CN112154209A - Aav相容的层粘连蛋白—连接子聚合蛋白 - Google Patents
Aav相容的层粘连蛋白—连接子聚合蛋白 Download PDFInfo
- Publication number
- CN112154209A CN112154209A CN201980029037.8A CN201980029037A CN112154209A CN 112154209 A CN112154209 A CN 112154209A CN 201980029037 A CN201980029037 A CN 201980029037A CN 112154209 A CN112154209 A CN 112154209A
- Authority
- CN
- China
- Prior art keywords
- gly
- leu
- pro
- arg
- cys
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108010076039 Polyproteins Proteins 0.000 title description 5
- 108010085895 Laminin Proteins 0.000 claims abstract description 102
- 238000000034 method Methods 0.000 claims abstract description 67
- 230000014509 gene expression Effects 0.000 claims abstract description 56
- 210000002469 basement membrane Anatomy 0.000 claims abstract description 41
- 230000002950 deficient Effects 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims description 74
- 150000007523 nucleic acids Chemical group 0.000 claims description 57
- 239000013598 vector Substances 0.000 claims description 44
- 108700019146 Transgenes Proteins 0.000 claims description 37
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 31
- 238000006116 polymerization reaction Methods 0.000 claims description 24
- 208000024891 symptom Diseases 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 108010008097 laminin alpha 2 Proteins 0.000 claims description 21
- 239000013607 AAV vector Substances 0.000 claims description 20
- 241000702421 Dependoparvovirus Species 0.000 claims description 20
- 210000000578 peripheral nerve Anatomy 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 10
- 201000006938 muscular dystrophy Diseases 0.000 claims description 10
- 230000007812 deficiency Effects 0.000 claims description 8
- 208000011580 syndromic disease Diseases 0.000 claims description 7
- 206010016654 Fibrosis Diseases 0.000 claims description 4
- 206010028289 Muscle atrophy Diseases 0.000 claims description 4
- 230000007830 nerve conduction Effects 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 230000008929 regeneration Effects 0.000 claims description 4
- 238000011069 regeneration method Methods 0.000 claims description 4
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 3
- 208000036831 Moderate mental retardation Diseases 0.000 claims description 3
- 208000004756 Respiratory Insufficiency Diseases 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 208000037976 chronic inflammation Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 201000004193 respiratory failure Diseases 0.000 claims description 3
- 208000034800 Leukoencephalopathies Diseases 0.000 claims description 2
- 102000007547 Laminin Human genes 0.000 abstract description 98
- 241000124008 Mammalia Species 0.000 abstract description 8
- 239000013603 viral vector Substances 0.000 abstract description 4
- 108020004414 DNA Proteins 0.000 description 179
- 210000004027 cell Anatomy 0.000 description 110
- 108090000623 proteins and genes Proteins 0.000 description 104
- 241000282414 Homo sapiens Species 0.000 description 95
- 241000699666 Mus <mouse, genus> Species 0.000 description 87
- 102000004169 proteins and genes Human genes 0.000 description 79
- 235000018102 proteins Nutrition 0.000 description 76
- 239000002773 nucleotide Substances 0.000 description 44
- 125000003729 nucleotide group Chemical group 0.000 description 44
- 108010057670 laminin 1 Proteins 0.000 description 42
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 40
- 210000001519 tissue Anatomy 0.000 description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 34
- 102000039446 nucleic acids Human genes 0.000 description 34
- 108020004707 nucleic acids Proteins 0.000 description 34
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 27
- 230000035772 mutation Effects 0.000 description 27
- 230000027455 binding Effects 0.000 description 25
- 201000010099 disease Diseases 0.000 description 25
- 230000006870 function Effects 0.000 description 25
- 150000001413 amino acids Chemical group 0.000 description 24
- 210000003205 muscle Anatomy 0.000 description 24
- 108010076504 Protein Sorting Signals Proteins 0.000 description 23
- 239000003814 drug Substances 0.000 description 23
- 210000002845 virion Anatomy 0.000 description 23
- 230000001225 therapeutic effect Effects 0.000 description 22
- 238000011282 treatment Methods 0.000 description 21
- 102000004405 Collectins Human genes 0.000 description 20
- 108090000909 Collectins Proteins 0.000 description 20
- 108090000765 processed proteins & peptides Proteins 0.000 description 20
- 125000006850 spacer group Chemical group 0.000 description 20
- 241000699670 Mus sp. Species 0.000 description 19
- 230000007547 defect Effects 0.000 description 19
- 230000000694 effects Effects 0.000 description 19
- 230000001105 regulatory effect Effects 0.000 description 19
- 108010047857 aspartylglycine Proteins 0.000 description 18
- 102000004196 processed proteins & peptides Human genes 0.000 description 18
- 108010050848 glycylleucine Proteins 0.000 description 17
- 239000007924 injection Substances 0.000 description 17
- 238000002347 injection Methods 0.000 description 17
- 229920001184 polypeptide Polymers 0.000 description 17
- 230000001939 inductive effect Effects 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 108010047562 NGR peptide Proteins 0.000 description 15
- 210000000234 capsid Anatomy 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 238000013518 transcription Methods 0.000 description 15
- 230000035897 transcription Effects 0.000 description 15
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 14
- 241000880493 Leptailurus serval Species 0.000 description 14
- 101100309040 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) lea-1 gene Proteins 0.000 description 14
- 241000700605 Viruses Species 0.000 description 14
- 210000004116 schwann cell Anatomy 0.000 description 14
- 108010026333 seryl-proline Proteins 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 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 13
- 101150035390 mag gene Proteins 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 108010038633 aspartylglutamate Proteins 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 239000002502 liposome Substances 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 108010029020 prolylglycine Proteins 0.000 description 12
- 108091026890 Coding region Proteins 0.000 description 11
- 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 11
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 11
- 108010077245 asparaginyl-proline Proteins 0.000 description 11
- 239000003623 enhancer Substances 0.000 description 11
- 238000001415 gene therapy Methods 0.000 description 11
- 108010081551 glycylphenylalanine Proteins 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 238000011160 research Methods 0.000 description 11
- 102100036597 Basement membrane-specific heparan sulfate proteoglycan core protein Human genes 0.000 description 10
- 241000701022 Cytomegalovirus Species 0.000 description 10
- 101000972489 Homo sapiens Laminin subunit alpha-1 Proteins 0.000 description 10
- 102100022746 Laminin subunit alpha-1 Human genes 0.000 description 10
- 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 10
- 108010088225 Nestin Proteins 0.000 description 10
- 102000008730 Nestin Human genes 0.000 description 10
- 108700026244 Open Reading Frames Proteins 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 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 10
- 108010085325 histidylproline Proteins 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 210000005055 nestin Anatomy 0.000 description 10
- 108010008217 nidogen Proteins 0.000 description 10
- 108010049224 perlecan Proteins 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 108010016616 cysteinylglycine Proteins 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 9
- 108010020688 glycylhistidine Proteins 0.000 description 9
- 108010057821 leucylproline Proteins 0.000 description 9
- 230000023105 myelination Effects 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- 230000003612 virological effect Effects 0.000 description 9
- 235000017274 Diospyros sandwicensis Nutrition 0.000 description 8
- 102000001039 Dystrophin Human genes 0.000 description 8
- 108010069091 Dystrophin Proteins 0.000 description 8
- 102000012545 EGF-like domains Human genes 0.000 description 8
- 108050002150 EGF-like domains Proteins 0.000 description 8
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
- 101000959594 Homo sapiens Agrin Proteins 0.000 description 8
- 241000282838 Lama Species 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
- 108010087924 alanylproline Proteins 0.000 description 8
- 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 8
- 239000002552 dosage form Substances 0.000 description 8
- 108010089804 glycyl-threonine Proteins 0.000 description 8
- 108010037850 glycylvaline Proteins 0.000 description 8
- 108010025306 histidylleucine Proteins 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 108010027338 isoleucylcysteine Proteins 0.000 description 8
- 108090000565 Capsid Proteins Proteins 0.000 description 7
- 102100023321 Ceruloplasmin Human genes 0.000 description 7
- CCQOOWAONKGYKQ-BYPYZUCNSA-N Gly-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)CN CCQOOWAONKGYKQ-BYPYZUCNSA-N 0.000 description 7
- 101000972491 Homo sapiens Laminin subunit alpha-2 Proteins 0.000 description 7
- 229940110339 Long-acting muscarinic antagonist Drugs 0.000 description 7
- -1 RNA) Chemical class 0.000 description 7
- PURRNJBBXDDWLX-ZDLURKLDSA-N Ser-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CO)N)O PURRNJBBXDDWLX-ZDLURKLDSA-N 0.000 description 7
- VVZDBPBZHLQPPB-XVKPBYJWSA-N Val-Glu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VVZDBPBZHLQPPB-XVKPBYJWSA-N 0.000 description 7
- 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 7
- 230000002776 aggregation Effects 0.000 description 7
- 238000004220 aggregation Methods 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 108010013835 arginine glutamate Proteins 0.000 description 7
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 7
- 108010060035 arginylproline Proteins 0.000 description 7
- 108010060199 cysteinylproline Proteins 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 150000004676 glycans Chemical class 0.000 description 7
- 108010072405 glycyl-aspartyl-glycine Proteins 0.000 description 7
- 108010015792 glycyllysine Proteins 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 108010044426 integrins Proteins 0.000 description 7
- 102000006495 integrins Human genes 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 108010070643 prolylglutamic acid Proteins 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 108010061238 threonyl-glycine Proteins 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- 101150079978 AGRN gene Proteins 0.000 description 6
- 108700019743 Agrin Proteins 0.000 description 6
- 102100040026 Agrin Human genes 0.000 description 6
- SVHRPCMZTWZROG-DCAQKATOSA-N Arg-Cys-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCN=C(N)N)N SVHRPCMZTWZROG-DCAQKATOSA-N 0.000 description 6
- SVABRQFIHCSNCI-FOHZUACHSA-N Asp-Gly-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O SVABRQFIHCSNCI-FOHZUACHSA-N 0.000 description 6
- SSNJZBGOMNLSLA-CIUDSAMLSA-N Cys-Leu-Asn Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O SSNJZBGOMNLSLA-CIUDSAMLSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- DZMVESFTHXSSPZ-XVYDVKMFSA-N His-Ala-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DZMVESFTHXSSPZ-XVYDVKMFSA-N 0.000 description 6
- 108010065920 Insulin Lispro Proteins 0.000 description 6
- WGNOPSQMIQERPK-UHFFFAOYSA-N Leu-Asn-Pro Natural products CC(C)CC(N)C(=O)NC(CC(=O)N)C(=O)N1CCCC1C(=O)O WGNOPSQMIQERPK-UHFFFAOYSA-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
- WUHBLPVELFTPQK-KKUMJFAQSA-N Leu-Tyr-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O WUHBLPVELFTPQK-KKUMJFAQSA-N 0.000 description 6
- 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 6
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 6
- NMELOOXSGDRBRU-YUMQZZPRSA-N Pro-Glu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1 NMELOOXSGDRBRU-YUMQZZPRSA-N 0.000 description 6
- 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 6
- QQWNRERCGGZOKG-WEDXCCLWSA-N Thr-Gly-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O QQWNRERCGGZOKG-WEDXCCLWSA-N 0.000 description 6
- COYSIHFOCOMGCF-UHFFFAOYSA-N Val-Arg-Gly Natural products CC(C)C(N)C(=O)NC(C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-UHFFFAOYSA-N 0.000 description 6
- 108010005233 alanylglutamic acid Proteins 0.000 description 6
- 108010047495 alanylglycine Proteins 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 108010078144 glutaminyl-glycine Proteins 0.000 description 6
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 6
- 108010034529 leucyl-lysine Proteins 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 108010063431 methionyl-aspartyl-glycine Proteins 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- 208000015380 nutritional deficiency disease Diseases 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 108010031719 prolyl-serine Proteins 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 108010003137 tyrosyltyrosine Proteins 0.000 description 6
- WJRXVTCKASUIFF-FXQIFTODSA-N Ala-Cys-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WJRXVTCKASUIFF-FXQIFTODSA-N 0.000 description 5
- YHBDGLZYNIARKJ-GUBZILKMSA-N Ala-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N YHBDGLZYNIARKJ-GUBZILKMSA-N 0.000 description 5
- DDPXDCKYWDGZAL-BQBZGAKWSA-N Asn-Gly-Arg Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N DDPXDCKYWDGZAL-BQBZGAKWSA-N 0.000 description 5
- QXOPPIDJKPEKCW-GUBZILKMSA-N Asn-Pro-Arg Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O QXOPPIDJKPEKCW-GUBZILKMSA-N 0.000 description 5
- AWXDRZJQCVHCIT-DCAQKATOSA-N Asn-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(N)=O AWXDRZJQCVHCIT-DCAQKATOSA-N 0.000 description 5
- XIDSGDJNUJRUHE-VEVYYDQMSA-N Asn-Thr-Met Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(O)=O XIDSGDJNUJRUHE-VEVYYDQMSA-N 0.000 description 5
- YNCHFVRXEQFPBY-BQBZGAKWSA-N Asp-Gly-Arg Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N YNCHFVRXEQFPBY-BQBZGAKWSA-N 0.000 description 5
- AYFVRYXNDHBECD-YUMQZZPRSA-N Asp-Leu-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AYFVRYXNDHBECD-YUMQZZPRSA-N 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- BIVLWXQGXJLGKG-BIIVOSGPSA-N Cys-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N)C(=O)O BIVLWXQGXJLGKG-BIIVOSGPSA-N 0.000 description 5
- SBDVXRYCOIEYNV-YUMQZZPRSA-N Cys-His-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N SBDVXRYCOIEYNV-YUMQZZPRSA-N 0.000 description 5
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 5
- PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 5
- FXLVSYVJDPCIHH-STQMWFEESA-N Gly-Phe-Arg Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FXLVSYVJDPCIHH-STQMWFEESA-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
- 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 5
- FKESCSGWBPUTPN-FOHZUACHSA-N Gly-Thr-Asn Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O FKESCSGWBPUTPN-FOHZUACHSA-N 0.000 description 5
- RHRLHXQWHCNJKR-PMVVWTBXSA-N Gly-Thr-His Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 RHRLHXQWHCNJKR-PMVVWTBXSA-N 0.000 description 5
- 229930186217 Glycolipid Natural products 0.000 description 5
- JKGHDYGZRDWHGA-SRVKXCTJSA-N Leu-Asn-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JKGHDYGZRDWHGA-SRVKXCTJSA-N 0.000 description 5
- YKNBJXOJTURHCU-DCAQKATOSA-N Leu-Asp-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YKNBJXOJTURHCU-DCAQKATOSA-N 0.000 description 5
- RVVBWTWPNFDYBE-SRVKXCTJSA-N Leu-Glu-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVVBWTWPNFDYBE-SRVKXCTJSA-N 0.000 description 5
- NEEOBPIXKWSBRF-IUCAKERBSA-N Leu-Glu-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O NEEOBPIXKWSBRF-IUCAKERBSA-N 0.000 description 5
- 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 5
- 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 5
- 208000002720 Malnutrition Diseases 0.000 description 5
- 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 5
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 5
- 101100133572 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) nog-2 gene Proteins 0.000 description 5
- SEPNOAFMZLLCEW-UBHSHLNASA-N Phe-Ala-Val Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O SEPNOAFMZLLCEW-UBHSHLNASA-N 0.000 description 5
- NOXSEHJOXCWRHK-DCAQKATOSA-N Pro-Cys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1 NOXSEHJOXCWRHK-DCAQKATOSA-N 0.000 description 5
- FUOGXAQMNJMBFG-WPRPVWTQSA-N Pro-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FUOGXAQMNJMBFG-WPRPVWTQSA-N 0.000 description 5
- VGYBYGQXZJDZJU-XQXXSGGOSA-N Thr-Glu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VGYBYGQXZJDZJU-XQXXSGGOSA-N 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 201000006815 congenital muscular dystrophy Diseases 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 230000013020 embryo development Effects 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 5
- 108010049041 glutamylalanine Proteins 0.000 description 5
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 5
- 108010078326 glycyl-glycyl-valine Proteins 0.000 description 5
- 108010087823 glycyltyrosine Proteins 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000007918 intramuscular administration Methods 0.000 description 5
- 108010042502 laminin A Proteins 0.000 description 5
- 108010009298 lysylglutamic acid Proteins 0.000 description 5
- 230000001071 malnutrition Effects 0.000 description 5
- 235000000824 malnutrition Nutrition 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 208000018360 neuromuscular disease Diseases 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 108010053725 prolylvaline Proteins 0.000 description 5
- 239000013608 rAAV vector Substances 0.000 description 5
- 230000008439 repair process Effects 0.000 description 5
- 210000002027 skeletal muscle Anatomy 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- JBGSZRYCXBPWGX-BQBZGAKWSA-N Ala-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CCCN=C(N)N JBGSZRYCXBPWGX-BQBZGAKWSA-N 0.000 description 4
- PAIHPOGPJVUFJY-WDSKDSINSA-N Ala-Glu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O PAIHPOGPJVUFJY-WDSKDSINSA-N 0.000 description 4
- 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 4
- MDNAVFBZPROEHO-UHFFFAOYSA-N Ala-Lys-Val Natural products CC(C)C(C(O)=O)NC(=O)C(NC(=O)C(C)N)CCCCN MDNAVFBZPROEHO-UHFFFAOYSA-N 0.000 description 4
- WNHNMKOFKCHKKD-BFHQHQDPSA-N Ala-Thr-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O WNHNMKOFKCHKKD-BFHQHQDPSA-N 0.000 description 4
- 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 4
- GXCSUJQOECMKPV-CIUDSAMLSA-N Arg-Ala-Gln Chemical compound C[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O GXCSUJQOECMKPV-CIUDSAMLSA-N 0.000 description 4
- GIVATXIGCXFQQA-FXQIFTODSA-N Arg-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N GIVATXIGCXFQQA-FXQIFTODSA-N 0.000 description 4
- QIWYWCYNUMJBTC-CIUDSAMLSA-N Arg-Cys-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O QIWYWCYNUMJBTC-CIUDSAMLSA-N 0.000 description 4
- LUVODTFFSXVOAG-ACZMJKKPSA-N Asn-Cys-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)N LUVODTFFSXVOAG-ACZMJKKPSA-N 0.000 description 4
- OLVIPTLKNSAYRJ-YUMQZZPRSA-N Asn-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N OLVIPTLKNSAYRJ-YUMQZZPRSA-N 0.000 description 4
- SBHUBSDEZQFJHJ-CIUDSAMLSA-N Asp-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(O)=O SBHUBSDEZQFJHJ-CIUDSAMLSA-N 0.000 description 4
- SPKCGKRUYKMDHP-GUDRVLHUSA-N Asp-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N SPKCGKRUYKMDHP-GUDRVLHUSA-N 0.000 description 4
- WAEDSQFVZJUHLI-BYULHYEWSA-N Asp-Val-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O WAEDSQFVZJUHLI-BYULHYEWSA-N 0.000 description 4
- 102000010970 Connexin Human genes 0.000 description 4
- 108050001175 Connexin Proteins 0.000 description 4
- JIVJXVJMOBVCJF-ZLUOBGJFSA-N Cys-Asn-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)C(=O)N JIVJXVJMOBVCJF-ZLUOBGJFSA-N 0.000 description 4
- OIMUAKUQOUEPCZ-WHFBIAKZSA-N Cys-Asn-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O OIMUAKUQOUEPCZ-WHFBIAKZSA-N 0.000 description 4
- YFAFBAPQHGULQT-HJPIBITLSA-N Cys-Ile-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CS)N YFAFBAPQHGULQT-HJPIBITLSA-N 0.000 description 4
