJKPIOU-KKUMJFAQSA-N Leu-Lys-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O KPYAOIVPJKPIOU-KKUMJFAQSA-N 0.000 description 20
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 19
- 108010068380 arginylarginine Proteins 0.000 description 19
- 108010070643 prolylglutamic acid Proteins 0.000 description 19
- 230000001105 regulatory effect Effects 0.000 description 18
- YQAQQKPWFOBSMU-WDCWCFNPSA-N Glu-Thr-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O YQAQQKPWFOBSMU-WDCWCFNPSA-N 0.000 description 17
- 108010020688 glycylhistidine Proteins 0.000 description 17
- 210000002845 virion Anatomy 0.000 description 17
- ZJLORAAXDAJLDC-CQDKDKBSSA-N Ala-Tyr-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O ZJLORAAXDAJLDC-CQDKDKBSSA-N 0.000 description 16
- 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 16
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 16
- 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 16
- VFEHSAJCWWHDBH-RHYQMDGZSA-N Thr-Arg-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VFEHSAJCWWHDBH-RHYQMDGZSA-N 0.000 description 16
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 16
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 16
- 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 16
- 201000010099 disease Diseases 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 108010008237 glutamyl-valyl-glycine Proteins 0.000 description 16
- 108010057821 leucylproline Proteins 0.000 description 16
- 108010009298 lysylglutamic acid Proteins 0.000 description 16
- 108010073101 phenylalanylleucine Proteins 0.000 description 16
- 108020004705 Codon Proteins 0.000 description 15
- MUSGDMDGNGXULI-DCAQKATOSA-N Glu-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O MUSGDMDGNGXULI-DCAQKATOSA-N 0.000 description 15
- 108010090894 prolylleucine Proteins 0.000 description 15
- JQFJNGVSGOUQDH-XIRDDKMYSA-N Arg-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCN=C(N)N)N)C(O)=O)=CNC2=C1 JQFJNGVSGOUQDH-XIRDDKMYSA-N 0.000 description 14
- HYIFFZAQXPUEAU-QWRGUYRKSA-N Leu-Gly-Leu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C HYIFFZAQXPUEAU-QWRGUYRKSA-N 0.000 description 14
- VUBIPAHVHMZHCM-KKUMJFAQSA-N Leu-Tyr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CC=C(O)C=C1 VUBIPAHVHMZHCM-KKUMJFAQSA-N 0.000 description 14
- PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 description 14
- ILZAUMFXKSIUEF-SRVKXCTJSA-N Ser-Ser-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ILZAUMFXKSIUEF-SRVKXCTJSA-N 0.000 description 14
- VYQQQIRHIFALGE-UWJYBYFXSA-N Tyr-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VYQQQIRHIFALGE-UWJYBYFXSA-N 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- JGDGLDNAQJJGJI-AVGNSLFASA-N Arg-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N JGDGLDNAQJJGJI-AVGNSLFASA-N 0.000 description 13
- SUMJNGAMIQSNGX-TUAOUCFPSA-N Arg-Val-Pro Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N1CCC[C@@H]1C(O)=O SUMJNGAMIQSNGX-TUAOUCFPSA-N 0.000 description 13
- REPPKAMYTOJTFC-DCAQKATOSA-N Leu-Arg-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O REPPKAMYTOJTFC-DCAQKATOSA-N 0.000 description 13
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 13
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 13
- WYBVBIHNJWOLCJ-UHFFFAOYSA-N N-L-arginyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCCN=C(N)N WYBVBIHNJWOLCJ-UHFFFAOYSA-N 0.000 description 13
- 108010047495 alanylglycine Proteins 0.000 description 13
- 108010068265 aspartyltyrosine Proteins 0.000 description 13
- 230000028993 immune response Effects 0.000 description 13
- 108010064235 lysylglycine Proteins 0.000 description 13
- GADKFYNESXNRLC-WDSKDSINSA-N Asn-Pro Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O GADKFYNESXNRLC-WDSKDSINSA-N 0.000 description 12
- UJGRZQYSNYTCAX-SRVKXCTJSA-N Asp-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UJGRZQYSNYTCAX-SRVKXCTJSA-N 0.000 description 12
- YIWFXZNIBQBFHR-LURJTMIESA-N Gly-His Chemical compound [NH3+]CC(=O)N[C@H](C([O-])=O)CC1=CN=CN1 YIWFXZNIBQBFHR-LURJTMIESA-N 0.000 description 12
- 241000712003 Human respirovirus 3 Species 0.000 description 12
- QAHFGYLFLVGBNW-DCAQKATOSA-N Met-Ala-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN QAHFGYLFLVGBNW-DCAQKATOSA-N 0.000 description 12
- 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 12
- GHPQVUYZQQGEDA-BIIVOSGPSA-N Ser-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N)C(=O)O GHPQVUYZQQGEDA-BIIVOSGPSA-N 0.000 description 12
- XXXAXOWMBOKTRN-XPUUQOCRSA-N Ser-Gly-Val Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O XXXAXOWMBOKTRN-XPUUQOCRSA-N 0.000 description 12
- KOVXHANYYYMBRF-IRIUXVKKSA-N Tyr-Glu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O KOVXHANYYYMBRF-IRIUXVKKSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 108010016616 cysteinylglycine Proteins 0.000 description 12
- BGGAIXWIZCIFSG-XDTLVQLUSA-N Ala-Tyr-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O BGGAIXWIZCIFSG-XDTLVQLUSA-N 0.000 description 11
- LVMUGODRNHFGRA-AVGNSLFASA-N Arg-Leu-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O LVMUGODRNHFGRA-AVGNSLFASA-N 0.000 description 11
- QCVXMEHGFUMKCO-YUMQZZPRSA-N Asp-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O QCVXMEHGFUMKCO-YUMQZZPRSA-N 0.000 description 11
- UQHGAYSULGRWRG-WHFBIAKZSA-N Glu-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(O)=O UQHGAYSULGRWRG-WHFBIAKZSA-N 0.000 description 11
- UHPAZODVFFYEEL-QWRGUYRKSA-N Gly-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)CN UHPAZODVFFYEEL-QWRGUYRKSA-N 0.000 description 11
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 11
- IMAKMJCBYCSMHM-AVGNSLFASA-N Lys-Glu-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN IMAKMJCBYCSMHM-AVGNSLFASA-N 0.000 description 11
- PWONLXBUSVIZPH-RHYQMDGZSA-N Thr-Val-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O PWONLXBUSVIZPH-RHYQMDGZSA-N 0.000 description 11
- HPYDSVWYXXKHRD-VIFPVBQESA-N Tyr-Gly Chemical compound [O-]C(=O)CNC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 HPYDSVWYXXKHRD-VIFPVBQESA-N 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- SOBIAADAMRHGKH-CIUDSAMLSA-N Ala-Leu-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O SOBIAADAMRHGKH-CIUDSAMLSA-N 0.000 description 10
- LRPXYSGPOBVBEH-IUCAKERBSA-N Glu-Gly-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O LRPXYSGPOBVBEH-IUCAKERBSA-N 0.000 description 10
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 10
- OGUUKPXUTHOIAV-SDDRHHMPSA-N Leu-Glu-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N OGUUKPXUTHOIAV-SDDRHHMPSA-N 0.000 description 10
- XGDCYUQSFDQISZ-BQBZGAKWSA-N Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O XGDCYUQSFDQISZ-BQBZGAKWSA-N 0.000 description 10
- XZFYRXDAULDNFX-UHFFFAOYSA-N N-L-cysteinyl-L-phenylalanine Natural products SCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XZFYRXDAULDNFX-UHFFFAOYSA-N 0.000 description 10
- 238000012300 Sequence Analysis Methods 0.000 description 10
- DKGRNFUXVTYRAS-UBHSHLNASA-N Ser-Ser-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O DKGRNFUXVTYRAS-UBHSHLNASA-N 0.000 description 10
- ILVGMCVCQBJPSH-WDSKDSINSA-N Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO ILVGMCVCQBJPSH-WDSKDSINSA-N 0.000 description 10
- 108010005233 alanylglutamic acid Proteins 0.000 description 10
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 10
- 108010048818 seryl-histidine Proteins 0.000 description 10
- 108010080629 tryptophan-leucine Proteins 0.000 description 10
- 108010084932 tryptophyl-proline Proteins 0.000 description 10
- IPWKGIFRRBGCJO-IMJSIDKUSA-N Ala-Ser Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O IPWKGIFRRBGCJO-IMJSIDKUSA-N 0.000 description 9
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 description 9
- CYXCAHZVPFREJD-LURJTMIESA-N Arg-Gly-Gly Chemical compound NC(=N)NCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O CYXCAHZVPFREJD-LURJTMIESA-N 0.000 description 9
- 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 9
- NTQDELBZOMWXRS-IWGUZYHVSA-N Asp-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O NTQDELBZOMWXRS-IWGUZYHVSA-N 0.000 description 9
- 241000712083 Canine morbillivirus Species 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 9
- PXXGVUVQWQGGIG-YUMQZZPRSA-N Glu-Gly-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N PXXGVUVQWQGGIG-YUMQZZPRSA-N 0.000 description 9
- CUPSDFQZTVVTSK-GUBZILKMSA-N Glu-Lys-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O CUPSDFQZTVVTSK-GUBZILKMSA-N 0.000 description 9
- YBTCBQBIJKGSJP-BQBZGAKWSA-N Glu-Pro Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O YBTCBQBIJKGSJP-BQBZGAKWSA-N 0.000 description 9
- MXJYXYDREQWUMS-XKBZYTNZSA-N Glu-Thr-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O MXJYXYDREQWUMS-XKBZYTNZSA-N 0.000 description 9
- JBCLFWXMTIKCCB-VIFPVBQESA-N Gly-Phe Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-VIFPVBQESA-N 0.000 description 9
- KSZCCRIGNVSHFH-UWVGGRQHSA-N Leu-Arg-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O KSZCCRIGNVSHFH-UWVGGRQHSA-N 0.000 description 9
- BPANDPNDMJHFEV-CIUDSAMLSA-N Leu-Asp-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O BPANDPNDMJHFEV-CIUDSAMLSA-N 0.000 description 9
- WIDZHJTYKYBLSR-DCAQKATOSA-N Leu-Glu-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WIDZHJTYKYBLSR-DCAQKATOSA-N 0.000 description 9
- WXUOJXIGOPMDJM-SRVKXCTJSA-N Leu-Lys-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O WXUOJXIGOPMDJM-SRVKXCTJSA-N 0.000 description 9
- GNRPTBRHRRZCMA-RWMBFGLXSA-N Leu-Met-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@@H]1C(=O)O)N GNRPTBRHRRZCMA-RWMBFGLXSA-N 0.000 description 9
- 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 9
- AXVIGSRGTMNSJU-YESZJQIVSA-N Leu-Tyr-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N AXVIGSRGTMNSJU-YESZJQIVSA-N 0.000 description 9
- NQOQDINRVQCAKD-ULQDDVLXSA-N Lys-Tyr-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCCCN)N NQOQDINRVQCAKD-ULQDDVLXSA-N 0.000 description 9
- YCUSPBPZVJDMII-YUMQZZPRSA-N Met-Gly-Glu Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O YCUSPBPZVJDMII-YUMQZZPRSA-N 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- GLJZDMZJHFXJQG-BZSNNMDCSA-N Phe-Ser-Phe Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O GLJZDMZJHFXJQG-BZSNNMDCSA-N 0.000 description 9
- WOIFYRZPIORBRY-AVGNSLFASA-N Pro-Lys-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O WOIFYRZPIORBRY-AVGNSLFASA-N 0.000 description 9
- GVMUJUPXFQFBBZ-GUBZILKMSA-N Ser-Lys-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GVMUJUPXFQFBBZ-GUBZILKMSA-N 0.000 description 9
- RQXDSYQXBCRXBT-GUBZILKMSA-N Ser-Met-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RQXDSYQXBCRXBT-GUBZILKMSA-N 0.000 description 9
- BZOSBRIDWSSTFN-AVGNSLFASA-N Val-Leu-Met Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](C(C)C)N BZOSBRIDWSSTFN-AVGNSLFASA-N 0.000 description 9
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 9
- 108010038633 aspartylglutamate Proteins 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 108010075431 glycyl-alanyl-phenylalanine Proteins 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 9
- 108010020532 tyrosyl-proline Proteins 0.000 description 9
- XVZCXCTYGHPNEM-IHRRRGAJSA-N (2s)-1-[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O XVZCXCTYGHPNEM-IHRRRGAJSA-N 0.000 description 8
- UWQJHXKARZWDIJ-ZLUOBGJFSA-N Ala-Ala-Cys Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(O)=O UWQJHXKARZWDIJ-ZLUOBGJFSA-N 0.000 description 8
- YWWATNIVMOCSAV-UBHSHLNASA-N Ala-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YWWATNIVMOCSAV-UBHSHLNASA-N 0.000 description 8
- PJNSIUPOXFBHDM-GUBZILKMSA-N Ala-Arg-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O PJNSIUPOXFBHDM-GUBZILKMSA-N 0.000 description 8
- CWEAKSWWKHGTRJ-BQBZGAKWSA-N Ala-Gly-Met Chemical compound [H]N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O CWEAKSWWKHGTRJ-BQBZGAKWSA-N 0.000 description 8
- YHKANGMVQWRMAP-DCAQKATOSA-N Ala-Leu-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YHKANGMVQWRMAP-DCAQKATOSA-N 0.000 description 8
- GFEDXKNBZMPEDM-KZVJFYERSA-N Ala-Met-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GFEDXKNBZMPEDM-KZVJFYERSA-N 0.000 description 8
- ADSGHMXEAZJJNF-DCAQKATOSA-N Ala-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N ADSGHMXEAZJJNF-DCAQKATOSA-N 0.000 description 8
- CQJHFKKGZXKZBC-BPNCWPANSA-N Ala-Pro-Tyr Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CQJHFKKGZXKZBC-BPNCWPANSA-N 0.000 description 8
- 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 8
- KUFVXLQLDHJVOG-SHGPDSBTSA-N Ala-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C)N)O KUFVXLQLDHJVOG-SHGPDSBTSA-N 0.000 description 8
- IETUUAHKCHOQHP-KZVJFYERSA-N Ala-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](C)N)[C@@H](C)O)C(O)=O IETUUAHKCHOQHP-KZVJFYERSA-N 0.000 description 8
- QRIYOHQJRDHFKF-UWJYBYFXSA-N Ala-Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 QRIYOHQJRDHFKF-UWJYBYFXSA-N 0.000 description 8
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 8
- OMSKGWFGWCQFBD-KZVJFYERSA-N Ala-Val-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OMSKGWFGWCQFBD-KZVJFYERSA-N 0.000 description 8
- DBKNLHKEVPZVQC-LPEHRKFASA-N Arg-Ala-Pro Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(O)=O DBKNLHKEVPZVQC-LPEHRKFASA-N 0.000 description 8
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 8
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 8
- UHFUZWSZQKMDSX-DCAQKATOSA-N Arg-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UHFUZWSZQKMDSX-DCAQKATOSA-N 0.000 description 8
- CLICCYPMVFGUOF-IHRRRGAJSA-N Arg-Lys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O CLICCYPMVFGUOF-IHRRRGAJSA-N 0.000 description 8
- JOADBFCFJGNIKF-GUBZILKMSA-N Arg-Met-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O JOADBFCFJGNIKF-GUBZILKMSA-N 0.000 description 8
- VVJTWSRNMJNDPN-IUCAKERBSA-N Arg-Met-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O VVJTWSRNMJNDPN-IUCAKERBSA-N 0.000 description 8
- IJYZHIOOBGIINM-WDSKDSINSA-N Arg-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N IJYZHIOOBGIINM-WDSKDSINSA-N 0.000 description 8
- KXOPYFNQLVUOAQ-FXQIFTODSA-N Arg-Ser-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KXOPYFNQLVUOAQ-FXQIFTODSA-N 0.000 description 8
- KMFPQTITXUKJOV-DCAQKATOSA-N Arg-Ser-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O KMFPQTITXUKJOV-DCAQKATOSA-N 0.000 description 8
- ICRHGPYYXMWHIE-LPEHRKFASA-N Arg-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ICRHGPYYXMWHIE-LPEHRKFASA-N 0.000 description 8
- QHUOOCKNNURZSL-IHRRRGAJSA-N Arg-Tyr-Ser 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](CO)C(O)=O QHUOOCKNNURZSL-IHRRRGAJSA-N 0.000 description 8
- ISVACHFCVRKIDG-SRVKXCTJSA-N Arg-Val-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O ISVACHFCVRKIDG-SRVKXCTJSA-N 0.000 description 8
- UDSVWSUXKYXSTR-QWRGUYRKSA-N Asn-Gly-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O UDSVWSUXKYXSTR-QWRGUYRKSA-N 0.000 description 8
- XLDMSQYOYXINSZ-QXEWZRGKSA-N Asn-Val-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N XLDMSQYOYXINSZ-QXEWZRGKSA-N 0.000 description 8
- MYOHQBFRJQFIDZ-KKUMJFAQSA-N Asp-Leu-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MYOHQBFRJQFIDZ-KKUMJFAQSA-N 0.000 description 8
- VSMYBNPOHYAXSD-GUBZILKMSA-N Asp-Lys-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O VSMYBNPOHYAXSD-GUBZILKMSA-N 0.000 description 8
- GPPIDDWYKJPRES-YDHLFZDLSA-N Asp-Phe-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O GPPIDDWYKJPRES-YDHLFZDLSA-N 0.000 description 8
- BKOIIURTQAJHAT-GUBZILKMSA-N Asp-Pro-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 BKOIIURTQAJHAT-GUBZILKMSA-N 0.000 description 8
- NXTYATMDWQYLGJ-BQBZGAKWSA-N Cys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CS NXTYATMDWQYLGJ-BQBZGAKWSA-N 0.000 description 8
- RSUVOPBMWMTVDI-XEGUGMAKSA-N Glu-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)C)C(O)=O)=CNC2=C1 RSUVOPBMWMTVDI-XEGUGMAKSA-N 0.000 description 8
- NCWOMXABNYEPLY-NRPADANISA-N Glu-Ala-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O NCWOMXABNYEPLY-NRPADANISA-N 0.000 description 8
- HPJLZFTUUJKWAJ-JHEQGTHGSA-N Glu-Gly-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O HPJLZFTUUJKWAJ-JHEQGTHGSA-N 0.000 description 8
- XMPAXPSENRSOSV-RYUDHWBXSA-N Glu-Gly-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XMPAXPSENRSOSV-RYUDHWBXSA-N 0.000 description 8
- TWYFJOHWGCCRIR-DCAQKATOSA-N Glu-Pro-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O TWYFJOHWGCCRIR-DCAQKATOSA-N 0.000 description 8
- VNCNWQPIQYAMAK-ACZMJKKPSA-N Glu-Ser-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O VNCNWQPIQYAMAK-ACZMJKKPSA-N 0.000 description 8
- RMWAOBGCZZSJHE-UMNHJUIQSA-N Glu-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N RMWAOBGCZZSJHE-UMNHJUIQSA-N 0.000 description 8
- 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 8
- VXKCPBPQEKKERH-IUCAKERBSA-N Gly-Arg-Pro Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N1CCC[C@H]1C(O)=O VXKCPBPQEKKERH-IUCAKERBSA-N 0.000 description 8
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 8
- QPCVIQJVRGXUSA-LURJTMIESA-N Gly-Gly-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)CNC(=O)CN QPCVIQJVRGXUSA-LURJTMIESA-N 0.000 description 8
- PFMUCCYYAAFKTH-YFKPBYRVSA-N Gly-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)CN PFMUCCYYAAFKTH-YFKPBYRVSA-N 0.000 description 8
- YHYDTTUSJXGTQK-UWVGGRQHSA-N Gly-Met-Leu Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(C)C)C(O)=O YHYDTTUSJXGTQK-UWVGGRQHSA-N 0.000 description 8
- FJWSJWACLMTDMI-WPRPVWTQSA-N Gly-Met-Val Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(O)=O FJWSJWACLMTDMI-WPRPVWTQSA-N 0.000 description 8
- HAOUOFNNJJLVNS-BQBZGAKWSA-N Gly-Pro-Ser Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O HAOUOFNNJJLVNS-BQBZGAKWSA-N 0.000 description 8
- 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 8
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 8
- BAYQNCWLXIDLHX-ONGXEEELSA-N Gly-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN BAYQNCWLXIDLHX-ONGXEEELSA-N 0.000 description 8
- BNMRSWQOHIQTFL-JSGCOSHPSA-N Gly-Val-Phe Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 BNMRSWQOHIQTFL-JSGCOSHPSA-N 0.000 description 8
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 8
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 8
- LJHGALIOHLRRQN-DCAQKATOSA-N Leu-Ala-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N LJHGALIOHLRRQN-DCAQKATOSA-N 0.000 description 8
- KWTVLKBOQATPHJ-SRVKXCTJSA-N Leu-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(C)C)N KWTVLKBOQATPHJ-SRVKXCTJSA-N 0.000 description 8
- CUXRXAIAVYLVFD-ULQDDVLXSA-N Leu-Arg-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CUXRXAIAVYLVFD-ULQDDVLXSA-N 0.000 description 8
- CLVUXCBGKUECIT-HJGDQZAQSA-N Leu-Asp-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CLVUXCBGKUECIT-HJGDQZAQSA-N 0.000 description 8
- LLBQJYDYOLIQAI-JYJNAYRXSA-N Leu-Glu-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LLBQJYDYOLIQAI-JYJNAYRXSA-N 0.000 description 8
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 8
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 8
- IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 8
- ZRHDPZAAWLXXIR-SRVKXCTJSA-N Leu-Lys-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O ZRHDPZAAWLXXIR-SRVKXCTJSA-N 0.000 description 8
- BGZCJDGBBUUBHA-KKUMJFAQSA-N Leu-Lys-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O BGZCJDGBBUUBHA-KKUMJFAQSA-N 0.000 description 8
- 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 8
- YWKNKRAKOCLOLH-OEAJRASXSA-N Leu-Phe-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CC1=CC=CC=C1 YWKNKRAKOCLOLH-OEAJRASXSA-N 0.000 description 8
- FYPWFNKQVVEELI-ULQDDVLXSA-N Leu-Phe-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=CC=C1 FYPWFNKQVVEELI-ULQDDVLXSA-N 0.000 description 8
- CHJKEDSZNSONPS-DCAQKATOSA-N Leu-Pro-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O CHJKEDSZNSONPS-DCAQKATOSA-N 0.000 description 8
- GOFJOGXGMPHOGL-DCAQKATOSA-N Leu-Ser-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(C)C GOFJOGXGMPHOGL-DCAQKATOSA-N 0.000 description 8
- 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 8
- OZTZJMUZVAVJGY-BZSNNMDCSA-N Leu-Tyr-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N OZTZJMUZVAVJGY-BZSNNMDCSA-N 0.000 description 8
- BGGTYDNTOYRTTR-MEYUZBJRSA-N Leu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(C)C)N)O BGGTYDNTOYRTTR-MEYUZBJRSA-N 0.000 description 8
- VQHUBNVKFFLWRP-ULQDDVLXSA-N Leu-Tyr-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=C(O)C=C1 VQHUBNVKFFLWRP-ULQDDVLXSA-N 0.000 description 8
- FBNPMTNBFFAMMH-UHFFFAOYSA-N Leu-Val-Arg Natural products CC(C)CC(N)C(=O)NC(C(C)C)C(=O)NC(C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-UHFFFAOYSA-N 0.000 description 8
- WGLAORUKDGRINI-WDCWCFNPSA-N Lys-Glu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGLAORUKDGRINI-WDCWCFNPSA-N 0.000 description 8
- ISHNZELVUVPCHY-ZETCQYMHSA-N Lys-Gly-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O ISHNZELVUVPCHY-ZETCQYMHSA-N 0.000 description 8
- PFZWARWVRNTPBR-IHPCNDPISA-N Lys-Leu-Trp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCCN)N PFZWARWVRNTPBR-IHPCNDPISA-N 0.000 description 8
- YSZNURNVYFUEHC-BQBZGAKWSA-N Lys-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(O)=O YSZNURNVYFUEHC-BQBZGAKWSA-N 0.000 description 8
- IEIHKHYMBIYQTH-YESZJQIVSA-N Lys-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CCCCN)N)C(=O)O IEIHKHYMBIYQTH-YESZJQIVSA-N 0.000 description 8
- WEDDFMCSUNNZJR-WDSKDSINSA-N Met-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(O)=O WEDDFMCSUNNZJR-WDSKDSINSA-N 0.000 description 8
- XPVCDCMPKCERFT-GUBZILKMSA-N Met-Ser-Arg Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XPVCDCMPKCERFT-GUBZILKMSA-N 0.000 description 8
- DSZFTPCSFVWMKP-DCAQKATOSA-N Met-Ser-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN DSZFTPCSFVWMKP-DCAQKATOSA-N 0.000 description 8
- KYXDADPHSNFWQX-VEVYYDQMSA-N Met-Thr-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O KYXDADPHSNFWQX-VEVYYDQMSA-N 0.000 description 8
- CIIJWIAORKTXAH-FJXKBIBVSA-N Met-Thr-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O CIIJWIAORKTXAH-FJXKBIBVSA-N 0.000 description 8
- MUDYEFAKNSTFAI-JYJNAYRXSA-N Met-Tyr-Val Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O MUDYEFAKNSTFAI-JYJNAYRXSA-N 0.000 description 8
- 108010079364 N-glycylalanine Proteins 0.000 description 8
- DPUOLKQSMYLRDR-UBHSHLNASA-N Phe-Arg-Ala Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 DPUOLKQSMYLRDR-UBHSHLNASA-N 0.000 description 8
- AGYXCMYVTBYGCT-ULQDDVLXSA-N Phe-Arg-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O AGYXCMYVTBYGCT-ULQDDVLXSA-N 0.000 description 8
- JEGFCFLCRSJCMA-IHRRRGAJSA-N Phe-Arg-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N JEGFCFLCRSJCMA-IHRRRGAJSA-N 0.000 description 8
- KJJROSNFBRWPHS-JYJNAYRXSA-N Phe-Glu-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KJJROSNFBRWPHS-JYJNAYRXSA-N 0.000 description 8
- BPCLGWHVPVTTFM-QWRGUYRKSA-N Phe-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O BPCLGWHVPVTTFM-QWRGUYRKSA-N 0.000 description 8
- BSKMOCNNLNDIMU-CDMKHQONSA-N Phe-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O BSKMOCNNLNDIMU-CDMKHQONSA-N 0.000 description 8
- BPIMVBKDLSBKIJ-FCLVOEFKSA-N Phe-Thr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 BPIMVBKDLSBKIJ-FCLVOEFKSA-N 0.000 description 8
- ZVJGAXNBBKPYOE-HKUYNNGSSA-N Phe-Trp-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(O)=O)C1=CC=CC=C1 ZVJGAXNBBKPYOE-HKUYNNGSSA-N 0.000 description 8
- NWVMQNAELALJFW-RNXOBYDBSA-N Phe-Trp-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 NWVMQNAELALJFW-RNXOBYDBSA-N 0.000 description 8
- JTKGCYOOJLUETJ-ULQDDVLXSA-N Phe-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 JTKGCYOOJLUETJ-ULQDDVLXSA-N 0.000 description 8
- RGMLUHANLDVMPB-ULQDDVLXSA-N Phe-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N RGMLUHANLDVMPB-ULQDDVLXSA-N 0.000 description 8
- KIZQGKLMXKGDIV-BQBZGAKWSA-N Pro-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 KIZQGKLMXKGDIV-BQBZGAKWSA-N 0.000 description 8
- NHDVNAKDACFHPX-GUBZILKMSA-N Pro-Arg-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O NHDVNAKDACFHPX-GUBZILKMSA-N 0.000 description 8
- VCYJKOLZYPYGJV-AVGNSLFASA-N Pro-Arg-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VCYJKOLZYPYGJV-AVGNSLFASA-N 0.000 description 8
- XYSXOCIWCPFOCG-IHRRRGAJSA-N Pro-Leu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XYSXOCIWCPFOCG-IHRRRGAJSA-N 0.000 description 8
- XQPHBAKJJJZOBX-SRVKXCTJSA-N Pro-Lys-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O XQPHBAKJJJZOBX-SRVKXCTJSA-N 0.000 description 8
- RPLMFKUKFZOTER-AVGNSLFASA-N Pro-Met-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1 RPLMFKUKFZOTER-AVGNSLFASA-N 0.000 description 8
- WHNJMTHJGCEKGA-ULQDDVLXSA-N Pro-Phe-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WHNJMTHJGCEKGA-ULQDDVLXSA-N 0.000 description 8
- FNGOXVQBBCMFKV-CIUDSAMLSA-N Pro-Ser-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O FNGOXVQBBCMFKV-CIUDSAMLSA-N 0.000 description 8
- MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 8
- GVUVRRPYYDHHGK-VQVTYTSYSA-N Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 GVUVRRPYYDHHGK-VQVTYTSYSA-N 0.000 description 8
- YHUBAXGAAYULJY-ULQDDVLXSA-N Pro-Tyr-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O YHUBAXGAAYULJY-ULQDDVLXSA-N 0.000 description 8
- IALSFJSONJZBKB-HRCADAONSA-N Pro-Tyr-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N3CCC[C@@H]3C(=O)O IALSFJSONJZBKB-HRCADAONSA-N 0.000 description 8
- IMNVAOPEMFDAQD-NHCYSSNCSA-N Pro-Val-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O IMNVAOPEMFDAQD-NHCYSSNCSA-N 0.000 description 8
- VDHGTOHMHHQSKG-JYJNAYRXSA-N Pro-Val-Phe Chemical compound CC(C)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O VDHGTOHMHHQSKG-JYJNAYRXSA-N 0.000 description 8
- HRNQLKCLPVKZNE-CIUDSAMLSA-N Ser-Ala-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O HRNQLKCLPVKZNE-CIUDSAMLSA-N 0.000 description 8
- 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 8
- RZEQTVHJZCIUBT-WDSKDSINSA-N Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N RZEQTVHJZCIUBT-WDSKDSINSA-N 0.000 description 8
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 8
- 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 8
- 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 8
- 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 8
- XNCUYZKGQOCOQH-YUMQZZPRSA-N Ser-Leu-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O XNCUYZKGQOCOQH-YUMQZZPRSA-N 0.000 description 8
- VZQRNAYURWAEFE-KKUMJFAQSA-N Ser-Leu-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 VZQRNAYURWAEFE-KKUMJFAQSA-N 0.000 description 8
- XNXRTQZTFVMJIJ-DCAQKATOSA-N Ser-Met-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O XNXRTQZTFVMJIJ-DCAQKATOSA-N 0.000 description 8
- UPLYXVPQLJVWMM-KKUMJFAQSA-N Ser-Phe-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O UPLYXVPQLJVWMM-KKUMJFAQSA-N 0.000 description 8
- 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 8
- HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 8
- LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 description 8
- NADLKBTYNKUJEP-KATARQTJSA-N Ser-Thr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NADLKBTYNKUJEP-KATARQTJSA-N 0.000 description 8
- ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 8
- SNXUIBACCONSOH-BWBBJGPYSA-N Ser-Thr-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CO)C(O)=O SNXUIBACCONSOH-BWBBJGPYSA-N 0.000 description 8
- OJFFAQFRCVPHNN-JYBASQMISA-N Ser-Thr-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O OJFFAQFRCVPHNN-JYBASQMISA-N 0.000 description 8
- HAYADTTXNZFUDM-IHRRRGAJSA-N Ser-Tyr-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O HAYADTTXNZFUDM-IHRRRGAJSA-N 0.000 description 8
- IGROJMCBGRFRGI-YTLHQDLWSA-N Thr-Ala-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O IGROJMCBGRFRGI-YTLHQDLWSA-N 0.000 description 8
- MQCPGOZXFSYJPS-KZVJFYERSA-N Thr-Ala-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MQCPGOZXFSYJPS-KZVJFYERSA-N 0.000 description 8
- BIENEHRYNODTLP-HJGDQZAQSA-N Thr-Glu-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)O)N)O BIENEHRYNODTLP-HJGDQZAQSA-N 0.000 description 8
- OQCXTUQTKQFDCX-HTUGSXCWSA-N Thr-Glu-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N)O OQCXTUQTKQFDCX-HTUGSXCWSA-N 0.000 description 8
- XOTBWOCSLMBGMF-SUSMZKCASA-N Thr-Glu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOTBWOCSLMBGMF-SUSMZKCASA-N 0.000 description 8
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 8
- JLNMFGCJODTXDH-WEDXCCLWSA-N Thr-Lys-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O JLNMFGCJODTXDH-WEDXCCLWSA-N 0.000 description 8
- QOLYAJSZHIJCTO-VQVTYTSYSA-N Thr-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O QOLYAJSZHIJCTO-VQVTYTSYSA-N 0.000 description 8
- CJEHCEOXPLASCK-MEYUZBJRSA-N Thr-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=C(O)C=C1 CJEHCEOXPLASCK-MEYUZBJRSA-N 0.000 description 8
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 8
- 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 8
- YTVJTXJTNRWJCR-JBACZVJFSA-N Trp-Phe-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N YTVJTXJTNRWJCR-JBACZVJFSA-N 0.000 description 8
- HTHCZRWCFXMENJ-KKUMJFAQSA-N Tyr-Arg-Glu 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](CCC(O)=O)C(O)=O HTHCZRWCFXMENJ-KKUMJFAQSA-N 0.000 description 8
- XKDOQXAXKFQWQJ-SRVKXCTJSA-N Tyr-Cys-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O XKDOQXAXKFQWQJ-SRVKXCTJSA-N 0.000 description 8
- KCPFDGNYAMKZQP-KBPBESRZSA-N Tyr-Gly-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O KCPFDGNYAMKZQP-KBPBESRZSA-N 0.000 description 8
- GULIUBBXCYPDJU-CQDKDKBSSA-N Tyr-Leu-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 GULIUBBXCYPDJU-CQDKDKBSSA-N 0.000 description 8
- DWAMXBFJNZIHMC-KBPBESRZSA-N Tyr-Leu-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O DWAMXBFJNZIHMC-KBPBESRZSA-N 0.000 description 8
- QQCCSDWLVIEPSF-BVSLBCMMSA-N Tyr-Met-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=C(O)C=C1 QQCCSDWLVIEPSF-BVSLBCMMSA-N 0.000 description 8
- 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 8
- PLVVHGFEMSDRET-IHPCNDPISA-N Tyr-Ser-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=C(C=C3)O)N PLVVHGFEMSDRET-IHPCNDPISA-N 0.000 description 8
- 108010064997 VPY tripeptide Proteins 0.000 description 8
- SMKXLHVZIFKQRB-GUBZILKMSA-N Val-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](C(C)C)N SMKXLHVZIFKQRB-GUBZILKMSA-N 0.000 description 8
- AZSHAZJLOZQYAY-FXQIFTODSA-N Val-Ala-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O AZSHAZJLOZQYAY-FXQIFTODSA-N 0.000 description 8
- DNOOLPROHJWCSQ-RCWTZXSCSA-N Val-Arg-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DNOOLPROHJWCSQ-RCWTZXSCSA-N 0.000 description 8
- LNYOXPDEIZJDEI-NHCYSSNCSA-N Val-Asn-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N LNYOXPDEIZJDEI-NHCYSSNCSA-N 0.000 description 8
- URIRWLJVWHYLET-ONGXEEELSA-N Val-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)C(C)C URIRWLJVWHYLET-ONGXEEELSA-N 0.000 description 8
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 8
- 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 8
- QPPZEDOTPZOSEC-RCWTZXSCSA-N Val-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](C(C)C)N)O QPPZEDOTPZOSEC-RCWTZXSCSA-N 0.000 description 8
- JMCOXFSCTGKLLB-FKBYEOEOSA-N Val-Phe-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N JMCOXFSCTGKLLB-FKBYEOEOSA-N 0.000 description 8
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 8
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 8
- UEXPMFIAZZHEAD-HSHDSVGOSA-N Val-Thr-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](C(C)C)N)O UEXPMFIAZZHEAD-HSHDSVGOSA-N 0.000 description 8
- PFMSJVIPEZMKSC-DZKIICNBSA-N Val-Tyr-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N PFMSJVIPEZMKSC-DZKIICNBSA-N 0.000 description 8
- PMKQKNBISAOSRI-XHSDSOJGSA-N Val-Tyr-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N PMKQKNBISAOSRI-XHSDSOJGSA-N 0.000 description 8
- 241000711975 Vesicular stomatitis virus Species 0.000 description 8
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 8
- 108010045023 alanyl-prolyl-tyrosine Proteins 0.000 description 8
- 108010087924 alanylproline Proteins 0.000 description 8
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 8
- 108010089442 arginyl-leucyl-alanyl-arginine Proteins 0.000 description 8
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 8
- 108010084758 arginyl-tyrosyl-aspartic acid Proteins 0.000 description 8
- 108010047857 aspartylglycine Proteins 0.000 description 8
- 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 8
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 8
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 8
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 8
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 8
- 108010066198 glycyl-leucyl-phenylalanine Proteins 0.000 description 8
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 8
- 108010037850 glycylvaline Proteins 0.000 description 8
- 108010076756 leucyl-alanyl-phenylalanine Proteins 0.000 description 8
- 108010051673 leucyl-glycyl-phenylalanine Proteins 0.000 description 8
- 108010030617 leucyl-phenylalanyl-valine Proteins 0.000 description 8
- 108010091871 leucylmethionine Proteins 0.000 description 8
- 108010012058 leucyltyrosine Proteins 0.000 description 8
- 210000004072 lung Anatomy 0.000 description 8
- 108010038320 lysylphenylalanine Proteins 0.000 description 8
- 108010082795 phenylalanyl-arginyl-arginine Proteins 0.000 description 8
- 108010071207 serylmethionine Proteins 0.000 description 8
- 108010071635 tyrosyl-prolyl-arginine Proteins 0.000 description 8
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 8
- BTYTYHBSJKQBQA-GCJQMDKQSA-N Ala-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)O BTYTYHBSJKQBQA-GCJQMDKQSA-N 0.000 description 7
- 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 7
- CBCCCLMNOBLBSC-XVYDVKMFSA-N Ala-His-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O CBCCCLMNOBLBSC-XVYDVKMFSA-N 0.000 description 7
- ZBLQIYPCUWZSRZ-QEJZJMRPSA-N Ala-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 ZBLQIYPCUWZSRZ-QEJZJMRPSA-N 0.000 description 7
- DCGLNNVKIZXQOJ-FXQIFTODSA-N Arg-Asn-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N DCGLNNVKIZXQOJ-FXQIFTODSA-N 0.000 description 7
- YSUVMPICYVWRBX-VEVYYDQMSA-N Arg-Asp-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O YSUVMPICYVWRBX-VEVYYDQMSA-N 0.000 description 7
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 7
- 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 7
- YCYXHLZRUSJITQ-SRVKXCTJSA-N Arg-Pro-Pro Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 YCYXHLZRUSJITQ-SRVKXCTJSA-N 0.000 description 7
- KEZVOBAKAXHMOF-GUBZILKMSA-N Arg-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N KEZVOBAKAXHMOF-GUBZILKMSA-N 0.000 description 7
- RRVBEKYEFMCDIF-WHFBIAKZSA-N Asn-Cys-Gly Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N)C(=O)N RRVBEKYEFMCDIF-WHFBIAKZSA-N 0.000 description 7
- YVXRYLVELQYAEQ-SRVKXCTJSA-N Asn-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N YVXRYLVELQYAEQ-SRVKXCTJSA-N 0.000 description 7
- HNXWVVHIGTZTBO-LKXGYXEUSA-N Asn-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O HNXWVVHIGTZTBO-LKXGYXEUSA-N 0.000 description 7
- FLJVGAFLZVBBNG-BPUTZDHNSA-N Asn-Trp-Arg Chemical compound N[C@@H](CC(=O)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O FLJVGAFLZVBBNG-BPUTZDHNSA-N 0.000 description 7
- MYRLSKYSMXNLLA-LAEOZQHASA-N Asn-Val-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MYRLSKYSMXNLLA-LAEOZQHASA-N 0.000 description 7
- XOASPVGNFAMYBD-WFBYXXMGSA-N Asp-Trp-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O XOASPVGNFAMYBD-WFBYXXMGSA-N 0.000 description 7
- GIKOVDMXBAFXDF-NHCYSSNCSA-N Asp-Val-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GIKOVDMXBAFXDF-NHCYSSNCSA-N 0.000 description 7
- TVYMKYUSZSVOAG-ZLUOBGJFSA-N Cys-Ala-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O TVYMKYUSZSVOAG-ZLUOBGJFSA-N 0.000 description 7
- KSMSFCBQBQPFAD-GUBZILKMSA-N Cys-Pro-Pro Chemical compound SC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 KSMSFCBQBQPFAD-GUBZILKMSA-N 0.000 description 7
- JIVJQYNNAYFXDG-LKXGYXEUSA-N Cys-Thr-Asn Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O JIVJQYNNAYFXDG-LKXGYXEUSA-N 0.000 description 7
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 7
- ITYRYNUZHPNCIK-GUBZILKMSA-N Glu-Ala-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O ITYRYNUZHPNCIK-GUBZILKMSA-N 0.000 description 7
- ZOXBSICWUDAOHX-GUBZILKMSA-N Glu-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCC(O)=O ZOXBSICWUDAOHX-GUBZILKMSA-N 0.000 description 7
- WATXSTJXNBOHKD-LAEOZQHASA-N Glu-Asp-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O WATXSTJXNBOHKD-LAEOZQHASA-N 0.000 description 7
- YBAFDPFAUTYYRW-YUMQZZPRSA-N Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O YBAFDPFAUTYYRW-YUMQZZPRSA-N 0.000 description 7
- VSRCAOIHMGCIJK-SRVKXCTJSA-N Glu-Leu-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VSRCAOIHMGCIJK-SRVKXCTJSA-N 0.000 description 7
- ILWHFUZZCFYSKT-AVGNSLFASA-N Glu-Lys-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O ILWHFUZZCFYSKT-AVGNSLFASA-N 0.000 description 7
- ZAPFAWQHBOHWLL-GUBZILKMSA-N Glu-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N ZAPFAWQHBOHWLL-GUBZILKMSA-N 0.000 description 7
- GUOWMVFLAJNPDY-CIUDSAMLSA-N Glu-Ser-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(O)=O GUOWMVFLAJNPDY-CIUDSAMLSA-N 0.000 description 7
- JWNZHMSRZXXGTM-XKBZYTNZSA-N Glu-Ser-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JWNZHMSRZXXGTM-XKBZYTNZSA-N 0.000 description 7
- CGWHAXBNGYQBBK-JBACZVJFSA-N Glu-Trp-Tyr Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(O)=O)N)C(O)=O)C1=CC=C(O)C=C1 CGWHAXBNGYQBBK-JBACZVJFSA-N 0.000 description 7
- UZWUBBRJWFTHTD-LAEOZQHASA-N Glu-Val-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCC(O)=O UZWUBBRJWFTHTD-LAEOZQHASA-N 0.000 description 7
- FUESBOMYALLFNI-VKHMYHEASA-N Gly-Asn Chemical compound NCC(=O)N[C@H](C(O)=O)CC(N)=O FUESBOMYALLFNI-VKHMYHEASA-N 0.000 description 7
- XRTDOIOIBMAXCT-NKWVEPMBSA-N Gly-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)CN)C(=O)O XRTDOIOIBMAXCT-NKWVEPMBSA-N 0.000 description 7
- CVFOYJJOZYYEPE-KBPBESRZSA-N Gly-Lys-Tyr Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CVFOYJJOZYYEPE-KBPBESRZSA-N 0.000 description 7
- UMRIXLHPZZIOML-OALUTQOASA-N Gly-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)CN UMRIXLHPZZIOML-OALUTQOASA-N 0.000 description 7
- FLUVGKKRRMLNPU-CQDKDKBSSA-N His-Ala-Phe Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O FLUVGKKRRMLNPU-CQDKDKBSSA-N 0.000 description 7
- ZNPRMNDAFQKATM-LKTVYLICSA-N His-Ala-Tyr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZNPRMNDAFQKATM-LKTVYLICSA-N 0.000 description 7
- DMAPKBANYNZHNR-ULQDDVLXSA-N His-Val-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N DMAPKBANYNZHNR-ULQDDVLXSA-N 0.000 description 7
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 7
- UCOCBWDBHCUPQP-DCAQKATOSA-N Leu-Arg-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O UCOCBWDBHCUPQP-DCAQKATOSA-N 0.000 description 7
- VIWUBXKCYJGNCL-SRVKXCTJSA-N Leu-Asn-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 VIWUBXKCYJGNCL-SRVKXCTJSA-N 0.000 description 7
- RZXLZBIUTDQHJQ-SRVKXCTJSA-N Leu-Lys-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O RZXLZBIUTDQHJQ-SRVKXCTJSA-N 0.000 description 7
- ZDBMWELMUCLUPL-QEJZJMRPSA-N Leu-Phe-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 ZDBMWELMUCLUPL-QEJZJMRPSA-N 0.000 description 7
- VKVDRTGWLVZJOM-DCAQKATOSA-N Leu-Val-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O VKVDRTGWLVZJOM-DCAQKATOSA-N 0.000 description 7
- PNPYKQFJGRFYJE-GUBZILKMSA-N Lys-Ala-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNPYKQFJGRFYJE-GUBZILKMSA-N 0.000 description 7
- NTSPQIONFJUMJV-AVGNSLFASA-N Lys-Arg-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O NTSPQIONFJUMJV-AVGNSLFASA-N 0.000 description 7
- CIOWSLJGLSUOME-BQBZGAKWSA-N Lys-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O CIOWSLJGLSUOME-BQBZGAKWSA-N 0.000 description 7
- DCRWPTBMWMGADO-AVGNSLFASA-N Lys-Glu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DCRWPTBMWMGADO-AVGNSLFASA-N 0.000 description 7
- ORVFEGYUJITPGI-IHRRRGAJSA-N Lys-Leu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCCCN ORVFEGYUJITPGI-IHRRRGAJSA-N 0.000 description 7
- IPSDPDAOSAEWCN-RHYQMDGZSA-N Lys-Met-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IPSDPDAOSAEWCN-RHYQMDGZSA-N 0.000 description 7
- ZUGVARDEGWMMLK-SRVKXCTJSA-N Lys-Ser-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN ZUGVARDEGWMMLK-SRVKXCTJSA-N 0.000 description 7
- DRRXXZBXDMLGFC-IHRRRGAJSA-N Lys-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN DRRXXZBXDMLGFC-IHRRRGAJSA-N 0.000 description 7
- 108010047562 NGR peptide Proteins 0.000 description 7
- 101710141454 Nucleoprotein Proteins 0.000 description 7
- ALHULIGNEXGFRM-QWRGUYRKSA-N Phe-Cys-Gly Chemical compound OC(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](N)CC1=CC=CC=C1 ALHULIGNEXGFRM-QWRGUYRKSA-N 0.000 description 7
- OQTDZEJJWWAGJT-KKUMJFAQSA-N Phe-Lys-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O OQTDZEJJWWAGJT-KKUMJFAQSA-N 0.000 description 7
- VIIRRNQMMIHYHQ-XHSDSOJGSA-N Phe-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N VIIRRNQMMIHYHQ-XHSDSOJGSA-N 0.000 description 7
- JARJPEMLQAWNBR-GUBZILKMSA-N Pro-Asp-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JARJPEMLQAWNBR-GUBZILKMSA-N 0.000 description 7
- AFXCXDQNRXTSBD-FJXKBIBVSA-N Pro-Gly-Thr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O AFXCXDQNRXTSBD-FJXKBIBVSA-N 0.000 description 7
- RVQDZELMXZRSSI-IUCAKERBSA-N Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 RVQDZELMXZRSSI-IUCAKERBSA-N 0.000 description 7
- UBRXAVQWXOWRSJ-ZLUOBGJFSA-N Ser-Asn-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CO)N)C(=O)N UBRXAVQWXOWRSJ-ZLUOBGJFSA-N 0.000 description 7
- MOVJSUIKUNCVMG-ZLUOBGJFSA-N Ser-Cys-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O)N)O MOVJSUIKUNCVMG-ZLUOBGJFSA-N 0.000 description 7
- QKQDTEYDEIJPNK-GUBZILKMSA-N Ser-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO QKQDTEYDEIJPNK-GUBZILKMSA-N 0.000 description 7
- SVWQEIRZHHNBIO-WHFBIAKZSA-N Ser-Gly-Cys Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CS)C(O)=O SVWQEIRZHHNBIO-WHFBIAKZSA-N 0.000 description 7
- 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 7
- 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 7
- HZNFKPJCGZXKIC-DCAQKATOSA-N Ser-His-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CO)N HZNFKPJCGZXKIC-DCAQKATOSA-N 0.000 description 7
- ZIFYDQAFEMIZII-GUBZILKMSA-N Ser-Leu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZIFYDQAFEMIZII-GUBZILKMSA-N 0.000 description 7
- UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 description 7
- IXZHZUGGKLRHJD-DCAQKATOSA-N Ser-Leu-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IXZHZUGGKLRHJD-DCAQKATOSA-N 0.000 description 7
- NAXBBCLCEOTAIG-RHYQMDGZSA-N Thr-Arg-Lys Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O NAXBBCLCEOTAIG-RHYQMDGZSA-N 0.000 description 7
- JBHMLZSKIXMVFS-XVSYOHENSA-N Thr-Asn-Phe 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=CC=C1)C(O)=O JBHMLZSKIXMVFS-XVSYOHENSA-N 0.000 description 7
- 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 7
- LECUEEHKUFYOOV-ZJDVBMNYSA-N Thr-Thr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](N)[C@@H](C)O LECUEEHKUFYOOV-ZJDVBMNYSA-N 0.000 description 7
- JAWUQFCGNVEDRN-MEYUZBJRSA-N Thr-Tyr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O JAWUQFCGNVEDRN-MEYUZBJRSA-N 0.000 description 7
- QAXCHNZDPLSFPC-PJODQICGSA-N Trp-Ala-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 QAXCHNZDPLSFPC-PJODQICGSA-N 0.000 description 7
- YLRLHDFMMWDYTK-KKUMJFAQSA-N Tyr-Cys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YLRLHDFMMWDYTK-KKUMJFAQSA-N 0.000 description 7
- DMWNPLOERDAHSY-MEYUZBJRSA-N Tyr-Leu-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DMWNPLOERDAHSY-MEYUZBJRSA-N 0.000 description 7
- CDKZJGMPZHPAJC-ULQDDVLXSA-N Tyr-Leu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 CDKZJGMPZHPAJC-ULQDDVLXSA-N 0.000 description 7
- ZOBLBMGJKVJVEV-BZSNNMDCSA-N Tyr-Lys-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N)O ZOBLBMGJKVJVEV-BZSNNMDCSA-N 0.000 description 7
- 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 7
- QPZMOUMNTGTEFR-ZKWXMUAHSA-N Val-Asn-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N QPZMOUMNTGTEFR-ZKWXMUAHSA-N 0.000 description 7
- IQQYYFPCWKWUHW-YDHLFZDLSA-N Val-Asn-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N IQQYYFPCWKWUHW-YDHLFZDLSA-N 0.000 description 7
- VLOYGOZDPGYWFO-LAEOZQHASA-N Val-Asp-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VLOYGOZDPGYWFO-LAEOZQHASA-N 0.000 description 7
- NXRAUQGGHPCJIB-RCOVLWMOSA-N Val-Gly-Asn Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O NXRAUQGGHPCJIB-RCOVLWMOSA-N 0.000 description 7
- ZIGZPYJXIWLQFC-QTKMDUPCSA-N Val-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C(C)C)N)O ZIGZPYJXIWLQFC-QTKMDUPCSA-N 0.000 description 7
- UOUIMEGEPSBZIV-ULQDDVLXSA-N Val-Lys-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UOUIMEGEPSBZIV-ULQDDVLXSA-N 0.000 description 7
- BGTDGENDNWGMDQ-KJEVXHAQSA-N Val-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C(C)C)N)O BGTDGENDNWGMDQ-KJEVXHAQSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 108010060035 arginylproline Proteins 0.000 description 7
- 210000003837 chick embryo Anatomy 0.000 description 7
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 7
- 108010034507 methionyltryptophan Proteins 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 108010031719 prolyl-serine Proteins 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- 108010035534 tyrosyl-leucyl-alanine Proteins 0.000 description 7
- 230000001018 virulence Effects 0.000 description 7
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 6
- WRDANSJTFOHBPI-FXQIFTODSA-N Ala-Arg-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N WRDANSJTFOHBPI-FXQIFTODSA-N 0.000 description 6
- PXKLCFFSVLKOJM-ACZMJKKPSA-N Ala-Asn-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PXKLCFFSVLKOJM-ACZMJKKPSA-N 0.000 description 6
- ZIWWTZWAKYBUOB-CIUDSAMLSA-N Ala-Asp-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O ZIWWTZWAKYBUOB-CIUDSAMLSA-N 0.000 description 6
- GRPHQEMIFDPKOE-HGNGGELXSA-N Ala-His-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O GRPHQEMIFDPKOE-HGNGGELXSA-N 0.000 description 6
- IHMCQESUJVZTKW-UBHSHLNASA-N Ala-Phe-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 IHMCQESUJVZTKW-UBHSHLNASA-N 0.000 description 6
- VRTOMXFZHGWHIJ-KZVJFYERSA-N Ala-Thr-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VRTOMXFZHGWHIJ-KZVJFYERSA-N 0.000 description 6
- YJHKTAMKPGFJCT-NRPADANISA-N Ala-Val-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O YJHKTAMKPGFJCT-NRPADANISA-N 0.000 description 6
- DFCIPNHFKOQAME-FXQIFTODSA-N Arg-Ala-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O DFCIPNHFKOQAME-FXQIFTODSA-N 0.000 description 6
- HULHGJZIZXCPLD-FXQIFTODSA-N Arg-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N HULHGJZIZXCPLD-FXQIFTODSA-N 0.000 description 6
- XVLLUZMFSAYKJV-GUBZILKMSA-N Arg-Asp-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XVLLUZMFSAYKJV-GUBZILKMSA-N 0.000 description 6
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 6
- COXMUHNBYCVVRG-DCAQKATOSA-N Arg-Leu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O COXMUHNBYCVVRG-DCAQKATOSA-N 0.000 description 6
- LRPZJPMQGKGHSG-XGEHTFHBSA-N Arg-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)O LRPZJPMQGKGHSG-XGEHTFHBSA-N 0.000 description 6
- GJFYPBDMUGGLFR-NKWVEPMBSA-N Asn-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CC(=O)N)N)C(=O)O GJFYPBDMUGGLFR-NKWVEPMBSA-N 0.000 description 6
- NCFJQJRLQJEECD-NHCYSSNCSA-N Asn-Leu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O NCFJQJRLQJEECD-NHCYSSNCSA-N 0.000 description 6
- WXVGISRWSYGEDK-KKUMJFAQSA-N Asn-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)N)N WXVGISRWSYGEDK-KKUMJFAQSA-N 0.000 description 6
- 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 6
- OOXUBGLNDRGOKT-FXQIFTODSA-N Asn-Ser-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OOXUBGLNDRGOKT-FXQIFTODSA-N 0.000 description 6
- IPPFAOCLQSGHJV-WFBYXXMGSA-N Asn-Trp-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O IPPFAOCLQSGHJV-WFBYXXMGSA-N 0.000 description 6
- SKQTXVZTCGSRJS-SRVKXCTJSA-N Asn-Tyr-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O SKQTXVZTCGSRJS-SRVKXCTJSA-N 0.000 description 6
- DATSKXOXPUAOLK-KKUMJFAQSA-N Asn-Tyr-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O DATSKXOXPUAOLK-KKUMJFAQSA-N 0.000 description 6
- QXHVOUSPVAWEMX-ZLUOBGJFSA-N Asp-Asp-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O QXHVOUSPVAWEMX-ZLUOBGJFSA-N 0.000 description 6
- KHGPWGKPYHPOIK-QWRGUYRKSA-N Asp-Gly-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KHGPWGKPYHPOIK-QWRGUYRKSA-N 0.000 description 6
- HKEZZWQWXWGASX-KKUMJFAQSA-N Asp-Leu-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 HKEZZWQWXWGASX-KKUMJFAQSA-N 0.000 description 6
- RVMXMLSYBTXCAV-VEVYYDQMSA-N Asp-Pro-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RVMXMLSYBTXCAV-VEVYYDQMSA-N 0.000 description 6
- JSHWXQIZOCVWIA-ZKWXMUAHSA-N Asp-Ser-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JSHWXQIZOCVWIA-ZKWXMUAHSA-N 0.000 description 6
- SQJSYLDKQBZQTG-FXQIFTODSA-N Cys-Asn-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N SQJSYLDKQBZQTG-FXQIFTODSA-N 0.000 description 6
- XLLSMEFANRROJE-GUBZILKMSA-N Cys-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N XLLSMEFANRROJE-GUBZILKMSA-N 0.000 description 6
- LLUXQOVDMQZMPJ-KKUMJFAQSA-N Cys-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CS)CC1=CC=C(O)C=C1 LLUXQOVDMQZMPJ-KKUMJFAQSA-N 0.000 description 6
- PCRVDEANNSYGTA-IHRRRGAJSA-N Cys-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CS)CC1=CC=C(O)C=C1 PCRVDEANNSYGTA-IHRRRGAJSA-N 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- XXCDTYBVGMPIOA-FXQIFTODSA-N Glu-Asp-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XXCDTYBVGMPIOA-FXQIFTODSA-N 0.000 description 6
- RAUDKMVXNOWDLS-WDSKDSINSA-N Glu-Gly-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O RAUDKMVXNOWDLS-WDSKDSINSA-N 0.000 description 6
- LWYUQLZOIORFFJ-XKBZYTNZSA-N Glu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O LWYUQLZOIORFFJ-XKBZYTNZSA-N 0.000 description 6
- ZALGPUWUVHOGAE-GVXVVHGQSA-N Glu-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZALGPUWUVHOGAE-GVXVVHGQSA-N 0.000 description 6
- PUUYVMYCMIWHFE-BQBZGAKWSA-N Gly-Ala-Arg Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PUUYVMYCMIWHFE-BQBZGAKWSA-N 0.000 description 6
- XCLCVBYNGXEVDU-WHFBIAKZSA-N Gly-Asn-Ser Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O XCLCVBYNGXEVDU-WHFBIAKZSA-N 0.000 description 6
- XQHSBNVACKQWAV-WHFBIAKZSA-N Gly-Asp-Asn Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O XQHSBNVACKQWAV-WHFBIAKZSA-N 0.000 description 6
- FUTAPPOITCCWTH-WHFBIAKZSA-N Gly-Asp-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FUTAPPOITCCWTH-WHFBIAKZSA-N 0.000 description 6
- LXXLEUBUOMCAMR-NKWVEPMBSA-N Gly-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)CN)C(=O)O LXXLEUBUOMCAMR-NKWVEPMBSA-N 0.000 description 6
- FQKKPCWTZZEDIC-XPUUQOCRSA-N Gly-His-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 FQKKPCWTZZEDIC-XPUUQOCRSA-N 0.000 description 6
- IUZGUFAJDBHQQV-YUMQZZPRSA-N Gly-Leu-Asn Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IUZGUFAJDBHQQV-YUMQZZPRSA-N 0.000 description 6
- LLZXNUUIBOALNY-QWRGUYRKSA-N Gly-Leu-Lys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN LLZXNUUIBOALNY-QWRGUYRKSA-N 0.000 description 6
- IEGFSKKANYKBDU-QWHCGFSZSA-N Gly-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)CN)C(=O)O IEGFSKKANYKBDU-QWHCGFSZSA-N 0.000 description 6
- YOBGUCWZPXJHTN-BQBZGAKWSA-N Gly-Ser-Arg Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YOBGUCWZPXJHTN-BQBZGAKWSA-N 0.000 description 6
- FGPLUIQCSKGLTI-WDSKDSINSA-N Gly-Ser-Glu Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O FGPLUIQCSKGLTI-WDSKDSINSA-N 0.000 description 6
- MKIAPEZXQDILRR-YUMQZZPRSA-N Gly-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)CN MKIAPEZXQDILRR-YUMQZZPRSA-N 0.000 description 6
- MVADCDSCFTXCBT-CIUDSAMLSA-N His-Asp-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O MVADCDSCFTXCBT-CIUDSAMLSA-N 0.000 description 6
- LMMPTUVWHCFTOT-GARJFASQSA-N His-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O LMMPTUVWHCFTOT-GARJFASQSA-N 0.000 description 6
- VHOLZZKNEBBHTH-YUMQZZPRSA-N His-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CNC=N1 VHOLZZKNEBBHTH-YUMQZZPRSA-N 0.000 description 6
- FDQYIRHBVVUTJF-ZETCQYMHSA-N His-Gly-Gly Chemical compound [O-]C(=O)CNC(=O)CNC(=O)[C@@H]([NH3+])CC1=CN=CN1 FDQYIRHBVVUTJF-ZETCQYMHSA-N 0.000 description 6
- MMFKFJORZBJVNF-UWVGGRQHSA-N His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MMFKFJORZBJVNF-UWVGGRQHSA-N 0.000 description 6
- RNMNYMDTESKEAJ-KKUMJFAQSA-N His-Leu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 RNMNYMDTESKEAJ-KKUMJFAQSA-N 0.000 description 6
- SGLXGEDPYJPGIQ-ACRUOGEOSA-N His-Phe-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)NC(=O)[C@H](CC3=CN=CN3)N SGLXGEDPYJPGIQ-ACRUOGEOSA-N 0.000 description 6
- PYNPBMCLAKTHJL-SRVKXCTJSA-N His-Pro-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O PYNPBMCLAKTHJL-SRVKXCTJSA-N 0.000 description 6
- 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 6
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 6