- XMVZMBGFIOQONW-GARJFASQSA-N Cys-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N)C(=O)O XMVZMBGFIOQONW-GARJFASQSA-N 0.000 description 4
- BOMGEMDZTNZESV-QWRGUYRKSA-N Cys-Tyr-Gly Chemical compound SC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 BOMGEMDZTNZESV-QWRGUYRKSA-N 0.000 description 4
- 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 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 108091029865 Exogenous DNA Proteins 0.000 description 4
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 4
- PCKOTDPDHIBGRW-CIUDSAMLSA-N Gln-Cys-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)N)N)CN=C(N)N PCKOTDPDHIBGRW-CIUDSAMLSA-N 0.000 description 4
- QFTRCUPCARNIPZ-XHNCKOQMSA-N Gln-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)N)N)C(=O)O QFTRCUPCARNIPZ-XHNCKOQMSA-N 0.000 description 4
- HHQCBFGKQDMWSP-GUBZILKMSA-N Gln-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HHQCBFGKQDMWSP-GUBZILKMSA-N 0.000 description 4
- JTWZNMUVQWWGOX-SOUVJXGZSA-N Gln-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CCC(=O)N)N)C(=O)O JTWZNMUVQWWGOX-SOUVJXGZSA-N 0.000 description 4
- SAEBUDRWKUXLOM-ACZMJKKPSA-N Glu-Cys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O SAEBUDRWKUXLOM-ACZMJKKPSA-N 0.000 description 4
- 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 4
- 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 4
- OGCIHJPYKVSMTE-YUMQZZPRSA-N Gly-Arg-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O OGCIHJPYKVSMTE-YUMQZZPRSA-N 0.000 description 4
- BEQGFMIBZFNROK-JGVFFNPUSA-N Gly-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)CN)C(=O)O BEQGFMIBZFNROK-JGVFFNPUSA-N 0.000 description 4
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 4
- SWQALSGKVLYKDT-UHFFFAOYSA-N Gly-Ile-Ala Natural products NCC(=O)NC(C(C)CC)C(=O)NC(C)C(O)=O SWQALSGKVLYKDT-UHFFFAOYSA-N 0.000 description 4
- LIXWIUAORXJNBH-QWRGUYRKSA-N Gly-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN LIXWIUAORXJNBH-QWRGUYRKSA-N 0.000 description 4
- UUYBFNKHOCJCHT-VHSXEESVSA-N Gly-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN UUYBFNKHOCJCHT-VHSXEESVSA-N 0.000 description 4
- GGLIDLCEPDHEJO-BQBZGAKWSA-N Gly-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)CN GGLIDLCEPDHEJO-BQBZGAKWSA-N 0.000 description 4
- WJUYPBBCSSLVJE-CIUDSAMLSA-N His-Asn-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N WJUYPBBCSSLVJE-CIUDSAMLSA-N 0.000 description 4
- DFHVLUKTTVTCKY-PBCZWWQYSA-N His-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CN=CN1)N)O DFHVLUKTTVTCKY-PBCZWWQYSA-N 0.000 description 4
- 101100127663 Homo sapiens LAMA2 gene Proteins 0.000 description 4
- PNDMHTTXXPUQJH-RWRJDSDZSA-N Ile-Glu-Thr Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@H](O)C)C(=O)O PNDMHTTXXPUQJH-RWRJDSDZSA-N 0.000 description 4
- RMNMUUCYTMLWNA-ZPFDUUQYSA-N Ile-Lys-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RMNMUUCYTMLWNA-ZPFDUUQYSA-N 0.000 description 4
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 4
- 101150089565 LAMA2 gene Proteins 0.000 description 4
- DLCXCECTCPKKCD-GUBZILKMSA-N Leu-Gln-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O DLCXCECTCPKKCD-GUBZILKMSA-N 0.000 description 4
- 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 4
- HYMLKESRWLZDBR-WEDXCCLWSA-N Leu-Gly-Thr Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O HYMLKESRWLZDBR-WEDXCCLWSA-N 0.000 description 4
- CFZZDVMBRYFFNU-QWRGUYRKSA-N Leu-His-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(O)=O CFZZDVMBRYFFNU-QWRGUYRKSA-N 0.000 description 4
- UBZGNBKMIJHOHL-BZSNNMDCSA-N Leu-Leu-Phe Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 UBZGNBKMIJHOHL-BZSNNMDCSA-N 0.000 description 4
- UCBPDSYUVAAHCD-UWVGGRQHSA-N Leu-Pro-Gly Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UCBPDSYUVAAHCD-UWVGGRQHSA-N 0.000 description 4
- 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 4
- CNGOEHJCLVCJHN-SRVKXCTJSA-N Lys-Pro-Glu Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O CNGOEHJCLVCJHN-SRVKXCTJSA-N 0.000 description 4
- RPWQJSBMXJSCPD-XUXIUFHCSA-N Lys-Val-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)C(C)C)C(O)=O RPWQJSBMXJSCPD-XUXIUFHCSA-N 0.000 description 4
- GTRWUQSSISWRTL-NAKRPEOUSA-N Met-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCSC)N GTRWUQSSISWRTL-NAKRPEOUSA-N 0.000 description 4
- 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 4
- MCIXMYKSPQUMJG-SRVKXCTJSA-N Phe-Ser-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MCIXMYKSPQUMJG-SRVKXCTJSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- BNBBNGZZKQUWCD-IUCAKERBSA-N Pro-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H]1CCCN1 BNBBNGZZKQUWCD-IUCAKERBSA-N 0.000 description 4
- HQVPQXMCQKXARZ-FXQIFTODSA-N Pro-Cys-Ser Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O HQVPQXMCQKXARZ-FXQIFTODSA-N 0.000 description 4
- BBFRBZYKHIKFBX-GMOBBJLQSA-N Pro-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@@H]1CCCN1 BBFRBZYKHIKFBX-GMOBBJLQSA-N 0.000 description 4
- LEIKGVHQTKHOLM-IUCAKERBSA-N Pro-Pro-Gly Chemical compound OC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 LEIKGVHQTKHOLM-IUCAKERBSA-N 0.000 description 4
- 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 4
- COLJZWUVZIXSSS-CIUDSAMLSA-N Ser-Cys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N COLJZWUVZIXSSS-CIUDSAMLSA-N 0.000 description 4
- CKDXFSPMIDSMGV-GUBZILKMSA-N Ser-Pro-Val Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O CKDXFSPMIDSMGV-GUBZILKMSA-N 0.000 description 4
- OLKICIBQRVSQMA-SRVKXCTJSA-N Ser-Ser-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OLKICIBQRVSQMA-SRVKXCTJSA-N 0.000 description 4
- JEDIEMIJYSRUBB-FOHZUACHSA-N Thr-Asp-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O JEDIEMIJYSRUBB-FOHZUACHSA-N 0.000 description 4
- DHPPWTOLRWYIDS-XKBZYTNZSA-N Thr-Cys-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O DHPPWTOLRWYIDS-XKBZYTNZSA-N 0.000 description 4
- MMTOHPRBJKEZHT-BWBBJGPYSA-N Thr-Cys-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O MMTOHPRBJKEZHT-BWBBJGPYSA-N 0.000 description 4
- XPNSAQMEAVSQRD-FBCQKBJTSA-N Thr-Gly-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)NCC(O)=O XPNSAQMEAVSQRD-FBCQKBJTSA-N 0.000 description 4
- AYCQVUUPIJHJTA-IXOXFDKPSA-N Thr-His-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O AYCQVUUPIJHJTA-IXOXFDKPSA-N 0.000 description 4
- HUPLKEHTTQBXSC-YJRXYDGGSA-N Thr-Ser-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HUPLKEHTTQBXSC-YJRXYDGGSA-N 0.000 description 4
- VIWQOOBRKCGSDK-RYQLBKOJSA-N Trp-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)O VIWQOOBRKCGSDK-RYQLBKOJSA-N 0.000 description 4
- DDHFMBDACJYSKW-AQZXSJQPSA-N Trp-Thr-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O DDHFMBDACJYSKW-AQZXSJQPSA-N 0.000 description 4
- ZNFPUOSTMUMUDR-JRQIVUDYSA-N Tyr-Asn-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZNFPUOSTMUMUDR-JRQIVUDYSA-N 0.000 description 4
- MOCXXGZHHSPNEJ-AVGNSLFASA-N Tyr-Cys-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O MOCXXGZHHSPNEJ-AVGNSLFASA-N 0.000 description 4
- ZLFHAAGHGQBQQN-GUBZILKMSA-N Val-Ala-Pro Natural products CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O ZLFHAAGHGQBQQN-GUBZILKMSA-N 0.000 description 4
- COYSIHFOCOMGCF-WPRPVWTQSA-N Val-Arg-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-WPRPVWTQSA-N 0.000 description 4
- WFENBJPLZMPVAX-XVKPBYJWSA-N Val-Gly-Glu Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O WFENBJPLZMPVAX-XVKPBYJWSA-N 0.000 description 4
- OTJMMKPMLUNTQT-AVGNSLFASA-N Val-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N OTJMMKPMLUNTQT-AVGNSLFASA-N 0.000 description 4
- GBIUHAYJGWVNLN-UHFFFAOYSA-N Val-Ser-Pro Natural products CC(C)C(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O GBIUHAYJGWVNLN-UHFFFAOYSA-N 0.000 description 4
- YQYFYUSYEDNLSD-YEPSODPASA-N Val-Thr-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O YQYFYUSYEDNLSD-YEPSODPASA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 108010011559 alanylphenylalanine Proteins 0.000 description 4
- 108010001271 arginyl-glutamyl-arginine Proteins 0.000 description 4
- 108010068380 arginylarginine Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 108010054813 diprotin B Proteins 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 4
- 238000001476 gene delivery Methods 0.000 description 4
- 108010084264 glycyl-glycyl-cysteine Proteins 0.000 description 4
- 108010066198 glycyl-leucyl-phenylalanine Proteins 0.000 description 4
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 4
- 108010010147 glycylglutamine Proteins 0.000 description 4
- 108010045383 histidyl-glycyl-glutamic acid Proteins 0.000 description 4
- 108010036413 histidylglycine Proteins 0.000 description 4
- 108010092114 histidylphenylalanine Proteins 0.000 description 4
- 108010018006 histidylserine Proteins 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 108010003700 lysyl aspartic acid Proteins 0.000 description 4
- 108010017391 lysylvaline Proteins 0.000 description 4
- 108091070501 miRNA Proteins 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 239000013615 primer Substances 0.000 description 4
- 108010087846 prolyl-prolyl-glycine Proteins 0.000 description 4
- 108010090894 prolylleucine Proteins 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 108010048818 seryl-histidine Proteins 0.000 description 4
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 4
- 230000000392 somatic effect Effects 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- IKWHIGGRTYBSIW-OBJOEFQTSA-N (2s)-2-[[(2s)-2-[[(2s)-1-(2-aminoacetyl)pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoic acid Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN IKWHIGGRTYBSIW-OBJOEFQTSA-N 0.000 description 3
- MKZCBYZBCINNJN-DLOVCJGASA-N Ala-Asp-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MKZCBYZBCINNJN-DLOVCJGASA-N 0.000 description 3
- PIXQDIGKDNNOOV-GUBZILKMSA-N Ala-Lys-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O PIXQDIGKDNNOOV-GUBZILKMSA-N 0.000 description 3
- BFMIRJBURUXDRG-DLOVCJGASA-N Ala-Phe-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 BFMIRJBURUXDRG-DLOVCJGASA-N 0.000 description 3
- 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 3
- OLVCTPPSXNRGKV-GUBZILKMSA-N Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OLVCTPPSXNRGKV-GUBZILKMSA-N 0.000 description 3
- HCBKAOZYACJUEF-XQXXSGGOSA-N Ala-Thr-Gln Chemical compound N[C@@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCC(N)=O)C(=O)O HCBKAOZYACJUEF-XQXXSGGOSA-N 0.000 description 3
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 3
- 108010010777 Arg-Gly-Asp-Gly Proteins 0.000 description 3
- PHHRSPBBQUFULD-UWVGGRQHSA-N Arg-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N PHHRSPBBQUFULD-UWVGGRQHSA-N 0.000 description 3
- 108010051330 Arg-Pro-Gly-Pro Proteins 0.000 description 3
- ATABBWFGOHKROJ-GUBZILKMSA-N Arg-Pro-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O ATABBWFGOHKROJ-GUBZILKMSA-N 0.000 description 3
- LXTGAOAXPSJWOU-DCAQKATOSA-N Asn-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](CC(=O)N)N LXTGAOAXPSJWOU-DCAQKATOSA-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
- KZYSHAMXEBPJBD-JRQIVUDYSA-N Asn-Thr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KZYSHAMXEBPJBD-JRQIVUDYSA-N 0.000 description 3
- WQAOZCVOOYUWKG-LSJOCFKGSA-N Asn-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CC(=O)N)N WQAOZCVOOYUWKG-LSJOCFKGSA-N 0.000 description 3
- KHBLRHKVXICFMY-GUBZILKMSA-N Asp-Glu-Lys Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O KHBLRHKVXICFMY-GUBZILKMSA-N 0.000 description 3
- DTNUIAJCPRMNBT-WHFBIAKZSA-N Asp-Gly-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O DTNUIAJCPRMNBT-WHFBIAKZSA-N 0.000 description 3
- HAFCJCDJGIOYPW-WDSKDSINSA-N Asp-Gly-Gln Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O HAFCJCDJGIOYPW-WDSKDSINSA-N 0.000 description 3
- KLYPOCBLKMPBIQ-GHCJXIJMSA-N Asp-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N KLYPOCBLKMPBIQ-GHCJXIJMSA-N 0.000 description 3
- OEDJQRXNDRUGEU-SRVKXCTJSA-N Asp-Leu-His Chemical compound N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O OEDJQRXNDRUGEU-SRVKXCTJSA-N 0.000 description 3
- YVHGKXAOSVBGJV-CIUDSAMLSA-N Asp-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N YVHGKXAOSVBGJV-CIUDSAMLSA-N 0.000 description 3
- ZVGRHIRJLWBWGJ-ACZMJKKPSA-N Asp-Ser-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZVGRHIRJLWBWGJ-ACZMJKKPSA-N 0.000 description 3
- FIRWLDUOFOULCA-XIRDDKMYSA-N Asp-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)O)N FIRWLDUOFOULCA-XIRDDKMYSA-N 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- OCEHKDFAWQIBHH-FXQIFTODSA-N Cys-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N OCEHKDFAWQIBHH-FXQIFTODSA-N 0.000 description 3
- SBMGKDLRJLYZCU-BIIVOSGPSA-N Cys-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N)C(=O)O SBMGKDLRJLYZCU-BIIVOSGPSA-N 0.000 description 3
- YRKJQKATZOTUEN-ACZMJKKPSA-N Cys-Gln-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N YRKJQKATZOTUEN-ACZMJKKPSA-N 0.000 description 3
- ZHCCYSDALWJITB-SRVKXCTJSA-N Cys-Phe-Cys Chemical compound N[C@@H](CS)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CS)C(O)=O ZHCCYSDALWJITB-SRVKXCTJSA-N 0.000 description 3
- NITLUESFANGEIW-BQBZGAKWSA-N Cys-Pro-Gly Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O NITLUESFANGEIW-BQBZGAKWSA-N 0.000 description 3
- BCWIFCLVCRAIQK-ZLUOBGJFSA-N Cys-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)O BCWIFCLVCRAIQK-ZLUOBGJFSA-N 0.000 description 3
- SRZZZTMJARUVPI-JBDRJPRFSA-N Cys-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N SRZZZTMJARUVPI-JBDRJPRFSA-N 0.000 description 3
- MQQLYEHXSBJTRK-FXQIFTODSA-N Cys-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N MQQLYEHXSBJTRK-FXQIFTODSA-N 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 3
- FJAYYNIXQNERSO-ACZMJKKPSA-N Gln-Cys-Asp Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N FJAYYNIXQNERSO-ACZMJKKPSA-N 0.000 description 3
- IPHGBVYWRKCGKG-FXQIFTODSA-N Gln-Cys-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O IPHGBVYWRKCGKG-FXQIFTODSA-N 0.000 description 3
- NSORZJXKUQFEKL-JGVFFNPUSA-N Gln-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCC(=O)N)N)C(=O)O NSORZJXKUQFEKL-JGVFFNPUSA-N 0.000 description 3
- QBLMTCRYYTVUQY-GUBZILKMSA-N Gln-Leu-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QBLMTCRYYTVUQY-GUBZILKMSA-N 0.000 description 3
- PIUPHASDUFSHTF-CIUDSAMLSA-N Gln-Pro-Asn Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)N)N)C(=O)N[C@@H](CC(=O)N)C(=O)O PIUPHASDUFSHTF-CIUDSAMLSA-N 0.000 description 3
- UTKUTMJSWKKHEM-WDSKDSINSA-N Glu-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O UTKUTMJSWKKHEM-WDSKDSINSA-N 0.000 description 3
- RQNYYRHRKSVKAB-GUBZILKMSA-N Glu-Cys-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O RQNYYRHRKSVKAB-GUBZILKMSA-N 0.000 description 3
- FBEJIDRSQCGFJI-GUBZILKMSA-N Glu-Leu-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FBEJIDRSQCGFJI-GUBZILKMSA-N 0.000 description 3
- OHWJUIXZHVIXJJ-GUBZILKMSA-N Glu-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N OHWJUIXZHVIXJJ-GUBZILKMSA-N 0.000 description 3
- FGSGPLRPQCZBSQ-AVGNSLFASA-N Glu-Phe-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O FGSGPLRPQCZBSQ-AVGNSLFASA-N 0.000 description 3
- HLYCMRDRWGSTPZ-CIUDSAMLSA-N Glu-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CS)C(=O)O HLYCMRDRWGSTPZ-CIUDSAMLSA-N 0.000 description 3
- BIYNPVYAZOUVFQ-CIUDSAMLSA-N Glu-Pro-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O BIYNPVYAZOUVFQ-CIUDSAMLSA-N 0.000 description 3
- LZEUDRYSAZAJIO-AUTRQRHGSA-N Glu-Val-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZEUDRYSAZAJIO-AUTRQRHGSA-N 0.000 description 3
- QSDKBRMVXSWAQE-BFHQHQDPSA-N Gly-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN QSDKBRMVXSWAQE-BFHQHQDPSA-N 0.000 description 3
- JXYMPBCYRKWJEE-BQBZGAKWSA-N Gly-Arg-Ala Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O JXYMPBCYRKWJEE-BQBZGAKWSA-N 0.000 description 3
- RQZGFWKQLPJOEQ-YUMQZZPRSA-N Gly-Arg-Gln Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)CN)CN=C(N)N RQZGFWKQLPJOEQ-YUMQZZPRSA-N 0.000 description 3
- 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 3
- UXJHNZODTMHWRD-WHFBIAKZSA-N Gly-Asn-Ala Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O UXJHNZODTMHWRD-WHFBIAKZSA-N 0.000 description 3
- NZAFOTBEULLEQB-WDSKDSINSA-N Gly-Asn-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)CN NZAFOTBEULLEQB-WDSKDSINSA-N 0.000 description 3
- LLXVQPKEQQCISF-YUMQZZPRSA-N Gly-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CN LLXVQPKEQQCISF-YUMQZZPRSA-N 0.000 description 3
- QSVCIFZPGLOZGH-WDSKDSINSA-N Gly-Glu-Ser Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O QSVCIFZPGLOZGH-WDSKDSINSA-N 0.000 description 3
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 3
- 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 3
- 229920002971 Heparan sulfate Polymers 0.000 description 3
- CZXKZMQKXQZDEX-YUMQZZPRSA-N His-Gly-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N CZXKZMQKXQZDEX-YUMQZZPRSA-N 0.000 description 3
- VTMLJMNQHKBPON-QWRGUYRKSA-N His-Gly-His Chemical compound C([C@H](N)C(=O)NCC(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 VTMLJMNQHKBPON-QWRGUYRKSA-N 0.000 description 3
- AIPUZFXMXAHZKY-QWRGUYRKSA-N His-Leu-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AIPUZFXMXAHZKY-QWRGUYRKSA-N 0.000 description 3
- QTUSJASXLGLJSR-OSUNSFLBSA-N Ile-Arg-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N QTUSJASXLGLJSR-OSUNSFLBSA-N 0.000 description 3
- JDAWAWXGAUZPNJ-ZPFDUUQYSA-N Ile-Glu-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N JDAWAWXGAUZPNJ-ZPFDUUQYSA-N 0.000 description 3
- DFFTXLCCDFYRKD-MBLNEYKQSA-N Ile-Gly-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N DFFTXLCCDFYRKD-MBLNEYKQSA-N 0.000 description 3
- HGCNKOLVKRAVHD-UHFFFAOYSA-N L-Met-L-Phe Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 HGCNKOLVKRAVHD-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WUFYAPWIHCUMLL-CIUDSAMLSA-N Leu-Asn-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O WUFYAPWIHCUMLL-CIUDSAMLSA-N 0.000 description 3
- FIJMQLGQLBLBOL-HJGDQZAQSA-N Leu-Asn-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FIJMQLGQLBLBOL-HJGDQZAQSA-N 0.000 description 3
- ZTLGVASZOIKNIX-DCAQKATOSA-N Leu-Gln-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZTLGVASZOIKNIX-DCAQKATOSA-N 0.000 description 3
- QDSKNVXKLPQNOJ-GVXVVHGQSA-N Leu-Gln-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O QDSKNVXKLPQNOJ-GVXVVHGQSA-N 0.000 description 3
- OXRLYTYUXAQTHP-YUMQZZPRSA-N Leu-Gly-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(O)=O OXRLYTYUXAQTHP-YUMQZZPRSA-N 0.000 description 3
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 3
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 3
- IDGZVZJLYFTXSL-DCAQKATOSA-N Leu-Ser-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IDGZVZJLYFTXSL-DCAQKATOSA-N 0.000 description 3
- FDBTVENULFNTAL-XQQFMLRXSA-N Leu-Val-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N FDBTVENULFNTAL-XQQFMLRXSA-N 0.000 description 3
- 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 3
- 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 3
- 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 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108010077077 Osteonectin Proteins 0.000 description 3
- HCTXJGRYAACKOB-SRVKXCTJSA-N Phe-Asn-Asp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N HCTXJGRYAACKOB-SRVKXCTJSA-N 0.000 description 3
- HNFUGJUZJRYUHN-JSGCOSHPSA-N Phe-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 HNFUGJUZJRYUHN-JSGCOSHPSA-N 0.000 description 3
- 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 3
- TXPUNZXZDVJUJQ-LPEHRKFASA-N Pro-Asn-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N2CCC[C@@H]2C(=O)O TXPUNZXZDVJUJQ-LPEHRKFASA-N 0.000 description 3
- HXOLCSYHGRNXJJ-IHRRRGAJSA-N Pro-Asp-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HXOLCSYHGRNXJJ-IHRRRGAJSA-N 0.000 description 3
- AIZVVCMAFRREQS-GUBZILKMSA-N Pro-Cys-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AIZVVCMAFRREQS-GUBZILKMSA-N 0.000 description 3
- QXNSKJLSLYCTMT-FXQIFTODSA-N Pro-Cys-Asp Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O QXNSKJLSLYCTMT-FXQIFTODSA-N 0.000 description 3
- OGRYXQOUFHAMPI-DCAQKATOSA-N Pro-Cys-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O OGRYXQOUFHAMPI-DCAQKATOSA-N 0.000 description 3
- XJROSHJRQTXWAE-XGEHTFHBSA-N Pro-Cys-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJROSHJRQTXWAE-XGEHTFHBSA-N 0.000 description 3
- YKQNVTOIYFQMLW-IHRRRGAJSA-N Pro-Cys-Tyr Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H]1NCCC1)C1=CC=C(O)C=C1 YKQNVTOIYFQMLW-IHRRRGAJSA-N 0.000 description 3
- LSIWVWRUTKPXDS-DCAQKATOSA-N Pro-Gln-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LSIWVWRUTKPXDS-DCAQKATOSA-N 0.000 description 3
- BODDREDDDRZUCF-QTKMDUPCSA-N Pro-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]2CCCN2)O BODDREDDDRZUCF-QTKMDUPCSA-N 0.000 description 3
- FXGIMYRVJJEIIM-UWVGGRQHSA-N Pro-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 FXGIMYRVJJEIIM-UWVGGRQHSA-N 0.000 description 3
- 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 3
- POQFNPILEQEODH-FXQIFTODSA-N Pro-Ser-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O POQFNPILEQEODH-FXQIFTODSA-N 0.000 description 3
- GOMUXSCOIWIJFP-GUBZILKMSA-N Pro-Ser-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GOMUXSCOIWIJFP-GUBZILKMSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- JJKSSJVYOVRJMZ-FXQIFTODSA-N Ser-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)CN=C(N)N JJKSSJVYOVRJMZ-FXQIFTODSA-N 0.000 description 3
- NRCJWSGXMAPYQX-LPEHRKFASA-N Ser-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CO)N)C(=O)O NRCJWSGXMAPYQX-LPEHRKFASA-N 0.000 description 3
- OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 3
- IFPBAGJBHSNYPR-ZKWXMUAHSA-N Ser-Ile-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O IFPBAGJBHSNYPR-ZKWXMUAHSA-N 0.000 description 3
- 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 3
- KCNSGAMPBPYUAI-CIUDSAMLSA-N Ser-Leu-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O KCNSGAMPBPYUAI-CIUDSAMLSA-N 0.000 description 3
- 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 3
- BDMWLJLPPUCLNV-XGEHTFHBSA-N Ser-Thr-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BDMWLJLPPUCLNV-XGEHTFHBSA-N 0.000 description 3
- OSFZCEQJLWCIBG-BZSNNMDCSA-N Ser-Tyr-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OSFZCEQJLWCIBG-BZSNNMDCSA-N 0.000 description 3
- 108091027967 Small hairpin RNA Proteins 0.000 description 3
- GKMYGVQDGVYCPC-IUKAMOBKSA-N Thr-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)N GKMYGVQDGVYCPC-IUKAMOBKSA-N 0.000 description 3
- QWMPARMKIDVBLV-VZFHVOOUSA-N Thr-Cys-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O QWMPARMKIDVBLV-VZFHVOOUSA-N 0.000 description 3
- LYGKYFKSZTUXGZ-ZDLURKLDSA-N Thr-Cys-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)NCC(O)=O LYGKYFKSZTUXGZ-ZDLURKLDSA-N 0.000 description 3
- VEWZSFGRQDUAJM-YJRXYDGGSA-N Thr-Cys-Tyr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N)O VEWZSFGRQDUAJM-YJRXYDGGSA-N 0.000 description 3
- XXNLGZRRSKPSGF-HTUGSXCWSA-N Thr-Gln-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N)O XXNLGZRRSKPSGF-HTUGSXCWSA-N 0.000 description 3
- SHOMROOOQBDGRL-JHEQGTHGSA-N Thr-Glu-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O SHOMROOOQBDGRL-JHEQGTHGSA-N 0.000 description 3
- JQAWYCUUFIMTHE-WLTAIBSBSA-N Thr-Gly-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JQAWYCUUFIMTHE-WLTAIBSBSA-N 0.000 description 3
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 3
- MROIJTGJGIDEEJ-RCWTZXSCSA-N Thr-Pro-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 MROIJTGJGIDEEJ-RCWTZXSCSA-N 0.000 description 3
- AKHDFZHUPGVFEJ-YEPSODPASA-N Thr-Val-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AKHDFZHUPGVFEJ-YEPSODPASA-N 0.000 description 3
- WVAKXMOGMWLWHK-VJBMBRPKSA-N Trp-Trp-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N WVAKXMOGMWLWHK-VJBMBRPKSA-N 0.000 description 3
- IJUTXXAXQODRMW-KBPBESRZSA-N Tyr-Gly-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)NCC(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O IJUTXXAXQODRMW-KBPBESRZSA-N 0.000 description 3
- MWUYSCVVPVITMW-IGNZVWTISA-N Tyr-Tyr-Ala Chemical compound C([C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 MWUYSCVVPVITMW-IGNZVWTISA-N 0.000 description 3
- ZXAGTABZUOMUDO-GVXVVHGQSA-N Val-Glu-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZXAGTABZUOMUDO-GVXVVHGQSA-N 0.000 description 3
- JZWZACGUZVCQPS-RNJOBUHISA-N Val-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N JZWZACGUZVCQPS-RNJOBUHISA-N 0.000 description 3
- WUFHZIRMAZZWRS-OSUNSFLBSA-N Val-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)N WUFHZIRMAZZWRS-OSUNSFLBSA-N 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 3
- 108010018691 arginyl-threonyl-arginine Proteins 0.000 description 3
- 108010010430 asparagine-proline-alanine Proteins 0.000 description 3
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 3
- 108010093581 aspartyl-proline Proteins 0.000 description 3
- 108010092854 aspartyllysine Proteins 0.000 description 3
- 108010068265 aspartyltyrosine Proteins 0.000 description 3
- 208000025341 autosomal recessive disease Diseases 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 208000020832 chronic kidney disease Diseases 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 210000004292 cytoskeleton Anatomy 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 3
- 108010040856 glutamyl-cysteinyl-alanine Proteins 0.000 description 3
- 108010062266 glycyl-glycyl-argininal Proteins 0.000 description 3
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 3
- 108010040030 histidinoalanine Proteins 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000001114 immunoprecipitation Methods 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 238000007913 intrathecal administration Methods 0.000 description 3
- 108010009114 laminin beta2 Proteins 0.000 description 3
- 108010012058 leucyltyrosine Proteins 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 239000002679 microRNA Substances 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 239000002088 nanocapsule Substances 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 108010004914 prolylarginine Proteins 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000004055 small Interfering RNA Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 108010071097 threonyl-lysyl-proline Proteins 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 108010080629 tryptophan-leucine Proteins 0.000 description 3
- 108010073969 valyllysine Proteins 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 2
- AXFMEGAFCUULFV-BLFANLJRSA-N (2s)-2-[[(2s)-1-[(2s,3r)-2-amino-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]pentanedioic acid Chemical compound CC[C@@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AXFMEGAFCUULFV-BLFANLJRSA-N 0.000 description 2
- CUVSTAMIHSSVKL-UWVGGRQHSA-N (4s)-4-[(2-aminoacetyl)amino]-5-[[(2s)-6-amino-1-(carboxymethylamino)-1-oxohexan-2-yl]amino]-5-oxopentanoic acid Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN CUVSTAMIHSSVKL-UWVGGRQHSA-N 0.000 description 2
- FCPBCJMDBJLGQA-AJNGGQMLSA-N 2-[[(2s)-1-[(2s)-2-[[(2s)-1-[(2s)-2-aminopropanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]acetic acid Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@H](C(=O)NCC(O)=O)CCC1 FCPBCJMDBJLGQA-AJNGGQMLSA-N 0.000 description 2
- 102100036601 Aggrecan core protein Human genes 0.000 description 2
- 108010067219 Aggrecans Proteins 0.000 description 2
- VBDMWOKJZDCFJM-FXQIFTODSA-N Ala-Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N VBDMWOKJZDCFJM-FXQIFTODSA-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
- 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 2
- DAEFQZCYZKRTLR-ZLUOBGJFSA-N Ala-Cys-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(O)=O DAEFQZCYZKRTLR-ZLUOBGJFSA-N 0.000 description 2
- FRFDXQWNDZMREB-ACZMJKKPSA-N Ala-Cys-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O FRFDXQWNDZMREB-ACZMJKKPSA-N 0.000 description 2
- AWAXZRDKUHOPBO-GUBZILKMSA-N Ala-Gln-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O AWAXZRDKUHOPBO-GUBZILKMSA-N 0.000 description 2
- SFNFGFDRYJKZKN-XQXXSGGOSA-N Ala-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C)N)O SFNFGFDRYJKZKN-XQXXSGGOSA-N 0.000 description 2
- PUBLUECXJRHTBK-ACZMJKKPSA-N Ala-Glu-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O PUBLUECXJRHTBK-ACZMJKKPSA-N 0.000 description 2
- BTBUEVAGZCKULD-XPUUQOCRSA-N Ala-Gly-His Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BTBUEVAGZCKULD-XPUUQOCRSA-N 0.000 description 2
- OBVSBEYOMDWLRJ-BFHQHQDPSA-N Ala-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N OBVSBEYOMDWLRJ-BFHQHQDPSA-N 0.000 description 2
- JEPNLGMEZMCFEX-QSFUFRPTSA-N Ala-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C)N JEPNLGMEZMCFEX-QSFUFRPTSA-N 0.000 description 2
- HQJKCXHQNUCKMY-GHCJXIJMSA-N Ala-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C)N HQJKCXHQNUCKMY-GHCJXIJMSA-N 0.000 description 2
- 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 2
- SUMYEVXWCAYLLJ-GUBZILKMSA-N Ala-Leu-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O SUMYEVXWCAYLLJ-GUBZILKMSA-N 0.000 description 2
- CCDFBRZVTDDJNM-GUBZILKMSA-N Ala-Leu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O CCDFBRZVTDDJNM-GUBZILKMSA-N 0.000 description 2
- SDZRIBWEVVRDQI-CIUDSAMLSA-N Ala-Lys-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O SDZRIBWEVVRDQI-CIUDSAMLSA-N 0.000 description 2
- BDQNLQSWRAPHGU-DLOVCJGASA-N Ala-Phe-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)O)N BDQNLQSWRAPHGU-DLOVCJGASA-N 0.000 description 2
- OSRZOHXQCUFIQG-FPMFFAJLSA-N Ala-Phe-Pro Chemical compound C([C@H](NC(=O)[C@@H]([NH3+])C)C(=O)N1[C@H](CCC1)C([O-])=O)C1=CC=CC=C1 OSRZOHXQCUFIQG-FPMFFAJLSA-N 0.000 description 2
- MSWSRLGNLKHDEI-ACZMJKKPSA-N Ala-Ser-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O MSWSRLGNLKHDEI-ACZMJKKPSA-N 0.000 description 2
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 2
- QKHWNPQNOHEFST-VZFHVOOUSA-N Ala-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C)N)O QKHWNPQNOHEFST-VZFHVOOUSA-N 0.000 description 2
- 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 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
- OTOXOKCIIQLMFH-KZVJFYERSA-N Arg-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N OTOXOKCIIQLMFH-KZVJFYERSA-N 0.000 description 2
- BHSYMWWMVRPCPA-CYDGBPFRSA-N Arg-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CCCN=C(N)N BHSYMWWMVRPCPA-CYDGBPFRSA-N 0.000 description 2
- WOPFJPHVBWKZJH-SRVKXCTJSA-N Arg-Arg-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O WOPFJPHVBWKZJH-SRVKXCTJSA-N 0.000 description 2
- RWWPBOUMKFBHAL-FXQIFTODSA-N Arg-Asn-Cys Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(O)=O RWWPBOUMKFBHAL-FXQIFTODSA-N 0.000 description 2
- NONSEUUPKITYQT-BQBZGAKWSA-N Arg-Asn-Gly Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N)CN=C(N)N NONSEUUPKITYQT-BQBZGAKWSA-N 0.000 description 2
- IIABBYGHLYWVOS-FXQIFTODSA-N Arg-Asn-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O IIABBYGHLYWVOS-FXQIFTODSA-N 0.000 description 2
- 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 2
- FEZJJKXNPSEYEV-CIUDSAMLSA-N Arg-Gln-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O FEZJJKXNPSEYEV-CIUDSAMLSA-N 0.000 description 2
- PTVGLOCPAVYPFG-CIUDSAMLSA-N Arg-Gln-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O PTVGLOCPAVYPFG-CIUDSAMLSA-N 0.000 description 2
- QAODJPUKWNNNRP-DCAQKATOSA-N Arg-Glu-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QAODJPUKWNNNRP-DCAQKATOSA-N 0.000 description 2
- WVNFNPGXYADPPO-BQBZGAKWSA-N Arg-Gly-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O WVNFNPGXYADPPO-BQBZGAKWSA-N 0.000 description 2
- PCQXGEUALSFGIA-WDSOQIARSA-N Arg-His-Trp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O PCQXGEUALSFGIA-WDSOQIARSA-N 0.000 description 2
- NVUIWHJLPSZZQC-CYDGBPFRSA-N Arg-Ile-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NVUIWHJLPSZZQC-CYDGBPFRSA-N 0.000 description 2
- YQGZIRIYGHNSQO-ZPFDUUQYSA-N Arg-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N YQGZIRIYGHNSQO-ZPFDUUQYSA-N 0.000 description 2
- LKDHUGLXOHYINY-XUXIUFHCSA-N Arg-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N LKDHUGLXOHYINY-XUXIUFHCSA-N 0.000 description 2
- OFIYLHVAAJYRBC-HJWJTTGWSA-N Arg-Ile-Phe Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O OFIYLHVAAJYRBC-HJWJTTGWSA-N 0.000 description 2
- 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 2
- GMFAGHNRXPSSJS-SRVKXCTJSA-N Arg-Leu-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GMFAGHNRXPSSJS-SRVKXCTJSA-N 0.000 description 2
- 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 2
- NMRHDSAOIURTNT-RWMBFGLXSA-N Arg-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NMRHDSAOIURTNT-RWMBFGLXSA-N 0.000 description 2
- YVTHEZNOKSAWRW-DCAQKATOSA-N Arg-Lys-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O YVTHEZNOKSAWRW-DCAQKATOSA-N 0.000 description 2
- NGTYEHIRESTSRX-UWVGGRQHSA-N Arg-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N NGTYEHIRESTSRX-UWVGGRQHSA-N 0.000 description 2
- FOQFHANLUJDQEE-GUBZILKMSA-N Arg-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CS)C(=O)O FOQFHANLUJDQEE-GUBZILKMSA-N 0.000 description 2
- HGKHPCFTRQDHCU-IUCAKERBSA-N Arg-Pro-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HGKHPCFTRQDHCU-IUCAKERBSA-N 0.000 description 2
- QHVRVUNEAIFTEK-SZMVWBNQSA-N Arg-Pro-Trp Chemical compound N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O QHVRVUNEAIFTEK-SZMVWBNQSA-N 0.000 description 2
- VUGWHBXPMAHEGZ-SRVKXCTJSA-N Arg-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCN=C(N)N VUGWHBXPMAHEGZ-SRVKXCTJSA-N 0.000 description 2
- VRTWYUYCJGNFES-CIUDSAMLSA-N Arg-Ser-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O VRTWYUYCJGNFES-CIUDSAMLSA-N 0.000 description 2
- 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 2
- BRCVLJZIIFBSPF-ZLUOBGJFSA-N Asn-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N BRCVLJZIIFBSPF-ZLUOBGJFSA-N 0.000 description 2
- GMRGSBAMMMVDGG-GUBZILKMSA-N Asn-Arg-Arg Chemical compound C(C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)CN=C(N)N GMRGSBAMMMVDGG-GUBZILKMSA-N 0.000 description 2
- HOIFSHOLNKQCSA-FXQIFTODSA-N Asn-Arg-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O HOIFSHOLNKQCSA-FXQIFTODSA-N 0.000 description 2
- CQMQJWRCRQSBAF-BPUTZDHNSA-N Asn-Arg-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)N)N CQMQJWRCRQSBAF-BPUTZDHNSA-N 0.000 description 2
- PCKRJVZAQZWNKM-WHFBIAKZSA-N Asn-Asn-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O PCKRJVZAQZWNKM-WHFBIAKZSA-N 0.000 description 2
- JRVABKHPWDRUJF-UBHSHLNASA-N Asn-Asn-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)N JRVABKHPWDRUJF-UBHSHLNASA-N 0.000 description 2
- VWJFQGXPYOPXJH-ZLUOBGJFSA-N Asn-Cys-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)C(=O)N VWJFQGXPYOPXJH-ZLUOBGJFSA-N 0.000 description 2
- FJIRXKVEDFLLOQ-SRVKXCTJSA-N Asn-Cys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)N FJIRXKVEDFLLOQ-SRVKXCTJSA-N 0.000 description 2
- HYQYLOSCICEYTR-YUMQZZPRSA-N Asn-Gly-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O HYQYLOSCICEYTR-YUMQZZPRSA-N 0.000 description 2
- GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 description 2
- 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 2
- TZFQICWZWFNIKU-KKUMJFAQSA-N Asn-Leu-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 TZFQICWZWFNIKU-KKUMJFAQSA-N 0.000 description 2
- FTNRWCPWDWRPAV-BZSNNMDCSA-N Asn-Phe-Phe Chemical compound C([C@H](NC(=O)[C@H](CC(N)=O)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 FTNRWCPWDWRPAV-BZSNNMDCSA-N 0.000 description 2
- OSZBYGVKAFZWKC-FXQIFTODSA-N Asn-Pro-Cys Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(O)=O OSZBYGVKAFZWKC-FXQIFTODSA-N 0.000 description 2
- NPZJLGMWMDNQDD-GHCJXIJMSA-N Asn-Ser-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NPZJLGMWMDNQDD-GHCJXIJMSA-N 0.000 description 2
- HPASIOLTWSNMFB-OLHMAJIHSA-N Asn-Thr-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O HPASIOLTWSNMFB-OLHMAJIHSA-N 0.000 description 2
- GOPFMQJUQDLUFW-LKXGYXEUSA-N Asn-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O GOPFMQJUQDLUFW-LKXGYXEUSA-N 0.000 description 2
- UPAGTDJAORYMEC-VHWLVUOQSA-N Asn-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)N)N UPAGTDJAORYMEC-VHWLVUOQSA-N 0.000 description 2
- IPAQILGYEQFCFO-NYVOZVTQSA-N Asn-Trp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)NC(=O)[C@H](CC(=O)N)N IPAQILGYEQFCFO-NYVOZVTQSA-N 0.000 description 2
- YNQMEIJEWSHOEO-SRVKXCTJSA-N Asn-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O YNQMEIJEWSHOEO-SRVKXCTJSA-N 0.000 description 2
- PQKSVQSMTHPRIB-ZKWXMUAHSA-N Asn-Val-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O PQKSVQSMTHPRIB-ZKWXMUAHSA-N 0.000 description 2
- NECWUSYTYSIFNC-DLOVCJGASA-N Asp-Ala-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 NECWUSYTYSIFNC-DLOVCJGASA-N 0.000 description 2
- 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 2
- ICAYWNTWHRRAQP-FXQIFTODSA-N Asp-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N ICAYWNTWHRRAQP-FXQIFTODSA-N 0.000 description 2
- 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 2
- UWOPETAWXDZUJR-ACZMJKKPSA-N Asp-Cys-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O UWOPETAWXDZUJR-ACZMJKKPSA-N 0.000 description 2
- WJHYGGVCWREQMO-GHCJXIJMSA-N Asp-Cys-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WJHYGGVCWREQMO-GHCJXIJMSA-N 0.000 description 2
- LXKLDWVHXNZQGB-SRVKXCTJSA-N Asp-Cys-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)O)N)O LXKLDWVHXNZQGB-SRVKXCTJSA-N 0.000 description 2
- 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 2
- YDJVIBMKAMQPPP-LAEOZQHASA-N Asp-Glu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O YDJVIBMKAMQPPP-LAEOZQHASA-N 0.000 description 2
- BIVYLQMZPHDUIH-WHFBIAKZSA-N Asp-Gly-Cys Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N)C(=O)O BIVYLQMZPHDUIH-WHFBIAKZSA-N 0.000 description 2
- KHGPWGKPYHPOIK-QWRGUYRKSA-N Asp-Gly-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KHGPWGKPYHPOIK-QWRGUYRKSA-N 0.000 description 2
- WSXDIZFNQYTUJB-SRVKXCTJSA-N Asp-His-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O WSXDIZFNQYTUJB-SRVKXCTJSA-N 0.000 description 2
- GBSUGIXJAAKZOW-GMOBBJLQSA-N Asp-Ile-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O GBSUGIXJAAKZOW-GMOBBJLQSA-N 0.000 description 2
- JNNVNVRBYUJYGS-CIUDSAMLSA-N Asp-Leu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O JNNVNVRBYUJYGS-CIUDSAMLSA-N 0.000 description 2
- 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 2
- KFAFUJMGHVVYRC-DCAQKATOSA-N Asp-Leu-Met Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O KFAFUJMGHVVYRC-DCAQKATOSA-N 0.000 description 2
- IVPNEDNYYYFAGI-GARJFASQSA-N Asp-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N IVPNEDNYYYFAGI-GARJFASQSA-N 0.000 description 2
- GKWFMNNNYZHJHV-SRVKXCTJSA-N Asp-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(O)=O GKWFMNNNYZHJHV-SRVKXCTJSA-N 0.000 description 2
- NVFSJIXJZCDICF-SRVKXCTJSA-N Asp-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N NVFSJIXJZCDICF-SRVKXCTJSA-N 0.000 description 2
- RPUYTJJZXQBWDT-SRVKXCTJSA-N Asp-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N RPUYTJJZXQBWDT-SRVKXCTJSA-N 0.000 description 2
- NONWUQAWAANERO-BZSNNMDCSA-N Asp-Phe-Tyr Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 NONWUQAWAANERO-BZSNNMDCSA-N 0.000 description 2
- 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 2
- BWJZSLQJNBSUPM-FXQIFTODSA-N Asp-Pro-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O BWJZSLQJNBSUPM-FXQIFTODSA-N 0.000 description 2
- DWOSGXZMLQNDBN-FXQIFTODSA-N Asp-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CS)C(=O)O DWOSGXZMLQNDBN-FXQIFTODSA-N 0.000 description 2
- MVRGBQGZSDJBSM-GMOBBJLQSA-N Asp-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)N MVRGBQGZSDJBSM-GMOBBJLQSA-N 0.000 description 2
- ZBYLEBZCVKLPCY-FXQIFTODSA-N Asp-Ser-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZBYLEBZCVKLPCY-FXQIFTODSA-N 0.000 description 2
- XXAMCEGRCZQGEM-ZLUOBGJFSA-N Asp-Ser-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O XXAMCEGRCZQGEM-ZLUOBGJFSA-N 0.000 description 2
- BRRPVTUFESPTCP-ACZMJKKPSA-N Asp-Ser-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O BRRPVTUFESPTCP-ACZMJKKPSA-N 0.000 description 2
- NBKLEMWHDLAUEM-CIUDSAMLSA-N Asp-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N NBKLEMWHDLAUEM-CIUDSAMLSA-N 0.000 description 2
- JSHWXQIZOCVWIA-ZKWXMUAHSA-N Asp-Ser-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JSHWXQIZOCVWIA-ZKWXMUAHSA-N 0.000 description 2
- UTLCRGFJFSZWAW-OLHMAJIHSA-N Asp-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O UTLCRGFJFSZWAW-OLHMAJIHSA-N 0.000 description 2
- OQMGSMNZVHYDTQ-ZKWXMUAHSA-N Asp-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N OQMGSMNZVHYDTQ-ZKWXMUAHSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 108091033409 CRISPR Proteins 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- PLBJMUUEGBBHRH-ZLUOBGJFSA-N Cys-Ala-Asn Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O PLBJMUUEGBBHRH-ZLUOBGJFSA-N 0.000 description 2
- GMXSSZUVDNPRMA-FXQIFTODSA-N Cys-Arg-Asp Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GMXSSZUVDNPRMA-FXQIFTODSA-N 0.000 description 2