- 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 6
- OGCQGUIWMSBHRZ-CIUDSAMLSA-N Leu-Asn-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OGCQGUIWMSBHRZ-CIUDSAMLSA-N 0.000 description 6
- TWQIYNGNYNJUFM-NHCYSSNCSA-N Leu-Asn-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O TWQIYNGNYNJUFM-NHCYSSNCSA-N 0.000 description 6
- DLCOFDAHNMMQPP-SRVKXCTJSA-N Leu-Asp-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DLCOFDAHNMMQPP-SRVKXCTJSA-N 0.000 description 6
- CSFVADKICPDRRF-KKUMJFAQSA-N Leu-His-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CN=CN1 CSFVADKICPDRRF-KKUMJFAQSA-N 0.000 description 6
- 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 6
- LZHJZLHSRGWBBE-IHRRRGAJSA-N Leu-Lys-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LZHJZLHSRGWBBE-IHRRRGAJSA-N 0.000 description 6
- IBSGMIPRBMPMHE-IHRRRGAJSA-N Leu-Met-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(O)=O IBSGMIPRBMPMHE-IHRRRGAJSA-N 0.000 description 6
- KWLWZYMNUZJKMZ-IHRRRGAJSA-N Leu-Pro-Leu Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O KWLWZYMNUZJKMZ-IHRRRGAJSA-N 0.000 description 6
- KIZIOFNVSOSKJI-CIUDSAMLSA-N Leu-Ser-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N KIZIOFNVSOSKJI-CIUDSAMLSA-N 0.000 description 6
- ADJWHHZETYAAAX-SRVKXCTJSA-N Leu-Ser-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N ADJWHHZETYAAAX-SRVKXCTJSA-N 0.000 description 6
- SVBJIZVVYJYGLA-DCAQKATOSA-N Leu-Ser-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O SVBJIZVVYJYGLA-DCAQKATOSA-N 0.000 description 6
- KPJJOZUXFOLGMQ-CIUDSAMLSA-N Lys-Asp-Asn Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N KPJJOZUXFOLGMQ-CIUDSAMLSA-N 0.000 description 6
- 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 6
- GQFDWEDHOQRNLC-QWRGUYRKSA-N Lys-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN GQFDWEDHOQRNLC-QWRGUYRKSA-N 0.000 description 6
- CANPXOLVTMKURR-WEDXCCLWSA-N Lys-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN CANPXOLVTMKURR-WEDXCCLWSA-N 0.000 description 6
- PINHPJWGVBKQII-SRVKXCTJSA-N Lys-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N PINHPJWGVBKQII-SRVKXCTJSA-N 0.000 description 6
- OIQSIMFSVLLWBX-VOAKCMCISA-N Lys-Leu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OIQSIMFSVLLWBX-VOAKCMCISA-N 0.000 description 6
- OZVXDDFYCQOPFD-XQQFMLRXSA-N Lys-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N OZVXDDFYCQOPFD-XQQFMLRXSA-N 0.000 description 6
- GILLQRYAWOMHED-DCAQKATOSA-N Lys-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN GILLQRYAWOMHED-DCAQKATOSA-N 0.000 description 6
- SQUTUWHAAWJYES-GUBZILKMSA-N Met-Asp-Arg Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SQUTUWHAAWJYES-GUBZILKMSA-N 0.000 description 6
- HSJIGJRZYUADSS-IHRRRGAJSA-N Met-Lys-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HSJIGJRZYUADSS-IHRRRGAJSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 108060004795 Methyltransferase Proteins 0.000 description 6
- 108700026244 Open Reading Frames Proteins 0.000 description 6
- LDSOBEJVGGVWGD-DLOVCJGASA-N Phe-Asp-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 LDSOBEJVGGVWGD-DLOVCJGASA-N 0.000 description 6
- FRPVPGRXUKFEQE-YDHLFZDLSA-N Phe-Asp-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O FRPVPGRXUKFEQE-YDHLFZDLSA-N 0.000 description 6
- XEXSSIBQYNKFBX-KBPBESRZSA-N Phe-Gly-His Chemical compound C([C@H](N)C(=O)NCC(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)C1=CC=CC=C1 XEXSSIBQYNKFBX-KBPBESRZSA-N 0.000 description 6
- PMKIMKUGCSVFSV-CQDKDKBSSA-N Phe-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC2=CC=CC=C2)N PMKIMKUGCSVFSV-CQDKDKBSSA-N 0.000 description 6
- 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 6
- GPSMLZQVIIYLDK-ULQDDVLXSA-N Phe-Lys-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O GPSMLZQVIIYLDK-ULQDDVLXSA-N 0.000 description 6
- JLLJTMHNXQTMCK-UBHSHLNASA-N Phe-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 JLLJTMHNXQTMCK-UBHSHLNASA-N 0.000 description 6
- KQUMFXGQTSAEJE-PMVMPFDFSA-N Phe-Trp-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=CC=C1 KQUMFXGQTSAEJE-PMVMPFDFSA-N 0.000 description 6
- MTHRMUXESFIAMS-DCAQKATOSA-N Pro-Asn-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O MTHRMUXESFIAMS-DCAQKATOSA-N 0.000 description 6
- ULIWFCCJIOEHMU-BQBZGAKWSA-N Pro-Gly-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 ULIWFCCJIOEHMU-BQBZGAKWSA-N 0.000 description 6
- VYWNORHENYEQDW-YUMQZZPRSA-N Pro-Gly-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 VYWNORHENYEQDW-YUMQZZPRSA-N 0.000 description 6
- VTFXTWDFPTWNJY-RHYQMDGZSA-N Pro-Leu-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VTFXTWDFPTWNJY-RHYQMDGZSA-N 0.000 description 6
- QHSSUIHLAIWXEE-IHRRRGAJSA-N Pro-Tyr-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O QHSSUIHLAIWXEE-IHRRRGAJSA-N 0.000 description 6
- LTFSLKWFMWZEBD-IMJSIDKUSA-N Ser-Asn Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(N)=O LTFSLKWFMWZEBD-IMJSIDKUSA-N 0.000 description 6
- VAUMZJHYZQXZBQ-WHFBIAKZSA-N Ser-Asn-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O VAUMZJHYZQXZBQ-WHFBIAKZSA-N 0.000 description 6
- UGJRQLURDVGULT-LKXGYXEUSA-N Ser-Asn-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UGJRQLURDVGULT-LKXGYXEUSA-N 0.000 description 6
- OWCVUSJMEBGMOK-YUMQZZPRSA-N Ser-Lys-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O OWCVUSJMEBGMOK-YUMQZZPRSA-N 0.000 description 6
- JLKWJWPDXPKKHI-FXQIFTODSA-N Ser-Pro-Asn Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CC(=O)N)C(=O)O JLKWJWPDXPKKHI-FXQIFTODSA-N 0.000 description 6
- RXUOAOOZIWABBW-XGEHTFHBSA-N Ser-Thr-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RXUOAOOZIWABBW-XGEHTFHBSA-N 0.000 description 6
- YXEYTHXDRDAIOJ-CWRNSKLLSA-N Ser-Trp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CO)N)C(=O)O YXEYTHXDRDAIOJ-CWRNSKLLSA-N 0.000 description 6
- SIEBDTCABMZCLF-XGEHTFHBSA-N Ser-Val-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SIEBDTCABMZCLF-XGEHTFHBSA-N 0.000 description 6
- VIBXMCZWVUOZLA-OLHMAJIHSA-N Thr-Asn-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O VIBXMCZWVUOZLA-OLHMAJIHSA-N 0.000 description 6
- YBXMGKCLOPDEKA-NUMRIWBASA-N Thr-Asp-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YBXMGKCLOPDEKA-NUMRIWBASA-N 0.000 description 6
- SXAGUVRFGJSFKC-ZEILLAHLSA-N Thr-His-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SXAGUVRFGJSFKC-ZEILLAHLSA-N 0.000 description 6
- XIULAFZYEKSGAJ-IXOXFDKPSA-N Thr-Leu-His Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 XIULAFZYEKSGAJ-IXOXFDKPSA-N 0.000 description 6
- 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 6
- IQXWAJUIAQLZNX-IHPCNDPISA-N Trp-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N IQXWAJUIAQLZNX-IHPCNDPISA-N 0.000 description 6
- GZOCMHSZGGJBCX-ULQDDVLXSA-N Tyr-Lys-Met Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(O)=O GZOCMHSZGGJBCX-ULQDDVLXSA-N 0.000 description 6
- RGYCVIZZTUBSSG-JYJNAYRXSA-N Tyr-Pro-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O RGYCVIZZTUBSSG-JYJNAYRXSA-N 0.000 description 6
- YDPFWRVQHFWBKI-GVXVVHGQSA-N Val-Glu-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N YDPFWRVQHFWBKI-GVXVVHGQSA-N 0.000 description 6
- AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 6
- VPGCVZRRBYOGCD-AVGNSLFASA-N Val-Lys-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O VPGCVZRRBYOGCD-AVGNSLFASA-N 0.000 description 6
- OFTXTCGQJXTNQS-XGEHTFHBSA-N Val-Thr-Ser Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](C(C)C)N)O OFTXTCGQJXTNQS-XGEHTFHBSA-N 0.000 description 6
- STTYIMSDIYISRG-UHFFFAOYSA-N Valyl-Serine Chemical compound CC(C)C(N)C(=O)NC(CO)C(O)=O STTYIMSDIYISRG-UHFFFAOYSA-N 0.000 description 6
- 108010067390 Viral Proteins Proteins 0.000 description 6
- 108010011559 alanylphenylalanine Proteins 0.000 description 6
- 125000003275 alpha amino acid group Chemical group 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 238000002649 immunization Methods 0.000 description 6
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 238000012163 sequencing technique Methods 0.000 description 6
- 108010026333 seryl-proline Proteins 0.000 description 6
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 6
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 229940125575 vaccine candidate Drugs 0.000 description 6
- 108010000998 wheylin-2 peptide Proteins 0.000 description 6
- FJVAQLJNTSUQPY-CIUDSAMLSA-N Ala-Ala-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN FJVAQLJNTSUQPY-CIUDSAMLSA-N 0.000 description 5
- ZPXCNXMJEZKRLU-LSJOCFKGSA-N Ala-His-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CN=CN1 ZPXCNXMJEZKRLU-LSJOCFKGSA-N 0.000 description 5
- OQWQTGBOFPJOIF-DLOVCJGASA-N Ala-Lys-His Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N OQWQTGBOFPJOIF-DLOVCJGASA-N 0.000 description 5
- NVCIXQYNWYTLDO-IHRRRGAJSA-N Arg-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCCN=C(N)N)N NVCIXQYNWYTLDO-IHRRRGAJSA-N 0.000 description 5
- RTDZQOFEGPWSJD-AVGNSLFASA-N Arg-Leu-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O RTDZQOFEGPWSJD-AVGNSLFASA-N 0.000 description 5
- FSNVAJOPUDVQAR-AVGNSLFASA-N Arg-Lys-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FSNVAJOPUDVQAR-AVGNSLFASA-N 0.000 description 5
- MFFOYNGMOYFPBD-DCAQKATOSA-N Asn-Arg-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O MFFOYNGMOYFPBD-DCAQKATOSA-N 0.000 description 5
- DQTIWTULBGLJBL-DCAQKATOSA-N Asn-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)N)N DQTIWTULBGLJBL-DCAQKATOSA-N 0.000 description 5
- HLTLEIXYIJDFOY-ZLUOBGJFSA-N Asn-Cys-Asn Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O HLTLEIXYIJDFOY-ZLUOBGJFSA-N 0.000 description 5
- IIFDPDVJAHQFSR-WHFBIAKZSA-N Asn-Glu Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O IIFDPDVJAHQFSR-WHFBIAKZSA-N 0.000 description 5
- PNHQRQTVBRDIEF-CIUDSAMLSA-N Asn-Leu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)N)N PNHQRQTVBRDIEF-CIUDSAMLSA-N 0.000 description 5
- MYCSPQIARXTUTP-SRVKXCTJSA-N Asn-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(=O)N)N MYCSPQIARXTUTP-SRVKXCTJSA-N 0.000 description 5
- 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 5
- VLDRQOHCMKCXLY-SRVKXCTJSA-N Asn-Ser-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O VLDRQOHCMKCXLY-SRVKXCTJSA-N 0.000 description 5
- NSTBNYOKCZKOMI-AVGNSLFASA-N Asn-Tyr-Glu Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O NSTBNYOKCZKOMI-AVGNSLFASA-N 0.000 description 5
- UWMIZBCTVWVMFI-FXQIFTODSA-N Asp-Ala-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UWMIZBCTVWVMFI-FXQIFTODSA-N 0.000 description 5
- ZLGKHJHFYSRUBH-FXQIFTODSA-N Asp-Arg-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLGKHJHFYSRUBH-FXQIFTODSA-N 0.000 description 5
- ILJQISGMGXRZQQ-IHRRRGAJSA-N Asp-Arg-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ILJQISGMGXRZQQ-IHRRRGAJSA-N 0.000 description 5
- 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 5
- CJUKAWUWBZCTDQ-SRVKXCTJSA-N Asp-Leu-Lys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O CJUKAWUWBZCTDQ-SRVKXCTJSA-N 0.000 description 5
- QNMKWNONJGKJJC-NHCYSSNCSA-N Asp-Leu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O QNMKWNONJGKJJC-NHCYSSNCSA-N 0.000 description 5
- MYLZFUMPZCPJCJ-NHCYSSNCSA-N Asp-Lys-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O MYLZFUMPZCPJCJ-NHCYSSNCSA-N 0.000 description 5
- HRVQDZOWMLFAOD-BIIVOSGPSA-N Asp-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N)C(=O)O HRVQDZOWMLFAOD-BIIVOSGPSA-N 0.000 description 5
- SFJUYBCDQBAYAJ-YDHLFZDLSA-N Asp-Val-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SFJUYBCDQBAYAJ-YDHLFZDLSA-N 0.000 description 5
- 241000711404 Avian avulavirus 1 Species 0.000 description 5
- BCSYBBMFGLHCOA-ACZMJKKPSA-N Cys-Glu-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(O)=O BCSYBBMFGLHCOA-ACZMJKKPSA-N 0.000 description 5
- ANPADMNVVOOYKW-DCAQKATOSA-N Cys-His-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ANPADMNVVOOYKW-DCAQKATOSA-N 0.000 description 5
- QQOWCDCBFFBRQH-IXOXFDKPSA-N Cys-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CS)N)O QQOWCDCBFFBRQH-IXOXFDKPSA-N 0.000 description 5
- DGQJGBDBFVGLGL-ZKWXMUAHSA-N Cys-Val-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N DGQJGBDBFVGLGL-ZKWXMUAHSA-N 0.000 description 5
- HJIFPJUEOGZWRI-GUBZILKMSA-N Glu-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N HJIFPJUEOGZWRI-GUBZILKMSA-N 0.000 description 5
- MRWYPDWDZSLWJM-ACZMJKKPSA-N Glu-Ser-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O MRWYPDWDZSLWJM-ACZMJKKPSA-N 0.000 description 5
- JSIQVRIXMINMTA-ZDLURKLDSA-N Glu-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O JSIQVRIXMINMTA-ZDLURKLDSA-N 0.000 description 5
- DTLLNDVORUEOTM-WDCWCFNPSA-N Glu-Thr-Lys Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O DTLLNDVORUEOTM-WDCWCFNPSA-N 0.000 description 5
- PAWIVEIWWYGBAM-YUMQZZPRSA-N Gly-Leu-Ala Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O PAWIVEIWWYGBAM-YUMQZZPRSA-N 0.000 description 5
- GGAPHLIUUTVYMX-QWRGUYRKSA-N Gly-Phe-Ser Chemical compound OC[C@@H](C([O-])=O)NC(=O)[C@@H](NC(=O)C[NH3+])CC1=CC=CC=C1 GGAPHLIUUTVYMX-QWRGUYRKSA-N 0.000 description 5
- 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 5
- JFFAPRNXXLRINI-NHCYSSNCSA-N His-Asp-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O JFFAPRNXXLRINI-NHCYSSNCSA-N 0.000 description 5
- WYWBYSPRCFADBM-GARJFASQSA-N His-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O WYWBYSPRCFADBM-GARJFASQSA-N 0.000 description 5
- LVWIJITYHRZHBO-IXOXFDKPSA-N His-Leu-Thr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LVWIJITYHRZHBO-IXOXFDKPSA-N 0.000 description 5
- SOYCWSKCUVDLMC-AVGNSLFASA-N His-Pro-Arg Chemical compound N[C@@H](Cc1cnc[nH]1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(=N)N)C(=O)O SOYCWSKCUVDLMC-AVGNSLFASA-N 0.000 description 5
- STGQSBKUYSPPIG-CIUDSAMLSA-N His-Ser-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CN=CN1 STGQSBKUYSPPIG-CIUDSAMLSA-N 0.000 description 5
- QTMKFZAYZKBFRC-BZSNNMDCSA-N His-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CC3=CN=CN3)N)O QTMKFZAYZKBFRC-BZSNNMDCSA-N 0.000 description 5
- SYPULFZAGBBIOM-GVXVVHGQSA-N His-Val-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N SYPULFZAGBBIOM-GVXVVHGQSA-N 0.000 description 5
- VCSBGUACOYUIGD-CIUDSAMLSA-N Leu-Asn-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VCSBGUACOYUIGD-CIUDSAMLSA-N 0.000 description 5
- DLFAACQHIRSQGG-CIUDSAMLSA-N Leu-Asp-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O DLFAACQHIRSQGG-CIUDSAMLSA-N 0.000 description 5
- ZDSNOSQHMJBRQN-SRVKXCTJSA-N Leu-Asp-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N ZDSNOSQHMJBRQN-SRVKXCTJSA-N 0.000 description 5
- WCTCIIAGNMFYAO-DCAQKATOSA-N Leu-Cys-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O WCTCIIAGNMFYAO-DCAQKATOSA-N 0.000 description 5
- AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 description 5
- KCXUCYYZNZFGLL-SRVKXCTJSA-N Lys-Ala-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O KCXUCYYZNZFGLL-SRVKXCTJSA-N 0.000 description 5
- YNNPKXBBRZVIRX-IHRRRGAJSA-N Lys-Arg-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O YNNPKXBBRZVIRX-IHRRRGAJSA-N 0.000 description 5
- CKSXSQUVEYCDIW-AVGNSLFASA-N Lys-Arg-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)N CKSXSQUVEYCDIW-AVGNSLFASA-N 0.000 description 5
- ZAWOJFFMBANLGE-CIUDSAMLSA-N Lys-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N ZAWOJFFMBANLGE-CIUDSAMLSA-N 0.000 description 5
- KNKJPYAZQUFLQK-IHRRRGAJSA-N Lys-His-Arg Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCCCN)N KNKJPYAZQUFLQK-IHRRRGAJSA-N 0.000 description 5
- LJADEBULDNKJNK-IHRRRGAJSA-N Lys-Leu-Val Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LJADEBULDNKJNK-IHRRRGAJSA-N 0.000 description 5
- QLFAPXUXEBAWEK-NHCYSSNCSA-N Lys-Val-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QLFAPXUXEBAWEK-NHCYSSNCSA-N 0.000 description 5
- TZLYIHDABYBOCJ-FXQIFTODSA-N Met-Asp-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O TZLYIHDABYBOCJ-FXQIFTODSA-N 0.000 description 5
- SRILZRSXIKRGBF-HRCADAONSA-N Phe-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N SRILZRSXIKRGBF-HRCADAONSA-N 0.000 description 5
- ROHDXJUFQVRDAV-UWVGGRQHSA-N Phe-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 ROHDXJUFQVRDAV-UWVGGRQHSA-N 0.000 description 5
- CPRLKHJUFAXVTD-ULQDDVLXSA-N Pro-Leu-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CPRLKHJUFAXVTD-ULQDDVLXSA-N 0.000 description 5
- 108010079005 RDV peptide Proteins 0.000 description 5
- BYIROAKULFFTEK-CIUDSAMLSA-N Ser-Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO BYIROAKULFFTEK-CIUDSAMLSA-N 0.000 description 5
- QBUWQRKEHJXTOP-DCAQKATOSA-N Ser-His-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QBUWQRKEHJXTOP-DCAQKATOSA-N 0.000 description 5
- NQZFFLBPNDLTPO-DLOVCJGASA-N Ser-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)N NQZFFLBPNDLTPO-DLOVCJGASA-N 0.000 description 5
- WBAXJMCUFIXCNI-WDSKDSINSA-N Ser-Pro Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WBAXJMCUFIXCNI-WDSKDSINSA-N 0.000 description 5
- AXKJPUBALUNJEO-UBHSHLNASA-N Ser-Trp-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(O)=O AXKJPUBALUNJEO-UBHSHLNASA-N 0.000 description 5
- HYLXOQURIOCKIH-VQVTYTSYSA-N Thr-Arg Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N HYLXOQURIOCKIH-VQVTYTSYSA-N 0.000 description 5
- GLQFKOVWXPPFTP-VEVYYDQMSA-N Thr-Arg-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GLQFKOVWXPPFTP-VEVYYDQMSA-N 0.000 description 5
- SKHPKKYKDYULDH-HJGDQZAQSA-N Thr-Asn-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O SKHPKKYKDYULDH-HJGDQZAQSA-N 0.000 description 5
- MECLEFZMPPOEAC-VOAKCMCISA-N Thr-Leu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MECLEFZMPPOEAC-VOAKCMCISA-N 0.000 description 5
- SCCKSNREWHMKOJ-SRVKXCTJSA-N Tyr-Asn-Ser Chemical compound N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O SCCKSNREWHMKOJ-SRVKXCTJSA-N 0.000 description 5
- DANHCMVVXDXOHN-SRVKXCTJSA-N Tyr-Asp-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DANHCMVVXDXOHN-SRVKXCTJSA-N 0.000 description 5
- AKLNEFNQWLHIGY-QWRGUYRKSA-N Tyr-Gly-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N)O AKLNEFNQWLHIGY-QWRGUYRKSA-N 0.000 description 5
- FGVFBDZSGQTYQX-UFYCRDLUSA-N Tyr-Phe-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O FGVFBDZSGQTYQX-UFYCRDLUSA-N 0.000 description 5
- LVFZXRQQQDTBQH-IRIUXVKKSA-N Tyr-Thr-Glu 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](CCC(O)=O)C(O)=O LVFZXRQQQDTBQH-IRIUXVKKSA-N 0.000 description 5
- 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 5
- FOADDSDHGRFUOC-DZKIICNBSA-N Val-Glu-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N FOADDSDHGRFUOC-DZKIICNBSA-N 0.000 description 5
- BGXVHVMJZCSOCA-AVGNSLFASA-N Val-Pro-Lys Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)O)N BGXVHVMJZCSOCA-AVGNSLFASA-N 0.000 description 5
- KSFXWENSJABBFI-ZKWXMUAHSA-N Val-Ser-Asn Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KSFXWENSJABBFI-ZKWXMUAHSA-N 0.000 description 5
- PQSNETRGCRUOGP-KKHAAJSZSA-N Val-Thr-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(N)=O PQSNETRGCRUOGP-KKHAAJSZSA-N 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 108010018006 histidylserine Proteins 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 208000030500 lower respiratory tract disease Diseases 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 108010051242 phenylalanylserine Proteins 0.000 description 5
- 230000008488 polyadenylation Effects 0.000 description 5
- 108010029020 prolylglycine Proteins 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000002103 transcriptional effect Effects 0.000 description 5
- 108010051110 tyrosyl-lysine Proteins 0.000 description 5
- FXKNPWNXPQZLES-ZLUOBGJFSA-N Ala-Asn-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O FXKNPWNXPQZLES-ZLUOBGJFSA-N 0.000 description 4
- WYBVBIHNJWOLCJ-IUCAKERBSA-N Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N WYBVBIHNJWOLCJ-IUCAKERBSA-N 0.000 description 4
- WMEVEPXNCMKNGH-IHRRRGAJSA-N Arg-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N WMEVEPXNCMKNGH-IHRRRGAJSA-N 0.000 description 4
- DNLQVHBBMPZUGJ-BQBZGAKWSA-N Arg-Ser-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O DNLQVHBBMPZUGJ-BQBZGAKWSA-N 0.000 description 4
- WCZXPVPHUMYLMS-VEVYYDQMSA-N Arg-Thr-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O WCZXPVPHUMYLMS-VEVYYDQMSA-N 0.000 description 4
- WIDVAWAQBRAKTI-YUMQZZPRSA-N Asn-Leu-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O WIDVAWAQBRAKTI-YUMQZZPRSA-N 0.000 description 4
- ATHZHGQSAIJHQU-XIRDDKMYSA-N Asn-Trp-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ATHZHGQSAIJHQU-XIRDDKMYSA-N 0.000 description 4
- QCLHLXDWRKOHRR-GUBZILKMSA-N Asp-Glu-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)N QCLHLXDWRKOHRR-GUBZILKMSA-N 0.000 description 4
- LNENWJXDHCFVOF-DCAQKATOSA-N Asp-His-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)O)N LNENWJXDHCFVOF-DCAQKATOSA-N 0.000 description 4
- ORRJQLIATJDMQM-HJGDQZAQSA-N Asp-Leu-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O ORRJQLIATJDMQM-HJGDQZAQSA-N 0.000 description 4
- GGRSYTUJHAZTFN-IHRRRGAJSA-N Asp-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O GGRSYTUJHAZTFN-IHRRRGAJSA-N 0.000 description 4
- VNXQRBXEQXLERQ-CIUDSAMLSA-N Asp-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N VNXQRBXEQXLERQ-CIUDSAMLSA-N 0.000 description 4
- IWLZBRTUIVXZJD-OLHMAJIHSA-N Asp-Thr-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O IWLZBRTUIVXZJD-OLHMAJIHSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 108091006027 G proteins Proteins 0.000 description 4
- 102000030782 GTP binding Human genes 0.000 description 4
- 108091000058 GTP-Binding Proteins 0.000 description 4
- TVUWMSBGMVAHSJ-KBPBESRZSA-N Gly-Leu-Phe Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 TVUWMSBGMVAHSJ-KBPBESRZSA-N 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- JWTKVPMQCCRPQY-SRVKXCTJSA-N His-Asn-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JWTKVPMQCCRPQY-SRVKXCTJSA-N 0.000 description 4
- VIJMRAIWYWRXSR-CIUDSAMLSA-N His-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CN=CN1 VIJMRAIWYWRXSR-CIUDSAMLSA-N 0.000 description 4
- POZULHZYLPGXMR-ONGXEEELSA-N Leu-Gly-Val Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O POZULHZYLPGXMR-ONGXEEELSA-N 0.000 description 4
- URHJPNHRQMQGOZ-RHYQMDGZSA-N Leu-Thr-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(O)=O URHJPNHRQMQGOZ-RHYQMDGZSA-N 0.000 description 4
- HGLKOTPFWOMPOB-MEYUZBJRSA-N Leu-Thr-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HGLKOTPFWOMPOB-MEYUZBJRSA-N 0.000 description 4
- YIBOAHAOAWACDK-QEJZJMRPSA-N Lys-Ala-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YIBOAHAOAWACDK-QEJZJMRPSA-N 0.000 description 4
- 241000282560 Macaca mulatta Species 0.000 description 4
- 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 4
- 241000711408 Murine respirovirus Species 0.000 description 4
- 101710144128 Non-structural protein 2 Proteins 0.000 description 4
- 101710199667 Nuclear export protein Proteins 0.000 description 4
- PSKRILMFHNIUAO-JYJNAYRXSA-N Phe-Glu-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N PSKRILMFHNIUAO-JYJNAYRXSA-N 0.000 description 4
- FXYXBEZMRACDDR-KKUMJFAQSA-N Phe-His-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(O)=O FXYXBEZMRACDDR-KKUMJFAQSA-N 0.000 description 4
- KPDRZQUWJKTMBP-DCAQKATOSA-N Pro-Asp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1 KPDRZQUWJKTMBP-DCAQKATOSA-N 0.000 description 4
- XQSREVQDGCPFRJ-STQMWFEESA-N Pro-Gly-Phe Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O XQSREVQDGCPFRJ-STQMWFEESA-N 0.000 description 4
- 208000035415 Reinfection Diseases 0.000 description 4
- 102000004389 Ribonucleoproteins Human genes 0.000 description 4
- 108010081734 Ribonucleoproteins Proteins 0.000 description 4
- 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 4
- VBKBDLMWICBSCY-IMJSIDKUSA-N Ser-Asp Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O VBKBDLMWICBSCY-IMJSIDKUSA-N 0.000 description 4
- BGOWRLSWJCVYAQ-CIUDSAMLSA-N Ser-Asp-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O BGOWRLSWJCVYAQ-CIUDSAMLSA-N 0.000 description 4
- QYSFWUIXDFJUDW-DCAQKATOSA-N Ser-Leu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYSFWUIXDFJUDW-DCAQKATOSA-N 0.000 description 4
- PPQRSMGDOHLTBE-UWVGGRQHSA-N Ser-Phe Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PPQRSMGDOHLTBE-UWVGGRQHSA-N 0.000 description 4
- YOSLMIPKOUAHKI-OLHMAJIHSA-N Thr-Asp-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O YOSLMIPKOUAHKI-OLHMAJIHSA-N 0.000 description 4
- NLJKZUGAIIRWJN-LKXGYXEUSA-N Thr-Asp-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)O NLJKZUGAIIRWJN-LKXGYXEUSA-N 0.000 description 4
- BVOVIGCHYNFJBZ-JXUBOQSCSA-N Thr-Leu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O BVOVIGCHYNFJBZ-JXUBOQSCSA-N 0.000 description 4
- FDQXPJCLVPFKJW-KJEVXHAQSA-N Thr-Met-Tyr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N)O FDQXPJCLVPFKJW-KJEVXHAQSA-N 0.000 description 4
- WPSKTVVMQCXPRO-BWBBJGPYSA-N Thr-Ser-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WPSKTVVMQCXPRO-BWBBJGPYSA-N 0.000 description 4
- PDSLRCZINIDLMU-QWRGUYRKSA-N Tyr-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PDSLRCZINIDLMU-QWRGUYRKSA-N 0.000 description 4
- KXUKIBHIVRYOIP-ZKWXMUAHSA-N Val-Asp-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N KXUKIBHIVRYOIP-ZKWXMUAHSA-N 0.000 description 4
- DDNIHOWRDOXXPF-NGZCFLSTSA-N Val-Asp-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N DDNIHOWRDOXXPF-NGZCFLSTSA-N 0.000 description 4
- DJEVQCWNMQOABE-RCOVLWMOSA-N Val-Gly-Asp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N DJEVQCWNMQOABE-RCOVLWMOSA-N 0.000 description 4
- QWCZXKIFPWPQHR-JYJNAYRXSA-N Val-Pro-Tyr Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QWCZXKIFPWPQHR-JYJNAYRXSA-N 0.000 description 4
- PDASTHRLDFOZMG-JYJNAYRXSA-N Val-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=C(O)C=C1 PDASTHRLDFOZMG-JYJNAYRXSA-N 0.000 description 4
- 230000006978 adaptation Effects 0.000 description 4
- 230000000890 antigenic effect Effects 0.000 description 4
- 108010029539 arginyl-prolyl-proline Proteins 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 108010017391 lysylvaline Proteins 0.000 description 4
- 229940041323 measles vaccine Drugs 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 108010018625 phenylalanylarginine Proteins 0.000 description 4
- 230000003362 replicative effect Effects 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 229940031626 subunit vaccine Drugs 0.000 description 4
- 230000005030 transcription termination Effects 0.000 description 4
- 108010009962 valyltyrosine Proteins 0.000 description 4
- 108010027345 wheylin-1 peptide Proteins 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- FBLMOFHNVQBKRR-IHRRRGAJSA-N Arg-Asp-Tyr Chemical compound NC(N)=NCCC[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 FBLMOFHNVQBKRR-IHRRRGAJSA-N 0.000 description 3