- CLDCTNHPILWQCW-CIUDSAMLSA-N Cys-Arg-Glu Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N CLDCTNHPILWQCW-CIUDSAMLSA-N 0.000 description 2
- QLCPDGRAEJSYQM-LPEHRKFASA-N Cys-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N)C(=O)O QLCPDGRAEJSYQM-LPEHRKFASA-N 0.000 description 2
- XGIAHEUULGOZHH-GUBZILKMSA-N Cys-Arg-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N XGIAHEUULGOZHH-GUBZILKMSA-N 0.000 description 2
- QDFBJJABJKOLTD-FXQIFTODSA-N Cys-Asn-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QDFBJJABJKOLTD-FXQIFTODSA-N 0.000 description 2
- KLLFLHBKSJAUMZ-ACZMJKKPSA-N Cys-Asn-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N KLLFLHBKSJAUMZ-ACZMJKKPSA-N 0.000 description 2
- NDUSUIGBMZCOIL-ZKWXMUAHSA-N Cys-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N NDUSUIGBMZCOIL-ZKWXMUAHSA-N 0.000 description 2
- FWYBFUDWUUFLDN-FXQIFTODSA-N Cys-Asp-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N FWYBFUDWUUFLDN-FXQIFTODSA-N 0.000 description 2
- VZKXOWRNJDEGLZ-WHFBIAKZSA-N Cys-Asp-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O VZKXOWRNJDEGLZ-WHFBIAKZSA-N 0.000 description 2
- BMHBJCVEXUBGFI-BIIVOSGPSA-N Cys-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CS)N)C(=O)O BMHBJCVEXUBGFI-BIIVOSGPSA-N 0.000 description 2
- MWZSCEAYQCMROW-GUBZILKMSA-N Cys-Gln-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CS)N MWZSCEAYQCMROW-GUBZILKMSA-N 0.000 description 2
- FIADUEYFRSCCIK-CIUDSAMLSA-N Cys-Glu-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FIADUEYFRSCCIK-CIUDSAMLSA-N 0.000 description 2
- UUOYKFNULIOCGJ-GUBZILKMSA-N Cys-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](CS)N UUOYKFNULIOCGJ-GUBZILKMSA-N 0.000 description 2
- GCDLPNRHPWBKJJ-WDSKDSINSA-N Cys-Gly-Glu Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O GCDLPNRHPWBKJJ-WDSKDSINSA-N 0.000 description 2
- VNXXMHTZQGGDSG-CIUDSAMLSA-N Cys-His-Asn Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(O)=O VNXXMHTZQGGDSG-CIUDSAMLSA-N 0.000 description 2
- WTNLLMQAFPOCTJ-GARJFASQSA-N Cys-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CS)N)C(=O)O WTNLLMQAFPOCTJ-GARJFASQSA-N 0.000 description 2
- PJWIPBIMSKJTIE-DCAQKATOSA-N Cys-His-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CS)N PJWIPBIMSKJTIE-DCAQKATOSA-N 0.000 description 2
- SRIRHERUAMYIOQ-CIUDSAMLSA-N Cys-Leu-Ser Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O SRIRHERUAMYIOQ-CIUDSAMLSA-N 0.000 description 2
- VOBMMKMWSIVIOA-SRVKXCTJSA-N Cys-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N VOBMMKMWSIVIOA-SRVKXCTJSA-N 0.000 description 2
- IDFVDSBJNMPBSX-SRVKXCTJSA-N Cys-Lys-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O IDFVDSBJNMPBSX-SRVKXCTJSA-N 0.000 description 2
- WTEJFWOJHCJDML-FXQIFTODSA-N Cys-Met-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CS)C(O)=O WTEJFWOJHCJDML-FXQIFTODSA-N 0.000 description 2
- MFMDKTLJCUBQIC-MXAVVETBSA-N Cys-Phe-Ile Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MFMDKTLJCUBQIC-MXAVVETBSA-N 0.000 description 2
- KJJASVYBTKRYSN-FXQIFTODSA-N Cys-Pro-Asp Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CS)N)C(=O)N[C@@H](CC(=O)O)C(=O)O KJJASVYBTKRYSN-FXQIFTODSA-N 0.000 description 2
- DQUWSUWXPWGTQT-DCAQKATOSA-N Cys-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CS DQUWSUWXPWGTQT-DCAQKATOSA-N 0.000 description 2
- DTFJUSWYECELTM-BPUTZDHNSA-N Cys-Pro-Trp Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CS)N)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O DTFJUSWYECELTM-BPUTZDHNSA-N 0.000 description 2
- LKHMGNHQULEPFY-ACZMJKKPSA-N Cys-Ser-Glu Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O LKHMGNHQULEPFY-ACZMJKKPSA-N 0.000 description 2
- ABLQPNMKLMFDQU-BIIVOSGPSA-N Cys-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CS)N)C(=O)O ABLQPNMKLMFDQU-BIIVOSGPSA-N 0.000 description 2
- NDNZRWUDUMTITL-FXQIFTODSA-N Cys-Ser-Val Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NDNZRWUDUMTITL-FXQIFTODSA-N 0.000 description 2
- 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 2
- ZLFRUAFDAIFNHN-LKXGYXEUSA-N Cys-Thr-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N)O ZLFRUAFDAIFNHN-LKXGYXEUSA-N 0.000 description 2
- JIZRUFJGHPIYPS-SRVKXCTJSA-N Cys-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)O JIZRUFJGHPIYPS-SRVKXCTJSA-N 0.000 description 2
- FCXJJTRGVAZDER-FXQIFTODSA-N Cys-Val-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O FCXJJTRGVAZDER-FXQIFTODSA-N 0.000 description 2
- VIOQRFNAZDMVLO-NRPADANISA-N Cys-Val-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VIOQRFNAZDMVLO-NRPADANISA-N 0.000 description 2
- 108010090461 DFG peptide Proteins 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 2
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 2
- WQWMZOIPXWSZNE-WDSKDSINSA-N Gln-Asp-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O WQWMZOIPXWSZNE-WDSKDSINSA-N 0.000 description 2
- CXFUMJQFZVCETK-FXQIFTODSA-N Gln-Cys-Gln Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O CXFUMJQFZVCETK-FXQIFTODSA-N 0.000 description 2
- UVAOVENCIONMJP-GUBZILKMSA-N Gln-Cys-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O UVAOVENCIONMJP-GUBZILKMSA-N 0.000 description 2
- VNCLJDOTEPPBBD-GUBZILKMSA-N Gln-Cys-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)N)N VNCLJDOTEPPBBD-GUBZILKMSA-N 0.000 description 2
- MFLMFRZBAJSGHK-ACZMJKKPSA-N Gln-Cys-Ser Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O)N MFLMFRZBAJSGHK-ACZMJKKPSA-N 0.000 description 2
- IVCOYUURLWQDJQ-LPEHRKFASA-N Gln-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O IVCOYUURLWQDJQ-LPEHRKFASA-N 0.000 description 2
- VOLVNCMGXWDDQY-LPEHRKFASA-N Gln-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N)C(=O)O VOLVNCMGXWDDQY-LPEHRKFASA-N 0.000 description 2
- LVSYIKGMLRHKME-IUCAKERBSA-N Gln-Gly-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N LVSYIKGMLRHKME-IUCAKERBSA-N 0.000 description 2
- DQPOBSRQNWOBNA-GUBZILKMSA-N Gln-His-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(O)=O DQPOBSRQNWOBNA-GUBZILKMSA-N 0.000 description 2
- QKCZZAZNMMVICF-DCAQKATOSA-N Gln-Leu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O QKCZZAZNMMVICF-DCAQKATOSA-N 0.000 description 2
- FGWRYRAVBVOHIB-XIRDDKMYSA-N Gln-Pro-Trp Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)N)N)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O FGWRYRAVBVOHIB-XIRDDKMYSA-N 0.000 description 2
- YPFFHGRJCUBXPX-NHCYSSNCSA-N Gln-Pro-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O)C(O)=O YPFFHGRJCUBXPX-NHCYSSNCSA-N 0.000 description 2
- OKARHJKJTKFQBM-ACZMJKKPSA-N Gln-Ser-Asn Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N OKARHJKJTKFQBM-ACZMJKKPSA-N 0.000 description 2
- SYZZMPFLOLSMHL-XHNCKOQMSA-N Gln-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)C(=O)O SYZZMPFLOLSMHL-XHNCKOQMSA-N 0.000 description 2
- ININBLZFFVOQIO-JHEQGTHGSA-N Gln-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N)O ININBLZFFVOQIO-JHEQGTHGSA-N 0.000 description 2
- UEILCTONAMOGBR-RWRJDSDZSA-N Gln-Thr-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UEILCTONAMOGBR-RWRJDSDZSA-N 0.000 description 2
- CGYDXNKRIMJMLV-GUBZILKMSA-N Glu-Arg-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O CGYDXNKRIMJMLV-GUBZILKMSA-N 0.000 description 2
- 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 2
- KKCUFHUTMKQQCF-SRVKXCTJSA-N Glu-Arg-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O KKCUFHUTMKQQCF-SRVKXCTJSA-N 0.000 description 2
- OJGLIOXAKGFFDW-SRVKXCTJSA-N Glu-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N OJGLIOXAKGFFDW-SRVKXCTJSA-N 0.000 description 2
- AKJRHDMTEJXTPV-ACZMJKKPSA-N Glu-Asn-Ala Chemical compound C[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCC(O)=O)C(O)=O AKJRHDMTEJXTPV-ACZMJKKPSA-N 0.000 description 2
- VAZZOGXDUQSVQF-NUMRIWBASA-N Glu-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N)O VAZZOGXDUQSVQF-NUMRIWBASA-N 0.000 description 2
- CKOFNWCLWRYUHK-XHNCKOQMSA-N Glu-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O CKOFNWCLWRYUHK-XHNCKOQMSA-N 0.000 description 2
- LSTFYPOGBGFIPP-FXQIFTODSA-N Glu-Cys-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O LSTFYPOGBGFIPP-FXQIFTODSA-N 0.000 description 2
- KIMXNQXJJWWVIN-AVGNSLFASA-N Glu-Cys-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)N)O KIMXNQXJJWWVIN-AVGNSLFASA-N 0.000 description 2
- FKGNJUCQKXQNRA-NRPADANISA-N Glu-Cys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O FKGNJUCQKXQNRA-NRPADANISA-N 0.000 description 2
- XMVLTPMCUJTJQP-FXQIFTODSA-N Glu-Gln-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N XMVLTPMCUJTJQP-FXQIFTODSA-N 0.000 description 2
- LRPXYSGPOBVBEH-IUCAKERBSA-N Glu-Gly-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O LRPXYSGPOBVBEH-IUCAKERBSA-N 0.000 description 2
- KRGZZKWSBGPLKL-IUCAKERBSA-N Glu-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N KRGZZKWSBGPLKL-IUCAKERBSA-N 0.000 description 2
- XIKYNVKEUINBGL-IUCAKERBSA-N Glu-His-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(O)=O XIKYNVKEUINBGL-IUCAKERBSA-N 0.000 description 2
- NJPQBTJSYCKCNS-HVTMNAMFSA-N Glu-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCC(=O)O)N NJPQBTJSYCKCNS-HVTMNAMFSA-N 0.000 description 2
- BKRQSECBKKCCKW-HVTMNAMFSA-N Glu-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N BKRQSECBKKCCKW-HVTMNAMFSA-N 0.000 description 2
- 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 2
- IOUQWHIEQYQVFD-JYJNAYRXSA-N Glu-Leu-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IOUQWHIEQYQVFD-JYJNAYRXSA-N 0.000 description 2
- ZWMYUDZLXAQHCK-CIUDSAMLSA-N Glu-Met-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O ZWMYUDZLXAQHCK-CIUDSAMLSA-N 0.000 description 2
- 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 2
- RXESHTOTINOODU-JYJNAYRXSA-N Glu-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCC(=O)O)N RXESHTOTINOODU-JYJNAYRXSA-N 0.000 description 2
- ITVBKCZZLJUUHI-HTUGSXCWSA-N Glu-Phe-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ITVBKCZZLJUUHI-HTUGSXCWSA-N 0.000 description 2
- BFEZQZKEPRKKHV-SRVKXCTJSA-N Glu-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCCCN)C(=O)O BFEZQZKEPRKKHV-SRVKXCTJSA-N 0.000 description 2
- GMVCSRBOSIUTFC-FXQIFTODSA-N Glu-Ser-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O GMVCSRBOSIUTFC-FXQIFTODSA-N 0.000 description 2
- BXSZPACYCMNKLS-AVGNSLFASA-N Glu-Ser-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O BXSZPACYCMNKLS-AVGNSLFASA-N 0.000 description 2
- 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 2
- 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 2
- XOEKMEAOMXMURD-JYJNAYRXSA-N Glu-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](CCC(=O)O)N)O XOEKMEAOMXMURD-JYJNAYRXSA-N 0.000 description 2
- BKMOHWJHXQLFEX-IRIUXVKKSA-N Glu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCC(=O)O)N)O BKMOHWJHXQLFEX-IRIUXVKKSA-N 0.000 description 2
- FGGKGJHCVMYGCD-UKJIMTQDSA-N Glu-Val-Ile 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)CC)C(O)=O FGGKGJHCVMYGCD-UKJIMTQDSA-N 0.000 description 2
- 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 2
- VSVZIEVNUYDAFR-YUMQZZPRSA-N Gly-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN VSVZIEVNUYDAFR-YUMQZZPRSA-N 0.000 description 2
- GWCRIHNSVMOBEQ-BQBZGAKWSA-N Gly-Arg-Ser Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O GWCRIHNSVMOBEQ-BQBZGAKWSA-N 0.000 description 2
- 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 2
- 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 2
- GNBMOZPQUXTCRW-STQMWFEESA-N Gly-Asn-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)CN)C(O)=O)=CNC2=C1 GNBMOZPQUXTCRW-STQMWFEESA-N 0.000 description 2
- 108010050006 Gly-Asp-Gly-Arg Proteins 0.000 description 2
- YZACQYVWLCQWBT-BQBZGAKWSA-N Gly-Cys-Arg Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O YZACQYVWLCQWBT-BQBZGAKWSA-N 0.000 description 2
- LGQZOQRDEUIZJY-YUMQZZPRSA-N Gly-Cys-Lys Chemical compound NCCCC[C@H](NC(=O)[C@H](CS)NC(=O)CN)C(O)=O LGQZOQRDEUIZJY-YUMQZZPRSA-N 0.000 description 2
- VNBNZUAPOYGRDB-ZDLURKLDSA-N Gly-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)CN)O VNBNZUAPOYGRDB-ZDLURKLDSA-N 0.000 description 2
- JSNNHGHYGYMVCK-XVKPBYJWSA-N Gly-Glu-Val Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O JSNNHGHYGYMVCK-XVKPBYJWSA-N 0.000 description 2
- IDOGEHIWMJMAHT-BYPYZUCNSA-N Gly-Gly-Cys Chemical compound NCC(=O)NCC(=O)N[C@@H](CS)C(O)=O IDOGEHIWMJMAHT-BYPYZUCNSA-N 0.000 description 2
- FSPVILZGHUJOHS-QWRGUYRKSA-N Gly-His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CNC=N1 FSPVILZGHUJOHS-QWRGUYRKSA-N 0.000 description 2
- YNIMVVJTPWCUJH-KBPBESRZSA-N Gly-His-Tyr Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YNIMVVJTPWCUJH-KBPBESRZSA-N 0.000 description 2
- DGKBSGNCMCLDSL-BYULHYEWSA-N Gly-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN DGKBSGNCMCLDSL-BYULHYEWSA-N 0.000 description 2
- HMHRTKOWRUPPNU-RCOVLWMOSA-N Gly-Ile-Gly Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O HMHRTKOWRUPPNU-RCOVLWMOSA-N 0.000 description 2
- AAHSHTLISQUZJL-QSFUFRPTSA-N Gly-Ile-Ile Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AAHSHTLISQUZJL-QSFUFRPTSA-N 0.000 description 2
- COVXELOAORHTND-LSJOCFKGSA-N Gly-Ile-Val Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O COVXELOAORHTND-LSJOCFKGSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- LHYJCVCQPWRMKZ-WEDXCCLWSA-N Gly-Leu-Thr Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LHYJCVCQPWRMKZ-WEDXCCLWSA-N 0.000 description 2
- MIIVFRCYJABHTQ-ONGXEEELSA-N Gly-Leu-Val Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O MIIVFRCYJABHTQ-ONGXEEELSA-N 0.000 description 2
- BXICSAQLIHFDDL-YUMQZZPRSA-N Gly-Lys-Asn Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BXICSAQLIHFDDL-YUMQZZPRSA-N 0.000 description 2
- PTIIBFKSLCYQBO-NHCYSSNCSA-N Gly-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CN PTIIBFKSLCYQBO-NHCYSSNCSA-N 0.000 description 2
- 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 2
- QVDGHDFFYHKJPN-QWRGUYRKSA-N Gly-Phe-Cys Chemical compound NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CS)C(O)=O QVDGHDFFYHKJPN-QWRGUYRKSA-N 0.000 description 2
- QAMMIGULQSIRCD-IRXDYDNUSA-N Gly-Phe-Tyr Chemical compound C([C@H](NC(=O)C[NH3+])C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C([O-])=O)C1=CC=CC=C1 QAMMIGULQSIRCD-IRXDYDNUSA-N 0.000 description 2
- JYPCXBJRLBHWME-IUCAKERBSA-N Gly-Pro-Arg Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JYPCXBJRLBHWME-IUCAKERBSA-N 0.000 description 2
- NSVOVKWEKGEOQB-LURJTMIESA-N Gly-Pro-Gly Chemical compound NCC(=O)N1CCC[C@H]1C(=O)NCC(O)=O NSVOVKWEKGEOQB-LURJTMIESA-N 0.000 description 2
- OOCFXNOVSLSHAB-IUCAKERBSA-N Gly-Pro-Pro Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OOCFXNOVSLSHAB-IUCAKERBSA-N 0.000 description 2
- LBDXVCBAJJNJNN-WHFBIAKZSA-N Gly-Ser-Cys Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(O)=O LBDXVCBAJJNJNN-WHFBIAKZSA-N 0.000 description 2
- JSLVAHYTAJJEQH-QWRGUYRKSA-N Gly-Ser-Phe Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JSLVAHYTAJJEQH-QWRGUYRKSA-N 0.000 description 2
- WCORRBXVISTKQL-WHFBIAKZSA-N Gly-Ser-Ser Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WCORRBXVISTKQL-WHFBIAKZSA-N 0.000 description 2
- RJVZMGQMJOQIAX-GJZGRUSLSA-N Gly-Trp-Met Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCSC)C(O)=O RJVZMGQMJOQIAX-GJZGRUSLSA-N 0.000 description 2
- NWOSHVVPKDQKKT-RYUDHWBXSA-N Gly-Tyr-Gln Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O NWOSHVVPKDQKKT-RYUDHWBXSA-N 0.000 description 2
- KBBFOULZCHWGJX-KBPBESRZSA-N Gly-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)CN)O KBBFOULZCHWGJX-KBPBESRZSA-N 0.000 description 2
- DNVDEMWIYLVIQU-RCOVLWMOSA-N Gly-Val-Asp Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O DNVDEMWIYLVIQU-RCOVLWMOSA-N 0.000 description 2
- DKJWUIYLMLUBDX-XPUUQOCRSA-N Gly-Val-Cys Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)O DKJWUIYLMLUBDX-XPUUQOCRSA-N 0.000 description 2
- NGRPGJGKJMUGDM-XVKPBYJWSA-N Gly-Val-Gln Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O NGRPGJGKJMUGDM-XVKPBYJWSA-N 0.000 description 2
- XINDHUAGVGCNSF-QSFUFRPTSA-N His-Ala-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XINDHUAGVGCNSF-QSFUFRPTSA-N 0.000 description 2
- YPLYIXGKCRQZGW-SRVKXCTJSA-N His-Arg-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O YPLYIXGKCRQZGW-SRVKXCTJSA-N 0.000 description 2
- SYMSVYVUSPSAAO-IHRRRGAJSA-N His-Arg-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O SYMSVYVUSPSAAO-IHRRRGAJSA-N 0.000 description 2
- LYSVCKOXIDKEEL-SRVKXCTJSA-N His-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CN=CN1 LYSVCKOXIDKEEL-SRVKXCTJSA-N 0.000 description 2
- VOKCBYNCZVSILJ-KKUMJFAQSA-N His-Asn-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC2=CN=CN2)N)O VOKCBYNCZVSILJ-KKUMJFAQSA-N 0.000 description 2
- 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 2
- UJWYPUUXIAKEES-CUJWVEQBSA-N His-Cys-Thr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UJWYPUUXIAKEES-CUJWVEQBSA-N 0.000 description 2
- PQKCQZHAGILVIM-NKIYYHGXSA-N His-Glu-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)Cc1cnc[nH]1)C(O)=O PQKCQZHAGILVIM-NKIYYHGXSA-N 0.000 description 2
- HAPWZEVRQYGLSG-IUCAKERBSA-N His-Gly-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O HAPWZEVRQYGLSG-IUCAKERBSA-N 0.000 description 2
- 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 2
- LBQAHBIVXQSBIR-HVTMNAMFSA-N His-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N LBQAHBIVXQSBIR-HVTMNAMFSA-N 0.000 description 2
- MPXGJGBXCRQQJE-MXAVVETBSA-N His-Ile-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O MPXGJGBXCRQQJE-MXAVVETBSA-N 0.000 description 2
- ORERHHPZDDEMSC-VGDYDELISA-N His-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N ORERHHPZDDEMSC-VGDYDELISA-N 0.000 description 2
- UROVZOUMHNXPLZ-AVGNSLFASA-N His-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 UROVZOUMHNXPLZ-AVGNSLFASA-N 0.000 description 2
- GUXQAPACZVVOKX-AVGNSLFASA-N His-Lys-Gln Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N GUXQAPACZVVOKX-AVGNSLFASA-N 0.000 description 2
- YAEKRYQASVCDLK-JYJNAYRXSA-N His-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=CN=CN2)N YAEKRYQASVCDLK-JYJNAYRXSA-N 0.000 description 2
- BZAQOPHNBFOOJS-DCAQKATOSA-N His-Pro-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O BZAQOPHNBFOOJS-DCAQKATOSA-N 0.000 description 2
- QCBYAHHNOHBXIH-UWVGGRQHSA-N His-Pro-Gly Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)C1=CN=CN1 QCBYAHHNOHBXIH-UWVGGRQHSA-N 0.000 description 2
- PZAJPILZRFPYJJ-SRVKXCTJSA-N His-Ser-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O PZAJPILZRFPYJJ-SRVKXCTJSA-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
- FBOMZVOKCZMDIG-XQQFMLRXSA-N His-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N FBOMZVOKCZMDIG-XQQFMLRXSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001008558 Homo sapiens Laminin subunit beta-2 Proteins 0.000 description 2
- 101000946306 Homo sapiens Laminin subunit gamma-1 Proteins 0.000 description 2
- AQCUAZTZSPQJFF-ZKWXMUAHSA-N Ile-Ala-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O AQCUAZTZSPQJFF-ZKWXMUAHSA-N 0.000 description 2
- VAXBXNPRXPHGHG-BJDJZHNGSA-N Ile-Ala-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)O)N VAXBXNPRXPHGHG-BJDJZHNGSA-N 0.000 description 2
- MKWSZEHGHSLNPF-NAKRPEOUSA-N Ile-Ala-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O)N MKWSZEHGHSLNPF-NAKRPEOUSA-N 0.000 description 2
- ASCFJMSGKUIRDU-ZPFDUUQYSA-N Ile-Arg-Gln Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O ASCFJMSGKUIRDU-ZPFDUUQYSA-N 0.000 description 2
- UAVQIQOOBXFKRC-BYULHYEWSA-N Ile-Asn-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O UAVQIQOOBXFKRC-BYULHYEWSA-N 0.000 description 2
- CTHAJJYOHOBUDY-GHCJXIJMSA-N Ile-Cys-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N CTHAJJYOHOBUDY-GHCJXIJMSA-N 0.000 description 2
- VQUCKIAECLVLAD-SVSWQMSJSA-N Ile-Cys-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N VQUCKIAECLVLAD-SVSWQMSJSA-N 0.000 description 2
- KMBPQYKVZBMRMH-PEFMBERDSA-N Ile-Gln-Asn Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O KMBPQYKVZBMRMH-PEFMBERDSA-N 0.000 description 2
- NHJKZMDIMMTVCK-QXEWZRGKSA-N Ile-Gly-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N NHJKZMDIMMTVCK-QXEWZRGKSA-N 0.000 description 2
- NYEYYMLUABXDMC-NHCYSSNCSA-N Ile-Gly-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)O)N NYEYYMLUABXDMC-NHCYSSNCSA-N 0.000 description 2
- HYLIOBDWPQNLKI-HVTMNAMFSA-N Ile-His-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N HYLIOBDWPQNLKI-HVTMNAMFSA-N 0.000 description 2
- URWXDJAEEGBADB-TUBUOCAGSA-N Ile-His-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N URWXDJAEEGBADB-TUBUOCAGSA-N 0.000 description 2
- AFERFBZLVUFWRA-HTFCKZLJSA-N Ile-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)O)N AFERFBZLVUFWRA-HTFCKZLJSA-N 0.000 description 2
- HUORUFRRJHELPD-MNXVOIDGSA-N Ile-Leu-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N HUORUFRRJHELPD-MNXVOIDGSA-N 0.000 description 2
- BKPPWVSPSIUXHZ-OSUNSFLBSA-N Ile-Met-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N BKPPWVSPSIUXHZ-OSUNSFLBSA-N 0.000 description 2
- KLJKJVXDHVUMMZ-KKPKCPPISA-N Ile-Phe-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N KLJKJVXDHVUMMZ-KKPKCPPISA-N 0.000 description 2
- IITVUURPOYGCTD-NAKRPEOUSA-N Ile-Pro-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IITVUURPOYGCTD-NAKRPEOUSA-N 0.000 description 2
- KCTIFOCXAIUQQK-QXEWZRGKSA-N Ile-Pro-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O KCTIFOCXAIUQQK-QXEWZRGKSA-N 0.000 description 2
- XOZOSAUOGRPCES-STECZYCISA-N Ile-Pro-Tyr Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XOZOSAUOGRPCES-STECZYCISA-N 0.000 description 2
- SHVFUCSSACPBTF-VGDYDELISA-N Ile-Ser-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N SHVFUCSSACPBTF-VGDYDELISA-N 0.000 description 2
- RQJUKVXWAKJDBW-SVSWQMSJSA-N Ile-Ser-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N RQJUKVXWAKJDBW-SVSWQMSJSA-N 0.000 description 2
- HXIDVIFHRYRXLZ-NAKRPEOUSA-N Ile-Ser-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)O)N HXIDVIFHRYRXLZ-NAKRPEOUSA-N 0.000 description 2
- SAEWJTCJQVZQNZ-IUKAMOBKSA-N Ile-Thr-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N SAEWJTCJQVZQNZ-IUKAMOBKSA-N 0.000 description 2
- YBKKLDBBPFIXBQ-MBLNEYKQSA-N Ile-Thr-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)O)N YBKKLDBBPFIXBQ-MBLNEYKQSA-N 0.000 description 2
- ANTFEOSJMAUGIB-KNZXXDILSA-N Ile-Thr-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@@H]1C(=O)O)N ANTFEOSJMAUGIB-KNZXXDILSA-N 0.000 description 2
- JZBVBOKASHNXAD-NAKRPEOUSA-N Ile-Val-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N JZBVBOKASHNXAD-NAKRPEOUSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 108060004056 Integrin alpha Chain Proteins 0.000 description 2
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 2
- 208000037161 Laminin subunit alpha 2-related congenital muscular dystrophy Diseases 0.000 description 2
- MJOZZTKJZQFKDK-GUBZILKMSA-N Leu-Ala-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(N)=O MJOZZTKJZQFKDK-GUBZILKMSA-N 0.000 description 2
- QPRQGENIBFLVEB-BJDJZHNGSA-N Leu-Ala-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O QPRQGENIBFLVEB-BJDJZHNGSA-N 0.000 description 2
- 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 2
- WGNOPSQMIQERPK-GARJFASQSA-N Leu-Asn-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N WGNOPSQMIQERPK-GARJFASQSA-N 0.000 description 2
- MMEDVBWCMGRKKC-GARJFASQSA-N Leu-Asp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N MMEDVBWCMGRKKC-GARJFASQSA-N 0.000 description 2
- 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 2
- PPBKJAQJAUHZKX-SRVKXCTJSA-N Leu-Cys-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC(C)C PPBKJAQJAUHZKX-SRVKXCTJSA-N 0.000 description 2
- VFQOCUQGMUXTJR-DCAQKATOSA-N Leu-Cys-Met Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)O)N VFQOCUQGMUXTJR-DCAQKATOSA-N 0.000 description 2
- HUEBCHPSXSQUGN-GARJFASQSA-N Leu-Cys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N HUEBCHPSXSQUGN-GARJFASQSA-N 0.000 description 2
- VPKIQULSKFVCSM-SRVKXCTJSA-N Leu-Gln-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VPKIQULSKFVCSM-SRVKXCTJSA-N 0.000 description 2
- DXYBNWJZJVSZAE-GUBZILKMSA-N Leu-Gln-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N DXYBNWJZJVSZAE-GUBZILKMSA-N 0.000 description 2
- LOLUPZNNADDTAA-AVGNSLFASA-N Leu-Gln-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LOLUPZNNADDTAA-AVGNSLFASA-N 0.000 description 2
- 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 2
- 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 2
- LAGPXKYZCCTSGQ-JYJNAYRXSA-N Leu-Glu-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LAGPXKYZCCTSGQ-JYJNAYRXSA-N 0.000 description 2
- FMEICTQWUKNAGC-YUMQZZPRSA-N Leu-Gly-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O FMEICTQWUKNAGC-YUMQZZPRSA-N 0.000 description 2
- LAPSXOAUPNOINL-YUMQZZPRSA-N Leu-Gly-Asp Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O LAPSXOAUPNOINL-YUMQZZPRSA-N 0.000 description 2
- APFJUBGRZGMQFF-QWRGUYRKSA-N Leu-Gly-Lys Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN APFJUBGRZGMQFF-QWRGUYRKSA-N 0.000 description 2
- 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 2
- BTNXKBVLWJBTNR-SRVKXCTJSA-N Leu-His-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(O)=O BTNXKBVLWJBTNR-SRVKXCTJSA-N 0.000 description 2
- 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 2
- HGFGEMSVBMCFKK-MNXVOIDGSA-N Leu-Ile-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O HGFGEMSVBMCFKK-MNXVOIDGSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- LVTJJOJKDCVZGP-QWRGUYRKSA-N Leu-Lys-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O LVTJJOJKDCVZGP-QWRGUYRKSA-N 0.000 description 2
- FKQPWMZLIIATBA-AJNGGQMLSA-N Leu-Lys-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FKQPWMZLIIATBA-AJNGGQMLSA-N 0.000 description 2
- ZAVCJRJOQKIOJW-KKUMJFAQSA-N Leu-Phe-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CC=CC=C1 ZAVCJRJOQKIOJW-KKUMJFAQSA-N 0.000 description 2
- RRVCZCNFXIFGRA-DCAQKATOSA-N Leu-Pro-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O RRVCZCNFXIFGRA-DCAQKATOSA-N 0.000 description 2
- XXXXOVFBXRERQL-ULQDDVLXSA-N Leu-Pro-Phe Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XXXXOVFBXRERQL-ULQDDVLXSA-N 0.000 description 2
- 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 2
- AKVBOOKXVAMKSS-GUBZILKMSA-N Leu-Ser-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O AKVBOOKXVAMKSS-GUBZILKMSA-N 0.000 description 2
- 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 2
- 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 2
- PPGBXYKMUMHFBF-KATARQTJSA-N Leu-Ser-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PPGBXYKMUMHFBF-KATARQTJSA-N 0.000 description 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
- 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 2
- WFCKERTZVCQXKH-KBPBESRZSA-N Leu-Tyr-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O WFCKERTZVCQXKH-KBPBESRZSA-N 0.000 description 2
- SEOXPEFQEOYURL-PMVMPFDFSA-N Leu-Tyr-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O SEOXPEFQEOYURL-PMVMPFDFSA-N 0.000 description 2
- MVJRBCJCRYGCKV-GVXVVHGQSA-N Leu-Val-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O MVJRBCJCRYGCKV-GVXVVHGQSA-N 0.000 description 2
- 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 2
- WSXTWLJHTLRFLW-SRVKXCTJSA-N Lys-Ala-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O WSXTWLJHTLRFLW-SRVKXCTJSA-N 0.000 description 2
- 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 2
- QYOXSYXPHUHOJR-GUBZILKMSA-N Lys-Asn-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYOXSYXPHUHOJR-GUBZILKMSA-N 0.000 description 2
- FACUGMGEFUEBTI-SRVKXCTJSA-N Lys-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCCCN FACUGMGEFUEBTI-SRVKXCTJSA-N 0.000 description 2
- KPJJOZUXFOLGMQ-CIUDSAMLSA-N Lys-Asp-Asn Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N KPJJOZUXFOLGMQ-CIUDSAMLSA-N 0.000 description 2
- XTONYTDATVADQH-CIUDSAMLSA-N Lys-Cys-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O XTONYTDATVADQH-CIUDSAMLSA-N 0.000 description 2
- RDIILCRAWOSDOQ-CIUDSAMLSA-N Lys-Cys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RDIILCRAWOSDOQ-CIUDSAMLSA-N 0.000 description 2
- HEWWNLVEWBJBKA-WDCWCFNPSA-N Lys-Gln-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCCN HEWWNLVEWBJBKA-WDCWCFNPSA-N 0.000 description 2
- GCMWRRQAKQXDED-IUCAKERBSA-N Lys-Glu-Gly Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)N[C@@H](CCC([O-])=O)C(=O)NCC([O-])=O GCMWRRQAKQXDED-IUCAKERBSA-N 0.000 description 2
- RFQATBGBLDAKGI-VHSXEESVSA-N Lys-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCCCN)N)C(=O)O RFQATBGBLDAKGI-VHSXEESVSA-N 0.000 description 2
- QBEPTBMRQALPEV-MNXVOIDGSA-N Lys-Ile-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN QBEPTBMRQALPEV-MNXVOIDGSA-N 0.000 description 2
- URGPVYGVWLIRGT-DCAQKATOSA-N Lys-Met-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O URGPVYGVWLIRGT-DCAQKATOSA-N 0.000 description 2
- PDIDTSZKKFEDMB-UWVGGRQHSA-N Lys-Pro-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O PDIDTSZKKFEDMB-UWVGGRQHSA-N 0.000 description 2
- LECIJRIRMVOFMH-ULQDDVLXSA-N Lys-Pro-Phe Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 LECIJRIRMVOFMH-ULQDDVLXSA-N 0.000 description 2
- CTJUSALVKAWFFU-CIUDSAMLSA-N Lys-Ser-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N CTJUSALVKAWFFU-CIUDSAMLSA-N 0.000 description 2
- GIKFNMZSGYAPEJ-HJGDQZAQSA-N Lys-Thr-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O GIKFNMZSGYAPEJ-HJGDQZAQSA-N 0.000 description 2
- QVTDVTONTRSQMF-WDCWCFNPSA-N Lys-Thr-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CCCCN QVTDVTONTRSQMF-WDCWCFNPSA-N 0.000 description 2
- 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 2
- UZWMJZSOXGOVIN-LURJTMIESA-N Met-Gly-Gly Chemical compound CSCC[C@H](N)C(=O)NCC(=O)NCC(O)=O UZWMJZSOXGOVIN-LURJTMIESA-N 0.000 description 2
- QZPXMHVKPHJNTR-DCAQKATOSA-N Met-Leu-Asn Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O QZPXMHVKPHJNTR-DCAQKATOSA-N 0.000 description 2
- HAQLBBVZAGMESV-IHRRRGAJSA-N Met-Lys-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O HAQLBBVZAGMESV-IHRRRGAJSA-N 0.000 description 2
- QQPMHUCGDRJFQK-RHYQMDGZSA-N Met-Thr-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QQPMHUCGDRJFQK-RHYQMDGZSA-N 0.000 description 2
- PVSPJQWHEIQTEH-JYJNAYRXSA-N Met-Val-Tyr Chemical compound CSCC[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 PVSPJQWHEIQTEH-JYJNAYRXSA-N 0.000 description 2
- IQJMEDDVOGMTKT-SRVKXCTJSA-N Met-Val-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IQJMEDDVOGMTKT-SRVKXCTJSA-N 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 101100127662 Mus musculus Lama1 gene Proteins 0.000 description 2
- 101000881173 Mus musculus SPARC Proteins 0.000 description 2
- 108010079364 N-glycylalanine Proteins 0.000 description 2
- 108010034522 NNQQ peptide Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000009328 Perro Species 0.000 description 2
- NOFBJKKOPKJDCO-KKXDTOCCSA-N Phe-Ala-Tyr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NOFBJKKOPKJDCO-KKXDTOCCSA-N 0.000 description 2
- 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 2
- 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 2
- UUWCIPUVJJIEEP-SRVKXCTJSA-N Phe-Asn-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N UUWCIPUVJJIEEP-SRVKXCTJSA-N 0.000 description 2
- MECSIDWUTYRHRJ-KKUMJFAQSA-N Phe-Asn-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O MECSIDWUTYRHRJ-KKUMJFAQSA-N 0.000 description 2
- 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 2
- UEXCHCYDPAIVDE-SRVKXCTJSA-N Phe-Asp-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 UEXCHCYDPAIVDE-SRVKXCTJSA-N 0.000 description 2
- IQXOZIDWLZYYAW-IHRRRGAJSA-N Phe-Asp-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N IQXOZIDWLZYYAW-IHRRRGAJSA-N 0.000 description 2
- MQVFHOPCKNTHGT-MELADBBJSA-N Phe-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O MQVFHOPCKNTHGT-MELADBBJSA-N 0.000 description 2
- FGXIJNMDRCZVDE-KKUMJFAQSA-N Phe-Cys-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N FGXIJNMDRCZVDE-KKUMJFAQSA-N 0.000 description 2
- HOYQLNNGMHXZDW-KKUMJFAQSA-N Phe-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O HOYQLNNGMHXZDW-KKUMJFAQSA-N 0.000 description 2
- HBGFEEQFVBWYJQ-KBPBESRZSA-N Phe-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 HBGFEEQFVBWYJQ-KBPBESRZSA-N 0.000 description 2
- NPLGQVKZFGJWAI-QWHCGFSZSA-N Phe-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O NPLGQVKZFGJWAI-QWHCGFSZSA-N 0.000 description 2
- BVHFFNYBKRTSIU-MEYUZBJRSA-N Phe-His-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BVHFFNYBKRTSIU-MEYUZBJRSA-N 0.000 description 2
- METZZBCMDXHFMK-BZSNNMDCSA-N Phe-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N METZZBCMDXHFMK-BZSNNMDCSA-N 0.000 description 2
- RMKGXGPQIPLTFC-KKUMJFAQSA-N Phe-Lys-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O RMKGXGPQIPLTFC-KKUMJFAQSA-N 0.000 description 2
- ZUQACJLOHYRVPJ-DKIMLUQUSA-N Phe-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 ZUQACJLOHYRVPJ-DKIMLUQUSA-N 0.000 description 2
- XZQYIJALMGEUJD-OEAJRASXSA-N Phe-Lys-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XZQYIJALMGEUJD-OEAJRASXSA-N 0.000 description 2
- YDUGVDGFKNXFPL-IXOXFDKPSA-N Phe-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N)O YDUGVDGFKNXFPL-IXOXFDKPSA-N 0.000 description 2
- GNRMAQSIROFNMI-IXOXFDKPSA-N Phe-Thr-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GNRMAQSIROFNMI-IXOXFDKPSA-N 0.000 description 2
- LKRUQZQZMXMKEQ-SFJXLCSZSA-N Phe-Trp-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LKRUQZQZMXMKEQ-SFJXLCSZSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 2
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
- AJLVKXCNXIJHDV-CIUDSAMLSA-N Pro-Ala-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O AJLVKXCNXIJHDV-CIUDSAMLSA-N 0.000 description 2
- FZHBZMDRDASUHN-NAKRPEOUSA-N Pro-Ala-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1)C(O)=O FZHBZMDRDASUHN-NAKRPEOUSA-N 0.000 description 2
- CQZNGNCAIXMAIQ-UBHSHLNASA-N Pro-Ala-Phe Chemical compound C[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O CQZNGNCAIXMAIQ-UBHSHLNASA-N 0.000 description 2
- LNLNHXIQPGKRJQ-SRVKXCTJSA-N Pro-Arg-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1 LNLNHXIQPGKRJQ-SRVKXCTJSA-N 0.000 description 2
- ICTZKEXYDDZZFP-SRVKXCTJSA-N Pro-Arg-Pro Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCCN1 ICTZKEXYDDZZFP-SRVKXCTJSA-N 0.000 description 2
- VPVHXWGPALPDGP-GUBZILKMSA-N Pro-Asn-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VPVHXWGPALPDGP-GUBZILKMSA-N 0.000 description 2
- CJZTUKSFZUSNCC-FXQIFTODSA-N Pro-Asp-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 CJZTUKSFZUSNCC-FXQIFTODSA-N 0.000 description 2
- LUGOKRWYNMDGTD-FXQIFTODSA-N Pro-Cys-Asn Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O LUGOKRWYNMDGTD-FXQIFTODSA-N 0.000 description 2
- ZPPVJIJMIKTERM-YUMQZZPRSA-N Pro-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]1CCCN1 ZPPVJIJMIKTERM-YUMQZZPRSA-N 0.000 description 2
- PULPZRAHVFBVTO-DCAQKATOSA-N Pro-Glu-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PULPZRAHVFBVTO-DCAQKATOSA-N 0.000 description 2
- VPFGPKIWSDVTOY-SRVKXCTJSA-N Pro-Glu-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O VPFGPKIWSDVTOY-SRVKXCTJSA-N 0.000 description 2
- PTLOFJZJADCNCD-DCAQKATOSA-N Pro-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1 PTLOFJZJADCNCD-DCAQKATOSA-N 0.000 description 2
- JMVQDLDPDBXAAX-YUMQZZPRSA-N Pro-Gly-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 JMVQDLDPDBXAAX-YUMQZZPRSA-N 0.000 description 2
- 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 2
- FEPSEIDIPBMIOS-QXEWZRGKSA-N Pro-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 FEPSEIDIPBMIOS-QXEWZRGKSA-N 0.000 description 2
- FEVDNIBDCRKMER-IUCAKERBSA-N Pro-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1 FEVDNIBDCRKMER-IUCAKERBSA-N 0.000 description 2
- DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 2
- QEWBZBLXDKIQPS-STQMWFEESA-N Pro-Gly-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QEWBZBLXDKIQPS-STQMWFEESA-N 0.000 description 2
- BAKAHWWRCCUDAF-IHRRRGAJSA-N Pro-His-Lys Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@H]1NCCC1)C1=CN=CN1 BAKAHWWRCCUDAF-IHRRRGAJSA-N 0.000 description 2
- IBGCFJDLCYTKPW-NAKRPEOUSA-N Pro-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 IBGCFJDLCYTKPW-NAKRPEOUSA-N 0.000 description 2
- UREQLMJCKFLLHM-NAKRPEOUSA-N Pro-Ile-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O UREQLMJCKFLLHM-NAKRPEOUSA-N 0.000 description 2
- FMLRRBDLBJLJIK-DCAQKATOSA-N Pro-Leu-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 FMLRRBDLBJLJIK-DCAQKATOSA-N 0.000 description 2
- DWPXHLIBFQLKLK-CYDGBPFRSA-N Pro-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 DWPXHLIBFQLKLK-CYDGBPFRSA-N 0.000 description 2
- RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 description 2
- SEZGGSHLMROBFX-CIUDSAMLSA-N Pro-Ser-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O SEZGGSHLMROBFX-CIUDSAMLSA-N 0.000 description 2
- KIDXAAQVMNLJFQ-KZVJFYERSA-N Pro-Thr-Ala Chemical compound C[C@@H](O)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](C)C(O)=O KIDXAAQVMNLJFQ-KZVJFYERSA-N 0.000 description 2
- HRIXMVRZRGFKNQ-HJGDQZAQSA-N Pro-Thr-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HRIXMVRZRGFKNQ-HJGDQZAQSA-N 0.000 description 2
- GNFHQWNCSSPOBT-ULQDDVLXSA-N Pro-Trp-Gln Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CCC(=O)N)C(=O)O GNFHQWNCSSPOBT-ULQDDVLXSA-N 0.000 description 2
- BVTYXOFTHDXSNI-IHRRRGAJSA-N Pro-Tyr-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=C(O)C=C1 BVTYXOFTHDXSNI-IHRRRGAJSA-N 0.000 description 2
- QKWYXRPICJEQAJ-KJEVXHAQSA-N Pro-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@@H]2CCCN2)O QKWYXRPICJEQAJ-KJEVXHAQSA-N 0.000 description 2
- OOZJHTXCLJUODH-QXEWZRGKSA-N Pro-Val-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 OOZJHTXCLJUODH-QXEWZRGKSA-N 0.000 description 2
- 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 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 108010001267 Protein Subunits Proteins 0.000 description 2
- 102000002067 Protein Subunits Human genes 0.000 description 2
- 108010079005 RDV peptide Proteins 0.000 description 2
- 108010025216 RVF peptide Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- UBRXAVQWXOWRSJ-ZLUOBGJFSA-N Ser-Asn-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CO)N)C(=O)N UBRXAVQWXOWRSJ-ZLUOBGJFSA-N 0.000 description 2
- SWSRFJZZMNLMLY-ZKWXMUAHSA-N Ser-Asp-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O SWSRFJZZMNLMLY-ZKWXMUAHSA-N 0.000 description 2
- KCFKKAQKRZBWJB-ZLUOBGJFSA-N Ser-Cys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O KCFKKAQKRZBWJB-ZLUOBGJFSA-N 0.000 description 2
- RFBKULCUBJAQFT-BIIVOSGPSA-N Ser-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CO)N)C(=O)O RFBKULCUBJAQFT-BIIVOSGPSA-N 0.000 description 2
- WKLJLEXEENIYQE-SRVKXCTJSA-N Ser-Cys-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WKLJLEXEENIYQE-SRVKXCTJSA-N 0.000 description 2
- HVKMTOIAYDOJPL-NRPADANISA-N Ser-Gln-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVKMTOIAYDOJPL-NRPADANISA-N 0.000 description 2
- SQBLRDDJTUJDMV-ACZMJKKPSA-N Ser-Glu-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O SQBLRDDJTUJDMV-ACZMJKKPSA-N 0.000 description 2
- UFKPDBLKLOBMRH-XHNCKOQMSA-N Ser-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)C(=O)O UFKPDBLKLOBMRH-XHNCKOQMSA-N 0.000 description 2
- BPMRXBZYPGYPJN-WHFBIAKZSA-N Ser-Gly-Asn Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O BPMRXBZYPGYPJN-WHFBIAKZSA-N 0.000 description 2
- IOVHBRCQOGWAQH-ZKWXMUAHSA-N Ser-Gly-Ile Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IOVHBRCQOGWAQH-ZKWXMUAHSA-N 0.000 description 2
- 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 2
- CJINPXGSKSZQNE-KBIXCLLPSA-N Ser-Ile-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O CJINPXGSKSZQNE-KBIXCLLPSA-N 0.000 description 2
- JIPVNVNKXJLFJF-BJDJZHNGSA-N Ser-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N JIPVNVNKXJLFJF-BJDJZHNGSA-N 0.000 description 2
- 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 2
- HEUVHBXOVZONPU-BJDJZHNGSA-N Ser-Leu-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HEUVHBXOVZONPU-BJDJZHNGSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- HJAXVYLCKDPPDF-SRVKXCTJSA-N Ser-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N HJAXVYLCKDPPDF-SRVKXCTJSA-N 0.000 description 2
- 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 2
- AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 2
- PPCZVWHJWJFTFN-ZLUOBGJFSA-N Ser-Ser-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O PPCZVWHJWJFTFN-ZLUOBGJFSA-N 0.000 description 2
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 2
- 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 2
- 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 2
- SOACHCFYJMCMHC-BWBBJGPYSA-N Ser-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)O SOACHCFYJMCMHC-BWBBJGPYSA-N 0.000 description 2
- FHXGMDRKJHKLKW-QWRGUYRKSA-N Ser-Tyr-Gly Chemical compound OC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 FHXGMDRKJHKLKW-QWRGUYRKSA-N 0.000 description 2
- PCMZJFMUYWIERL-ZKWXMUAHSA-N Ser-Val-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PCMZJFMUYWIERL-ZKWXMUAHSA-N 0.000 description 2
- UKKROEYWYIHWBD-ZKWXMUAHSA-N Ser-Val-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O UKKROEYWYIHWBD-ZKWXMUAHSA-N 0.000 description 2