- OTZMRMHZCMZOJZ-SRVKXCTJSA-N Arg-Leu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O OTZMRMHZCMZOJZ-SRVKXCTJSA-N 0.000 description 3
- UZGFHWIJWPUPOH-IHRRRGAJSA-N Arg-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UZGFHWIJWPUPOH-IHRRRGAJSA-N 0.000 description 3
- KLKHFFMNGWULBN-VKHMYHEASA-N Asn-Gly Chemical compound NC(=O)C[C@H](N)C(=O)NCC(O)=O KLKHFFMNGWULBN-VKHMYHEASA-N 0.000 description 3
- JQSWHKKUZMTOIH-QWRGUYRKSA-N Asn-Gly-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N JQSWHKKUZMTOIH-QWRGUYRKSA-N 0.000 description 3
- HMUKKNAMNSXDBB-CIUDSAMLSA-N Asn-Met-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(O)=O HMUKKNAMNSXDBB-CIUDSAMLSA-N 0.000 description 3
- AMGQTNHANMRPOE-LKXGYXEUSA-N Asn-Thr-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O AMGQTNHANMRPOE-LKXGYXEUSA-N 0.000 description 3
- CBHVAFXKOYAHOY-NHCYSSNCSA-N Asn-Val-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O CBHVAFXKOYAHOY-NHCYSSNCSA-N 0.000 description 3
- SLHOOKXYTYAJGQ-XVYDVKMFSA-N Asp-Ala-His Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 SLHOOKXYTYAJGQ-XVYDVKMFSA-N 0.000 description 3
- CUQDCPXNZPDYFQ-ZLUOBGJFSA-N Asp-Ser-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O CUQDCPXNZPDYFQ-ZLUOBGJFSA-N 0.000 description 3
- 108090000994 Catalytic RNA Proteins 0.000 description 3
- 102000053642 Catalytic RNA Human genes 0.000 description 3
- 241000282552 Chlorocebus aethiops Species 0.000 description 3
- GTFYQOVVVJASOA-ACZMJKKPSA-N Glu-Ser-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N GTFYQOVVVJASOA-ACZMJKKPSA-N 0.000 description 3
- SABZDFAAOJATBR-QWRGUYRKSA-N Gly-Cys-Phe Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SABZDFAAOJATBR-QWRGUYRKSA-N 0.000 description 3
- FNXSYBOHALPRHV-ONGXEEELSA-N Gly-Val-Lys Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN FNXSYBOHALPRHV-ONGXEEELSA-N 0.000 description 3
- KAFZDWMZKGQDEE-SRVKXCTJSA-N His-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KAFZDWMZKGQDEE-SRVKXCTJSA-N 0.000 description 3
- LJUIEESLIAZSFR-SRVKXCTJSA-N His-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N LJUIEESLIAZSFR-SRVKXCTJSA-N 0.000 description 3
- CCUSLCQWVMWTIS-IXOXFDKPSA-N His-Thr-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O CCUSLCQWVMWTIS-IXOXFDKPSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- QLROSWPKSBORFJ-BQBZGAKWSA-N L-Prolyl-L-glutamic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 QLROSWPKSBORFJ-BQBZGAKWSA-N 0.000 description 3
- RNKSNIBMTUYWSH-YFKPBYRVSA-N L-prolylglycine Chemical compound [O-]C(=O)CNC(=O)[C@@H]1CCC[NH2+]1 RNKSNIBMTUYWSH-YFKPBYRVSA-N 0.000 description 3
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 3
- QIJVAFLRMVBHMU-KKUMJFAQSA-N Lys-Asp-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QIJVAFLRMVBHMU-KKUMJFAQSA-N 0.000 description 3
- SQJSXOQXJYAVRV-SRVKXCTJSA-N Lys-His-Asn Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N SQJSXOQXJYAVRV-SRVKXCTJSA-N 0.000 description 3
- 101150046652 M2 gene Proteins 0.000 description 3
- 241001559185 Mammalian rubulavirus 5 Species 0.000 description 3
- 229940124862 Measles virus vaccine Drugs 0.000 description 3
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 3
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 3
- YLDSJJOGQNEQJK-AVGNSLFASA-N Met-Pro-Leu Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YLDSJJOGQNEQJK-AVGNSLFASA-N 0.000 description 3
- 101150084044 P gene Proteins 0.000 description 3
- 102100034574 P protein Human genes 0.000 description 3
- 101710181008 P protein Proteins 0.000 description 3
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 3
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 3
- FPTXMUIBLMGTQH-ONGXEEELSA-N Phe-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 FPTXMUIBLMGTQH-ONGXEEELSA-N 0.000 description 3
- AWAYOWOUGVZXOB-BZSNNMDCSA-N Phe-Asn-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 AWAYOWOUGVZXOB-BZSNNMDCSA-N 0.000 description 3
- 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 3
- GRVMHFCZUIYNKQ-UFYCRDLUSA-N Phe-Phe-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O GRVMHFCZUIYNKQ-UFYCRDLUSA-N 0.000 description 3
- XDMMOISUAHXXFD-SRVKXCTJSA-N Phe-Ser-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O XDMMOISUAHXXFD-SRVKXCTJSA-N 0.000 description 3
- XNQMZHLAYFWSGJ-HTUGSXCWSA-N Phe-Thr-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XNQMZHLAYFWSGJ-HTUGSXCWSA-N 0.000 description 3
- 101710177166 Phosphoprotein Proteins 0.000 description 3
- HMNSRTLZAJHSIK-YUMQZZPRSA-N Pro-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 HMNSRTLZAJHSIK-YUMQZZPRSA-N 0.000 description 3
- RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 description 3
- OIDKVWTWGDWMHY-RYUDHWBXSA-N Pro-Tyr Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=C(O)C=C1 OIDKVWTWGDWMHY-RYUDHWBXSA-N 0.000 description 3
- 229940124679 RSV vaccine Drugs 0.000 description 3
- 241000711897 Rinderpest morbillivirus Species 0.000 description 3
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 3
- 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 3
- XZKQVQKUZMAADP-IMJSIDKUSA-N Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(O)=O XZKQVQKUZMAADP-IMJSIDKUSA-N 0.000 description 3
- 101001039853 Sonchus yellow net virus Matrix protein Proteins 0.000 description 3
- 101710137500 T7 RNA polymerase Proteins 0.000 description 3
- BQBCIBCLXBKYHW-CSMHCCOUSA-N Thr-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@@H]([NH3+])[C@@H](C)O BQBCIBCLXBKYHW-CSMHCCOUSA-N 0.000 description 3
- 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 3
- IQPWNQRRAJHOKV-KATARQTJSA-N Thr-Ser-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN IQPWNQRRAJHOKV-KATARQTJSA-N 0.000 description 3
- IEZVHOULSUULHD-XGEHTFHBSA-N Thr-Ser-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O IEZVHOULSUULHD-XGEHTFHBSA-N 0.000 description 3
- GFJXBLSZOFWHAW-JYJNAYRXSA-N Tyr-His-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O GFJXBLSZOFWHAW-JYJNAYRXSA-N 0.000 description 3
- 108091023045 Untranslated Region Proteins 0.000 description 3
- 241000700618 Vaccinia virus Species 0.000 description 3
- 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 3
- GVRKWABULJAONN-VQVTYTSYSA-N Val-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GVRKWABULJAONN-VQVTYTSYSA-N 0.000 description 3
- IOUPEELXVYPCPG-UHFFFAOYSA-N Valylglycine Chemical compound CC(C)C(N)C(=O)NCC(O)=O IOUPEELXVYPCPG-UHFFFAOYSA-N 0.000 description 3
- 108020000999 Viral RNA Proteins 0.000 description 3
- 108010070944 alanylhistidine Proteins 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 108010004073 cysteinylcysteine Proteins 0.000 description 3
- 230000000120 cytopathologic effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 108010077112 prolyl-proline Proteins 0.000 description 3
- 108010079317 prolyl-tyrosine Proteins 0.000 description 3
- 108010004914 prolylarginine Proteins 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 108091092562 ribozyme Proteins 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000005029 transcription elongation Effects 0.000 description 3
- 230000005026 transcription initiation Effects 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- PIPTUBPKYFRLCP-NHCYSSNCSA-N Ala-Ala-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PIPTUBPKYFRLCP-NHCYSSNCSA-N 0.000 description 2
- WYPUMLRSQMKIJU-BPNCWPANSA-N Ala-Arg-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WYPUMLRSQMKIJU-BPNCWPANSA-N 0.000 description 2
- DPNZTBKGAUAZQU-DLOVCJGASA-N Ala-Leu-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N DPNZTBKGAUAZQU-DLOVCJGASA-N 0.000 description 2
- VKKYFICVTYKFIO-CIUDSAMLSA-N Arg-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N VKKYFICVTYKFIO-CIUDSAMLSA-N 0.000 description 2
- XPSGESXVBSQZPL-SRVKXCTJSA-N Arg-Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XPSGESXVBSQZPL-SRVKXCTJSA-N 0.000 description 2
- ITVINTQUZMQWJR-QXEWZRGKSA-N Arg-Asn-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O ITVINTQUZMQWJR-QXEWZRGKSA-N 0.000 description 2
- MSILNNHVVMMTHZ-UWVGGRQHSA-N Arg-His-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CN=CN1 MSILNNHVVMMTHZ-UWVGGRQHSA-N 0.000 description 2
- ROWCTNFEMKOIFQ-YUMQZZPRSA-N Arg-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N ROWCTNFEMKOIFQ-YUMQZZPRSA-N 0.000 description 2
- CGWVCWFQGXOUSJ-ULQDDVLXSA-N Arg-Tyr-Leu 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](CC(C)C)C(O)=O CGWVCWFQGXOUSJ-ULQDDVLXSA-N 0.000 description 2
- HUZGPXBILPMCHM-IHRRRGAJSA-N Asn-Arg-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HUZGPXBILPMCHM-IHRRRGAJSA-N 0.000 description 2
- VYLVOMUVLMGCRF-ZLUOBGJFSA-N Asn-Asp-Ser Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O VYLVOMUVLMGCRF-ZLUOBGJFSA-N 0.000 description 2
- HXWUJJADFMXNKA-BQBZGAKWSA-N Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O HXWUJJADFMXNKA-BQBZGAKWSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000712005 Bovine respirovirus 3 Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108091062157 Cis-regulatory element Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 208000002330 Congenital Heart Defects Diseases 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- BUXAPSQPMALTOY-WHFBIAKZSA-N Cys-Glu Chemical compound SC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O BUXAPSQPMALTOY-WHFBIAKZSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- SRZLHYPAOXBBSB-HJGDQZAQSA-N Glu-Arg-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SRZLHYPAOXBBSB-HJGDQZAQSA-N 0.000 description 2
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 2
- FIQQRCFQXGLOSZ-WDSKDSINSA-N Gly-Glu-Asp Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FIQQRCFQXGLOSZ-WDSKDSINSA-N 0.000 description 2
- DKEXFJVMVGETOO-LURJTMIESA-N Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CN DKEXFJVMVGETOO-LURJTMIESA-N 0.000 description 2
- FEUPVVCGQLNXNP-IRXDYDNUSA-N Gly-Phe-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 FEUPVVCGQLNXNP-IRXDYDNUSA-N 0.000 description 2
- 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 2
- IMRNSEPSPFQNHF-STQMWFEESA-N Gly-Ser-Trp Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)O IMRNSEPSPFQNHF-STQMWFEESA-N 0.000 description 2
- FKYQEVBRZSFAMJ-QWRGUYRKSA-N Gly-Ser-Tyr Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FKYQEVBRZSFAMJ-QWRGUYRKSA-N 0.000 description 2
- 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 2
- 108060003393 Granulin Proteins 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- JGFWUKYIQAEYAH-DCAQKATOSA-N His-Ser-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JGFWUKYIQAEYAH-DCAQKATOSA-N 0.000 description 2
- JATYGDHMDRAISQ-KKUMJFAQSA-N His-Tyr-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O JATYGDHMDRAISQ-KKUMJFAQSA-N 0.000 description 2
- 102100034349 Integrase Human genes 0.000 description 2
- CZCSUZMIRKFFFA-CIUDSAMLSA-N Leu-Ala-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O CZCSUZMIRKFFFA-CIUDSAMLSA-N 0.000 description 2
- XIRYQRLFHWWWTC-QEJZJMRPSA-N Leu-Ala-Phe Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XIRYQRLFHWWWTC-QEJZJMRPSA-N 0.000 description 2
- QVFGXCVIXXBFHO-AVGNSLFASA-N Leu-Glu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O QVFGXCVIXXBFHO-AVGNSLFASA-N 0.000 description 2
- KGCLIYGPQXUNLO-IUCAKERBSA-N Leu-Gly-Glu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O KGCLIYGPQXUNLO-IUCAKERBSA-N 0.000 description 2
- JLWZLIQRYCTYBD-IHRRRGAJSA-N Leu-Lys-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JLWZLIQRYCTYBD-IHRRRGAJSA-N 0.000 description 2
- NTISAKGPIGTIJJ-IUCAKERBSA-N Leu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(C)C NTISAKGPIGTIJJ-IUCAKERBSA-N 0.000 description 2
- VDIARPPNADFEAV-WEDXCCLWSA-N Leu-Thr-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O VDIARPPNADFEAV-WEDXCCLWSA-N 0.000 description 2
- DAYQSYGBCUKVKT-VOAKCMCISA-N Leu-Thr-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O DAYQSYGBCUKVKT-VOAKCMCISA-N 0.000 description 2
- KLSUAWUZBMAZCL-RHYQMDGZSA-N Leu-Thr-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(O)=O KLSUAWUZBMAZCL-RHYQMDGZSA-N 0.000 description 2
- XZNJZXJZBMBGGS-NHCYSSNCSA-N Leu-Val-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O XZNJZXJZBMBGGS-NHCYSSNCSA-N 0.000 description 2
- AAKRWBIIGKPOKQ-ONGXEEELSA-N Leu-Val-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AAKRWBIIGKPOKQ-ONGXEEELSA-N 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 101710085938 Matrix protein Proteins 0.000 description 2
- JHKXZYLNVJRAAJ-WDSKDSINSA-N Met-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(O)=O JHKXZYLNVJRAAJ-WDSKDSINSA-N 0.000 description 2
- DBXMFHGGHMXYHY-DCAQKATOSA-N Met-Leu-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O DBXMFHGGHMXYHY-DCAQKATOSA-N 0.000 description 2
- 208000005647 Mumps Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000005348 Neuraminidase Human genes 0.000 description 2
- 108010006232 Neuraminidase Proteins 0.000 description 2
- 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 238000002944 PCR assay Methods 0.000 description 2
- 241000282579 Pan Species 0.000 description 2
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108010089430 Phosphoproteins Proteins 0.000 description 2
- 102000007982 Phosphoproteins Human genes 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 208000000474 Poliomyelitis Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- IFMDQWDAJUMMJC-DCAQKATOSA-N Pro-Ala-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O IFMDQWDAJUMMJC-DCAQKATOSA-N 0.000 description 2
- XKHCJJPNXFBADI-DCAQKATOSA-N Pro-Asp-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O XKHCJJPNXFBADI-DCAQKATOSA-N 0.000 description 2
- ZKQOUHVVXABNDG-IUCAKERBSA-N Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 ZKQOUHVVXABNDG-IUCAKERBSA-N 0.000 description 2
- NFLNBHLMLYALOO-DCAQKATOSA-N Pro-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@@H]1CCCN1 NFLNBHLMLYALOO-DCAQKATOSA-N 0.000 description 2
- FHZJRBVMLGOHBX-GUBZILKMSA-N Pro-Pro-Asp Chemical compound OC(=O)C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1)C(O)=O FHZJRBVMLGOHBX-GUBZILKMSA-N 0.000 description 2
- CGSOWZUPLOKYOR-AVGNSLFASA-N Pro-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 CGSOWZUPLOKYOR-AVGNSLFASA-N 0.000 description 2
- FDMCIBSQRKFSTJ-RHYQMDGZSA-N Pro-Thr-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O FDMCIBSQRKFSTJ-RHYQMDGZSA-N 0.000 description 2
- CWZUFLWPEFHWEI-IHRRRGAJSA-N Pro-Tyr-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O CWZUFLWPEFHWEI-IHRRRGAJSA-N 0.000 description 2
- VEUACYMXJKXALX-IHRRRGAJSA-N Pro-Tyr-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O VEUACYMXJKXALX-IHRRRGAJSA-N 0.000 description 2
- YDTUEBLEAVANFH-RCWTZXSCSA-N Pro-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 YDTUEBLEAVANFH-RCWTZXSCSA-N 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 206010037742 Rabies Diseases 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 241001533467 Rubulavirus Species 0.000 description 2
- 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 2
- NLOAIFSWUUFQFR-CIUDSAMLSA-N Ser-Leu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O NLOAIFSWUUFQFR-CIUDSAMLSA-N 0.000 description 2
- JWOBLHJRDADHLN-KKUMJFAQSA-N Ser-Leu-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JWOBLHJRDADHLN-KKUMJFAQSA-N 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 108091027544 Subgenomic mRNA Proteins 0.000 description 2
- SLUWOCTZVGMURC-BFHQHQDPSA-N Thr-Gly-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O SLUWOCTZVGMURC-BFHQHQDPSA-N 0.000 description 2
- KRGDDWVBBDLPSJ-CUJWVEQBSA-N Thr-His-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O KRGDDWVBBDLPSJ-CUJWVEQBSA-N 0.000 description 2
- QNCFWHZVRNXAKW-OEAJRASXSA-N Thr-Lys-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QNCFWHZVRNXAKW-OEAJRASXSA-N 0.000 description 2
- GXDLGHLJTHMDII-WISUUJSJSA-N Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(O)=O GXDLGHLJTHMDII-WISUUJSJSA-N 0.000 description 2
- DSGIVWSDDRDJIO-ZXXMMSQZSA-N Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DSGIVWSDDRDJIO-ZXXMMSQZSA-N 0.000 description 2
- QYDKSNXSBXZPFK-ZJDVBMNYSA-N Thr-Thr-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYDKSNXSBXZPFK-ZJDVBMNYSA-N 0.000 description 2
- CKHWEVXPLJBEOZ-VQVTYTSYSA-N Thr-Val Chemical compound CC(C)[C@@H](C([O-])=O)NC(=O)[C@@H]([NH3+])[C@@H](C)O CKHWEVXPLJBEOZ-VQVTYTSYSA-N 0.000 description 2
- XNRJFXBORWMIPY-DCPHZVHLSA-N Trp-Ala-Phe Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O XNRJFXBORWMIPY-DCPHZVHLSA-N 0.000 description 2
- LYMVXFSTACVOLP-ZFWWWQNUSA-N Trp-Leu Chemical compound C1=CC=C2C(C[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C([O-])=O)=CNC2=C1 LYMVXFSTACVOLP-ZFWWWQNUSA-N 0.000 description 2
- ULHASJWZGUEUNN-XIRDDKMYSA-N Trp-Lys-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O ULHASJWZGUEUNN-XIRDDKMYSA-N 0.000 description 2
- QZOSVNLXLSNHQK-UWVGGRQHSA-N Tyr-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 QZOSVNLXLSNHQK-UWVGGRQHSA-N 0.000 description 2
- BSCBBPKDVOZICB-KKUMJFAQSA-N Tyr-Leu-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O BSCBBPKDVOZICB-KKUMJFAQSA-N 0.000 description 2
- JAGGEZACYAAMIL-CQDKDKBSSA-N Tyr-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=C(C=C1)O)N JAGGEZACYAAMIL-CQDKDKBSSA-N 0.000 description 2
- AVFGBGGRZOKSFS-KJEVXHAQSA-N Tyr-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O AVFGBGGRZOKSFS-KJEVXHAQSA-N 0.000 description 2
- CGGVNFJRZJUVAE-BYULHYEWSA-N Val-Asp-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N CGGVNFJRZJUVAE-BYULHYEWSA-N 0.000 description 2
- XWYUBUYQMOUFRQ-IFFSRLJSSA-N Val-Glu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)N)O XWYUBUYQMOUFRQ-IFFSRLJSSA-N 0.000 description 2
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 2
- HTONZBWRYUKUKC-RCWTZXSCSA-N Val-Thr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HTONZBWRYUKUKC-RCWTZXSCSA-N 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 108010013835 arginine glutamate Proteins 0.000 description 2
- 108010093581 aspartyl-proline Proteins 0.000 description 2
- 108010092854 aspartyllysine Proteins 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 208000028831 congenital heart disease Diseases 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 210000001840 diploid cell Anatomy 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012634 fragment Substances 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
- 108010087823 glycyltyrosine Proteins 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 208000010805 mumps infectious disease Diseases 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 229960005030 other vaccine in atc Drugs 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 108010024654 phenylalanyl-prolyl-alanine Proteins 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 201000005404 rubella Diseases 0.000 description 2
- 244000309458 single stranded enveloped RNA virus Species 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 108010073969 valyllysine Proteins 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- PNBMXFUTFSFLNU-BXRBKJIMSA-N (2s)-2-aminobutanedioic acid;(2s)-2-aminopropanoic acid Chemical compound C[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC(O)=O PNBMXFUTFSFLNU-BXRBKJIMSA-N 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- AXXVSCRPHPIDIW-UHFFFAOYSA-N 7h-purin-6-amine;7h-purine Chemical compound C1=NC=C2NC=NC2=N1.NC1=NC=NC2=C1NC=N2 AXXVSCRPHPIDIW-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 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
- PBAMJJXWDQXOJA-FXQIFTODSA-N Ala-Asp-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PBAMJJXWDQXOJA-FXQIFTODSA-N 0.000 description 1
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 1
- NJWJSLCQEDMGNC-MBLNEYKQSA-N Ala-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C)N)O NJWJSLCQEDMGNC-MBLNEYKQSA-N 0.000 description 1
- LBYMZCVBOKYZNS-CIUDSAMLSA-N Ala-Leu-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O LBYMZCVBOKYZNS-CIUDSAMLSA-N 0.000 description 1
- PMQXMXAASGFUDX-SRVKXCTJSA-N Ala-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCCN PMQXMXAASGFUDX-SRVKXCTJSA-N 0.000 description 1
- PEIBBAXIKUAYGN-UBHSHLNASA-N Ala-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 PEIBBAXIKUAYGN-UBHSHLNASA-N 0.000 description 1
- ZXKNLCPUNZPFGY-LEWSCRJBSA-N Ala-Tyr-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N ZXKNLCPUNZPFGY-LEWSCRJBSA-N 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- UISQLSIBJKEJSS-GUBZILKMSA-N Arg-Arg-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(O)=O UISQLSIBJKEJSS-GUBZILKMSA-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
- UFBURHXMKFQVLM-CIUDSAMLSA-N Arg-Glu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O UFBURHXMKFQVLM-CIUDSAMLSA-N 0.000 description 1
- CVKOQHYVDVYJSI-QTKMDUPCSA-N Arg-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCCN=C(N)N)N)O CVKOQHYVDVYJSI-QTKMDUPCSA-N 0.000 description 1
- ZDBWKBCKYJGKGP-DCAQKATOSA-N Arg-Leu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O ZDBWKBCKYJGKGP-DCAQKATOSA-N 0.000 description 1
- YBZMTKUDWXZLIX-UWVGGRQHSA-N Arg-Leu-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YBZMTKUDWXZLIX-UWVGGRQHSA-N 0.000 description 1
- LQJAALCCPOTJGB-YUMQZZPRSA-N Arg-Pro Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O LQJAALCCPOTJGB-YUMQZZPRSA-N 0.000 description 1
- BECXEHHOZNFFFX-IHRRRGAJSA-N Arg-Ser-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BECXEHHOZNFFFX-IHRRRGAJSA-N 0.000 description 1
- ZPWMEWYQBWSGAO-ZJDVBMNYSA-N Arg-Thr-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZPWMEWYQBWSGAO-ZJDVBMNYSA-N 0.000 description 1
- QCTOLCVIGRLMQS-HRCADAONSA-N Arg-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O QCTOLCVIGRLMQS-HRCADAONSA-N 0.000 description 1
- SJUXYGVRSGTPMC-IMJSIDKUSA-N Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O SJUXYGVRSGTPMC-IMJSIDKUSA-N 0.000 description 1
- QEYJFBMTSMLPKZ-ZKWXMUAHSA-N Asn-Ala-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O QEYJFBMTSMLPKZ-ZKWXMUAHSA-N 0.000 description 1
- RJUHZPRQRQLCFL-IMJSIDKUSA-N Asn-Asn Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O RJUHZPRQRQLCFL-IMJSIDKUSA-N 0.000 description 1
- UGXVKHRDGLYFKR-CIUDSAMLSA-N Asn-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(N)=O UGXVKHRDGLYFKR-CIUDSAMLSA-N 0.000 description 1
- BZMWJLLUAKSIMH-FXQIFTODSA-N Asn-Glu-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BZMWJLLUAKSIMH-FXQIFTODSA-N 0.000 description 1
- GFFRWIJAFFMQGM-NUMRIWBASA-N Asn-Glu-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GFFRWIJAFFMQGM-NUMRIWBASA-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
- UYXXMIZGHYKYAT-NHCYSSNCSA-N Asn-His-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)N)N UYXXMIZGHYKYAT-NHCYSSNCSA-N 0.000 description 1
- JLNFZLNDHONLND-GARJFASQSA-N Asn-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N JLNFZLNDHONLND-GARJFASQSA-N 0.000 description 1
- NUCUBYIUPVYGPP-XIRDDKMYSA-N Asn-Leu-Trp Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O NUCUBYIUPVYGPP-XIRDDKMYSA-N 0.000 description 1
- QJMCHPGWFZZRID-BQBZGAKWSA-N Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O QJMCHPGWFZZRID-BQBZGAKWSA-N 0.000 description 1
- NLDNNZKUSLAYFW-NHCYSSNCSA-N Asn-Lys-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NLDNNZKUSLAYFW-NHCYSSNCSA-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
- XTMZYFMTYJNABC-ZLUOBGJFSA-N Asn-Ser-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N XTMZYFMTYJNABC-ZLUOBGJFSA-N 0.000 description 1
- JXMREEPBRANWBY-VEVYYDQMSA-N Asn-Thr-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JXMREEPBRANWBY-VEVYYDQMSA-N 0.000 description 1
- FYRVDDJMNISIKJ-UWVGGRQHSA-N Asn-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FYRVDDJMNISIKJ-UWVGGRQHSA-N 0.000 description 1
- FAEIQWHBRBWUBN-FXQIFTODSA-N Asp-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N FAEIQWHBRBWUBN-FXQIFTODSA-N 0.000 description 1
- UGKZHCBLMLSANF-CIUDSAMLSA-N Asp-Asn-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O UGKZHCBLMLSANF-CIUDSAMLSA-N 0.000 description 1
- FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 description 1
- LKIYSIYBKYLKPU-BIIVOSGPSA-N Asp-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)N)C(=O)O LKIYSIYBKYLKPU-BIIVOSGPSA-N 0.000 description 1
- CKAJHWFHHFSCDT-WHFBIAKZSA-N Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O CKAJHWFHHFSCDT-WHFBIAKZSA-N 0.000 description 1
- XAJRHVUUVUPFQL-ACZMJKKPSA-N Asp-Glu-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XAJRHVUUVUPFQL-ACZMJKKPSA-N 0.000 description 1
- OAMLVOVXNKILLQ-BQBZGAKWSA-N Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O OAMLVOVXNKILLQ-BQBZGAKWSA-N 0.000 description 1
- AHWRSSLYSGLBGD-CIUDSAMLSA-N Asp-Pro-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AHWRSSLYSGLBGD-CIUDSAMLSA-N 0.000 description 1
- QTIZKMMLNUMHHU-DCAQKATOSA-N Asp-Pro-His Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O QTIZKMMLNUMHHU-DCAQKATOSA-N 0.000 description 1
- MGSVBZIBCCKGCY-ZLUOBGJFSA-N Asp-Ser-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MGSVBZIBCCKGCY-ZLUOBGJFSA-N 0.000 description 1
- YUELDQUPTAYEGM-XIRDDKMYSA-N Asp-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)O)N YUELDQUPTAYEGM-XIRDDKMYSA-N 0.000 description 1
- NALWOULWGHTVDA-UWVGGRQHSA-N Asp-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NALWOULWGHTVDA-UWVGGRQHSA-N 0.000 description 1
- NJLLRXWFPQQPHV-SRVKXCTJSA-N Asp-Tyr-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O NJLLRXWFPQQPHV-SRVKXCTJSA-N 0.000 description 1
- ALMIMUZAWTUNIO-BZSNNMDCSA-N Asp-Tyr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ALMIMUZAWTUNIO-BZSNNMDCSA-N 0.000 description 1
- XQFLFQWOBXPMHW-NHCYSSNCSA-N Asp-Val-His Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O XQFLFQWOBXPMHW-NHCYSSNCSA-N 0.000 description 1
- ZUNMTUPRQMWMHX-LSJOCFKGSA-N Asp-Val-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O ZUNMTUPRQMWMHX-LSJOCFKGSA-N 0.000 description 1
- 101000666833 Autographa californica nuclear polyhedrosis virus Uncharacterized 20.8 kDa protein in FGF-VUBI intergenic region Proteins 0.000 description 1
- 101000977027 Azospirillum brasilense Uncharacterized protein in nodG 5'region Proteins 0.000 description 1
- 101000962005 Bacillus thuringiensis Uncharacterized 23.6 kDa protein Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000712462 Bovine ephemeral fever virus Species 0.000 description 1
- 241000711895 Bovine orthopneumovirus Species 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- 101710117545 C protein Proteins 0.000 description 1
- 241001353878 Canine parainfluenza virus Species 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- AYKQJQVWUYEZNU-IMJSIDKUSA-N Cys-Asn Chemical compound SC[C@H](N)C(=O)N[C@H](C(O)=O)CC(N)=O AYKQJQVWUYEZNU-IMJSIDKUSA-N 0.000 description 1
- HNNGTYHNYDOSKV-FXQIFTODSA-N Cys-Cys-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)N HNNGTYHNYDOSKV-FXQIFTODSA-N 0.000 description 1