- SGZVZUCRAVSPKQ-FXQIFTODSA-N Ser-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N SGZVZUCRAVSPKQ-FXQIFTODSA-N 0.000 description 2
- MFQMZDPAZRZAPV-NAKRPEOUSA-N Ser-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)N MFQMZDPAZRZAPV-NAKRPEOUSA-N 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- TYVAWPFQYFPSBR-BFHQHQDPSA-N Thr-Ala-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)NCC(O)=O TYVAWPFQYFPSBR-BFHQHQDPSA-N 0.000 description 2
- JMQUAZXYFAEOIH-XGEHTFHBSA-N Thr-Arg-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N)O JMQUAZXYFAEOIH-XGEHTFHBSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- JXKMXEBNZCKSDY-JIOCBJNQSA-N Thr-Asp-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O JXKMXEBNZCKSDY-JIOCBJNQSA-N 0.000 description 2
- OHAJHDJOCKKJLV-LKXGYXEUSA-N Thr-Asp-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O OHAJHDJOCKKJLV-LKXGYXEUSA-N 0.000 description 2
- VUKVQVNKIIZBPO-HOUAVDHOSA-N Thr-Asp-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O VUKVQVNKIIZBPO-HOUAVDHOSA-N 0.000 description 2
- NRUPKQSXTJNQGD-XGEHTFHBSA-N Thr-Cys-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NRUPKQSXTJNQGD-XGEHTFHBSA-N 0.000 description 2
- UTCFSBBXPWKLTG-XKBZYTNZSA-N Thr-Cys-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O UTCFSBBXPWKLTG-XKBZYTNZSA-N 0.000 description 2
- ZLNWJMRLHLGKFX-SVSWQMSJSA-N Thr-Cys-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZLNWJMRLHLGKFX-SVSWQMSJSA-N 0.000 description 2
- RJBFAHKSFNNHAI-XKBZYTNZSA-N Thr-Gln-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N)O RJBFAHKSFNNHAI-XKBZYTNZSA-N 0.000 description 2
- ZQUKYJOKQBRBCS-GLLZPBPUSA-N Thr-Gln-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O ZQUKYJOKQBRBCS-GLLZPBPUSA-N 0.000 description 2
- UHBPFYOQQPFKQR-JHEQGTHGSA-N Thr-Gln-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O UHBPFYOQQPFKQR-JHEQGTHGSA-N 0.000 description 2
- LHEZGZQRLDBSRR-WDCWCFNPSA-N Thr-Glu-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LHEZGZQRLDBSRR-WDCWCFNPSA-N 0.000 description 2
- KCRQEJSKXAIULJ-FJXKBIBVSA-N Thr-Gly-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O KCRQEJSKXAIULJ-FJXKBIBVSA-N 0.000 description 2
- XFTYVCHLARBHBQ-FOHZUACHSA-N Thr-Gly-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O XFTYVCHLARBHBQ-FOHZUACHSA-N 0.000 description 2
- 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 2
- GMXIJHCBTZDAPD-QPHKQPEJSA-N Thr-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N GMXIJHCBTZDAPD-QPHKQPEJSA-N 0.000 description 2
- IMDMLDSVUSMAEJ-HJGDQZAQSA-N Thr-Leu-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IMDMLDSVUSMAEJ-HJGDQZAQSA-N 0.000 description 2
- RRRRCRYTLZVCEN-HJGDQZAQSA-N Thr-Leu-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O RRRRCRYTLZVCEN-HJGDQZAQSA-N 0.000 description 2
- RFKVQLIXNVEOMB-WEDXCCLWSA-N Thr-Leu-Gly Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)O)N)O RFKVQLIXNVEOMB-WEDXCCLWSA-N 0.000 description 2
- MGJLBZFUXUGMML-VOAKCMCISA-N Thr-Lys-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MGJLBZFUXUGMML-VOAKCMCISA-N 0.000 description 2
- QHUWWSQZTFLXPQ-FJXKBIBVSA-N Thr-Met-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O QHUWWSQZTFLXPQ-FJXKBIBVSA-N 0.000 description 2
- WVVOFCVMHAXGLE-LFSVMHDDSA-N Thr-Phe-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O WVVOFCVMHAXGLE-LFSVMHDDSA-N 0.000 description 2
- 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 2
- PZSDPRBZINDEJV-HTUGSXCWSA-N Thr-Phe-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O PZSDPRBZINDEJV-HTUGSXCWSA-N 0.000 description 2
- GYUUYCIXELGTJS-MEYUZBJRSA-N Thr-Phe-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O GYUUYCIXELGTJS-MEYUZBJRSA-N 0.000 description 2
- MXDOAJQRJBMGMO-FJXKBIBVSA-N Thr-Pro-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O MXDOAJQRJBMGMO-FJXKBIBVSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- NHQVWACSJZJCGJ-FLBSBUHZSA-N Thr-Thr-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NHQVWACSJZJCGJ-FLBSBUHZSA-N 0.000 description 2
- XEVHXNLPUBVQEX-DVJZZOLTSA-N Thr-Trp-Gly Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)NCC(=O)O)N)O XEVHXNLPUBVQEX-DVJZZOLTSA-N 0.000 description 2
- BEZTUFWTPVOROW-KJEVXHAQSA-N Thr-Tyr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O BEZTUFWTPVOROW-KJEVXHAQSA-N 0.000 description 2
- 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 2
- OGOYMQWIWHGTGH-KZVJFYERSA-N Thr-Val-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O OGOYMQWIWHGTGH-KZVJFYERSA-N 0.000 description 2
- MNYNCKZAEIAONY-XGEHTFHBSA-N Thr-Val-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O MNYNCKZAEIAONY-XGEHTFHBSA-N 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- IBBBOLAPFHRDHW-BPUTZDHNSA-N Trp-Asn-Arg Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N IBBBOLAPFHRDHW-BPUTZDHNSA-N 0.000 description 2
- FKAPNDWDLDWZNF-QEJZJMRPSA-N Trp-Asp-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N FKAPNDWDLDWZNF-QEJZJMRPSA-N 0.000 description 2
- IQLVYVFBJUWZNT-BPUTZDHNSA-N Trp-Cys-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N IQLVYVFBJUWZNT-BPUTZDHNSA-N 0.000 description 2
- AWYXDHQQFPZJNE-QEJZJMRPSA-N Trp-Gln-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N AWYXDHQQFPZJNE-QEJZJMRPSA-N 0.000 description 2
- ZJKZLNAECPIUTL-JBACZVJFSA-N Trp-Gln-Tyr Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=C(O)C=C1 ZJKZLNAECPIUTL-JBACZVJFSA-N 0.000 description 2
- RPVDDQYNBOVWLR-HOCLYGCPSA-N Trp-Gly-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O RPVDDQYNBOVWLR-HOCLYGCPSA-N 0.000 description 2
- UJRIVCPPPMYCNA-HOCLYGCPSA-N Trp-Leu-Gly Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N UJRIVCPPPMYCNA-HOCLYGCPSA-N 0.000 description 2
- RKISDJMICOREEL-QRTARXTBSA-N Trp-Val-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N RKISDJMICOREEL-QRTARXTBSA-N 0.000 description 2
- RWTFCAMQLFNPTK-UMPQAUOISA-N Trp-Val-Thr Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)=CNC2=C1 RWTFCAMQLFNPTK-UMPQAUOISA-N 0.000 description 2
- NOXKHHXSHQFSGJ-FQPOAREZSA-N Tyr-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NOXKHHXSHQFSGJ-FQPOAREZSA-N 0.000 description 2
- DXYWRYQRKPIGGU-BPNCWPANSA-N Tyr-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DXYWRYQRKPIGGU-BPNCWPANSA-N 0.000 description 2
- HSVPZJLMPLMPOX-BPNCWPANSA-N Tyr-Arg-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O HSVPZJLMPLMPOX-BPNCWPANSA-N 0.000 description 2
- CRWOSTCODDFEKZ-HRCADAONSA-N Tyr-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O CRWOSTCODDFEKZ-HRCADAONSA-N 0.000 description 2
- AYHSJESDFKREAR-KKUMJFAQSA-N Tyr-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AYHSJESDFKREAR-KKUMJFAQSA-N 0.000 description 2
- 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 2
- YWXMGBUGMLJMIP-IHPCNDPISA-N Tyr-Cys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC3=CC=C(C=C3)O)N YWXMGBUGMLJMIP-IHPCNDPISA-N 0.000 description 2
- PDKILSUYSUGCAO-JBACZVJFSA-N Tyr-Gln-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC3=CC=C(C=C3)O)N PDKILSUYSUGCAO-JBACZVJFSA-N 0.000 description 2
- PMDWYLVWHRTJIW-STQMWFEESA-N Tyr-Gly-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PMDWYLVWHRTJIW-STQMWFEESA-N 0.000 description 2
- LTSIAOZUVISRAQ-QWRGUYRKSA-N Tyr-Gly-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N)O LTSIAOZUVISRAQ-QWRGUYRKSA-N 0.000 description 2
- FNWGDMZVYBVAGJ-XEGUGMAKSA-N Tyr-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC1=CC=C(C=C1)O)N FNWGDMZVYBVAGJ-XEGUGMAKSA-N 0.000 description 2
- YYZPVPJCOGGQPC-JYJNAYRXSA-N Tyr-His-Gln 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(N)=O)C(O)=O YYZPVPJCOGGQPC-JYJNAYRXSA-N 0.000 description 2
- SFSZDJHNAICYSD-PMVMPFDFSA-N Tyr-His-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC3=CN=CN3)NC(=O)[C@H](CC4=CC=C(C=C4)O)N SFSZDJHNAICYSD-PMVMPFDFSA-N 0.000 description 2
- GQVZBMROTPEPIF-SRVKXCTJSA-N Tyr-Ser-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GQVZBMROTPEPIF-SRVKXCTJSA-N 0.000 description 2
- NHOVZGFNTGMYMI-KKUMJFAQSA-N Tyr-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NHOVZGFNTGMYMI-KKUMJFAQSA-N 0.000 description 2
- SYFHQHYTNCQCCN-MELADBBJSA-N Tyr-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O SYFHQHYTNCQCCN-MELADBBJSA-N 0.000 description 2
- XUIOBCQESNDTDE-FQPOAREZSA-N Tyr-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O XUIOBCQESNDTDE-FQPOAREZSA-N 0.000 description 2
- GPLTZEMVOCZVAV-UFYCRDLUSA-N Tyr-Tyr-Arg Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=C(O)C=C1 GPLTZEMVOCZVAV-UFYCRDLUSA-N 0.000 description 2
- 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 2
- AGDDLOQMXUQPDY-BZSNNMDCSA-N Tyr-Tyr-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O AGDDLOQMXUQPDY-BZSNNMDCSA-N 0.000 description 2
- RMRFSFXLFWWAJZ-HJOGWXRNSA-N Tyr-Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 RMRFSFXLFWWAJZ-HJOGWXRNSA-N 0.000 description 2
- 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 2
- IDKGBVZGNTYYCC-QXEWZRGKSA-N Val-Asn-Pro Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(O)=O IDKGBVZGNTYYCC-QXEWZRGKSA-N 0.000 description 2
- PVPAOIGJYHVWBT-KKHAAJSZSA-N Val-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N)O PVPAOIGJYHVWBT-KKHAAJSZSA-N 0.000 description 2
- ISERLACIZUGCDX-ZKWXMUAHSA-N Val-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N ISERLACIZUGCDX-ZKWXMUAHSA-N 0.000 description 2
- HZYOWMGWKKRMBZ-BYULHYEWSA-N Val-Asp-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N HZYOWMGWKKRMBZ-BYULHYEWSA-N 0.000 description 2
- 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 2
- QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 2
- BMGOFDMKDVVGJG-NHCYSSNCSA-N Val-Asp-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N BMGOFDMKDVVGJG-NHCYSSNCSA-N 0.000 description 2
- PFMAFMPJJSHNDW-ZKWXMUAHSA-N Val-Cys-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N PFMAFMPJJSHNDW-ZKWXMUAHSA-N 0.000 description 2
- FBVUOEYVGNMRMD-NAKRPEOUSA-N Val-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)N FBVUOEYVGNMRMD-NAKRPEOUSA-N 0.000 description 2
- CVIXTAITYJQMPE-LAEOZQHASA-N Val-Glu-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CVIXTAITYJQMPE-LAEOZQHASA-N 0.000 description 2
- 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 2
- DJEVQCWNMQOABE-RCOVLWMOSA-N Val-Gly-Asp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N DJEVQCWNMQOABE-RCOVLWMOSA-N 0.000 description 2
- 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 2
- FEFZWCSXEMVSPO-LSJOCFKGSA-N Val-His-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](C)C(O)=O FEFZWCSXEMVSPO-LSJOCFKGSA-N 0.000 description 2
- PYPZMFDMCCWNST-NAKRPEOUSA-N Val-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N PYPZMFDMCCWNST-NAKRPEOUSA-N 0.000 description 2
- 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 2
- 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 2
- RFKJNTRMXGCKFE-FHWLQOOXSA-N Val-Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC(C)C)C(O)=O)=CNC2=C1 RFKJNTRMXGCKFE-FHWLQOOXSA-N 0.000 description 2
- 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 2
- JVGHIFMSFBZDHH-WPRPVWTQSA-N Val-Met-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)O)N JVGHIFMSFBZDHH-WPRPVWTQSA-N 0.000 description 2
- XBJKAZATRJBDCU-GUBZILKMSA-N Val-Pro-Ala Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O XBJKAZATRJBDCU-GUBZILKMSA-N 0.000 description 2
- GQMNEJMFMCJJTD-NHCYSSNCSA-N Val-Pro-Gln Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O GQMNEJMFMCJJTD-NHCYSSNCSA-N 0.000 description 2
- SJRUJQFQVLMZFW-WPRPVWTQSA-N Val-Pro-Gly Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O SJRUJQFQVLMZFW-WPRPVWTQSA-N 0.000 description 2
- NHXZRXLFOBFMDM-AVGNSLFASA-N Val-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)C(C)C NHXZRXLFOBFMDM-AVGNSLFASA-N 0.000 description 2
- 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 2
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 2
- GBIUHAYJGWVNLN-AEJSXWLSSA-N Val-Ser-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N GBIUHAYJGWVNLN-AEJSXWLSSA-N 0.000 description 2
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 2
- UVHFONIHVHLDDQ-IFFSRLJSSA-N Val-Thr-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O UVHFONIHVHLDDQ-IFFSRLJSSA-N 0.000 description 2
- LCHZBEUVGAVMKS-RHYQMDGZSA-N Val-Thr-Leu Chemical compound CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)[C@@H](C)O)C(O)=O LCHZBEUVGAVMKS-RHYQMDGZSA-N 0.000 description 2
- JXCOEPXCBVCTRD-JYJNAYRXSA-N Val-Tyr-Arg Chemical compound CC(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 JXCOEPXCBVCTRD-JYJNAYRXSA-N 0.000 description 2
- VTIAEOKFUJJBTC-YDHLFZDLSA-N Val-Tyr-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N VTIAEOKFUJJBTC-YDHLFZDLSA-N 0.000 description 2
- LMVWCLDJNSBOEA-FKBYEOEOSA-N Val-Tyr-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N LMVWCLDJNSBOEA-FKBYEOEOSA-N 0.000 description 2
- VVIZITNVZUAEMI-DLOVCJGASA-N Val-Val-Gln Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCC(N)=O VVIZITNVZUAEMI-DLOVCJGASA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 2
- 108010003196 alanyl-prolyl-arginyl-prolyl-glycine Proteins 0.000 description 2
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 2
- 108010041407 alanylaspartic acid Proteins 0.000 description 2
- 108010044940 alanylglutamine Proteins 0.000 description 2
- 238000004873 anchoring Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 108010062796 arginyllysine Proteins 0.000 description 2
- 108010027234 aspartyl-glycyl-glutamyl-alanine Proteins 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003124 biologic agent Substances 0.000 description 2
- 239000013060 biological fluid Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 108010004073 cysteinylcysteine Proteins 0.000 description 2
- 108010069495 cysteinyltyrosine Proteins 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 239000000032 diagnostic agent Substances 0.000 description 2
- 229940039227 diagnostic agent Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- 208000028208 end stage renal disease Diseases 0.000 description 2
- 201000000523 end stage renal failure Diseases 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- CBOQJANXLMLOSS-UHFFFAOYSA-N ethyl vanillin Chemical compound CCOC1=CC(C=O)=CC=C1O CBOQJANXLMLOSS-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 2
- 230000001434 glomerular Effects 0.000 description 2
- 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 2
- JYPCXBJRLBHWME-UHFFFAOYSA-N glycyl-L-prolyl-L-arginine Natural products NCC(=O)N1CCCC1C(=O)NC(CCCN=C(N)N)C(O)=O JYPCXBJRLBHWME-UHFFFAOYSA-N 0.000 description 2
- 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 2
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 2
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 2
- 108010008671 glycyl-tryptophyl-methionine Proteins 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000010005 growth-factor like effect Effects 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 102000017777 integrin alpha chain Human genes 0.000 description 2
- 210000000876 intercostal muscle Anatomy 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 108010078274 isoleucylvaline Proteins 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 108010009932 leucyl-alanyl-glycyl-valine Proteins 0.000 description 2
- 108010030617 leucyl-phenylalanyl-valine Proteins 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 108010064235 lysylglycine Proteins 0.000 description 2
- 108010038320 lysylphenylalanine Proteins 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 238000009126 molecular therapy Methods 0.000 description 2
- 210000001087 myotubule Anatomy 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000009984 peri-natal effect Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229960003742 phenol Drugs 0.000 description 2
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 2
- 108010051242 phenylalanylserine Proteins 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 2
- 108010015796 prolylisoleucine Proteins 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- 210000003314 quadriceps muscle Anatomy 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 102200069890 rs104893963 Human genes 0.000 description 2
- 210000000518 sarcolemma Anatomy 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 108010033670 threonyl-aspartyl-tyrosine Proteins 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000003151 transfection method Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 108010029384 tryptophyl-histidine Proteins 0.000 description 2
- 108010084932 tryptophyl-proline Proteins 0.000 description 2
- 108010045269 tryptophyltryptophan Proteins 0.000 description 2
- 230000034512 ubiquitination Effects 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- VLAFRQCSFRYCLC-FXQIFTODSA-N (2s)-2-[[(2s)-2-[[2-[[(2s)-2-aminopropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]pentanedioic acid Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O VLAFRQCSFRYCLC-FXQIFTODSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- HXUVTXPOZRFMOY-NSHDSACASA-N 2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]acetic acid Chemical compound NCC(=O)NCC(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 HXUVTXPOZRFMOY-NSHDSACASA-N 0.000 description 1
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical group NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- AAQGRPOPTAUUBM-ZLUOBGJFSA-N Ala-Ala-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O AAQGRPOPTAUUBM-ZLUOBGJFSA-N 0.000 description 1
- YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 1
- 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 1
- CXRCVCURMBFFOL-FXQIFTODSA-N Ala-Ala-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O CXRCVCURMBFFOL-FXQIFTODSA-N 0.000 description 1
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 1
- ODWSTKXGQGYHSH-FXQIFTODSA-N Ala-Arg-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O ODWSTKXGQGYHSH-FXQIFTODSA-N 0.000 description 1
- SSSROGPPPVTHLX-FXQIFTODSA-N Ala-Arg-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O SSSROGPPPVTHLX-FXQIFTODSA-N 0.000 description 1
- UCIYCBSJBQGDGM-LPEHRKFASA-N Ala-Arg-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N UCIYCBSJBQGDGM-LPEHRKFASA-N 0.000 description 1
- YAXNATKKPOWVCP-ZLUOBGJFSA-N Ala-Asn-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O YAXNATKKPOWVCP-ZLUOBGJFSA-N 0.000 description 1
- XEXJJJRVTFGWIC-FXQIFTODSA-N Ala-Asn-Arg Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N XEXJJJRVTFGWIC-FXQIFTODSA-N 0.000 description 1
- XCVRVWZTXPCYJT-BIIVOSGPSA-N Ala-Asn-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N XCVRVWZTXPCYJT-BIIVOSGPSA-N 0.000 description 1
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 1
- HFBFSOAKPUZCCO-ZLUOBGJFSA-N Ala-Cys-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N HFBFSOAKPUZCCO-ZLUOBGJFSA-N 0.000 description 1
- CXQODNIBUNQWAS-CIUDSAMLSA-N Ala-Gln-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CXQODNIBUNQWAS-CIUDSAMLSA-N 0.000 description 1
- RXTBLQVXNIECFP-FXQIFTODSA-N Ala-Gln-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O RXTBLQVXNIECFP-FXQIFTODSA-N 0.000 description 1
- MPLOSMWGDNJSEV-WHFBIAKZSA-N Ala-Gly-Asp Chemical compound [H]N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MPLOSMWGDNJSEV-WHFBIAKZSA-N 0.000 description 1
- WMYJZJRILUVVRG-WDSKDSINSA-N Ala-Gly-Gln Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O WMYJZJRILUVVRG-WDSKDSINSA-N 0.000 description 1
- VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 1
- NBTGEURICRTMGL-WHFBIAKZSA-N Ala-Gly-Ser Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O NBTGEURICRTMGL-WHFBIAKZSA-N 0.000 description 1
- 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 1
- SHKGHIFSEAGTNL-DLOVCJGASA-N Ala-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CN=CN1 SHKGHIFSEAGTNL-DLOVCJGASA-N 0.000 description 1
- VNYMOTCMNHJGTG-JBDRJPRFSA-N Ala-Ile-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O VNYMOTCMNHJGTG-JBDRJPRFSA-N 0.000 description 1
- QQACQIHVWCVBBR-GVARAGBVSA-N Ala-Ile-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QQACQIHVWCVBBR-GVARAGBVSA-N 0.000 description 1
- NOGFDULFCFXBHB-CIUDSAMLSA-N Ala-Leu-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)O)N NOGFDULFCFXBHB-CIUDSAMLSA-N 0.000 description 1
- 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 1
- OYJCVIGKMXUVKB-GARJFASQSA-N Ala-Leu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N OYJCVIGKMXUVKB-GARJFASQSA-N 0.000 description 1
- UWIQWPWWZUHBAO-ZLIFDBKOSA-N Ala-Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@H](C)N)CC(C)C)C(O)=O)=CNC2=C1 UWIQWPWWZUHBAO-ZLIFDBKOSA-N 0.000 description 1