- XZFYRXDAULDNFX-UWVGGRQHSA-N Cys-Phe Chemical compound SC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XZFYRXDAULDNFX-UWVGGRQHSA-N 0.000 description 1
- WTEACWBAULENKE-SRVKXCTJSA-N Cys-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](CS)N WTEACWBAULENKE-SRVKXCTJSA-N 0.000 description 1
- GGRDJANMZPGMNS-CIUDSAMLSA-N Cys-Ser-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O GGRDJANMZPGMNS-CIUDSAMLSA-N 0.000 description 1
- WYVKPHCYMTWUCW-YUPRTTJUSA-N Cys-Thr Chemical compound C[C@@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)N)O WYVKPHCYMTWUCW-YUPRTTJUSA-N 0.000 description 1
- OELDIVRKHTYFNG-WDSKDSINSA-N Cys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CS OELDIVRKHTYFNG-WDSKDSINSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 241001502545 Dolphin morbillivirus Species 0.000 description 1
- 101000785191 Drosophila melanogaster Uncharacterized 50 kDa protein in type I retrotransposable element R1DM Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 101000747704 Enterobacteria phage N4 Uncharacterized protein Gp1 Proteins 0.000 description 1
- 101000861206 Enterococcus faecalis (strain ATCC 700802 / V583) Uncharacterized protein EF_A0048 Proteins 0.000 description 1
- 101710121417 Envelope glycoprotein Proteins 0.000 description 1
- 241001455610 Ephemerovirus Species 0.000 description 1
- 101000769180 Escherichia coli Uncharacterized 11.1 kDa protein Proteins 0.000 description 1
- 201000003542 Factor VIII deficiency Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150082239 G gene Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- PBEQPAZRHDVJQI-SRVKXCTJSA-N Glu-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N PBEQPAZRHDVJQI-SRVKXCTJSA-N 0.000 description 1
- CKRUHITYRFNUKW-WDSKDSINSA-N Glu-Asn-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O CKRUHITYRFNUKW-WDSKDSINSA-N 0.000 description 1
- ZZIFPJZQHRJERU-WDSKDSINSA-N Glu-Cys-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O ZZIFPJZQHRJERU-WDSKDSINSA-N 0.000 description 1
- PNAOVYHADQRJQU-GUBZILKMSA-N Glu-Cys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)N PNAOVYHADQRJQU-GUBZILKMSA-N 0.000 description 1
- KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
- NJCALAAIGREHDR-WDCWCFNPSA-N Glu-Leu-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NJCALAAIGREHDR-WDCWCFNPSA-N 0.000 description 1
- 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
- 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
- XEKAJTCACGEBOK-KKUMJFAQSA-N Glu-Met-Phe Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N XEKAJTCACGEBOK-KKUMJFAQSA-N 0.000 description 1
- HQOGXFLBAKJUMH-CIUDSAMLSA-N Glu-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)O)N HQOGXFLBAKJUMH-CIUDSAMLSA-N 0.000 description 1
- UERORLSAFUHDGU-AVGNSLFASA-N Glu-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](CCC(=O)O)N UERORLSAFUHDGU-AVGNSLFASA-N 0.000 description 1
- SYWCGQOIIARSIX-SRVKXCTJSA-N Glu-Pro-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O SYWCGQOIIARSIX-SRVKXCTJSA-N 0.000 description 1
- WIKMTDVSCUJIPJ-CIUDSAMLSA-N Glu-Ser-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WIKMTDVSCUJIPJ-CIUDSAMLSA-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
- BDISFWMLMNBTGP-NUMRIWBASA-N Glu-Thr-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O BDISFWMLMNBTGP-NUMRIWBASA-N 0.000 description 1
- VHPVBPCCWVDGJL-IRIUXVKKSA-N Glu-Thr-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VHPVBPCCWVDGJL-IRIUXVKKSA-N 0.000 description 1
- DLISPGXMKZTWQG-IFFSRLJSSA-N Glu-Thr-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O DLISPGXMKZTWQG-IFFSRLJSSA-N 0.000 description 1
- SITLTJHOQZFJGG-XPUUQOCRSA-N Glu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O SITLTJHOQZFJGG-XPUUQOCRSA-N 0.000 description 1
- XZRZILPOZBVTDB-GJZGRUSLSA-N Gly-Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)CN)C(O)=O)=CNC2=C1 XZRZILPOZBVTDB-GJZGRUSLSA-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
- CCBIBMKQNXHNIN-ZETCQYMHSA-N Gly-Leu-Gly Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O CCBIBMKQNXHNIN-ZETCQYMHSA-N 0.000 description 1
- IKAIKUBBJHFNBZ-LURJTMIESA-N Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-LURJTMIESA-N 0.000 description 1
- MHZXESQPPXOING-KBPBESRZSA-N Gly-Lys-Phe Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O MHZXESQPPXOING-KBPBESRZSA-N 0.000 description 1
- GAAHQHNCMIAYEX-UWVGGRQHSA-N Gly-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GAAHQHNCMIAYEX-UWVGGRQHSA-N 0.000 description 1
- XBGGUPMXALFZOT-VIFPVBQESA-N Gly-Tyr Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-VIFPVBQESA-N 0.000 description 1
- RIYIFUFFFBIOEU-KBPBESRZSA-N Gly-Tyr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 RIYIFUFFFBIOEU-KBPBESRZSA-N 0.000 description 1
- 241000941423 Grom virus Species 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 108010017480 Hemosiderin Proteins 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 208000037262 Hepatitis delta Diseases 0.000 description 1
- FRJIAZKQGSCKPQ-FSPLSTOPSA-N His-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CN=CN1 FRJIAZKQGSCKPQ-FSPLSTOPSA-N 0.000 description 1
- IPIVXQQRZXEUGW-UWJYBYFXSA-N His-Ala-His Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 IPIVXQQRZXEUGW-UWJYBYFXSA-N 0.000 description 1
- PDSUIXMZYNURGI-AVGNSLFASA-N His-Arg-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC1=CN=CN1 PDSUIXMZYNURGI-AVGNSLFASA-N 0.000 description 1
- PROLDOGUBQJNPG-RWMBFGLXSA-N His-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O PROLDOGUBQJNPG-RWMBFGLXSA-N 0.000 description 1
- MDCTVRUPVLZSPG-BQBZGAKWSA-N His-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CNC=N1 MDCTVRUPVLZSPG-BQBZGAKWSA-N 0.000 description 1
- WRPDZHJNLYNFFT-GEVIPFJHSA-N His-Thr Chemical compound C[C@@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N)O WRPDZHJNLYNFFT-GEVIPFJHSA-N 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 241000726041 Human respirovirus 1 Species 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 241000712431 Influenza A virus Species 0.000 description 1
- ZUKPVRWZDMRIEO-VKHMYHEASA-N L-cysteinylglycine Chemical compound SC[C@H]([NH3+])C(=O)NCC([O-])=O ZUKPVRWZDMRIEO-VKHMYHEASA-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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 101000976301 Leptospira interrogans Uncharacterized 35 kDa protein in sph 3'region Proteins 0.000 description 1
- PBCHMHROGNUXMK-DLOVCJGASA-N Leu-Ala-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 PBCHMHROGNUXMK-DLOVCJGASA-N 0.000 description 1
- USTCFDAQCLDPBD-XIRDDKMYSA-N Leu-Asn-Trp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N USTCFDAQCLDPBD-XIRDDKMYSA-N 0.000 description 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
- 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
- DZQMXBALGUHGJT-GUBZILKMSA-N Leu-Glu-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O DZQMXBALGUHGJT-GUBZILKMSA-N 0.000 description 1
- HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-N 0.000 description 1
- VGPCJSXPPOQPBK-YUMQZZPRSA-N Leu-Gly-Ser Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O VGPCJSXPPOQPBK-YUMQZZPRSA-N 0.000 description 1
- XWOBNBRUDDUEEY-UWVGGRQHSA-N Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 XWOBNBRUDDUEEY-UWVGGRQHSA-N 0.000 description 1
- OHZIZVWQXJPBJS-IXOXFDKPSA-N Leu-His-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OHZIZVWQXJPBJS-IXOXFDKPSA-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
- IAJFFZORSWOZPQ-SRVKXCTJSA-N Leu-Leu-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IAJFFZORSWOZPQ-SRVKXCTJSA-N 0.000 description 1
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 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
- HVHRPWQEQHIQJF-AVGNSLFASA-N Leu-Lys-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HVHRPWQEQHIQJF-AVGNSLFASA-N 0.000 description 1
- QNTJIDXQHWUBKC-BZSNNMDCSA-N Leu-Lys-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QNTJIDXQHWUBKC-BZSNNMDCSA-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
- UHNQRAFSEBGZFZ-YESZJQIVSA-N Leu-Phe-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N UHNQRAFSEBGZFZ-YESZJQIVSA-N 0.000 description 1
- JIHDFWWRYHSAQB-GUBZILKMSA-N Leu-Ser-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JIHDFWWRYHSAQB-GUBZILKMSA-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
- LRKCBIUDWAXNEG-CSMHCCOUSA-N Leu-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LRKCBIUDWAXNEG-CSMHCCOUSA-N 0.000 description 1
- LFSQWRSVPNKJGP-WDCWCFNPSA-N Leu-Thr-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(O)=O LFSQWRSVPNKJGP-WDCWCFNPSA-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
- UCRJTSIIAYHOHE-ULQDDVLXSA-N Leu-Tyr-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UCRJTSIIAYHOHE-ULQDDVLXSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- RVOMPSJXSRPFJT-DCAQKATOSA-N Lys-Ala-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVOMPSJXSRPFJT-DCAQKATOSA-N 0.000 description 1
- NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 description 1
- 108010062166 Lys-Asn-Asp Proteins 0.000 description 1
- AIPHUKOBUXJNKM-KKUMJFAQSA-N Lys-Cys-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O AIPHUKOBUXJNKM-KKUMJFAQSA-N 0.000 description 1
- UGTZHPSKYRIGRJ-YUMQZZPRSA-N Lys-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O UGTZHPSKYRIGRJ-YUMQZZPRSA-N 0.000 description 1
- DUTMKEAPLLUGNO-JYJNAYRXSA-N Lys-Glu-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O DUTMKEAPLLUGNO-JYJNAYRXSA-N 0.000 description 1
- VEGLGAOVLFODGC-GUBZILKMSA-N Lys-Glu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O VEGLGAOVLFODGC-GUBZILKMSA-N 0.000 description 1
- GHOIOYHDDKXIDX-SZMVWBNQSA-N Lys-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCCCN)C(O)=O)=CNC2=C1 GHOIOYHDDKXIDX-SZMVWBNQSA-N 0.000 description 1
- QZONCCHVHCOBSK-YUMQZZPRSA-N Lys-Gly-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O QZONCCHVHCOBSK-YUMQZZPRSA-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
- 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
- MUXNCRWTWBMNHX-SRVKXCTJSA-N Lys-Leu-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O MUXNCRWTWBMNHX-SRVKXCTJSA-N 0.000 description 1
- VUTWYNQUSJWBHO-BZSNNMDCSA-N Lys-Leu-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VUTWYNQUSJWBHO-BZSNNMDCSA-N 0.000 description 1
- HVAUKHLDSDDROB-KKUMJFAQSA-N Lys-Lys-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HVAUKHLDSDDROB-KKUMJFAQSA-N 0.000 description 1
- ODTZHNZPINULEU-KKUMJFAQSA-N Lys-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N ODTZHNZPINULEU-KKUMJFAQSA-N 0.000 description 1
- ZJSZPXISKMDJKQ-JYJNAYRXSA-N Lys-Phe-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=CC=C1 ZJSZPXISKMDJKQ-JYJNAYRXSA-N 0.000 description 1
- GHKXHCMRAUYLBS-CIUDSAMLSA-N Lys-Ser-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O GHKXHCMRAUYLBS-CIUDSAMLSA-N 0.000 description 1
- SEZADXQOJJTXPG-VFAJRCTISA-N Lys-Thr-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCCN)N)O SEZADXQOJJTXPG-VFAJRCTISA-N 0.000 description 1
- NROQVSYLPRLJIP-PMVMPFDFSA-N Lys-Trp-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NROQVSYLPRLJIP-PMVMPFDFSA-N 0.000 description 1
- RMKJOQSYLQQRFN-KKUMJFAQSA-N Lys-Tyr-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O RMKJOQSYLQQRFN-KKUMJFAQSA-N 0.000 description 1
- HONVOXINDBETTI-KKUMJFAQSA-N Lys-Tyr-Cys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CS)C(O)=O)CC1=CC=C(O)C=C1 HONVOXINDBETTI-KKUMJFAQSA-N 0.000 description 1
- OHXUUQDOBQKSNB-AVGNSLFASA-N Lys-Val-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OHXUUQDOBQKSNB-AVGNSLFASA-N 0.000 description 1
- TXTZMVNJIRZABH-ULQDDVLXSA-N Lys-Val-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 TXTZMVNJIRZABH-ULQDDVLXSA-N 0.000 description 1
- 241000711828 Lyssavirus Species 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 241001115401 Marburgvirus Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 101710127721 Membrane protein Proteins 0.000 description 1
- DLAFCQWUMFMZSN-GUBZILKMSA-N Met-Arg-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CCCN=C(N)N DLAFCQWUMFMZSN-GUBZILKMSA-N 0.000 description 1
- JQEBITVYKUCBMC-SRVKXCTJSA-N Met-Arg-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JQEBITVYKUCBMC-SRVKXCTJSA-N 0.000 description 1
- TUSOIZOVPJCMFC-FXQIFTODSA-N Met-Asp-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O TUSOIZOVPJCMFC-FXQIFTODSA-N 0.000 description 1
- MCNGIXXCMJAURZ-VEVYYDQMSA-N Met-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)N)O MCNGIXXCMJAURZ-VEVYYDQMSA-N 0.000 description 1
- HLZORBMOISUNIV-DCAQKATOSA-N Met-Ser-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C HLZORBMOISUNIV-DCAQKATOSA-N 0.000 description 1
- TUZSWDCTCGTVDJ-PJODQICGSA-N Met-Trp-Ala Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 TUZSWDCTCGTVDJ-PJODQICGSA-N 0.000 description 1
- LPNWWHBFXPNHJG-AVGNSLFASA-N Met-Val-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN LPNWWHBFXPNHJG-AVGNSLFASA-N 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 241000711941 Murine orthopneumovirus Species 0.000 description 1
- 241000699670 Mus sp. Species 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
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- 108010087066 N2-tryptophyllysine Proteins 0.000 description 1
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 1
- 101000658690 Neisseria meningitidis serogroup B Transposase for insertion sequence element IS1106 Proteins 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 108700005081 Overlapping Genes Proteins 0.000 description 1
- BRDYYVQTEJVRQT-HRCADAONSA-N Phe-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O BRDYYVQTEJVRQT-HRCADAONSA-N 0.000 description 1
- ZWJKVFAYPLPCQB-UNQGMJICSA-N Phe-Arg-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O ZWJKVFAYPLPCQB-UNQGMJICSA-N 0.000 description 1
- KAHUBGWSIQNZQQ-KKUMJFAQSA-N Phe-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 KAHUBGWSIQNZQQ-KKUMJFAQSA-N 0.000 description 1
- LXVFHIBXOWJTKZ-BZSNNMDCSA-N Phe-Asn-Tyr Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O LXVFHIBXOWJTKZ-BZSNNMDCSA-N 0.000 description 1
- JXWLMUIXUXLIJR-QWRGUYRKSA-N Phe-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 JXWLMUIXUXLIJR-QWRGUYRKSA-N 0.000 description 1
- JWQWPTLEOFNCGX-AVGNSLFASA-N Phe-Glu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 JWQWPTLEOFNCGX-AVGNSLFASA-N 0.000 description 1
- YTILBRIUASDGBL-BZSNNMDCSA-N Phe-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 YTILBRIUASDGBL-BZSNNMDCSA-N 0.000 description 1
- GZGPMBKUJDRICD-ULQDDVLXSA-N Phe-Pro-His Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)N)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O GZGPMBKUJDRICD-ULQDDVLXSA-N 0.000 description 1
- NYQBYASWHVRESG-MIMYLULJSA-N Phe-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 NYQBYASWHVRESG-MIMYLULJSA-N 0.000 description 1
- JMCOUWKXLXDERB-WMZOPIPTSA-N Phe-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=CC=C1 JMCOUWKXLXDERB-WMZOPIPTSA-N 0.000 description 1
- XALFIVXGQUEGKV-JSGCOSHPSA-N Phe-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 XALFIVXGQUEGKV-JSGCOSHPSA-N 0.000 description 1
- 241000711899 Phocine morbillivirus Species 0.000 description 1
- 101100271190 Plasmodium falciparum (isolate 3D7) ATAT gene Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 241000233872 Pneumocystis carinii Species 0.000 description 1
- 206010035737 Pneumonia viral Diseases 0.000 description 1
- XQLBWXHVZVBNJM-FXQIFTODSA-N Pro-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 XQLBWXHVZVBNJM-FXQIFTODSA-N 0.000 description 1
- OYEUSRAZOGIDBY-JYJNAYRXSA-N Pro-Arg-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OYEUSRAZOGIDBY-JYJNAYRXSA-N 0.000 description 1
- KIPIKSXPPLABPN-CIUDSAMLSA-N Pro-Glu-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1 KIPIKSXPPLABPN-CIUDSAMLSA-N 0.000 description 1
- VOZIBWWZSBIXQN-SRVKXCTJSA-N Pro-Glu-Lys Chemical compound NCCCC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1)C(O)=O VOZIBWWZSBIXQN-SRVKXCTJSA-N 0.000 description 1
- WFHYFCWBLSKEMS-KKUMJFAQSA-N Pro-Glu-Phe Chemical compound N([C@@H](CCC(=O)O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C(=O)[C@@H]1CCCN1 WFHYFCWBLSKEMS-KKUMJFAQSA-N 0.000 description 1
- CLNJSLSHKJECME-BQBZGAKWSA-N Pro-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1 CLNJSLSHKJECME-BQBZGAKWSA-N 0.000 description 1
- BEPSGCXDIVACBU-IUCAKERBSA-N Pro-His Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1NCCC1)C1=CN=CN1 BEPSGCXDIVACBU-IUCAKERBSA-N 0.000 description 1
- DTQIXTOJHKVEOH-DCAQKATOSA-N Pro-His-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CS)C(=O)O DTQIXTOJHKVEOH-DCAQKATOSA-N 0.000 description 1
- RMODQFBNDDENCP-IHRRRGAJSA-N Pro-Lys-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O RMODQFBNDDENCP-IHRRRGAJSA-N 0.000 description 1
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- 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
- VVAWNPIOYXAMAL-KJEVXHAQSA-N Pro-Thr-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VVAWNPIOYXAMAL-KJEVXHAQSA-N 0.000 description 1
- 101710132653 Protein M2 Proteins 0.000 description 1
- 101000748660 Pseudomonas savastanoi Uncharacterized 21 kDa protein in iaaL 5'region Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 238000010357 RNA editing Methods 0.000 description 1
- 230000026279 RNA modification Effects 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 206010062106 Respiratory tract infection viral Diseases 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 101000584469 Rice tungro bacilliform virus (isolate Philippines) Protein P1 Proteins 0.000 description 1
- 101150107578 SH gene Proteins 0.000 description 1
- BKOKTRCZXRIQPX-ZLUOBGJFSA-N Ser-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N BKOKTRCZXRIQPX-ZLUOBGJFSA-N 0.000 description 1
- WDXYVIIVDIDOSX-DCAQKATOSA-N Ser-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N WDXYVIIVDIDOSX-DCAQKATOSA-N 0.000 description 1
- RNFKSBPHLTZHLU-WHFBIAKZSA-N Ser-Cys-Gly Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N)O RNFKSBPHLTZHLU-WHFBIAKZSA-N 0.000 description 1
- LAFKUZYWNCHOHT-WHFBIAKZSA-N Ser-Glu Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O LAFKUZYWNCHOHT-WHFBIAKZSA-N 0.000 description 1
- LALNXSXEYFUUDD-GUBZILKMSA-N Ser-Glu-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LALNXSXEYFUUDD-GUBZILKMSA-N 0.000 description 1
- NFDYGNFETJVMSE-BQBZGAKWSA-N Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CO NFDYGNFETJVMSE-BQBZGAKWSA-N 0.000 description 1
- FUMGHWDRRFCKEP-CIUDSAMLSA-N Ser-Leu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O FUMGHWDRRFCKEP-CIUDSAMLSA-N 0.000 description 1
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 1
- HDBOEVPDIDDEPC-CIUDSAMLSA-N Ser-Lys-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O HDBOEVPDIDDEPC-CIUDSAMLSA-N 0.000 description 1
- XUDRHBPSPAPDJP-SRVKXCTJSA-N Ser-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO XUDRHBPSPAPDJP-SRVKXCTJSA-N 0.000 description 1
- WGDYNRCOQRERLZ-KKUMJFAQSA-N Ser-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N WGDYNRCOQRERLZ-KKUMJFAQSA-N 0.000 description 1
- PMCMLDNPAZUYGI-DCAQKATOSA-N Ser-Lys-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PMCMLDNPAZUYGI-DCAQKATOSA-N 0.000 description 1
- AXOHAHIUJHCLQR-IHRRRGAJSA-N Ser-Met-Tyr Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CO)N AXOHAHIUJHCLQR-IHRRRGAJSA-N 0.000 description 1
- UGTZYIPOBYXWRW-SRVKXCTJSA-N Ser-Phe-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O UGTZYIPOBYXWRW-SRVKXCTJSA-N 0.000 description 1
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 1
- NMZXJDSKEGFDLJ-DCAQKATOSA-N Ser-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CCCCN)C(=O)O NMZXJDSKEGFDLJ-DCAQKATOSA-N 0.000 description 1
- PCJLFYBAQZQOFE-KATARQTJSA-N Ser-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N)O PCJLFYBAQZQOFE-KATARQTJSA-N 0.000 description 1
- UYLKOSODXYSWMQ-XGEHTFHBSA-N Ser-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CO)N)O UYLKOSODXYSWMQ-XGEHTFHBSA-N 0.000 description 1
- QYBRQMLZDDJBSW-AVGNSLFASA-N Ser-Tyr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYBRQMLZDDJBSW-AVGNSLFASA-N 0.000 description 1
- VVKVHAOOUGNDPJ-SRVKXCTJSA-N Ser-Tyr-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O VVKVHAOOUGNDPJ-SRVKXCTJSA-N 0.000 description 1
- 241000144290 Sigmodon hispidus Species 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- 101710200413 Small hydrophobic protein Proteins 0.000 description 1
- 241001428894 Small ruminant morbillivirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 101000818096 Spirochaeta aurantia Uncharacterized 15.5 kDa protein in trpE 3'region Proteins 0.000 description 1
- 101000766081 Streptomyces ambofaciens Uncharacterized HTH-type transcriptional regulator in unstable DNA locus Proteins 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 101000804403 Synechococcus elongatus (strain PCC 7942 / FACHB-805) Uncharacterized HIT-like protein Synpcc7942_1390 Proteins 0.000 description 1
- 101000750910 Synechococcus elongatus (strain PCC 7942 / FACHB-805) Uncharacterized HTH-type transcriptional regulator Synpcc7942_2319 Proteins 0.000 description 1
- 101000644897 Synechococcus sp. (strain ATCC 27264 / PCC 7002 / PR-6) Uncharacterized protein SYNPCC7002_B0001 Proteins 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- OJRNZRROAIAHDL-LKXGYXEUSA-N Thr-Asn-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OJRNZRROAIAHDL-LKXGYXEUSA-N 0.000 description 1
- IOWJRKAVLALBQB-IWGUZYHVSA-N Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O IOWJRKAVLALBQB-IWGUZYHVSA-N 0.000 description 1
- UCCNDUPVIFOOQX-CUJWVEQBSA-N Thr-Cys-His Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 UCCNDUPVIFOOQX-CUJWVEQBSA-N 0.000 description 1
- AQAMPXBRJJWPNI-JHEQGTHGSA-N Thr-Gly-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AQAMPXBRJJWPNI-JHEQGTHGSA-N 0.000 description 1
- IGGFFPOIFHZYKC-PBCZWWQYSA-N Thr-His-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O IGGFFPOIFHZYKC-PBCZWWQYSA-N 0.000 description 1
- KZURUCDWKDEAFZ-XVSYOHENSA-N Thr-Phe-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O KZURUCDWKDEAFZ-XVSYOHENSA-N 0.000 description 1
- WYLAVUAWOUVUCA-XVSYOHENSA-N Thr-Phe-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O WYLAVUAWOUVUCA-XVSYOHENSA-N 0.000 description 1
- XKWABWFMQXMUMT-HJGDQZAQSA-N Thr-Pro-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XKWABWFMQXMUMT-HJGDQZAQSA-N 0.000 description 1
- AHERARIZBPOMNU-KATARQTJSA-N Thr-Ser-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O AHERARIZBPOMNU-KATARQTJSA-N 0.000 description 1
- GRIUMVXCJDKVPI-IZPVPAKOSA-N Thr-Thr-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GRIUMVXCJDKVPI-IZPVPAKOSA-N 0.000 description 1
- AXEJRUGTOJPZKG-XGEHTFHBSA-N Thr-Val-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)O)N)O AXEJRUGTOJPZKG-XGEHTFHBSA-N 0.000 description 1
- BPGDJSUFQKWUBK-KJEVXHAQSA-N Thr-Val-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BPGDJSUFQKWUBK-KJEVXHAQSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- AVYVKJMBNLPWRX-WFBYXXMGSA-N Trp-Ala-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 AVYVKJMBNLPWRX-WFBYXXMGSA-N 0.000 description 1
- TWJDQTTXXZDJKV-BPUTZDHNSA-N Trp-Arg-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O TWJDQTTXXZDJKV-BPUTZDHNSA-N 0.000 description 1
- NXJZCPKZIKTYLX-XEGUGMAKSA-N Trp-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N NXJZCPKZIKTYLX-XEGUGMAKSA-N 0.000 description 1
- 241000711955 Turkey rhinotracheitis virus Species 0.000 description 1
- RCLOWEZASFJFEX-KKUMJFAQSA-N Tyr-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RCLOWEZASFJFEX-KKUMJFAQSA-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
- ULHJJQYGMWONTD-HKUYNNGSSA-N Tyr-Gly-Trp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O ULHJJQYGMWONTD-HKUYNNGSSA-N 0.000 description 1
- ADECJAKCRKPSOR-ULQDDVLXSA-N Tyr-His-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O ADECJAKCRKPSOR-ULQDDVLXSA-N 0.000 description 1
- MVFQLSPDMMFCMW-KKUMJFAQSA-N Tyr-Leu-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O MVFQLSPDMMFCMW-KKUMJFAQSA-N 0.000 description 1
- FMXFHNSFABRVFZ-BZSNNMDCSA-N Tyr-Lys-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O FMXFHNSFABRVFZ-BZSNNMDCSA-N 0.000 description 1
- XYNFFTNEQDWZNY-ULQDDVLXSA-N Tyr-Met-His Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N XYNFFTNEQDWZNY-ULQDDVLXSA-N 0.000 description 1
- NKMFRGPKTIEXSK-ULQDDVLXSA-N Tyr-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N NKMFRGPKTIEXSK-ULQDDVLXSA-N 0.000 description 1
- CGWAPUBOXJWXMS-HOTGVXAUSA-N Tyr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 CGWAPUBOXJWXMS-HOTGVXAUSA-N 0.000 description 1
- KWKJGBHDYJOVCR-SRVKXCTJSA-N Tyr-Ser-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)O KWKJGBHDYJOVCR-SRVKXCTJSA-N 0.000 description 1
- ZPFLBLFITJCBTP-QWRGUYRKSA-N Tyr-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O ZPFLBLFITJCBTP-QWRGUYRKSA-N 0.000 description 1
- MFEVVAXTBZELLL-GGVZMXCHSA-N Tyr-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MFEVVAXTBZELLL-GGVZMXCHSA-N 0.000 description 1
- JAQGKXUEKGKTKX-HOTGVXAUSA-N Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 JAQGKXUEKGKTKX-HOTGVXAUSA-N 0.000 description 1
- UBTBGUDNDFZLGP-SRVKXCTJSA-N Val-Arg-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](C(C)C)C(=O)O)N UBTBGUDNDFZLGP-SRVKXCTJSA-N 0.000 description 1
- OQWNEUXPKHIEJO-NRPADANISA-N Val-Glu-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N OQWNEUXPKHIEJO-NRPADANISA-N 0.000 description 1
- UEHRGZCNLSWGHK-DLOVCJGASA-N Val-Glu-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UEHRGZCNLSWGHK-DLOVCJGASA-N 0.000 description 1
- PIFJAFRUVWZRKR-QMMMGPOBSA-N Val-Gly-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O PIFJAFRUVWZRKR-QMMMGPOBSA-N 0.000 description 1
- SYOMXKPPFZRELL-ONGXEEELSA-N Val-Gly-Lys Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N SYOMXKPPFZRELL-ONGXEEELSA-N 0.000 description 1
- JPPXDMBGXJBTIB-ULQDDVLXSA-N Val-His-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N JPPXDMBGXJBTIB-ULQDDVLXSA-N 0.000 description 1
- LYERIXUFCYVFFX-GVXVVHGQSA-N Val-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LYERIXUFCYVFFX-GVXVVHGQSA-N 0.000 description 1
- JKHXYJKMNSSFFL-IUCAKERBSA-N Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN JKHXYJKMNSSFFL-IUCAKERBSA-N 0.000 description 1
- RWOGENDAOGMHLX-DCAQKATOSA-N Val-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N RWOGENDAOGMHLX-DCAQKATOSA-N 0.000 description 1
- DIOSYUIWOQCXNR-ONGXEEELSA-N Val-Lys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O DIOSYUIWOQCXNR-ONGXEEELSA-N 0.000 description 1
- HPANGHISDXDUQY-ULQDDVLXSA-N Val-Lys-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N HPANGHISDXDUQY-ULQDDVLXSA-N 0.000 description 1