- QUIGLPSHIFPEOV-CIUDSAMLSA-N Ala-Lys-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O QUIGLPSHIFPEOV-CIUDSAMLSA-N 0.000 description 1
- MFMDKJIPHSWSBM-GUBZILKMSA-N Ala-Lys-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFMDKJIPHSWSBM-GUBZILKMSA-N 0.000 description 1
- FUKFQILQFQKHLE-DCAQKATOSA-N Ala-Lys-Met Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(O)=O FUKFQILQFQKHLE-DCAQKATOSA-N 0.000 description 1
- VHEVVUZDDUCAKU-FXQIFTODSA-N Ala-Met-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O VHEVVUZDDUCAKU-FXQIFTODSA-N 0.000 description 1
- KYDYGANDJHFBCW-DRZSPHRISA-N Ala-Phe-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N KYDYGANDJHFBCW-DRZSPHRISA-N 0.000 description 1
- WEZNQZHACPSMEF-QEJZJMRPSA-N Ala-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 WEZNQZHACPSMEF-QEJZJMRPSA-N 0.000 description 1
- YCRAFFCYWOUEOF-DLOVCJGASA-N Ala-Phe-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 YCRAFFCYWOUEOF-DLOVCJGASA-N 0.000 description 1
- GMGWOTQMUKYZIE-UBHSHLNASA-N Ala-Pro-Phe Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 GMGWOTQMUKYZIE-UBHSHLNASA-N 0.000 description 1
- KLALXKYLOMZDQT-ZLUOBGJFSA-N Ala-Ser-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(N)=O KLALXKYLOMZDQT-ZLUOBGJFSA-N 0.000 description 1
- RMAWDDRDTRSZIR-ZLUOBGJFSA-N Ala-Ser-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RMAWDDRDTRSZIR-ZLUOBGJFSA-N 0.000 description 1
- AUFACLFHBAGZEN-ZLUOBGJFSA-N Ala-Ser-Cys Chemical compound N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O AUFACLFHBAGZEN-ZLUOBGJFSA-N 0.000 description 1
- PEEYDECOOVQKRZ-DLOVCJGASA-N Ala-Ser-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PEEYDECOOVQKRZ-DLOVCJGASA-N 0.000 description 1
- ARHJJAAWNWOACN-FXQIFTODSA-N Ala-Ser-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O ARHJJAAWNWOACN-FXQIFTODSA-N 0.000 description 1
- XQNRANMFRPCFFW-GCJQMDKQSA-N Ala-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C)N)O XQNRANMFRPCFFW-GCJQMDKQSA-N 0.000 description 1
- QOIGKCBMXUCDQU-KDXUFGMBSA-N Ala-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N)O QOIGKCBMXUCDQU-KDXUFGMBSA-N 0.000 description 1
- CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 description 1
- 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 1
- AOAKQKVICDWCLB-UWJYBYFXSA-N Ala-Tyr-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N AOAKQKVICDWCLB-UWJYBYFXSA-N 0.000 description 1
- GCTANJIJJROSLH-GVARAGBVSA-N Ala-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C)N GCTANJIJJROSLH-GVARAGBVSA-N 0.000 description 1
- BOKLLPVAQDSLHC-FXQIFTODSA-N Ala-Val-Cys Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)O)N BOKLLPVAQDSLHC-FXQIFTODSA-N 0.000 description 1
- NLYYHIKRBRMAJV-AEJSXWLSSA-N Ala-Val-Pro Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N NLYYHIKRBRMAJV-AEJSXWLSSA-N 0.000 description 1
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 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
- 101800000379 Alpha-dystroglycan Proteins 0.000 description 1
- 102400000310 Alpha-dystroglycan Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- MCYJBCKCAPERSE-FXQIFTODSA-N Arg-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N MCYJBCKCAPERSE-FXQIFTODSA-N 0.000 description 1
- UXJCMQFPDWCHKX-DCAQKATOSA-N Arg-Arg-Glu Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O UXJCMQFPDWCHKX-DCAQKATOSA-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
- QPOARHANPULOTM-GMOBBJLQSA-N Arg-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N QPOARHANPULOTM-GMOBBJLQSA-N 0.000 description 1
- GHNDBBVSWOWYII-LPEHRKFASA-N Arg-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GHNDBBVSWOWYII-LPEHRKFASA-N 0.000 description 1
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 1
- JTWOBPNAVBESFW-FXQIFTODSA-N Arg-Cys-Asp Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)CN=C(N)N JTWOBPNAVBESFW-FXQIFTODSA-N 0.000 description 1
- GDVDRMUYICMNFJ-CIUDSAMLSA-N Arg-Cys-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O GDVDRMUYICMNFJ-CIUDSAMLSA-N 0.000 description 1
- VSPLYCLMFAUZRF-GUBZILKMSA-N Arg-Cys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCN=C(N)N)N VSPLYCLMFAUZRF-GUBZILKMSA-N 0.000 description 1
- DGFGDPVSDQPANQ-XGEHTFHBSA-N Arg-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCN=C(N)N)N)O DGFGDPVSDQPANQ-XGEHTFHBSA-N 0.000 description 1
- RWDVGVPHEWOZMO-GUBZILKMSA-N Arg-Cys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCNC(N)=N)C(O)=O RWDVGVPHEWOZMO-GUBZILKMSA-N 0.000 description 1
- GIVWETPOBCRTND-DCAQKATOSA-N Arg-Gln-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O GIVWETPOBCRTND-DCAQKATOSA-N 0.000 description 1
- JUWQNWXEGDYCIE-YUMQZZPRSA-N Arg-Gln-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O JUWQNWXEGDYCIE-YUMQZZPRSA-N 0.000 description 1
- YHQGEARSFILVHL-HJGDQZAQSA-N Arg-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N)O YHQGEARSFILVHL-HJGDQZAQSA-N 0.000 description 1
- LMPKCSXZJSXBBL-NHCYSSNCSA-N Arg-Gln-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O LMPKCSXZJSXBBL-NHCYSSNCSA-N 0.000 description 1
- XLWSGICNBZGYTA-CIUDSAMLSA-N Arg-Glu-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XLWSGICNBZGYTA-CIUDSAMLSA-N 0.000 description 1
- PBSOQGZLPFVXPU-YUMQZZPRSA-N Arg-Glu-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O PBSOQGZLPFVXPU-YUMQZZPRSA-N 0.000 description 1
- HPSVTWMFWCHKFN-GARJFASQSA-N Arg-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O HPSVTWMFWCHKFN-GARJFASQSA-N 0.000 description 1
- CYXCAHZVPFREJD-LURJTMIESA-N Arg-Gly-Gly Chemical compound NC(=N)NCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O CYXCAHZVPFREJD-LURJTMIESA-N 0.000 description 1
- RFXXUWGNVRJTNQ-QXEWZRGKSA-N Arg-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N RFXXUWGNVRJTNQ-QXEWZRGKSA-N 0.000 description 1
- 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 1
- SLNCSSWAIDUUGF-LSJOCFKGSA-N Arg-His-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O SLNCSSWAIDUUGF-LSJOCFKGSA-N 0.000 description 1
- UPKMBGAAEZGHOC-RWMBFGLXSA-N Arg-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O UPKMBGAAEZGHOC-RWMBFGLXSA-N 0.000 description 1
- 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 1
- RIQBRKVTFBWEDY-RHYQMDGZSA-N Arg-Lys-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RIQBRKVTFBWEDY-RHYQMDGZSA-N 0.000 description 1
- PAPSMOYMQDWIOR-AVGNSLFASA-N Arg-Lys-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PAPSMOYMQDWIOR-AVGNSLFASA-N 0.000 description 1
- FIQKRDXFTANIEJ-ULQDDVLXSA-N Arg-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N FIQKRDXFTANIEJ-ULQDDVLXSA-N 0.000 description 1
- IGFJVXOATGZTHD-UHFFFAOYSA-N Arg-Phe-His Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccccc1)C(=O)NC(Cc2c[nH]cn2)C(=O)O IGFJVXOATGZTHD-UHFFFAOYSA-N 0.000 description 1
- DNBMCNQKNOKOSD-DCAQKATOSA-N Arg-Pro-Gln Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O DNBMCNQKNOKOSD-DCAQKATOSA-N 0.000 description 1
- UULLJGQFCDXVTQ-CYDGBPFRSA-N Arg-Pro-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UULLJGQFCDXVTQ-CYDGBPFRSA-N 0.000 description 1
- YCYXHLZRUSJITQ-SRVKXCTJSA-N Arg-Pro-Pro Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 YCYXHLZRUSJITQ-SRVKXCTJSA-N 0.000 description 1
- 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 1
- OQPAZKMGCWPERI-GUBZILKMSA-N Arg-Ser-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O OQPAZKMGCWPERI-GUBZILKMSA-N 0.000 description 1
- YNSUUAOAFCVINY-OSUNSFLBSA-N Arg-Thr-Ile 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)CC)C(O)=O YNSUUAOAFCVINY-OSUNSFLBSA-N 0.000 description 1
- WTFIFQWLQXZLIZ-UMPQAUOISA-N Arg-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](CCCN=C(N)N)N)O WTFIFQWLQXZLIZ-UMPQAUOISA-N 0.000 description 1
- OGZBJJLRKQZRHL-KJEVXHAQSA-N Arg-Thr-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OGZBJJLRKQZRHL-KJEVXHAQSA-N 0.000 description 1
- QNYWYYNQSXANBL-WDSOQIARSA-N Arg-Trp-His Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N QNYWYYNQSXANBL-WDSOQIARSA-N 0.000 description 1
- BWMMKQPATDUYKB-IHRRRGAJSA-N Arg-Tyr-Asn Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 BWMMKQPATDUYKB-IHRRRGAJSA-N 0.000 description 1
- AOJYORNRFWWEIV-IHRRRGAJSA-N Arg-Tyr-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CC=C(O)C=C1 AOJYORNRFWWEIV-IHRRRGAJSA-N 0.000 description 1
- QJWLLRZTJFPCHA-STECZYCISA-N Arg-Tyr-Ile 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)CC)C(O)=O QJWLLRZTJFPCHA-STECZYCISA-N 0.000 description 1
- 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 1
- NMTANZXPDAHUKU-ULQDDVLXSA-N Arg-Tyr-Lys Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CC=C(O)C=C1 NMTANZXPDAHUKU-ULQDDVLXSA-N 0.000 description 1
- 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 1
- FXGMURPOWCKNAZ-JYJNAYRXSA-N Arg-Val-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FXGMURPOWCKNAZ-JYJNAYRXSA-N 0.000 description 1
- QLSRIZIDQXDQHK-RCWTZXSCSA-N Arg-Val-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QLSRIZIDQXDQHK-RCWTZXSCSA-N 0.000 description 1
- UTSMXMABBPFVJP-SZMVWBNQSA-N Arg-Val-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UTSMXMABBPFVJP-SZMVWBNQSA-N 0.000 description 1
- 102220547456 Arginine and glutamate-rich protein 1_S68R_mutation Human genes 0.000 description 1
- 102100026376 Artemin Human genes 0.000 description 1
- VDCIPFYVCICPEC-FXQIFTODSA-N Asn-Arg-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O VDCIPFYVCICPEC-FXQIFTODSA-N 0.000 description 1
- GXMSVVBIAMWMKO-BQBZGAKWSA-N Asn-Arg-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCN=C(N)N GXMSVVBIAMWMKO-BQBZGAKWSA-N 0.000 description 1
- 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 1
- RCENDENBBJFJHZ-ACZMJKKPSA-N Asn-Asn-Gln Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O RCENDENBBJFJHZ-ACZMJKKPSA-N 0.000 description 1
- WQSCVMQDZYTFQU-FXQIFTODSA-N Asn-Cys-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WQSCVMQDZYTFQU-FXQIFTODSA-N 0.000 description 1
- TWVTVZUGEDBAJF-ACZMJKKPSA-N Asn-Cys-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)N TWVTVZUGEDBAJF-ACZMJKKPSA-N 0.000 description 1
- ZMWDUIIACVLIHK-GHCJXIJMSA-N Asn-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)N ZMWDUIIACVLIHK-GHCJXIJMSA-N 0.000 description 1
- NNMUHYLAYUSTTN-FXQIFTODSA-N Asn-Gln-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O NNMUHYLAYUSTTN-FXQIFTODSA-N 0.000 description 1
- SRUUBQBAVNQZGJ-LAEOZQHASA-N Asn-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)N SRUUBQBAVNQZGJ-LAEOZQHASA-N 0.000 description 1
- ULRPXVNMIIYDDJ-ACZMJKKPSA-N Asn-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)N)N ULRPXVNMIIYDDJ-ACZMJKKPSA-N 0.000 description 1
- MECFLTFREHAZLH-ACZMJKKPSA-N Asn-Glu-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N MECFLTFREHAZLH-ACZMJKKPSA-N 0.000 description 1
- JREOBWLIZLXRIS-GUBZILKMSA-N Asn-Glu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JREOBWLIZLXRIS-GUBZILKMSA-N 0.000 description 1
- DMLSCRJBWUEALP-LAEOZQHASA-N Asn-Glu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O DMLSCRJBWUEALP-LAEOZQHASA-N 0.000 description 1
- JGIAYNNXZKKKOW-KKUMJFAQSA-N Asn-His-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)N)N JGIAYNNXZKKKOW-KKUMJFAQSA-N 0.000 description 1
- IBLAOXSULLECQZ-IUKAMOBKSA-N Asn-Ile-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC(N)=O IBLAOXSULLECQZ-IUKAMOBKSA-N 0.000 description 1
- BXUHCIXDSWRSBS-CIUDSAMLSA-N Asn-Leu-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O BXUHCIXDSWRSBS-CIUDSAMLSA-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
- FBODFHMLALOPHP-GUBZILKMSA-N Asn-Lys-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O FBODFHMLALOPHP-GUBZILKMSA-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
- 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 1
- UXHYOWXTJLBEPG-GSSVUCPTSA-N Asn-Thr-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UXHYOWXTJLBEPG-GSSVUCPTSA-N 0.000 description 1
- CBWCQCANJSGUOH-ZKWXMUAHSA-N Asn-Val-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O CBWCQCANJSGUOH-ZKWXMUAHSA-N 0.000 description 1
- JZLFYAAGGYMRIK-BYULHYEWSA-N Asn-Val-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O JZLFYAAGGYMRIK-BYULHYEWSA-N 0.000 description 1
- AECPDLSSUMDUAA-ZKWXMUAHSA-N Asn-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N AECPDLSSUMDUAA-ZKWXMUAHSA-N 0.000 description 1
- HPNDBHLITCHRSO-WHFBIAKZSA-N Asp-Ala-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)NCC(O)=O HPNDBHLITCHRSO-WHFBIAKZSA-N 0.000 description 1
- 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 1
- NJIKKGUVGUBICV-ZLUOBGJFSA-N Asp-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O NJIKKGUVGUBICV-ZLUOBGJFSA-N 0.000 description 1
- RGKKALNPOYURGE-ZKWXMUAHSA-N Asp-Ala-Val Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O RGKKALNPOYURGE-ZKWXMUAHSA-N 0.000 description 1
- MFMJRYHVLLEMQM-DCAQKATOSA-N Asp-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](CC(=O)O)N MFMJRYHVLLEMQM-DCAQKATOSA-N 0.000 description 1
- ZELQAFZSJOBEQS-ACZMJKKPSA-N Asp-Asn-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZELQAFZSJOBEQS-ACZMJKKPSA-N 0.000 description 1
- UGIBTKGQVWFTGX-BIIVOSGPSA-N Asp-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N)C(=O)O UGIBTKGQVWFTGX-BIIVOSGPSA-N 0.000 description 1
- KNMRXHIAVXHCLW-ZLUOBGJFSA-N Asp-Asn-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N)C(=O)O KNMRXHIAVXHCLW-ZLUOBGJFSA-N 0.000 description 1
- JGDBHIVECJGXJA-FXQIFTODSA-N Asp-Asp-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JGDBHIVECJGXJA-FXQIFTODSA-N 0.000 description 1
- WCFCYFDBMNFSPA-ACZMJKKPSA-N Asp-Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O WCFCYFDBMNFSPA-ACZMJKKPSA-N 0.000 description 1
- ZCKYZTGLXIEOKS-CIUDSAMLSA-N Asp-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)N ZCKYZTGLXIEOKS-CIUDSAMLSA-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
- FMWHSNJMHUNLAG-FXQIFTODSA-N Asp-Cys-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FMWHSNJMHUNLAG-FXQIFTODSA-N 0.000 description 1
- RSMIHCFQDCVVBR-CIUDSAMLSA-N Asp-Gln-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N RSMIHCFQDCVVBR-CIUDSAMLSA-N 0.000 description 1
- BKXPJCBEHWFSTF-ACZMJKKPSA-N Asp-Gln-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O BKXPJCBEHWFSTF-ACZMJKKPSA-N 0.000 description 1
- UFAQGGZUXVLONR-AVGNSLFASA-N Asp-Gln-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N)O UFAQGGZUXVLONR-AVGNSLFASA-N 0.000 description 1
- HSWYMWGDMPLTTH-FXQIFTODSA-N Asp-Glu-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HSWYMWGDMPLTTH-FXQIFTODSA-N 0.000 description 1
- GHODABZPVZMWCE-FXQIFTODSA-N Asp-Glu-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O GHODABZPVZMWCE-FXQIFTODSA-N 0.000 description 1
- VFUXXFVCYZPOQG-WDSKDSINSA-N Asp-Glu-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VFUXXFVCYZPOQG-WDSKDSINSA-N 0.000 description 1
- ZEDBMCPXPIYJLW-XHNCKOQMSA-N Asp-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)N)C(=O)O ZEDBMCPXPIYJLW-XHNCKOQMSA-N 0.000 description 1
- XDGBFDYXZCMYEX-NUMRIWBASA-N Asp-Glu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)N)O XDGBFDYXZCMYEX-NUMRIWBASA-N 0.000 description 1
- RRKCPMGSRIDLNC-AVGNSLFASA-N Asp-Glu-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RRKCPMGSRIDLNC-AVGNSLFASA-N 0.000 description 1
- VIRHEUMYXXLCBF-WDSKDSINSA-N Asp-Gly-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O VIRHEUMYXXLCBF-WDSKDSINSA-N 0.000 description 1
- 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 1
- PGUYEUCYVNZGGV-QWRGUYRKSA-N Asp-Gly-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PGUYEUCYVNZGGV-QWRGUYRKSA-N 0.000 description 1
- WSGVTKZFVJSJOG-RCOVLWMOSA-N Asp-Gly-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O WSGVTKZFVJSJOG-RCOVLWMOSA-N 0.000 description 1
- UBPMOJLRVMGTOQ-GARJFASQSA-N Asp-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)O)N)C(=O)O UBPMOJLRVMGTOQ-GARJFASQSA-N 0.000 description 1
- TZOZNVLBTAFJRW-UGYAYLCHSA-N Asp-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N TZOZNVLBTAFJRW-UGYAYLCHSA-N 0.000 description 1
- SPWXXPFDTMYTRI-IUKAMOBKSA-N Asp-Ile-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SPWXXPFDTMYTRI-IUKAMOBKSA-N 0.000 description 1
- 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 1
- NZWDWXSWUQCNMG-GARJFASQSA-N Asp-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N)C(=O)O NZWDWXSWUQCNMG-GARJFASQSA-N 0.000 description 1
- HJZLUGQGJWXJCJ-CIUDSAMLSA-N Asp-Pro-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJZLUGQGJWXJCJ-CIUDSAMLSA-N 0.000 description 1
- YFGUZQQCSDZRBN-DCAQKATOSA-N Asp-Pro-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YFGUZQQCSDZRBN-DCAQKATOSA-N 0.000 description 1
- XUVTWGPERWIERB-IHRRRGAJSA-N Asp-Pro-Phe Chemical compound N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O XUVTWGPERWIERB-IHRRRGAJSA-N 0.000 description 1
- FAUPLTGRUBTXNU-FXQIFTODSA-N Asp-Pro-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O FAUPLTGRUBTXNU-FXQIFTODSA-N 0.000 description 1
- 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 1
- MJJIHRWNWSQTOI-VEVYYDQMSA-N Asp-Thr-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O MJJIHRWNWSQTOI-VEVYYDQMSA-N 0.000 description 1
- 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 1
- NAAAPCLFJPURAM-HJGDQZAQSA-N Asp-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O NAAAPCLFJPURAM-HJGDQZAQSA-N 0.000 description 1
- RSMZEHCMIOKNMW-GSSVUCPTSA-N Asp-Thr-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RSMZEHCMIOKNMW-GSSVUCPTSA-N 0.000 description 1
- WOKXEQLPBLLWHC-IHRRRGAJSA-N Asp-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 WOKXEQLPBLLWHC-IHRRRGAJSA-N 0.000 description 1
- VHUKCUHLFMRHOD-MELADBBJSA-N Asp-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC(=O)O)N)C(=O)O VHUKCUHLFMRHOD-MELADBBJSA-N 0.000 description 1
- GZYDPEJSZYZWEF-MXAVVETBSA-N Asp-Val-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O GZYDPEJSZYZWEF-MXAVVETBSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 101150044789 Cap gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 206010060737 Congenital nephrotic syndrome Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- CVOZXIPULQQFNY-ZLUOBGJFSA-N Cys-Ala-Cys Chemical compound C[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CS)C(O)=O CVOZXIPULQQFNY-ZLUOBGJFSA-N 0.000 description 1
- LHLSSZYQFUNWRZ-NAKRPEOUSA-N Cys-Arg-Ile Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LHLSSZYQFUNWRZ-NAKRPEOUSA-N 0.000 description 1
- NLCZGISONIGRQP-DCAQKATOSA-N Cys-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N NLCZGISONIGRQP-DCAQKATOSA-N 0.000 description 1
- BYALSSDCQYHKMY-XGEHTFHBSA-N Cys-Arg-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N)O BYALSSDCQYHKMY-XGEHTFHBSA-N 0.000 description 1
- CPTUXCUWQIBZIF-ZLUOBGJFSA-N Cys-Asn-Ser Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O CPTUXCUWQIBZIF-ZLUOBGJFSA-N 0.000 description 1
- UWXFFVQPAMBETM-ZLUOBGJFSA-N Cys-Asp-Asn Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O UWXFFVQPAMBETM-ZLUOBGJFSA-N 0.000 description 1
- KIHRUISMQZVCNO-ZLUOBGJFSA-N Cys-Asp-Asp Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O KIHRUISMQZVCNO-ZLUOBGJFSA-N 0.000 description 1
- XABFFGOGKOORCG-CIUDSAMLSA-N Cys-Asp-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O XABFFGOGKOORCG-CIUDSAMLSA-N 0.000 description 1
- YZFCGHIBLBDZDA-ZLUOBGJFSA-N Cys-Asp-Ser Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O YZFCGHIBLBDZDA-ZLUOBGJFSA-N 0.000 description 1
- MGAWEOHYNIMOQJ-ACZMJKKPSA-N Cys-Gln-Asp Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N MGAWEOHYNIMOQJ-ACZMJKKPSA-N 0.000 description 1
- YZKOXEJTLWZOQL-GUBZILKMSA-N Cys-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CS)N YZKOXEJTLWZOQL-GUBZILKMSA-N 0.000 description 1
- PORWNQWEEIOIRH-XHNCKOQMSA-N Cys-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CS)N)C(=O)O PORWNQWEEIOIRH-XHNCKOQMSA-N 0.000 description 1
- YUZPQIQWXLRFBW-ACZMJKKPSA-N Cys-Glu-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O YUZPQIQWXLRFBW-ACZMJKKPSA-N 0.000 description 1
- UDPSLLFHOLGXBY-FXQIFTODSA-N Cys-Glu-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UDPSLLFHOLGXBY-FXQIFTODSA-N 0.000 description 1
- MUZAUPFGPMMZSS-GUBZILKMSA-N Cys-Glu-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)N MUZAUPFGPMMZSS-GUBZILKMSA-N 0.000 description 1
- XTHUKRLJRUVVBF-WHFBIAKZSA-N Cys-Gly-Ser Chemical compound SC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O XTHUKRLJRUVVBF-WHFBIAKZSA-N 0.000 description 1
- OXOQBEVULIBOSH-ZDLURKLDSA-N Cys-Gly-Thr Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O OXOQBEVULIBOSH-ZDLURKLDSA-N 0.000 description 1
- OWAFTBLVZNSIFO-SRVKXCTJSA-N Cys-His-His Chemical compound N[C@@H](CS)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O OWAFTBLVZNSIFO-SRVKXCTJSA-N 0.000 description 1