- GJNDXQBALKCYSZ-RYUDHWBXSA-N Val-Phe Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 GJNDXQBALKCYSZ-RYUDHWBXSA-N 0.000 description 1
- GIAZPLMMQOERPN-YUMQZZPRSA-N Val-Pro Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O GIAZPLMMQOERPN-YUMQZZPRSA-N 0.000 description 1
- LGXUZJIQCGXKGZ-QXEWZRGKSA-N Val-Pro-Asn Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)N)C(=O)O)N LGXUZJIQCGXKGZ-QXEWZRGKSA-N 0.000 description 1
- LTTQCQRTSHJPPL-ZKWXMUAHSA-N Val-Ser-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N LTTQCQRTSHJPPL-ZKWXMUAHSA-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
- NLNCNKIVJPEFBC-DLOVCJGASA-N Val-Val-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O NLNCNKIVJPEFBC-DLOVCJGASA-N 0.000 description 1
- 241000711970 Vesiculovirus Species 0.000 description 1
- 208000002365 Viral Bronchiolitis Diseases 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 101710165741 Virion-associated protein Proteins 0.000 description 1
- 101000916336 Xenopus laevis Transposon TX1 uncharacterized 82 kDa protein Proteins 0.000 description 1
- 241000701815 Xipapillomavirus 1 Species 0.000 description 1
- 101001000760 Zea mays Putative Pol polyprotein from transposon element Bs1 Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 101000678262 Zymomonas mobilis subsp. mobilis (strain ATCC 10988 / DSM 424 / LMG 404 / NCIMB 8938 / NRRL B-806 / ZM1) 65 kDa protein Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 210000001691 amnion Anatomy 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 244000037640 animal pathogen Species 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 108010059459 arginyl-threonyl-phenylalanine Proteins 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 description 1
- 229960003159 atovaquone Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 206010006475 bronchopulmonary dysplasia Diseases 0.000 description 1
- 102220351054 c.122G>A Human genes 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 239000002962 chemical mutagen Substances 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 230000000959 cryoprotective effect Effects 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 108010060199 cysteinylproline Proteins 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 108010073628 glutamyl-valyl-phenylalanine Proteins 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 description 1
- 108010027668 glycyl-alanyl-valine Proteins 0.000 description 1
- 108010089804 glycyl-threonine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000003067 hemagglutinative effect Effects 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000029570 hepatitis D virus infection Diseases 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 108010040030 histidinoalanine Proteins 0.000 description 1
- 108010036413 histidylglycine Proteins 0.000 description 1
- 210000003701 histiocyte Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000001739 intranuclear inclusion body Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960003213 live attenuated measles Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000017156 mRNA modification Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- MWNFNXOAMKFJAE-UHFFFAOYSA-N methanamine;silver Chemical compound [Ag].NC MWNFNXOAMKFJAE-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 101150061325 mv gene Proteins 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 108010012581 phenylalanylglutamate Proteins 0.000 description 1
- 108010083476 phenylalanyltryptophan Proteins 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- AHUJXUYEELPHRR-UHFFFAOYSA-N pyrimidine;1h-pyrimidine-2,4-dione Chemical group C1=CN=CN=C1.O=C1C=CNC(=O)N1 AHUJXUYEELPHRR-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000000601 reactogenic effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 208000023021 right upper quadrant abdominal pain Diseases 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- -1 sodium glutamate) Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000005758 transcription activity Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 108010044292 tryptophyltyrosine Proteins 0.000 description 1
- 108010003137 tyrosyltyrosine Proteins 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 208000009421 viral pneumonia Diseases 0.000 description 1
- 229960004854 viral vaccine Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18411—Morbillivirus, e.g. Measles virus, canine distemper
- C12N2760/18422—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18522—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18611—Respirovirus, e.g. Bovine, human parainfluenza 1,3
- C12N2760/18622—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Definitions
- This invention relates to isolated, recombinantly-generated, attenuated, nonsegmented, negative-sense, single stranded RNA viruses of the Order designated Mononegavirales having at least one attenuating mutation in the 3 * genomic promoter region and having at least one attenuating mutation in the RNA polymerase gene.
- This invention was made with Government support under a grant awarded by the Public Health Service. The Government has certain rights in the inventio .
- RNA viruses are uniquely organized and expressed.
- the genomic RNA of negative-sense, single stranded viruses serves two template functions in the context of a nucleocapsid: as a template for the synthesis of messenger RNAs (mRNAs) and as a template for the synthesis of the antigenome (+) strand.
- Negative- sense, single stranded RNA viruses encode and package their own RNA dependent RNA Polymerase .
- Messenger RNAs are only synthesized once the virus has been uncoated in the infected cell. Viral replication occurs after synthesis of the mRNAs and requires the continuous synthesis of viral proteins .
- the newly synthesized antigenome (+) strand serves as the template for generating further copies of the (-) strand genomic RNA.
- the polymerase complex actuates and achieves transcription and replication by engaging the cis- acting signals at the 3' end of the genome, in particular, the promoter region.
- Viral genes are then transcribed from the genome template unidirectionally from its 3' to its 5' end. There is always less mRNA made from the downstream genes (e.g., the polymerase gene (L) ) relative to their upstream neighbors (i.e., the nucleoprotein gene (N) ) . Therefore, there is always a gradient of mRNA abundance according to the position of the genes relative to the 3 ' -end of the genome.
- This Order contains three families of enveloped viruses with single stranded, nonsegmented RNA genomes of minus polarity (negative-sense) . These families are the Paramyxoviridae, Rhabdoviridae and Filoviridae. The family Paramyxoviridae has been further divided into two subfamilies, Paramyxovirinae and Pneumovirinae . The subfamily Paramyxovirinae contains three genera, Paramyxovirus , RuJulavirus and Morbillivirus .
- the subfamily Pneumovirinae contains the genus Pneumov ⁇ ru ⁇ .
- the new classification is based upon morphological criteria, the organization of the viral genome, biological activities and the sequence relationships of the proteins .
- the morphological distinguishing feature among enveloped viruses for the subfamily Paramyxovirinae is the size and shape of the nucleocapsids (diameter 18mm, 1mm in length, pitch of 5.5 nm) , which have a left-handed helical symmetry.
- the biological criteria are: 1) antigenic cross-reactivity between members of a genus, and 2) the presence of neuraminidase activity in the genera Paramyxovirus, Ru ulavirus and its absence in genus Mox ⁇ illiv ⁇ rus .
- variations in the coding potential of the P gene are considered, as is the presence of an extra gene (SH) in Rubulaviruses.
- Pneumoviruses can be distinguished from
- Paramyxovirinae morphologically because they contain narrow nucleocapsids .
- pneumoviruses have major differences in the number of protein-encoding cistrons (10 in pneumoviruses versus 6 in Paramyxovirinae) and an attachment protein (G) that is very different from that of Paramyxovirinae.
- G attachment protein
- the paramyxoviruses and pneumoviruses have six proteins that appear to correspond in function (N, P, M, G/H/HN, F and L) , only the latter two proteins exhibit significant sequence relatedness between the two subfamilies.
- pneumoviral proteins lack counterparts in most of the paramyxoviruses, namely the nonstructural proteins NS1 and NS2, the small hydrophobic protein SH, and a second protein M2.
- C and V lack counterparts in pneumoviruses.
- the basic genomic organization of pneumoviruses and paramyxoviruses is the same. The same is true of rhabdoviruses and filoviruses. Table 1 presents the current taxonomical classification of these viruses, together with examples of each genus.
- Sendai virus (mouse parainfluenza virus type 1) Human parainfluenza virus (PIV) types 1 and 3
- Bovine parainfluenza virus type 3 Genus Rubulavirus Simian virus 5 (SV) (Canine parainfluenza virus type 2) Mumps virus
- Newcastle disease virus (avian Paramyxovirus 1) Human parainfluenza virus types 2, 4a and 4b Genus Morbilliv ⁇ rus
- MV Measles virus
- CDV Painschivirus Canine distemper virus
- Peste-des-petits-ruminants virus Phocine distemper virus Rinderpest virus Subfamily Pneumovirinae Genus Pneu ovirus
- Marburg virus For many of these viruses, no vaccines of any kind are available. Thus, there is a need to develop vaccines against such human and animal pathogens. Such vaccines would have to elicit a protective immune response in the recipient. The qualitative and quantitative features of such a favorable response are extrapolated from those seen in survivors of natural virus infection, who, in general, are protected from reinfection by the same or highly related viruses for some significant duration thereafter.
- a variety of approaches can be considered in seeking to develop such vaccines, including the use of: (1) purified individual viral protein vaccines (subunit vaccines) ; (2) inactivated whole virus preparations; and (3) live, attenuated viruses.
- Subunit vaccines have the desirable feature of being pure, definable and relatively easily produced in abundance by various means, including recombinant DNA expression methods. To date, with the notable exception of hepatitis B surface antigen, viral subunit vaccines have generally only elicited short-lived and/or inadequate immunity, particularly in naive recipients .
- IPV polio
- hepatitis A Formalin inactivated whole virus preparations of polio (IPV) and hepatitis A have proven safe and efficacious.
- immunization with similarly inactivated whole viruses such as respiratory syncytial virus and measles virus vaccines elicited unfavorable immune responses and/or response profiles which predisposed vaccinees to exaggerated or aberrant disease when subsequently confronted with the natural or "wild-type M virus.
- RSV vaccine candidates were generated by cold passage or chemical mutagenesis. These RSV strains were found to have reduced virulence in seropositive adults. Unfortunately, they proved either over or under- attenuated when given to seronegative infants; in some cases, they also were found to lack genetic stability (5,6). Another vaccination approach using parenteral administration of live virus was ineffective and efforts along this line were discontinued (7) . Notably, these live RSV vaccines were never associated with disease enhancement as observed with the formalin- inactivated RSV vaccine described above. Currently, there are no RSV vaccines approved for administration to humans, although clinical trials are now in progress with cold-passaged, chemically mutagenized strains of RSV designated A2 and B-l.
- Appropriately attenuated live derivatives of wild- type viruses offer a distinct advantage as vaccine candidates.
- live, replicating agents they initiate infection in recipients during which viral gene products are expressed, processed and presented in the context of the vaccinee' s specific MHC class I and II molecules, eliciting humoral and cell-mediated immune responses, as well as the coordinate cytokine patterns, which parallel the protective immune profile of survivors of natural infection.
- This favorable immune response pattern is contrasted with the delimited responses elicited by inactivated or subunit vaccines, which typically are largely restricted to the humoral immune surveillance arm.
- the immune response profile elicited by some formalin inactivated whole virus vaccines e.g., measles and respiratory syncytial virus vaccines developed in the 1960's, have not only failed to provide sustained protection, but in fact have led to a predisposition to aberrant, exaggerated, and even fatal illness, when the vaccine recipient later confronted the wild- type virus.
- This propagation/passage scheme typically leads to the emergence of virus derivatives which are temperature sensitive, cold-adapted and/or altered in their host range -- one or all of which are changes from the wild-type, disease-causing viruses -- i.e., changes that may be associated with attenuation.
- live virus vaccines including those for the prevention of measles and mumps (which are paramyxoviruses) , and for protection against polio and rubella (which are positive strand RNA viruses) , have been generated by this approach and provide the mainstay of current childhood immunization regimens throughout the world. Nevertheless, this means for generating attenuated live virus vaccine candidates is lengthy and, at best, unpredictable, relying largely on the selective outgrowth of those randomly occurring genomic mutants with desirable attenuation characteristics. The resulting viruses may have the desired phenotype in vi tro , and even appear to be attenuated in animal models. However, all too often they remain either under- or overattenuated in the human or animal host for whom they are intended as vaccine candidates.
- At least one attenuating mutation in the 3 ' genomic promoter region is selected from the group consisting of nucleotide 26 (A ⁇ T) , nucleotide 42 (A ⁇ T or A ⁇ C) and nucleotide 96 (G - A) , where these nucleotides, as well as others delineated in this application (unless stated otherwise) , are presented in positive strand, antigenomic, that is, message (coding) sense, and at least one attenuating mutation in the RNA polymerase gene is selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 331 (isoleucine — > threonine) , 1409 (alanine -» threonine) , 1624 (threonine —> alanine) , 1649 (arginine — > methionine) , 1717 (aspartic acid — a
- At least one attenuating mutation in the 3' genomic promoter region is selected from the group consisting of nucleotide 23 (T — > C) , nucleotide 24 (C -> T) , nucleotide 28 (G - T) and nucleotide 45 (T - A)
- at least one attenuating mutation in the RNA polymerase gene is selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 942 (tyrosine —> histidine) , 992 (leucine —» phenylalanine) , 1292 (leucine —> phenylalanine) , and 1558 (threonine —» isoleucine) .
- At least one attenuating mutation in the 3 ' genomic promoter region is selected from the group consisting of nucleotide 4 (C — G) and the insertion of an additional A in the stretch of A's at nucleotides 6-11, and at least one attenuating mutation in the RNA polymerase gene is selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 353 (arginine — > lysine) , 451 (lysine — arginine) , 1229 (aspartic acid — asparagine) , 2029 (threonine —> isoleucine) and 2050 (asparagine — ⁇ aspartic acid) .
- Attenuated virus is used to prepare vaccines which elicit a protective immune response against the wild- type form of the virus .
- an isolated, positive strand, antigenomic message sense nucleic acid molecule or an isolated, negative strand genomic sense nucleic acid molecule having the complete viral nucleotide sequence (whether of wild- type virus or virus attenuated by non-recombinant means) is manipulated by introducing one or more of the attenuating mutations described in this application to generate an isolated, recombinantly-generated attenuated virus. This virus is then used to prepare vaccines which elicit a protective immune response against the wild-type form of the virus.
- such a complete wild- type or vaccine viral nucleotide sequence is used: (1) to design PCR primers for use in a PCR assay to detect the presence of the corresponding virus in a sample; or (2) to design and select peptides for use in an ELISA to detect the presence of the corresponding virus in a sample.
- Figure 1 depicts the passage history of the Editionston measles virus (15) .
- the abbreviations have the following meanings: HK - human kidney; HA - human amnion; CE(am) - chick embryo; CEF - chick embryo fibroblast; DK - dog kidney; WI-38 - human diploid cells; SK - sheep kidney; * - plaque cloning.
- the number following each abbreviation represents the number of passages .
- Figure 2 depicts a map of the measles virus genome showing putative cis-acting regulatory elements at and near the genome and antigenome termini.
- Top a schematic map of the measles virus genome, beginning at the 3 ' end with 52 nucleotides of leader sequence (1) and ending at the 5' terminus with 37 nucleotides of trailer sequence (t) . Gene boundaries are denoted by vertical bars; below each gene is the number of cistronic nucleotides.
- Bottom an expanded schematic view of the 3 ' extended genomic promoter regions of genome and antigenome, showing the position and sequence of the two highly conserved domains, A and B. The intervening intergenic trinucleotide is denoted as well. Nascent 5' RNAs encompassing the A' to B* regions are presumed to contain the regulatory sequence at which the N protein encapsidation initiates.
- Figure 3 depicts a genetic map of the RSV subgroup B wild- type strains designated 2B and 18537 (top portion) , the intergenic sequences of those strains (middle portion) and the 68 nucleotide overlap between the M2 and L genes (bottom portion) .
- the RSV 2B stain has six fewer nucleotides in the G gene, encoding two fewer amino acid residues in the G protein, as compared to the 18537 strain.
- the 2B strain has 145 nucleotides in the 5' trailer region, as compared to 149 nucleotides in the 18537 strain.
- the 2B strain has one more nucleotide in each of the NS-1, NS-2 and N genes, and one fewer nucleotide in each of the M and F genes, as compared to the 18537 strain.
- RNA viral genomes Transcription and replication of negative- sense, single stranded RNA viral genomes are achieved through the enzymatic activity of a multimeric protein acting on the ribonucleoprotein core (nucleocapsid) .
- Naked genomic RNA cannot serve as a template. Instead, these genomic sequences are recognized only when they are entirely encapsidated by the N protein into the nucleocapsid structure. It is only in that context that the genomic and antigenomic terminal promoter sequences are recognized to initiate the transcriptional or replication pathways .
- All paramyxoviruses require the two viral proteins, L and P, for these polymerase pathways to proceed.
- the pneumoviruses, including RSV also require the transcription elongation factor, M2, for the transcriptional pathway to proceed efficiently.
- Additional cofactors may also play a role, including perhaps the virus-encoded NSl and NS2 proteins, as well as perhaps host-cell encoded proteins.
- L protein which performs most, if not all, the enzymatic processes associated with transcription and replication, including initiation, and termination of ribonucleotide polymerization, capping and polyadenylation of mRNA transcripts, methylation and perhaps specific phosphorylation of P proteins.
- the L protein's central role in genomic transcription and replication is supported by its large size, sensitivity to mutations, and its catalytic level of abundance in the transcriptionally active viral complex (16) .
- L proteins consist of a linear array of domains whose concatenated structure integrates discrete functions (17) .
- three such delimited, discrete elements within the negative-sense virus L protein have been identified based on their relatedness to defined functional domains of other well-characterized proteins. These include: (1) a putative RNA template recognition and/or phosphodiester bond formation domain; (2) an RNA binding element; and (3) an ATP binding domain. All prior studies of L proteins of nonsegmented negative-sense, single stranded RNA viruses have revealed these putative functional elements (17) .
- the invention is believed to encompass a coordinate set of changes between the cis- acting regulatory signal (3' genomic promoter region) and the polymerase gene (L) which results in attenuation of the virus while retaining sufficient ability of the virus to replicate.
- Attenuation is optimized by rational mutations of the 3 ' genomic promoter region and the polymerase gene, which provide the desired balance of replication efficiency: so that the virus vaccine is no longer able to produce disease, yet retains its capacity to infect the vaccinee' s cells, to express sufficiently abundant gene products to elicit the full spectrum and profile of desirable immune responses, and to reproduce and disseminate sufficiently to maximize the abundance of the immune response elicited.
- Attenuating mutations in the extended promoter (3 * genomic promoter region) and in the polymerase gene are believed to affect the display of cis-acting signals and the conformation of the polymerase complex engaging these signals.
- the promoter RNA when encapsidated, the promoter RNA is coiled in a helical array. Changes in promoter sequence may affect the relative positions at which the conserved signals are displayed relative to one another.
- the measles wild-type 3' genomic promoter region has a pyrimidine (uracil) at positions 26 and 42 (the antigenomic message sense sequences have the purine adenine) .
- the vaccine strains have purines at those positions (the antigenomic message sense sequences have the corresponding pyrimidines; see Table 3 in Example 1 below) .
- the larger purines may change the distance and/or angular display between the conserved domains of the promoter (e.g, in measles, positions 1-11 and 87- 98) , resulting in an altered spatial presentation of the cis-acting signals to the polymerase.
- the attenuating mutations described herein may be introduced into viral strains by two methods :
- a preferred means of introducing attenuating mutations comprises making predetermined mutations using site-directed mutagenesis. These mutations are identified either by method (1) or by reference to closely-related viruses whose attenuating mutations are already known. One or more mutations are introduced into each of the 3 ' genomic promoter region and the polymerase gene. Cumulative effects of different combinations of coding and non-coding changes can also be assessed.
- the mutations to the 3 ' genomic promoter region and polymerase gene are introduced by standard recombinant DNA methods into a DNA copy of the viral genome.
- This may be a wild-type or a modified viral genome background (such as viruses modified by method (1)), thereby generating a new virus.
- Infectious clones or particles containing these attenuating mutations are generated using the cDNA "rescue" system, which has been applied to a variety of viruses, including Sendai virus (18) ; measles virus (19) ; respiratory syncytial virus (20) ; rabies (21) ; vesicular stomatitis virus (VSV) (15) ; and rinderpest virus (23); these references are hereby incorporated by reference.
- RNA polymerase promoter e.g., the T7 RNA polymerase promoter
- ribozyme sequence e.g., the hepatitis delta ribozyme
- This transcription vector provides the readily manipulable DNA template from which the RNA polymerase (e.g., T7 RNA polymerase) can faithfully transcribe a single-stranded RNA copy of the viral antigenome (or genome) with the precise, or nearly precise, 5' and 3' termini.
- the orientation of the viral genomic DNA copy and the flanking promoter and ribozyme sequences determine whether antigenome or genome RNA equivalents are transcribed.
- virus-specific trans-acting proteins needed to encapsidate the naked, single-stranded viral antigenome or genome RNA transcripts into functional nucleocapsid templates: the viral nucleocapsid (N or NP) protein, the polymerase-associated phosphoprotein (P) and the polymerase (L) protein. These proteins comprise the active viral RNA-dependent RNA polymerase which must engage this nucleocapsid template to achieve transcription and replication.
- the trans-acting proteins required for measles virus rescue are the encapsidating protein N, and the polymerase complex proteins, P and L.
- the encapsidating protein is designated NP
- the polymerase complex proteins are also referred to as P and L.
- the virus-specific trans-acting proteins include N, P and L, plus an additional protein, M2, the RSV-encoded transcription elongation factor.
- these viral trans-acting proteins are generated from one or more plasmid expression vectors encoding the required proteins, although some or all of the required trans-acting proteins may be produced within mammalian cells engineered to contain and express these virus-specific genes and gene products as stable transformants .
- the typical (although not necessarily exclusive) circumstances for rescue include an appropriate mammallian cell milieu in which T7 polymerase is present to drive transcription of the antigenomic (or genomic) single-stranded RNA from the viral genomic cDNA-containing transcription vector.
- this viral antigenome (or genome) RNA transcript is encapsidated into functional templates by the nucleocapsid protein and engaged by the required polymerase components produced concurrently from co- transfected expression plasmids encoding the required virus-specific trans-acting proteins.
- T7 polymerase is provided by recombinant vaccinia virus VTF7-3.
- This system requires that the rescued virus be separated from the vaccinia virus by physical or biochemical means or by repeated passaging in cells or tissues that are not a good host for poxvirus.
- MV cDNA rescue this requirement is avoided by creating a cell line that expresses T7 polymerase, as well as viral N and P proteins. Rescue is achieved by transfecting the genome expression vector and the L gene expression vector into the helper cell line.
- MVA-T7 which expresses the T7 RNA polymerase, but does not replicate in mammalian cells, are exploited to rescue RSV, Rinderpest virus and MV.
- synthetic full length antigenomic viral RNA are encapsidated, replicated and transcribed by viral polymerase proteins and replicated genomes are packaged into infectious virions .
- genome analogs have now been successfully rescued for Sendai and PIV-3 (25,27).
- the rescue system thus provides a composition which comprises a transcription vector comprising an isolated nucleic acid molecule encoding a genome or antigenome of a nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales having at least one attenuating mutation in the 3 ' genomic promoter region and having at least one attenuating mutation in the RNA polymerase gene, together with at least one expression vector which comprises at least one isolated nucleic acid molecule encoding the transacting proteins necessary for encapsidation, transcription and replication (e.g., N, P and L for measles virus; NP, P and L for PIV-3; N, P, L and M2 for RSV) .
- Host cells are then transformed or transfected with the at least two expression vectors just described. The host cells are cultured under conditions which permit the co-expression of these vectors so as to produce the infectious attenuated virus .
- the rescued infectious virus is then tested for its desired phenotype (temperature sensitivity, cold adaptation, plaque morphology, and transcription and replication attenuation), first by in vi tro means.
- the mutations at the cis-acting 3 ' genomic promoter region are also tested using the minireplicon system where the required trans-acting encapsidation and polymerase activities are provided by wild-type or vaccine helper viruses, or by plasmids expressing the N, P and different L genes harboring gene-specific attenuating mutations (19,28).
- Non-human primates provide the preferred animal model for the pathogenesis of human disease. These primates are first immunized with the attenuated, recombinantly-generated virus, then challenged with the wild-type form of the virus. Monkeys are infected by various routes, including but not limited to intranasal, intratracheal or subcutaneous routes of inoculation (29) . Experimentally infected rhesus and cynomolgus macaques have also served as animal models for studies of vaccine-induced protection against measles (30) . Protection is measured by such criteria as disease signs and symptoms, survival, virus shedding and antibody titers.
- the attenuated, recombinantly-generated virus is considered a viable vaccine candidate for testing in humans.
- the "rescued” virus is considered to be “recombinantly- generated", as are the progeny and later generations of the virus, which also incorporate the attenuating mutations.
- a codon containing an attenuating point mutation may be stabilized by introducing a second or a second plus a third mutation in the codon without changing the amino acid encoded by the codon bearing only the attenuating point mutation.
- Infectious virus clones containing the attenuating and stabilizing mutations are also generated using the cDNA "rescue" system described above.
- Measles virus serves as a useful model for this invention, because sequence data are now available as described herein for the disease-causing wild- type virus and for the disease-preventing vaccines which have a demonstrated history of efficacy.
- Measles virus was first isolated in tissue culture in 1954 (31) from an infected patient named David Editionston.
- This Edmonston strain of measles became the progenitor for many live-attenuated measles vaccines including Moraten, which is the current vaccine in the United States (AttenuvaxTM; Merck Sharp & Dohme, West Point, PA) and was licensed in 1968 and has proven to be efficacious.
- Aggressive immunization programs instituted in the mid to late 1960s resulted in the precipitous drop in reported measles cases from near 700,000 in 1965 to 1500 in 1983.
- other vaccine strains were also developed from the Editionston strain
- Live measles virus vaccine provides a success story of the development of an efficacious vaccine and provides a model for understanding the molecular mechanisms of viral vaccine attenuation among nonsegmented, negative-sense, single stranded RNA viruses. Because of its significance as a major cause of human morbidity and mortality, measles virus (MV) has been quite extensively studied. MV is a large, relatively spherical, enveloped particle composed of two compartments, a lipoprotein membrane and a ribonucleoprotein particle core, each having distinct biological functions (33) .
- the virion envelope is a host cell-derived plasma membrane modified by three virus-specified proteins: The hemagglutinin (H; approximately 80 kilodaltons (kD) ) and fusion (F 12 ; approximately 60 kD) glycoproteins project on the virion surface and confer host cell attachment and entry capacities to the viral particle (16) . Antibodies to H and/or F are considered protective since they neutralize the virus' ability to initiate infection (34,35,36).
- the matrix (M; approximately 37 kD) protein is the amphipathic protein lining the membrane's inner surface, which is thought to orchestrate virion morphogenesis and thus consummate virus reproduction (37) .
- the virion core contains the 15,894 nucleotide long genomic RNA upon which template activity is conferred by its intimate association with approximately 2600 molecules of the approximately 60 kD nucleocapsid (N) protein (38,39,40). Loosely associated with this approximately one micron long helical ribonucleoprotein particle are enzymatic levels of the viral RNA dependent RNA polymerase (L; approximately 240 kD) which in concert with the polymerase cofactor (P; approximately 70 kD) , and perhaps yet other virus-specified as well as host-encoded proteins, transcribes and replicates the MV genome sequences (41) .
- L viral RNA dependent RNA polymerase
- P polymerase cofactor
- C approximately 20 kD
- V approximately 45 kD
- the MV genome contains distinctive non-protein coding domains resembling those directing the transcriptional and replicative pathways of related viruses (16,42). These regulatory signals lie at the 3 ' and 5 ' ends of the MV genome and in short internal regions spanning each intercistroni ⁇ boundary.
- the former encode the putative promoter and/or regulatory sequence elements directing genomic transcription, genome and antigenome encapsidation, and replication.
- the latter signal transcription termination and polyadenylation of each monocistronic viral mRNA and then reinitiation of transcription of the next gene.
- the MV polymerase complex appears to respond to these signals much as the RNA-dependent RNA polymerases of other non-segmented negative strand RNA viruses (16,42,43,44). Transcription initiates at or near the 3' end of the MV genome and then proceeds in a 5 ' direction producing monocistronic mRNAs (40,42,45).
- stop/start signals which, in 3 ' to 5' order, are: a semi-conserved transcription termination/polyadenylation signal (A/G U/C UA A/U NN A 4 , where N may be any of the four bases) at which each monocistronic RNA is completed; a non-transcribed intergenic trinucleotide punctuation mark (CUU; except at the H:L boundary where it is CGU) ; and a semiconserved start signal for transcription initiation of the next gene (AGG A/G NN C/A A A/G G A/U, where N may be any of the four bases) (45,46).
- A/G U/C UA A/U NN A 4 where N may be any of the four bases
- each MV mRNA diminishes in parallel with the distance of the encoding gene from the genomic 3 ' end. This mRNA gradient directly corresponds to the relative abundance of each virus-specified protein. This indicates that MV protein expression is ultimately controlled at the transcriptional level (44) .
- the 3 ' and 5 ' MV genomic termini contain non-protein coding sequences with distinct parallels to the leader and trailer RNA encoding regions of VSV (42) .
- Nucleotides 1-55 define the region between the genomic 3' terminus and the beginning of the N gene, while 37 additional nucleotides can be found between the end of the L gene and the 5 ' terminus of the genome.
- MV does not transcribe these terminal regions into short, unmodified (+) or (-) sense leader RNAs (47,48,49) .
- leader readthrough transcripts including full-length polyadenylated leader :N, leader:N:P, leader:N:P:M, and of course full-length antigenome MV RNAs are transcribed (48,49).
- the short leader transcript the key operational element determining the switch from transcription to replication of the VSV single- stranded, negative polarity genome (50,51,52), seems absent in MV. This leads to consideration and exploration of alternative models for this crucial reproductive event (42) .
- Measles virus as well as all other Mononegavirales except the rhabdoviruse ⁇ , appears to have extended its terminal regulatory domains beyond the confines of leader and trailer encoding sequences (42) .
- these regions encompass the 107 3' genomic nucleotides (the "3' genomic promoter region”, also referred to as the “extended promoter”, which comprises 52 nucleotides encoding the leader region, followed by three intergenic nucleotides, and 52 nucleotides encoding the 5 ' untranslated region of N mRNA) and the 109 5' end nucleotides (69 encoding the 3 ' untranslated region of L mRNA, the intergenic trinucleotide and 37 nucleotides encoding the trailer) .
- the 3' genomic promoter region also referred to as the "extended promoter” which comprises 52 nucleotides encoding the leader region, followed by three intergenic nucleotides, and 52 nucleotides encoding the
- these discrete sequence elements may dictate alternative sites of transcription initiation -- the internal domain mandating transcription initiation at the N gene start site, and the 3* terminal domain directing antigenome production (42,48,53).
- these 3* extended genomic and antigenomic promoter regions encode the nascent 5 ' ends of antigenome and genome RNAs, respectively.
- Within these nascent RNAs reside as yet unidentified signals for N protein nucleation, another key regulatory element required for nucleocapsid template formation and consequently for amplification of transcription and replication.
- Figure 2 schematically shows the location and sequence of these highly conserved, putative cis-acting regulatory domains .
- Terminal non-protein coding regions similar in location, size and spacing are present in the genomes of other members of the genus Paramyxoviridae , though only 8-11 of their absolute terminal nucleotides are shared by MV (42,54) .
- the genomic terminii of the -brbillivirus canine distemper virus (CDV) displays a greater degree of homology with its MV relative: 73% of the nucleotides of the leader and trailer sequences of these two viruses are identical, including 16 of 18 at the absolute 3' termini and 17 of 18 at their 5' ends (55) . No accessory internal CDV genomic domain- sharing homology to that of the MV extended promoter has been found.
- CDV genomic nucleotides 85 and 104 and 15,587 and 15,606 in which 15 of the 20 nucleotides are complementary.
- CDV like MV contains an additional region within its non-coding 3' genomic and antigenomic ends that may provide important cis-acting promoter and/or regulatory signals (55) .
- the precise length of the 3 ' - leader region is identical among several members of the Family Paramyxoviridae (MV, CDV, PIV-3, BPV-3, SV and NDV). Further evidence for the importance of these extended, non-protein coding regions comes from analyses of a large number of distinct copy-back Defective Interfering Viruses (DIs) recently cloned from subacute sclerosing panencephalitis (SSPE) brain tissue. No DI with a stem shorter than the 95 5 ' terminal genomic nucleotides was found. This indicates that the minimal signals needed for MV DI RNA replication and encapsidation extend well beyond the 37 nucleotide long trailer sequence to encompass the additional internal putative regulatory domain (56) .
- DIs Defective Interfering Viruses
- this invention is directed to the concept that important virulence/attenuation determinants reside in viral genomic non-protein coding regulatory regions and in the transacting transcription/replication enzyme complex with which these cis-acting elements must interact.
- the cis-acting domains are found both at the 3' and 5' ends of the MV genome, flanking the six contiguous genes encoding viral structural proteins; and within the MV genome as short regions encompassing internal intergenic boundaries .
- the former encode the putative promoter and/or regulatory sequence elements directing the vital processes of genomic transcription, genome and antigenome encapsidation, and replication.
- RNA dependent RNA polymerase molecule can modulate transcription and/or replicative efficiency, thereby determining the abundance of cytopathic viral gene products and/or virion progeny.
- Proof of the concept of this invention for measles virus is obtained by first determining the nucleotide sequences of the non-coding regulatory regions (3 1 genomic promoter region) and the coding regions of the L gene (with predicted amino acid sequences) of the progenitor Editionston wild-type MV isolate, together with available measles vaccine strains derived from this isolate (see Figure 1) .
- Each measles virus genome listed above is 15,894 nucleotides in length.
- Translation of the L gene starts with the codon at nucleotides 9234-9236; the translation stop codon is at nucleotides 15783- 15785.
- the translated L protein is 2,183 amino acids long.
- nucleotide 2499 of 1983 wild-type measles virus is indicated as "G” in SEQ ID NO: 5.
- the base is actually a mixture of W G" and W C" .
- nucleotide 2143 of RubeovaxTM vaccine virus is indicated as “T” in SEQ ID NO: 9. In nine clones sequenced, this base was "T” in seven and W C" in two; thus, this base can be M T" or "C” .
- the Schwarz vaccine virus genome is identical to that of the Moraten vaccine virus genome (SEQ ID NO:ll), except that at nucleotides 4917 and 4924, Schwarz has a W C" instead of a "T” .
- Nucleotide differences distinguishing the 3 ' genomic promoter region and nucleotide and amino acid differences distinguishing the L gene and L protein sequences of the Edmonston wild- type isolate, vaccine strains and other independently isolated wild- type viruses were then compared and aligned (see Tables 3-5 in Example 1 below) .
- AIK-C vaccine strain nucleotide sequence differs from the published sequence (33) at 21 positions, including one insertion and one deletion.
- Several of these differences result in coding changes including two in the L gene (at amino acids 1477 and 2008) .
- the additional changes accrued within the L gene sequence as the measles progenitor strain is progressively attenuated to achieve a replicative capacity optimized for live vaccine purposes appears to be constrained and delimited.
- this limited tolerance in the number and location of L gene changes is imposed not only by the need to preserve the multifunctional capacities of the polymerase, but also by the preexisting 3' promoter changes with which the evolving L protein must interact to achieve transcription and replication.
- optimal virus attenuation requires coordinate (i.e., linked) changes in the polymerase protein and the cis-acting regulatory elements on which it acts.
- the 3 '-leader displays the least tolerance for change, allowing highly selected changes during the attenuation process at nucleotide position 26 (always the change of from “A” to “T"), and at position 42 (the change of from “A” to “C” or from “A” to “T”) (in antigenomic, message sense) .
- Zagreb only, there is a single further change, from "G” to "A” at position 96, which may be important when combined with Zagreb L gene-specific changes.
- the 3 ' -leader region seems to have undergone only one instance of genetic drift since 1954, with a change of "G” to "A” at position 50 (see Table 3) .
- the net change in the 3 ' genomic promoter region during the attenuation process is the replacement of two pyrimidines by two purines in genomic sense in all MV vaccine strains.
- the co- evolution of the L gene during these attenuation processes is believed to reflect selection of subtle changes favoring reproduction of the viruses in different host cells.
- All the vaccine strains were grown in chick embryo (CE) or chick embryo fibroblast (CEF) cells during their attenuation process ( Figure 1) .
- some vaccine strains have been exposed to unique host cells; i.e., Zagreb vaccine was grown in dog kidney cells and human diploid cells, while the AIK-C vaccine was adapted to sheep kidney cells. Moraten and RubeovaxTM were exclusively developed in CE and CEF.
- lineage-specific L gene changes position 1649 in RubeovaxTM, Moraten and Schwarz vaccines and the change at position 1717 in all vaccines
- individual vaccine-specific changes may provide additional fine tune modulation of virus replication/transcription for each vaccine strain.
- nucleotide 26 A — > T
- nucleotide 42 A ⁇ T or A ⁇ C
- nucleotide 96 G ⁇ A (in antigenomic, message sense)
- the key attenuating sites for the L protein are as follows: amino acid residues 331 (isoleucine -» threonine) , 1409 (alanine - threonine) , 1624 (threonine — alanine) , 1649 (arginine —» methionine) , 1717 (aspartic acid —> alanine) , 1936 (histidine -» tyrosine), 2074 (glutamine -> arginine) and 2114 (arginine — > lysine) .
- HPIV-3 Human parainfluenza virus type 3 (HPIV-3) is another nonsegmented, negative-sense, single stranded enveloped RNA virus.
- HPIV-3 belongs to the Family Paramyxoviridae (see Table 1) .
- the genome of HPIV-3 is 15,462 nucleotides long and encodes six non-overlapping protein-encoding genes (57) .
- NP corresponding to the N protein of MV
- M corresponding to the N protein of MV
- F hemagglutinin-neura inidase
- L hemagglutinin-neura inidase
- HPIV-3 Like MV, HPIV-3 consists of a 3 ⁇ -nonprotein coding leader region of 55 nucleotides, but unlike measles (where it is 37 nucleotides) , it has a 44 nucleotide long 5' -trailer region.
- the polymerase transcribes the genome in a linear, sequential, start- stop manner which is guided by transcription signals in the RNA template .
- Attempts to develop a live attenuated HPIV-3 vaccine by passaging the wild-type virus JS strain through cell culture at sub-optimal temperature has produced promising results (7,57).
- cp "cold passage" mutants were isolated for evaluation from different passage levels of the JS strain. One such mutant resulted from 45 serial passages and was designated cp45.
- This virus exhibited three interesting properties: (1) cold adaptation (ca) : the ability to replicate efficiently at the suboptimal temperature of 20°C; (2) temperature sensitivity (ts) : inability to replicate in vi tro at temperatures greater than or equal to 39°C; and (3) small plaque morphology.
- This mutant appeared to be a promising vaccine candidate because: (a) its ca , ts and small plaque phenotype is stable after passage in cell culture; (b) its replication is restricted in both the upper and lower respiratory tract of hamsters; and (c) it induced significant protection in hamsters against subsequent challenge with wild- type HPIV-3 (58,59).
- the cp45 strain has been grown in both fetal rhesus lung (FRhL) and Vero cells as follows:
- the PIV- 3 cp45 virus grown in FRhL cells was prepared by inoculating confluent FRhL cell monolayers in tissue culture flasks at an MOI 0.1-1.0.
- the infected cell cultures were fed with EMEM medium and incubated at 32°C.
- the virus was harvested by subjecting the cultures to one freeze-thaw cycle, pooling the fluids and then storing the virus at -70 °C.
- the PIV-3 cp45 virus grown in Vero cells was prepared by inoculating with virus a bioreactor culture of confluent monolayers of Vero cells on microcarrier beads which was continuously stirred. The infected bioreactor culture was maintained at 30°C. The virus was harvested 4-5 days later when syncytial CPE was observed. The culture fluid containing the virus was stored at -70 °C.
- nucleotide sequences (in positive strand, antigenomic, message sense) of the HPIV-3 JS wild- type strain (89) and the cp45 vaccine strain grown in FRhL and Vero cells, as well as the deduced amino acid sequences of the RNA polymerase (L protein) of these HPIV-3 viruses, are set forth as follows with reference to the appropriate SEQ ID NOS. contained herein:
- Each PIV-3 virus genome listed above is 15,462 nucleotides in length. Translation of the L gene starts with the codon at nucleotides 8646-8648; the translation stop codon is at nucleotides 15345- 15347. The translated L protein is 2,233 amino acids long.
- the key attenuating mutations for the HPIV-3 3' genomic promoter region are nucleotide 23 (T — > C) , nucleotide 24 (C — > T) , nucleotide 28 (G — > T) and nucleotide 45 (T — A) (in antigenomic, message sense).
- key attenuating sites for the L protein of HPIV- 3 include the following: amino acid residues 942 (tyrosine —> histidine) , 992 (leucine — phenylalanine) and 1558 (threonine —> isoleucine) .
- the Vero-grown cp45 mutant vaccine strain contains an additional mutation resulting from a coding change in the L gene at amino acid residue 1292 (leucine - phenylalanine) . It is understood that the nucleotide changes responsible for these amino acid changes are not limited to those set forth in Example 2 below; all changes in nucleotides which result in codons which are translated into these amino acids are within the scope of this invention.
- RSV Human respiratory syncytial virus
- RSV belongs to the Subfamily Pneumovirinae and the genus Pneumovirus (see Table 1) .
- a and B Two major subgroups of human RSV, designated A and B, have been identified based on reactivities of the F and G surface glycoproteins with monoclonal antibodies (62) . More recently, the A and B lineages of RSV strains have been confirmed by sequence analysis (63,64). Bovine, ovine, and caprine strains of this virus have also been isolated. The host specificity of the virus is most clearly associated with the G attachment protein, which is highly divergent between the human and the bovine/ovine strains (65,66), and may be influenced, at least in part, by receptor binding.
- RSV is the primary cause of serious viral pneumonia and bronchiolitis in infants and young children.
- Serious disease i.e., lower respiratory tract disease (LRD)
- LFD lower respiratory tract disease
- RSV additionally is associated with asthma and hyperreactive airways and it is a significant cause of mortality in "high risk" children with bronchopulmonary dysplasia and congenital heart disease (CHD) .
- CHD congenital heart disease
- RSV In adults, RSV generally presents as uncomplicated upper respiratory illness; however, in the elderly it rivals influenza as a predisposing factor in the development of serious LRD, particularly bacterial bronchitis and pneumonia. Disease is always confined to the respiratory tract, except in the severely immunocompromised, where dissemination to other organs can occur. Virus is spread to others by fomites contaminated with virus-containing respiratory secretions, and infection initiates through the nasal, oral, or conjunctival mucosa.
- RSV disease is seasonal and virus is usually isolated only in the winter months, e.g., from November to April in northern latitudes. The virus is ubiquitous, and over 90% of children have been infected at least once by 2 years of age. Multiple strains cocirculate. There is no direct evidence of antigenic drift (such as that seen with influenza A viruses) , but sequence studies demonstrating accumulation of amino acid changes in the hypervariable regions of the G protein and SH proteins suggest that immune pressure may drive virus evolution.
- the RSV virion consists of a ribonucleoprotein core contained within a lipoprotein envelope.
- the virions of pneumoviruses are similar in size and shape to those of all other paramyxoviruses. When visualized by negative staining and electron microscopy, virions are irregular in shape and range in diameter from 150-300 nm (74) .
- the nucleocapsid of this virus is a symmetrical helix similar to that of other paramyxoviruses, except that the helical diameter is 12-15 nm rather than 18nm.
- the envelope consists of a lipid bilayer that is derived from the host membrane and contains virally coded transmembrane surface glycoproteins . The viral glycoproteins mediate attachment and penetration and are organized separately into virion spikes. All members of paramyxovirus subfamily have hemagglutinating activity, but this function is not a defining feature for pneumoviruses, being absent in RSV but present in PVM (75) . Neuraminidase activity is present in members of the genera Paramyxovirus, Rubulavirus, and is absent in Morbillivirus and Pneumovirus of mice (PVM) (75) .
- RSV possesses two subgroups, designated A and B.
- the wild- type RSV (strain 2B) genome is a single strand of negative-sense RNA of 15,218 nucleotides (SEQ ID NO: 23) that are transcribed into ten major subgenomic mRNAs.
- Each of the ten mRNAs encodes a major polypeptide chain: Three are transmembrane surface proteins (G, F and SH) ; three are the proteins associated with genomic RNA to form the viral nucleocapsid (N, P and L) ; two are nonstructural proteins (NSl and NS2) which accumulate in the infected cells but are also present in the virion in trace amounts and may play a role in regulating transcription and replication; one is the nonglycosylated virion matrix protein (M) ; and the last is M2, another nonglycosylated protein recently shown to be an RSV- specified transcription elongation factor (see Figure 3) . These ten viral proteins account for nearly all of the viral coding capacity.
- the viral genome is encapsidated with the major nucleocapsid protein (N) , and is associated with the phosphoprotein (P) , and the large (L) polymerase protein. These three proteins have been shown to be necessary and sufficient for directing RNA replication of cDNA encoded RSV minigenomes (76) . Further studies have shown that for transcription to proceed with full processing, the M2 protein (ORF 1) is required (74) . When the M2 protein is missing, truncated transcripts predominate, and rescue of the full length genome does not occur (74) . Both the M (matrix protein) and the M2 proteins are internal virion-associated proteins that are not present in the nucleocapsid structure.
- the M protein is thought to render the nucleocapsid transcriptionally inactive before packaging and to mediate its association with the viral envelope.
- the NSl and NS2 proteins have only been detected in very small amounts in purified virions, and at this time are considered non-structural . Their functions are uncertain, though they may be regulators of transcription and replication.
- Three transmembrane surface glycoproteins are present in virions: G, F, and SH.
- G and F (fusion) are envelope glycoproteins that are known to mediate attachment and penetration of the virus into the host cell. In addition, these glycoproteins represent major independent immunogens (77) .
- Genomic RNA is neither capped nor polyadenylated (79) . In both the virion and intracellularly, genomic RNA is tightly associated with the N protein. The 3* end of the genomic RNA consists of a 44-nucleotide extragenic leader region that is presumed to contain the major viral promoter (Fig. 3) .
- the 3' genomic promoter region is followed by ten viral genes in the order 3 ' -NS1-NS2-N-P-M-SH-G-F-M2-L-5 ' (Fig. 3).
- the L gene is followed by a 145-149 nucleotide extragenic trailer region (see Figure 3) .
- Each gene begins with a conserved nine-nucleotide gene start signal 3 ' -GGGGCAAAU (except for the ten-nucleotide gene start signal of the L gene, which is 3 • -GGGACAAAAU; differences underlined) .
- transcription begins at the first nucleotide of the signal.
- Each gene terminates with a semi-conserved 12-14 nucleotide gene end (3' -A G U/G U/A ANNN U/A A 3 . 5 ) (where N can be any of the four bases) that directs transcription termination and polyadenylation (Fig. 3) .
- the first nine genes are non-overlapping and are separated by intergenic regions that range in size from 3 to 56 nucleotides for RSV B strains (Fig. 3) .
- the intergenic regions do not contain any conserved motifs or any obvious features of secondary structure and have been shown to have no influence on the preceding and succeeding gene expression in a minreplicon system (Fig. 3) .
- the last two RSV genes overlap by 68 nucleotides (Fig. 3) .
- the gene-start signal of the L gene is located inside of, rather than after, the M2 gene.
- This 68 nucleotide overlap sequence encodes the last 68 nucleotides of the M2 mRNA (exclusive of the Poly-A tail) , as well as the first 68 nucleotides of the L mRNA.
- the L gene start signal lies 68 nucleotides upstream of the M2 gene-end signal, resulting in gene overlap (Fig. 3) (74) .
- the presence of the M2 gene-end signal within the L gene results in a high frequency of premature termination of L gene transcripts.
- Full length L mRNA is much less abundant and is made when the polymerase fails to recognize the M2 gene-end motif. This results in much lower transcription of L mRNA.
- the gene overlap seems incompatible with a model of linear sequential transcription. It is not known whether the polymerase that exits the M2 gene jumps backward to the L gene-start signal or whether there is a second, internal promoter for L gene transcription (74) .
- the L gene is accessible by a small fraction of polymerases that fail to start transcription at the M2 gene-start signal and slide down the M2 gene to the L gene-start signal.
- the relative abundance of each RSV mRNA decreases with the distance of its gene from the promoter, presumably due to polymerase fall-off during sequential transcription (80) .
- Gene overlap is a second mechanism that reduces the synthesis of full length L mRNA.
- certain mRNAs have features that might reduce the efficiency of translation.
- the initiation codon for SH mRNA is in a suboptimal Kozak sequence context, while the G ORF begins at the second methionyl codon in the mRNA.
- RSV RNA replication is thought (74) to follow the model proposed from studies with vesicular stomatitis virus and Sendai virus (16,81). This involves a switch from the stop-start mode of mRNA synthesis to an antiterminator read- through mode. This results in synthesis of positive sense replication- intermediate (Rl) RNA that is an exact complementary copy of genomic RNA. This serves in turn as the template for the synthesis of progeny genomes.
- the mechanism involved in the switch to the antiterminator mode is proposed to involve cotranscriptional encapsidation of the nascent RNA by N protein (16,81). RNA replication in RSV like other nonsegmented negative-strand RNA viruses is dependent on ongoing protein synthesis (85) .
- Rl RNA has been detected for the standard virus as well as RSV-CAT minigenome (74,85).
- Rl RNA was 10-20 fold less abundant intracellularly than was the progeny genome both for the standard and the minigenome system.
- the nucleotide sequences (in positive strand, antigenomic, message sense) of various wild- type, vaccine and revertant RSV strains, as well as the deduced amino acid sequences of the RNA polymerase (L protein) of these RSV viruses, are set forth as follows with reference to the appropriate SEQ ID NOS. contained herein: L Protein Sequence
- Each RSV virus genome encodes an L protein that is 2,166 amino acids long. Genome length and other nucleotide information is as follows:
- the key attenuating mutations for the RSV subgroup B 3 ' genomic promoter region are nucleotide 4 (C - G) , and the insertion of an additional A in the stretch of A's at nucleotides 6-11 (in antigenomic message sense) .
- the key potentially attenuating sites for the L protein of RSV are as follows: amino acid residues 353 (arginine —> lysine), 451 (lysine —> arginine), 1229 (aspartic acid -» asparagine) , 2029 (threonine — isoleucine) and 2050 (asparagine — > aspartic acid) . It is understood that the nucleotide changes responsible for these amino acid changes. are not limited to those set forth in Example 3 below; all changes in nucleotides which result in codons which are translated into these amino acids are within the scope of this invention.
- the attenuated viruses of this invention exhibit a substantial reduction of virulence compared to wild- type viruses which infect human and animal hosts.
- the extent of attenuation is such that symptoms of infection will not arise in most immunized individuals, but the virus will retain sufficient replication competence to be infectious in and elicit the desired immune response profile in the vaccinee.
- the attenuated viruses of this invention may be used to formulate a vaccine. To do so, the attenuated virus is adjusted to an appropriate concentration and formulated with any suitable vaccine adjuvant, diluent or carrier.
- Physiologically acceptable media may be used as carriers. These include, but are not limited to: an appropriate isotonic medium, phosphate buffered saline and the like.
- Suitable adjuvants include, but are not limited to MPLTM (3-O-deacylated monophosphoryl lipid A; RIBI ImmunoChem Research, Inc., Hamilton, MT) and IL-12 (Genetics Institute, Cambridge, MA) .
- the formulation including the attenuated virus is intended for use as a vaccine.
- the attenuated virus may be mixed with cryoprotective additives or stabilizers such as proteins (e.g., albumin, gelatin), sugars (e.g., sucrose, lactose, sorbitol) , amino acids (e.g., sodium glutamate) , saline, or other protective agents.
- cryoprotective additives or stabilizers such as proteins (e.g., albumin, gelatin), sugars (e.g., sucrose, lactose, sorbitol) , amino acids (e.g., sodium glutamate) , saline, or other protective agents.
- This mixture is maintained in a liquid state, or is then dessicated or lyophilized for transport and storage and mixed with water immediately prior to administration.
- Formulations comprising the attenuated viruses of this invention are useful to immunize a human or animal subject to induce protection against infection by the wild-type counterpart of the attenuated virus.
- this invention further provides a method of immunizing a subject to induce protection against infection by an RNA virus of the Order Mononegavirales by administering to the subject an effective immunizing amount of a vaccine formulation incorporating an attenuated version of that virus as described hereinabove.
- a sufficient amount of the vaccine in an appropriate number of doses must be administered to the subject to elicit an immune response.
- Persons skilled in the art will readily be able to determine such amounts and dosages.
- Administration may be by any conventional effective form, such as intranasally, parenterally, orally, or topically applied to any mucosal surface such as intranasal, oral, eye, vaginal or rectal surface, such as by an aerosol spray.
- the preferred means of administration is by intranasal administration.
- an isolated nucleic acid molecule having the complete viral nucleotide sequence of either the wild- type viruses or vaccine viruses described herein is used to generate oligonucleotide probes (from either positive strand antigenomic message sense or negative strand complementary genomic sense) and to express peptides (from positive strand antigenomic message sense only) , which are used to detect the presence of those wild- type virus and/or vaccine strains in samples of body fluids and tissues.
- the nucleotide sequences are used to design highly specific and sensitive diagnostic tests to detect the presence of the virus in a sample.
- Polymerase chain reaction (PCR) primers are synthesized with sequences based on the viral wild- type or vaccine sequences described herein.
- test sample is subjected to reverse transcription of RNA, followed by PCR amplification of selected cDNA regions corresponding to the nucleotide sequence described herein which have nucleotides which are distinct for a defined strain of virus. Amplified PCR products are identified on gels and their specificity confirmed by hybridization with specific nucleotide probes.
- ELISA tests are used to detect the presence of antigens of the wild-type or vaccine viral strains.
- Peptides are designed and selected to contain one or more distinct residues based on the wild- type or vaccine sequences described herein. These peptides are then coupled to a hapten (e.g., keyhole limpet hemocyanin (KLH) and used to immunize animals (e.g., rabbits) for the production of monospecific polyclonal antibody.
- KLH keyhole limpet hemocyanin
- a selection of these polyclonal antibodies, or a combination of polyclonal and monoclonal antibodies can then be used in a "capture ELISA" to detect antigens produced by those viruses.
- Moraten MV vaccine virus was grown once, directly from the AttenuvaxTM vaccine vial (Lot #0716B) , the Schwarz vaccine virus was grown once (Lot 96G04/M179 G41D) , while the Zagreb and RubeovaxTM vaccine viruses were each grown twice in the Vero cells before RNAs were made for sequence analysis.
- MV wildtype isolate Montefiore (56) was passed 5-6 times in Vero cells before extraction of RNA materials and similarly, MV wildtype isolates 1977, 1983 (14) were grown 5-7 times before extracting materials for analysis.
- Edmonston wild-type isolate received from Dr. J. Beeler (CBER) (see Fig. 1) was the original
- RNA isolated from Vero cell passage material was amplified by the Reverse Transcriptase-PCR (Perkin-Elmer/Cetus) procedure using measles (Edmonston B strain (19)) specific primer pairs spanning the 3' and 5 ' promoter regions and the L gene of the viral genome .
- Table 2 presents these primer sequences .
- the primers of SEQ ID NOS: 35-54, 74, 77 and 78 are in antigenomic message sense .
- the primers of SEQ ID NOS: 55-73, 75, 76 and 79 are in genomic negative-sense. Table 2
- Vero-grown cp45 mutant vaccine strain contains an additional mutation resulting from a coding change in the L gene (marked with an asterisk in Table 6) at amino acid residue 1292 (leucine -» phenylalanine) .
- the first two amino acid changes in the L protein map to one of the highly conserved areas among all Paramyxovirus L genes.
- the fourth amino acid change maps to the area joining two conserved blocks corresponding to the change at amino acid 1717 in the MV vaccine strains.
- the temperature-sensitive (ts) phenotype is strongly associated with attenuation in vivo,- in addition, some non-ts mutations may also be attenuating. Identification of ts and non-ts attenuating mutations was achieved by sequence analysis and evaluation of ts, cold-adapted (ca) , and in vivo growth phenotypes of RSV mutants and revertants.
- nucl. pos. numbers are one larger than for 2B for M, SH & L genes At pos. 9853, the Lys-Arg change has reverted back to Lys in the 2B33F TS(+) strain
- Table 8 Sequence comparison between RSV 2B and 2B20L strains
- nucl. pos. numbers are one larger than for 2B for L gene
- RSV 2B33F differs from parental RSV 2B by two changes at the 3 ' genomic promoter region, two changes at the non-coding 5' -end of the gene, and four coding changes plus one non-coding (poly (A) motif) change in the RNA dependent RNA polymerase coding L gene.
- RSV 2B20L differs from its RSV 2B parent only at seven nucleotide positions, of which three are common with 2B33F virus, including two changes at the 3' genomic promoter and one coding change in the L gene. Two additional unique changes of 2B20L virus mapped to the coding region of the L gene. Potentially attenuating mutations at the non-coding 3' genomic promoter region and the RNA dependent RNA polymerase gene have been identified.
- This amino acid 451 mutation (Lys —> Arg) is amenable to stabilization in cDNA infectious clone constructs, by inserting a second mutation to stabilize the codon, thereby lessening the likelihood that it will revert back to Lys .
- Another wild- type RSV designated 18537 was also sequenced and compared to the sequence of the wild-type RSV 2B strain. With one exception, at all the critical residues described above, the two wildtype strains were identical.
- the codon ACA at nucleotides 14586-14588 encodes a Thr at amino acid 2029 of the L protein
- the codon ATT at nucleotides 14593-14595 encodes an lie at amino acid 2029 (the L gene start codon is at nucleotides 8509- 8511 in 18537, compared to 8502-8504 in 2B) .
- Bronchoalveolar lavage and transbronchial biopsies performed two days after admission to the hospital demonstrated reactive hyperplasia and alveolar lining cell desquamation with minimal chronic inflammation. No microorganisms were revealed by Gram, methenamine silver, or PAS stains. CT scans of the chest showed multiple, ill-defined, confluent nodules at the left lung base. Despite administration of empiric antimicrobials for opportunistic bacterial, mycobacterial, and fungal pathogens commonly responsible for pulmonary complications of advanced HIV disease, the patient became and remained febrile to
- Rhesus monkey kidney (RMK) tissue culture cells inoculated with the patient's lung biopsy material revealed cytopathic changes characteristic of measles virus infection. Confirmation was obtained using an immunofluorescence assay with monoclonal antibodies directed to measles virus. Based upon this diagnosis, oral ribavirin lOOO g B.I.D. was given for 14 days. Unfortunately, the patient progressively deteriorated, eventually dying two months later.
- the measles virus vaccine strain (Moraten) currently used in the United States as a component of the trivalent MMR vaccines, was obtained in its univalent form (AttenuvaxTM, Merck, Sharpe, & Dohme) . This virus was passaged once in Vero cells and total vaccine infected cellular RNA then was extracted as described above.
- RNA preparations were reverse transcribed (RT) to cDNA using random hexameric primers and Maloney murine leukemia virus reverse transcriptase (Perkin-Elmer/Cetus RT-PCR kit reagents, Perkin-Elmer- Cetus, Branchburg, NJ) .
- the cDNA then was amplified by PCR using measles virus-specific oligodeoxynucleotide primer pairs whose design was based on the Edmonston measles virus sequence described above.
- These PCR products comprised a set of overlapping DNA fragments spanning the entire 15,894 nucleotide long measles genome.
- a consensus genomic sequence was established by direct analysis of each PCR product, without cloning, using the dideoxy terminator cycle-sequencing method established by the manufacturer (ABI PRISM 377 sequencer and ABI PRISM DNA sequencing kit; Perkin- Elmer/Cetus, Foster City, CA) . Both strands of the PCR-amplified DNA products were analyzed to eliminate possible sequencing ambiguities.
- An ELISA test is used to detect the presence of RSV.
- Peptides are designed and selected based on homologies to the RSV sequences described herein to be specific for all subgroup B strains, or for individual wild- type, vaccine or revertant RSV subgroup B strains described herein. These peptides are then coupled to KLH and used to immunize rabbits for the production of monospecific polyclonal antibody. A selection of these polyclonal antibodies, or a combination of polyclonal and monoclonal antibodies is then used in a "capture ELISA" to detect the presence of an RSV antigen.
- GAAACAAACC CAGGATTGCT GAAATGATAT GTGACATTGA TACATATATC GTAGAGGCAG 900
- AAATGGGGGA AACTGCACCC TACATGGTAA TCCTGGAGAA CTCAATTCAG AACAAGTTCA 1080
- CCCATCTTCC AACCGGCACA CCCCTAGACA TTGACACTGC ATCGGAGTCC AGCCAAGATC 1560
- GGCAGAGATT CAGGCCGAGC ACTGGCCGAA GTTCTCAAGA AACCCGTTGC CAGCCGACAA 3060
- AGTATAGCCT ATCCGACGCT GTCCGAGATT AAGGGGGTGA TTGTCCACCG GCTAGAGGGG 6360
- GTGTGCAGCC AAAATGCCTT GTACCCGATG AGTCCTCTGC TCCAAGAATG CCTCCGGGGG 6540
- GGTTAGTCCC AACCTCTTCA CTGTCCCAAT TAAGGAAGCA GGCGAAGACT GCCATGCCCC 8760
- CAACTGTGTG CAACATGGTT TACACATGCT ATATGACCTA CCTCGACCTG TTGTTGAATG 13980
- Asp Ser Pro lie Val Thr Asn Lys lie Val Ala He Leu Glu Tyr Ala 20 25 30
- MOLECULE TYPE DNA (genomic)
- GGAACAAACC CAGGATTGCT GAAATGATAT GTGACATTGA TACATATATC GTAGAGGCAG 900
- AAATGGGGGA AACTGCACCA TACATGGTAA TCCTGGAGAA CTCAATTCAG AACAAGTTCA 1080
- CCCATCCTCC AACCGACACA CCCTTAGACA TTGACACTGC ATCGGAGTCC AGCCAAGATC 1560
- GGCAGAGATT CAGGCCGAGC ACTGGCTGAA GTTCTCAAGA AACCCGTTGC CAGCCGACAA 3060
- AGTATAGCCT ACCCGACGCT GTCCGAGATC AAGGGGGTGA TTGTCCACCG GCTAGAGGGG 6360
- GGTTAGTCCC AACCTCTTCA CTGTCCCAAT TAAGGAAGCA GGCGAAGACT GCCATGCCCC 8760
- CAACTGTGTG CAACATGGTT TACACATGCT ATATGACCTA CCTCGACCTG TTGTTGAATG 13980
- TTGTAGACCA TTACTCATGC TCTCTGACTT ATCTTCGGCG AGGATCGATC AAACAGATAA 14280 GATTGAGAGT TGATCCAGGA TTCATTTTCG ACGCCCTCGC TGAGGTAAAT GTCAGTCAGC 14340
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2682396P | 1996-09-27 | 1996-09-27 | |
US26823P | 1996-09-27 | ||
PCT/US1997/016718 WO1998013501A2 (en) | 1996-09-27 | 1997-09-19 | 3' genomic promoter region and polymerase gene mutations responsible for attenuation in viruses of the order designated mononegavirales |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0932684A2 true EP0932684A2 (de) | 1999-08-04 |
Family
ID=21833976
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP97942613A Withdrawn EP0932684A2 (de) | 1996-09-27 | 1997-09-19 | Mutationen in der genomischen 3'promoterregion und im polymerasegen, die für die attenuierung von viren der ordnung mononegavirales verantwortlich sind |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0932684A2 (de) |
JP (1) | JP2000517194A (de) |
KR (1) | KR20000048628A (de) |
CN (1) | CN1232504A (de) |
AU (1) | AU4427897A (de) |
BR (1) | BR9712138A (de) |
CA (1) | CA2265554A1 (de) |
WO (1) | WO1998013501A2 (de) |
Families Citing this family (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6887699B1 (en) | 1990-05-22 | 2005-05-03 | Medimmune Vaccines, Inc. | Recombinant negative strand RNA virus expression systems and vaccines |
US6410023B1 (en) * | 1997-05-23 | 2002-06-25 | United States Of America | Recombinant parainfluenza virus vaccines attenuated by deletion or ablation of a non-essential gene |
AU9389998A (en) * | 1997-09-19 | 1999-04-12 | American Cyanamid Company | Attenuated respiratory syncytial viruses |
AU767193B2 (en) * | 1998-03-26 | 2003-11-06 | Wyeth Holdings Corporation | Mutations responsible for attenuation in measles virus or human respiratory syncytial virus subgroup B |
EP1090108B1 (de) | 1998-06-03 | 2011-02-23 | Wyeth Holdings Corporation | Verfahren zum retten der rna-viren |
DK1085904T3 (da) | 1998-06-12 | 2013-02-25 | Sinai School Medicine | Svækkede minusstreng-vira med ændret interferon-antagonist-aktivitet til anvendelse som vacciner og lægemidler |
ATE384126T1 (de) | 1998-06-12 | 2008-02-15 | Sinai School Medicine | Interferon induzierende genetisch veränderte attenuierte viren |
US6146642A (en) | 1998-09-14 | 2000-11-14 | Mount Sinai School Of Medicine, Of The City University Of New York | Recombinant new castle disease virus RNA expression systems and vaccines |
US6544785B1 (en) | 1998-09-14 | 2003-04-08 | Mount Sinai School Of Medicine Of New York University | Helper-free rescue of recombinant negative strand RNA viruses |
US6764685B1 (en) | 2000-03-21 | 2004-07-20 | Medimmune Vaccines, Inc. | Recombinant parainfluenza virus expression systems and vaccines |
US6635416B2 (en) | 2000-04-10 | 2003-10-21 | Mount Sinai School Of Medicine Of New York University | Screening methods for identifying viral proteins with interferon antagonizing functions and potential antiviral agents |
DE60124098T2 (de) * | 2000-06-23 | 2007-04-05 | Wyeth Holdings Corp. | Modifiziertes Morbillivirus V Proteine |
US7361496B1 (en) | 2000-08-02 | 2008-04-22 | Wyeth | Rescue of mumps virus from cDNA |
KR100964413B1 (ko) | 2001-01-19 | 2010-06-15 | 비로노바티브 비.브이. | 감응성 포유류에서 호흡계 질환을 유발하는 바이러스 |
US8715922B2 (en) | 2001-01-19 | 2014-05-06 | ViroNovative | Virus causing respiratory tract illness in susceptible mammals |
EP2327418A1 (de) | 2002-02-21 | 2011-06-01 | MedImmune, LLC | Rekombinante Parainfluenza Virus basierte Expressions Systeme und Impfstoffe, die heterologe Antigene von anderen Viren enthalten |
US8012736B2 (en) | 2002-04-26 | 2011-09-06 | Medimmune, Llc | Multi plasmid system for the production of influenza virus |
US7465456B2 (en) | 2002-04-26 | 2008-12-16 | Medimmune, Llc | Multi plasmid system for the production of influenza virus |
DE60233038D1 (de) * | 2002-06-20 | 2009-09-03 | Pasteur Institut | Infektiöse cDNA eines zugelassenen Impfstammes des Masern Virus. Verwendung in immunogenen Zusammensetzungen |
DK1375670T3 (da) | 2002-06-20 | 2013-09-23 | Pasteur Institut | Rekombinante mæslingevira, der udtrykker epitoper af RNA-viras antigener, samt anvendelse af de rekombinante vira til fremstilling af vaccinesammensætninger |
CA2432738A1 (en) * | 2003-02-26 | 2004-08-26 | Philippe Despres | New dengue and west nile viruses proteins and genes coding the foregoing, and their use in vaccinal, therapeutic and diagnostic applications |
AU2004226369A1 (en) * | 2003-03-28 | 2004-10-14 | Medimmune, Llc | Compositions and methods involving respiratory syncytial virus subgroup B strain 9320 |
EP2494986A1 (de) | 2003-04-25 | 2012-09-05 | MedImmune Vaccines, Inc. | Metapneumovirusstämme und deren Verwendung in Impfstoffformulierungen und als Vektoren für die Expression antigener Sequenzen und Verfahren zur Ausbreitung des Virus |
WO2005018539A2 (en) | 2003-06-16 | 2005-03-03 | Medimmune Vaccines, Inc. | Influenza hemagglutinin and neuraminidase variants |
EP1697521B1 (de) | 2003-12-23 | 2010-06-02 | MedImmune, LLC | Multiplasmid-system zur erzeugung des grippevirus |
ES2393492T3 (es) | 2004-05-25 | 2012-12-21 | Medimmune, Llc | Variantes de hemaglutinina y neuraminidasa de influenza |
WO2006083286A2 (en) | 2004-06-01 | 2006-08-10 | Mount Sinai School Of Medicine Of New York University | Genetically engineered swine influenza virus and uses thereof |
EP1855713B1 (de) | 2005-02-15 | 2016-04-27 | Mount Sinai School of Medicine | Gentechnisch hergestellter pferde-influenza-virus und seine verwendungen |
WO2006098901A2 (en) | 2005-03-08 | 2006-09-21 | Medimmune Vaccines, Inc. | Influenza hemagglutinin and neuraminidase variants |
EP1917352A4 (de) | 2005-06-21 | 2009-03-25 | Medimmune Vaccines Inc | Verfahren und zusammensetzungen zur expression einer heterologen protease |
US7790434B2 (en) | 2005-06-21 | 2010-09-07 | Medimmune, Llc | Methods and compositions for expressing negative-sense viral RNA in canine cells |
EA016217B1 (ru) | 2005-12-02 | 2012-03-30 | Маунт Синай Скул Оф Медсин | Химерные вирусы, представляющие неприродные поверхностные белки, и их применение |
JP5491173B2 (ja) | 2006-04-19 | 2014-05-14 | メディミューン,エルエルシー | イヌ細胞中でマイナス鎖ウイルスrnaを発現させるための方法および組成物 |
EP2049662A4 (de) | 2006-07-21 | 2009-12-30 | Medimmune Llc | Verfahren und zusammensetzungen zur erhöhung des replikationsvermögens eines influenza-virus |
CN104278014A (zh) | 2006-08-09 | 2015-01-14 | 米迪缪尼有限公司 | 流感血凝素和神经氨酸酶变体 |
AU2007353532A1 (en) * | 2006-12-22 | 2008-11-20 | The Penn State Research Foundation | Modified polymerases and attenuated viruses and methods of use thereof |
JP5666905B2 (ja) | 2007-06-18 | 2015-02-12 | メディミューン,エルエルシー | ヘマグルチニンポリペプチド中に変化を有するインフルエンザbウイルス |
CA2730408A1 (en) | 2008-07-11 | 2010-01-14 | Chin-Fen Yang | Influenza hemagglutinin and neuraminidase variants |
DK2356135T3 (en) | 2008-11-05 | 2017-12-04 | Wyeth Llc | IMMUNOGEN MULTICOMPONENT COMPOSITION FOR THE PREVENTION OF BETA-HAEMOLYTIC STRUCTURAL TOC (BHS) DISEASE |
EP2393921B1 (de) | 2009-02-05 | 2015-07-15 | Icahn School of Medicine at Mount Sinai | Chimäres newcastle disease virus und seine verwendungen |
BRPI1008549A2 (pt) | 2009-02-12 | 2016-03-15 | Medimmune Llc | variantes de neuraminidase e hemaglutinina de influenza |
EP3009145A1 (de) | 2009-03-30 | 2016-04-20 | Mount Sinai School of Medicine of New York University | Impfstoffe gegen das grippevirus und ihre verwendungen |
WO2011014504A1 (en) | 2009-07-27 | 2011-02-03 | Mount Sinai School Of Medicine Of New York University | Recombinant influenza virus vectors and uses thereof |
JP5845180B2 (ja) | 2009-07-30 | 2016-01-20 | モウント シナイ スクール オフ メディシネ | インフルエンザウイルス及びそれらの使用 |
CN102939103A (zh) | 2010-03-30 | 2013-02-20 | 西奈山医学院 | 流感病毒疫苗及其应用 |
EP2420242A1 (de) | 2010-08-20 | 2012-02-22 | Lauer, Ulrich M. | Onkolytisches Masernvirus |
CN103906843B (zh) * | 2011-06-08 | 2016-12-07 | 维什瓦斯·乔希 | 双质粒哺乳动物表达*** |
EP2718445B1 (de) | 2011-06-08 | 2023-08-09 | Vishwas Joshi | Säugetierexpressionssystem mit zwei plasmiden zur herstellung rekombinanter proteine und viren |
EP2758075B1 (de) | 2011-09-20 | 2023-05-03 | Icahn School of Medicine at Mount Sinai | Influenzavirus-impfstoffe und verwendungen davon |
ES2752190T3 (es) | 2012-09-14 | 2020-04-03 | Us Health | Proteína Brachyury, vectores adenovirales que codifican proteína Brachyury y su uso |
AU2013362935B2 (en) | 2012-12-18 | 2018-10-04 | Icahn School Of Medicine At Mount Sinai | Influenza virus vaccines and uses thereof |
JP6596411B2 (ja) | 2013-03-14 | 2019-10-23 | アイカーン スクール オブ メディシン アット マウント サイナイ | ニューカッスル病ウイルス及びその使用 |
WO2014159960A1 (en) | 2013-03-14 | 2014-10-02 | Icahn School Of Medicine At Mount Sinai | Antibodies against influenza virus hemagglutinin and uses thereof |
KR102407019B1 (ko) | 2014-02-27 | 2022-06-08 | 머크 샤프 앤드 돔 코포레이션 | 암의 치료를 위한 결합 방법 |
JP2018504412A (ja) | 2015-01-23 | 2018-02-15 | アイカーン スクール オブ メディシン アット マウント サイナイ | インフルエンザウイルスワクチン接種レジメン |
US10029005B2 (en) | 2015-02-26 | 2018-07-24 | Boehringer Ingelheim Vetmedica Gmbh | Bivalent swine influenza virus vaccine |
CA2994694A1 (en) | 2015-08-03 | 2017-02-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Brachyury deletion mutants, non-yeast vectors encoding brachyury deletion mutants, and their use |
WO2017031404A1 (en) | 2015-08-20 | 2017-02-23 | University Of Rochester | Live-attenuated vaccine having mutations in viral polymerase for the treatment and prevention of canine influenza virus |
WO2017031401A2 (en) | 2015-08-20 | 2017-02-23 | University Of Rochester | Ns1 truncated virus for the development of canine influenza vaccines |
US10548966B2 (en) | 2015-08-20 | 2020-02-04 | University Of Rochester | Single-cycle virus for the development of canine influenza vaccines |
MX2018014955A (es) | 2016-06-03 | 2019-05-13 | Univ Rochester | Vacunas atenuadas vivas del virus de la influenza equina. |
CA3023143A1 (en) | 2016-06-15 | 2017-12-21 | Icahn School Of Medicine At Mount Sinai | Influenza virus hemagglutinin proteins and uses thereof |
CA3058652A1 (en) | 2017-04-07 | 2018-10-11 | Icahn School Of Medicine At Mount Sinai | Anti-influenza b virus neuraminidase antibodies and uses thereof |
JOP20190256A1 (ar) | 2017-05-12 | 2019-10-28 | Icahn School Med Mount Sinai | فيروسات داء نيوكاسل واستخداماتها |
AR114410A1 (es) | 2018-02-27 | 2020-09-02 | Univ Rochester | Vacuna multivalente contra influenza viva atenuada para prevenir y controlar el virus influenza equino (vie) en caballos |
US11166996B2 (en) | 2018-12-12 | 2021-11-09 | Flagship Pioneering Innovations V, Inc. | Anellovirus compositions and methods of use |
CA3130781A1 (en) | 2019-02-27 | 2020-09-03 | University Of Rochester | Multivalent live-attenuated influenza vaccine for prevention and control of equine influenza virus (eiv) in horses |
US11103576B1 (en) | 2020-06-15 | 2021-08-31 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Measles virus vaccine expressing SARS-COV-2 protein(s) |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU7007491A (en) * | 1990-02-02 | 1991-08-08 | Schweiz. Serum- & Impfinstitut Bern | Cdna corresponding to the genome of negative-strand rna viruses, and process for the production of infectious negative-strand rna viruses |
JP3045581B2 (ja) * | 1991-10-14 | 2000-05-29 | 社団法人北里研究所 | 麻疹ワクチンウイルス株同定方法 |
WO1993021306A1 (en) * | 1992-04-14 | 1993-10-28 | The Mount Sinai School Of Medicine Of The City University Of New York | Genetically engineered attenuated viruses |
TW275632B (de) * | 1992-04-21 | 1996-05-11 | American Cyanamid Co | |
IL105456A (en) * | 1992-04-21 | 1996-12-05 | American Home Prod | Vaccines of attenuated respiratory syncytial virus |
ES2210273T5 (es) * | 1994-07-18 | 2010-03-29 | Conzelmann, Karl-Klaus, Prof. Dr. | Virus con arn de cadena negativa no segmentado recombinante infeccioso. |
-
1997
- 1997-09-19 KR KR1019990702569A patent/KR20000048628A/ko not_active Application Discontinuation
- 1997-09-19 JP JP10515749A patent/JP2000517194A/ja not_active Ceased
- 1997-09-19 BR BR9712138-0A patent/BR9712138A/pt not_active Application Discontinuation
- 1997-09-19 CN CN97198321A patent/CN1232504A/zh active Pending
- 1997-09-19 EP EP97942613A patent/EP0932684A2/de not_active Withdrawn
- 1997-09-19 AU AU44278/97A patent/AU4427897A/en not_active Abandoned
- 1997-09-19 WO PCT/US1997/016718 patent/WO1998013501A2/en not_active Application Discontinuation
- 1997-09-19 CA CA002265554A patent/CA2265554A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO9813501A3 * |
Also Published As
Publication number | Publication date |
---|---|
WO1998013501A2 (en) | 1998-04-02 |
AU4427897A (en) | 1998-04-17 |
JP2000517194A (ja) | 2000-12-26 |
WO1998013501A3 (en) | 1998-08-13 |
CN1232504A (zh) | 1999-10-20 |
BR9712138A (pt) | 2000-01-18 |
CA2265554A1 (en) | 1998-04-02 |
KR20000048628A (ko) | 2000-07-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO1998013501A2 (en) | 3' genomic promoter region and polymerase gene mutations responsible for attenuation in viruses of the order designated mononegavirales | |
CA2302867A1 (en) | Attenuated respiratory syncytial viruses | |
JP4237268B2 (ja) | クローン化されたヌクレオチド配列からの弱毒化パラインフルエンザウィルスワクチンの製造 | |
US6790449B2 (en) | Methods for producing self-replicating infectious RSV particles comprising recombinant RSV genomes or antigenomes and the N, P, L, and M2 proteins | |
Yao et al. | Peptides corresponding to the heptad repeat sequence of human parainfluenza virus fusion protein are potent inhibitors of virus infection | |
US5993824A (en) | Production of attenuated respiratory syncytial virus vaccines from cloned nucleotide sequences | |
US7192593B2 (en) | Use of recombinant parainfluenza viruses (PIVs) as vectors to protect against infection and disease caused by PIV and other human pathogens | |
AU2020203460B2 (en) | Attenuation of human respiratory syncytial virus by genome scale codon-pair deoptimization | |
US6689367B1 (en) | Production of attenuated chimeric respiratory syncytial virus vaccines from cloned nucleotide sequences | |
MXPA01008108A (es) | Uso de virus de parainfluenza recombinante (pivs) como vectores para la proteccioncontra la infeccion y enfermedad provocadas por piv y otros patogenos humanos. | |
KR20110063863A (ko) | 생 약독화 호흡기 세포융합 바이러스 | |
US7208161B1 (en) | Production of attenuated parainfluenza virus vaccines from cloned nucleotide sequences | |
US7250171B1 (en) | Construction and use of recombinant parainfluenza viruses expressing a chimeric glycoprotein | |
AU767193B2 (en) | Mutations responsible for attenuation in measles virus or human respiratory syncytial virus subgroup B | |
AU8933001A (en) | 3' genomic promoter region and polymerase gene mutations responsible for attenuation in viruses of the order designated mononegavirales | |
MXPA00009256A (en) | Mutations responsible for attenuation in measles virus or human respiratory syncytial virus subgroup b | |
AU2002300291B2 (en) | Production Of Attenuated Parainfluenza Virus Vaccines From Cloned Nucleotide Sequences | |
AU5592201A (en) | Production of attenuated respiratory syncytial virus vaccines from cloned nucleotide sequences | |
AU5591601A (en) | Production of attenuated respiratory syncytial virus vaccines from cloned nucleotide sequences |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19990315 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU NL PT SE |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS Owner name: WYETH HOLDINGS CORPORATION |
|
17Q | First examination report despatched |
Effective date: 20030818 |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: 7A 61K 39/155 B Ipc: 7A 61K 39/165 B Ipc: 7C 12N 7/04 B Ipc: 7C 07K 14/145 B Ipc: 7C 07K 14/135 B Ipc: 7C 07K 14/115 B Ipc: 7C 07K 14/12 B Ipc: 7C 12N 15/40 B Ipc: 7C 12N 15/47 B Ipc: 7C 12N 15/45 A |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20050407 |