- UVZFZTWNHOQWNK-NAKRPEOUSA-N Cys-Ile-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UVZFZTWNHOQWNK-NAKRPEOUSA-N 0.000 description 1
- LKUCSUGWHYVYLP-GHCJXIJMSA-N Cys-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CS)N LKUCSUGWHYVYLP-GHCJXIJMSA-N 0.000 description 1
- ODDOYXKAHLKKQY-MMWGEVLESA-N Cys-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CS)N ODDOYXKAHLKKQY-MMWGEVLESA-N 0.000 description 1
- KXUKWRVYDYIPSQ-CIUDSAMLSA-N Cys-Leu-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O KXUKWRVYDYIPSQ-CIUDSAMLSA-N 0.000 description 1
- ABLJDBFJPUWQQB-DCAQKATOSA-N Cys-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N ABLJDBFJPUWQQB-DCAQKATOSA-N 0.000 description 1
- DYBIDOHFRRUMLW-CIUDSAMLSA-N Cys-Leu-Cys Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CS)C(O)=O DYBIDOHFRRUMLW-CIUDSAMLSA-N 0.000 description 1
- HKALUUKHYNEDRS-GUBZILKMSA-N Cys-Leu-Gln Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O HKALUUKHYNEDRS-GUBZILKMSA-N 0.000 description 1
- HBHMVBGGHDMPBF-GARJFASQSA-N Cys-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CS)N HBHMVBGGHDMPBF-GARJFASQSA-N 0.000 description 1
- BNCKELUXXUYRNY-GUBZILKMSA-N Cys-Lys-Glu Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N BNCKELUXXUYRNY-GUBZILKMSA-N 0.000 description 1
- KGIHMGPYGXBYJJ-SRVKXCTJSA-N Cys-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CS KGIHMGPYGXBYJJ-SRVKXCTJSA-N 0.000 description 1
- ZXCAQANTQWBICD-DCAQKATOSA-N Cys-Lys-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N ZXCAQANTQWBICD-DCAQKATOSA-N 0.000 description 1
- MKVKKORBPTUSNX-LPEHRKFASA-N Cys-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CS)N MKVKKORBPTUSNX-LPEHRKFASA-N 0.000 description 1
- HEPLXMBVMCXTBP-QWRGUYRKSA-N Cys-Phe-Gly Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O HEPLXMBVMCXTBP-QWRGUYRKSA-N 0.000 description 1
- MBRWOKXNHTUJMB-CIUDSAMLSA-N Cys-Pro-Glu Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O MBRWOKXNHTUJMB-CIUDSAMLSA-N 0.000 description 1
- 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 1
- ZGERHCJBLPQPGV-ACZMJKKPSA-N Cys-Ser-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N ZGERHCJBLPQPGV-ACZMJKKPSA-N 0.000 description 1
- NRVQLLDIJJEIIZ-VZFHVOOUSA-N Cys-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CS)N)O NRVQLLDIJJEIIZ-VZFHVOOUSA-N 0.000 description 1
- JRZMCSIUYGSJKP-ZKWXMUAHSA-N Cys-Val-Asn Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O JRZMCSIUYGSJKP-ZKWXMUAHSA-N 0.000 description 1
- IOLWXFWVYYCVTJ-NRPADANISA-N Cys-Val-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N IOLWXFWVYYCVTJ-NRPADANISA-N 0.000 description 1
- QQAYIVHVRFJICE-AEJSXWLSSA-N Cys-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CS)N QQAYIVHVRFJICE-AEJSXWLSSA-N 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 206010012559 Developmental delay Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 102100025682 Dystroglycan 1 Human genes 0.000 description 1
- 108010071885 Dystroglycans Proteins 0.000 description 1
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- YJIUYQKQBBQYHZ-ACZMJKKPSA-N Gln-Ala-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O YJIUYQKQBBQYHZ-ACZMJKKPSA-N 0.000 description 1
- REJJNXODKSHOKA-ACZMJKKPSA-N Gln-Ala-Asp Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N REJJNXODKSHOKA-ACZMJKKPSA-N 0.000 description 1
- JSYULGSPLTZDHM-NRPADANISA-N Gln-Ala-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O JSYULGSPLTZDHM-NRPADANISA-N 0.000 description 1
- RGXXLQWXBFNXTG-CIUDSAMLSA-N Gln-Arg-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O RGXXLQWXBFNXTG-CIUDSAMLSA-N 0.000 description 1
- LTLXPHKSQQILNF-CIUDSAMLSA-N Gln-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)CN=C(N)N LTLXPHKSQQILNF-CIUDSAMLSA-N 0.000 description 1
- ZFADFBPRMSBPOT-KKUMJFAQSA-N Gln-Arg-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O ZFADFBPRMSBPOT-KKUMJFAQSA-N 0.000 description 1
- XOKGKOQWADCLFQ-GARJFASQSA-N Gln-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XOKGKOQWADCLFQ-GARJFASQSA-N 0.000 description 1
- PHZYLYASFWHLHJ-FXQIFTODSA-N Gln-Asn-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PHZYLYASFWHLHJ-FXQIFTODSA-N 0.000 description 1
- AAOBFSKXAVIORT-GUBZILKMSA-N Gln-Asn-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O AAOBFSKXAVIORT-GUBZILKMSA-N 0.000 description 1
- JFSNBQJNDMXMQF-XHNCKOQMSA-N Gln-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N)C(=O)O JFSNBQJNDMXMQF-XHNCKOQMSA-N 0.000 description 1
- NKCZYEDZTKOFBG-GUBZILKMSA-N Gln-Gln-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NKCZYEDZTKOFBG-GUBZILKMSA-N 0.000 description 1
- GPISLLFQNHELLK-DCAQKATOSA-N Gln-Gln-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N GPISLLFQNHELLK-DCAQKATOSA-N 0.000 description 1
- KVXVVDFOZNYYKZ-DCAQKATOSA-N Gln-Gln-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KVXVVDFOZNYYKZ-DCAQKATOSA-N 0.000 description 1
- LVNILKSSFHCSJZ-IHRRRGAJSA-N Gln-Gln-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LVNILKSSFHCSJZ-IHRRRGAJSA-N 0.000 description 1
- NPTGGVQJYRSMCM-GLLZPBPUSA-N Gln-Gln-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NPTGGVQJYRSMCM-GLLZPBPUSA-N 0.000 description 1
- LLRJEFPKIIBGJP-DCAQKATOSA-N Gln-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](CCC(=O)N)N LLRJEFPKIIBGJP-DCAQKATOSA-N 0.000 description 1
- QQAPDATZKKTBIY-YUMQZZPRSA-N Gln-Gly-Met Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O QQAPDATZKKTBIY-YUMQZZPRSA-N 0.000 description 1
- JXFLPKSDLDEOQK-JHEQGTHGSA-N Gln-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O JXFLPKSDLDEOQK-JHEQGTHGSA-N 0.000 description 1
- GLEGHWQNGPMKHO-DCAQKATOSA-N Gln-His-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N GLEGHWQNGPMKHO-DCAQKATOSA-N 0.000 description 1
- NROSLUJMIQGFKS-IUCAKERBSA-N Gln-His-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N NROSLUJMIQGFKS-IUCAKERBSA-N 0.000 description 1
- CAXXTYYGFYTBPV-IUCAKERBSA-N Gln-Leu-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O CAXXTYYGFYTBPV-IUCAKERBSA-N 0.000 description 1
- VUVKKXPCKILIBD-AVGNSLFASA-N Gln-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)N)N VUVKKXPCKILIBD-AVGNSLFASA-N 0.000 description 1
- IOFDDSNZJDIGPB-GVXVVHGQSA-N Gln-Leu-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IOFDDSNZJDIGPB-GVXVVHGQSA-N 0.000 description 1
- FKXCBKCOSVIGCT-AVGNSLFASA-N Gln-Lys-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O FKXCBKCOSVIGCT-AVGNSLFASA-N 0.000 description 1
- JRHPEMVLTRADLJ-AVGNSLFASA-N Gln-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N JRHPEMVLTRADLJ-AVGNSLFASA-N 0.000 description 1
- SFAFZYYMAWOCIC-KKUMJFAQSA-N Gln-Phe-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N SFAFZYYMAWOCIC-KKUMJFAQSA-N 0.000 description 1
- QBEWLBKBGXVVPD-RYUDHWBXSA-N Gln-Phe-Gly Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N QBEWLBKBGXVVPD-RYUDHWBXSA-N 0.000 description 1
- FQCILXROGNOZON-YUMQZZPRSA-N Gln-Pro-Gly Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O FQCILXROGNOZON-YUMQZZPRSA-N 0.000 description 1
- LGWNISYVKDNJRP-FXQIFTODSA-N Gln-Ser-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGWNISYVKDNJRP-FXQIFTODSA-N 0.000 description 1
- UBRQJXFDVZNYJP-AVGNSLFASA-N Gln-Tyr-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O UBRQJXFDVZNYJP-AVGNSLFASA-N 0.000 description 1
- HPBKQFJXDUVNQV-FHWLQOOXSA-N Gln-Tyr-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O HPBKQFJXDUVNQV-FHWLQOOXSA-N 0.000 description 1
- VDMABHYXBULDGN-LAEOZQHASA-N Gln-Val-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O VDMABHYXBULDGN-LAEOZQHASA-N 0.000 description 1
- RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 1
- JJKKWYQVHRUSDG-GUBZILKMSA-N Glu-Ala-Lys Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O JJKKWYQVHRUSDG-GUBZILKMSA-N 0.000 description 1
- IRDASPPCLZIERZ-XHNCKOQMSA-N Glu-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N IRDASPPCLZIERZ-XHNCKOQMSA-N 0.000 description 1
- FYBSCGZLICNOBA-XQXXSGGOSA-N Glu-Ala-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FYBSCGZLICNOBA-XQXXSGGOSA-N 0.000 description 1
- WOMUDRVDJMHTCV-DCAQKATOSA-N Glu-Arg-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WOMUDRVDJMHTCV-DCAQKATOSA-N 0.000 description 1
- CVPXINNKRTZBMO-CIUDSAMLSA-N Glu-Arg-Asn Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)CN=C(N)N CVPXINNKRTZBMO-CIUDSAMLSA-N 0.000 description 1
- DIXKFOPPGWKZLY-CIUDSAMLSA-N Glu-Arg-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O DIXKFOPPGWKZLY-CIUDSAMLSA-N 0.000 description 1
- IYAUFWMUCGBFMQ-CIUDSAMLSA-N Glu-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)CN=C(N)N IYAUFWMUCGBFMQ-CIUDSAMLSA-N 0.000 description 1
- VTTSANCGJWLPNC-ZPFDUUQYSA-N Glu-Arg-Ile 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)CC)C(O)=O VTTSANCGJWLPNC-ZPFDUUQYSA-N 0.000 description 1
- PCBBLFVHTYNQGG-LAEOZQHASA-N Glu-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N PCBBLFVHTYNQGG-LAEOZQHASA-N 0.000 description 1
- XXCDTYBVGMPIOA-FXQIFTODSA-N Glu-Asp-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XXCDTYBVGMPIOA-FXQIFTODSA-N 0.000 description 1
- DSPQRJXOIXHOHK-WDSKDSINSA-N Glu-Asp-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O DSPQRJXOIXHOHK-WDSKDSINSA-N 0.000 description 1
- KLJMRPIBBLTDGE-ACZMJKKPSA-N Glu-Cys-Asn Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O KLJMRPIBBLTDGE-ACZMJKKPSA-N 0.000 description 1
- OBIHEDRRSMRKLU-ACZMJKKPSA-N Glu-Cys-Asp Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N OBIHEDRRSMRKLU-ACZMJKKPSA-N 0.000 description 1
- PKYAVRMYTBBRLS-FXQIFTODSA-N Glu-Cys-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O PKYAVRMYTBBRLS-FXQIFTODSA-N 0.000 description 1
- ZXLZWUQBRYGDNS-CIUDSAMLSA-N Glu-Cys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)N ZXLZWUQBRYGDNS-CIUDSAMLSA-N 0.000 description 1
- ZXQPJYWZSFGWJB-AVGNSLFASA-N Glu-Cys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)N ZXQPJYWZSFGWJB-AVGNSLFASA-N 0.000 description 1
- KVBPDJIFRQUQFY-ACZMJKKPSA-N Glu-Cys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O KVBPDJIFRQUQFY-ACZMJKKPSA-N 0.000 description 1
- GFLQTABMFBXRIY-GUBZILKMSA-N Glu-Gln-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GFLQTABMFBXRIY-GUBZILKMSA-N 0.000 description 1
- XHWLNISLUFEWNS-CIUDSAMLSA-N Glu-Gln-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O XHWLNISLUFEWNS-CIUDSAMLSA-N 0.000 description 1
- WLIPTFCZLHCNFD-LPEHRKFASA-N Glu-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)O)N)C(=O)O WLIPTFCZLHCNFD-LPEHRKFASA-N 0.000 description 1
- HTTSBEBKVNEDFE-AUTRQRHGSA-N Glu-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)O)N HTTSBEBKVNEDFE-AUTRQRHGSA-N 0.000 description 1
- CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 1
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 1
- BUAKRRKDHSSIKK-IHRRRGAJSA-N Glu-Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BUAKRRKDHSSIKK-IHRRRGAJSA-N 0.000 description 1
- OAGVHWYIBZMWLA-YFKPBYRVSA-N Glu-Gly-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)NCC(O)=O OAGVHWYIBZMWLA-YFKPBYRVSA-N 0.000 description 1
- 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 1
- BRKUZSLQMPNVFN-SRVKXCTJSA-N Glu-His-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BRKUZSLQMPNVFN-SRVKXCTJSA-N 0.000 description 1
- COSBSYQVPSODFX-GUBZILKMSA-N Glu-His-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N COSBSYQVPSODFX-GUBZILKMSA-N 0.000 description 1
- QXDXIXFSFHUYAX-MNXVOIDGSA-N Glu-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(O)=O QXDXIXFSFHUYAX-MNXVOIDGSA-N 0.000 description 1
- PJBVXVBTTFZPHJ-GUBZILKMSA-N Glu-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)O)N PJBVXVBTTFZPHJ-GUBZILKMSA-N 0.000 description 1
- IRXNJYPKBVERCW-DCAQKATOSA-N Glu-Leu-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O IRXNJYPKBVERCW-DCAQKATOSA-N 0.000 description 1
- IVGJYOOGJLFKQE-AVGNSLFASA-N Glu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N IVGJYOOGJLFKQE-AVGNSLFASA-N 0.000 description 1
- UGSVSNXPJJDJKL-SDDRHHMPSA-N Glu-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N UGSVSNXPJJDJKL-SDDRHHMPSA-N 0.000 description 1
- OQXDUSZKISQQSS-GUBZILKMSA-N Glu-Lys-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OQXDUSZKISQQSS-GUBZILKMSA-N 0.000 description 1
- SWRVAQHFBRZVNX-GUBZILKMSA-N Glu-Lys-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O SWRVAQHFBRZVNX-GUBZILKMSA-N 0.000 description 1
- OCJRHJZKGGSPRW-IUCAKERBSA-N Glu-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O OCJRHJZKGGSPRW-IUCAKERBSA-N 0.000 description 1
- YKBUCXNNBYZYAY-MNXVOIDGSA-N Glu-Lys-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O YKBUCXNNBYZYAY-MNXVOIDGSA-N 0.000 description 1
- ZGEJRLJEAMPEDV-SRVKXCTJSA-N Glu-Lys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)N ZGEJRLJEAMPEDV-SRVKXCTJSA-N 0.000 description 1
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 1
- AAJHGGDRKHYSDH-GUBZILKMSA-N Glu-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O AAJHGGDRKHYSDH-GUBZILKMSA-N 0.000 description 1
- DMYACXMQUABZIQ-NRPADANISA-N Glu-Ser-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O DMYACXMQUABZIQ-NRPADANISA-N 0.000 description 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
- QCMVGXDELYMZET-GLLZPBPUSA-N Glu-Thr-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QCMVGXDELYMZET-GLLZPBPUSA-N 0.000 description 1
- 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 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
- MIWJDJAMMKHUAR-ZVZYQTTQSA-N Glu-Trp-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCC(=O)O)N MIWJDJAMMKHUAR-ZVZYQTTQSA-N 0.000 description 1
- QOOFKCCZZWTCEP-AVGNSLFASA-N Glu-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O QOOFKCCZZWTCEP-AVGNSLFASA-N 0.000 description 1
- UUTGYDAKPISJAO-JYJNAYRXSA-N Glu-Tyr-Leu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 UUTGYDAKPISJAO-JYJNAYRXSA-N 0.000 description 1
- KIEICAOUSNYOLM-NRPADANISA-N Glu-Val-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O KIEICAOUSNYOLM-NRPADANISA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- FKJQNJCQTKUBCD-XPUUQOCRSA-N Gly-Ala-His Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O FKJQNJCQTKUBCD-XPUUQOCRSA-N 0.000 description 1
- JBRBACJPBZNFMF-YUMQZZPRSA-N Gly-Ala-Lys Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN JBRBACJPBZNFMF-YUMQZZPRSA-N 0.000 description 1
- QXPRJQPCFXMCIY-NKWVEPMBSA-N Gly-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN QXPRJQPCFXMCIY-NKWVEPMBSA-N 0.000 description 1
- LJPIRKICOISLKN-WHFBIAKZSA-N Gly-Ala-Ser Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O LJPIRKICOISLKN-WHFBIAKZSA-N 0.000 description 1
- UPOJUWHGMDJUQZ-IUCAKERBSA-N Gly-Arg-Arg Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UPOJUWHGMDJUQZ-IUCAKERBSA-N 0.000 description 1
- XUDLUKYPXQDCRX-BQBZGAKWSA-N Gly-Arg-Asn Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O XUDLUKYPXQDCRX-BQBZGAKWSA-N 0.000 description 1
- DTPOVRRYXPJJAZ-FJXKBIBVSA-N Gly-Arg-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N DTPOVRRYXPJJAZ-FJXKBIBVSA-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
- DUYYPIRFTLOAJQ-YUMQZZPRSA-N Gly-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)CN DUYYPIRFTLOAJQ-YUMQZZPRSA-N 0.000 description 1
- FMNHBTKMRFVGRO-FOHZUACHSA-N Gly-Asn-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CN FMNHBTKMRFVGRO-FOHZUACHSA-N 0.000 description 1
- GRIRDMVMJJDZKV-RCOVLWMOSA-N Gly-Asn-Val Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O GRIRDMVMJJDZKV-RCOVLWMOSA-N 0.000 description 1
- QSTLUOIOYLYLLF-WDSKDSINSA-N Gly-Asp-Glu Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QSTLUOIOYLYLLF-WDSKDSINSA-N 0.000 description 1
- FZQLXNIMCPJVJE-YUMQZZPRSA-N Gly-Asp-Leu Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O FZQLXNIMCPJVJE-YUMQZZPRSA-N 0.000 description 1
- YDWZGVCXMVLDQH-WHFBIAKZSA-N Gly-Cys-Asn Chemical compound NCC(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC(N)=O YDWZGVCXMVLDQH-WHFBIAKZSA-N 0.000 description 1
- JMQFHZWESBGPFC-WDSKDSINSA-N Gly-Gln-Asp Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O JMQFHZWESBGPFC-WDSKDSINSA-N 0.000 description 1
- AQLHORCVPGXDJW-IUCAKERBSA-N Gly-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)CN AQLHORCVPGXDJW-IUCAKERBSA-N 0.000 description 1
- JUGQPPOVWXSPKJ-RYUDHWBXSA-N Gly-Gln-Phe Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JUGQPPOVWXSPKJ-RYUDHWBXSA-N 0.000 description 1
- LJXWZPHEMJSNRC-KBPBESRZSA-N Gly-Gln-Trp Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O LJXWZPHEMJSNRC-KBPBESRZSA-N 0.000 description 1
- JLJLBWDKDRYOPA-RYUDHWBXSA-N Gly-Gln-Tyr Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 JLJLBWDKDRYOPA-RYUDHWBXSA-N 0.000 description 1
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 1
- HQRHFUYMGCHHJS-LURJTMIESA-N Gly-Gly-Arg Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N HQRHFUYMGCHHJS-LURJTMIESA-N 0.000 description 1
- UFPXDFOYHVEIPI-BYPYZUCNSA-N Gly-Gly-Asp Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O UFPXDFOYHVEIPI-BYPYZUCNSA-N 0.000 description 1
- XMPXVJIDADUOQB-RCOVLWMOSA-N Gly-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C([O-])=O)NC(=O)CNC(=O)C[NH3+] XMPXVJIDADUOQB-RCOVLWMOSA-N 0.000 description 1
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- UQJNXZSSGQIPIQ-FBCQKBJTSA-N Gly-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)CN UQJNXZSSGQIPIQ-FBCQKBJTSA-N 0.000 description 1
- TVDHVLGFJSHPAX-UWVGGRQHSA-N Gly-His-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 TVDHVLGFJSHPAX-UWVGGRQHSA-N 0.000 description 1
- ZKLYPEGLWFVRGF-IUCAKERBSA-N Gly-His-Gln Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZKLYPEGLWFVRGF-IUCAKERBSA-N 0.000 description 1
- YFGONBOFGGWKKY-VHSXEESVSA-N Gly-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)CN)C(=O)O YFGONBOFGGWKKY-VHSXEESVSA-N 0.000 description 1
- LPCKHUXOGVNZRS-YUMQZZPRSA-N Gly-His-Ser Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O LPCKHUXOGVNZRS-YUMQZZPRSA-N 0.000 description 1
- LUJVWKKYHSLULQ-ZKWXMUAHSA-N Gly-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN LUJVWKKYHSLULQ-ZKWXMUAHSA-N 0.000 description 1
- TWTPDFFBLQEBOE-IUCAKERBSA-N Gly-Leu-Gln Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O TWTPDFFBLQEBOE-IUCAKERBSA-N 0.000 description 1
- FHQRLHFYVZAQHU-IUCAKERBSA-N Gly-Lys-Gln Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O FHQRLHFYVZAQHU-IUCAKERBSA-N 0.000 description 1
- YKJUITHASJAGHO-HOTGVXAUSA-N Gly-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CN YKJUITHASJAGHO-HOTGVXAUSA-N 0.000 description 1
- OQQKUTVULYLCDG-ONGXEEELSA-N Gly-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)CN)C(O)=O OQQKUTVULYLCDG-ONGXEEELSA-N 0.000 description 1
- BBTCXWTXOXUNFX-IUCAKERBSA-N Gly-Met-Arg Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O BBTCXWTXOXUNFX-IUCAKERBSA-N 0.000 description 1
- UWQDKRIZSROAKS-FJXKBIBVSA-N Gly-Met-Thr Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UWQDKRIZSROAKS-FJXKBIBVSA-N 0.000 description 1
- IGOYNRWLWHWAQO-JTQLQIEISA-N Gly-Phe-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IGOYNRWLWHWAQO-JTQLQIEISA-N 0.000 description 1
- IBYOLNARKHMLBG-WHOFXGATSA-N Gly-Phe-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IBYOLNARKHMLBG-WHOFXGATSA-N 0.000 description 1
- 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 1
- QSQXZZCGPXQBPP-BQBZGAKWSA-N Gly-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)CN)C(=O)N[C@@H](CS)C(=O)O QSQXZZCGPXQBPP-BQBZGAKWSA-N 0.000 description 1
- ZZJVYSAQQMDIRD-UWVGGRQHSA-N Gly-Pro-His Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O ZZJVYSAQQMDIRD-UWVGGRQHSA-N 0.000 description 1
- ISSDODCYBOWWIP-GJZGRUSLSA-N Gly-Pro-Trp Chemical compound [H]NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O ISSDODCYBOWWIP-GJZGRUSLSA-N 0.000 description 1
- BMWFDYIYBAFROD-WPRPVWTQSA-N Gly-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN BMWFDYIYBAFROD-WPRPVWTQSA-N 0.000 description 1
- IRJWAYCXIYUHQE-WHFBIAKZSA-N Gly-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CN IRJWAYCXIYUHQE-WHFBIAKZSA-N 0.000 description 1
- YXTFLTJYLIAZQG-FJXKBIBVSA-N Gly-Thr-Arg Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YXTFLTJYLIAZQG-FJXKBIBVSA-N 0.000 description 1
- ZKJZBRHRWKLVSJ-ZDLURKLDSA-N Gly-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN)O ZKJZBRHRWKLVSJ-ZDLURKLDSA-N 0.000 description 1
- CQMFNTVQVLQRLT-JHEQGTHGSA-N Gly-Thr-Gln Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O CQMFNTVQVLQRLT-JHEQGTHGSA-N 0.000 description 1
- LLWQVJNHMYBLLK-CDMKHQONSA-N Gly-Thr-Phe Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LLWQVJNHMYBLLK-CDMKHQONSA-N 0.000 description 1
- CUVBTVWFVIIDOC-YEPSODPASA-N Gly-Thr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)CN CUVBTVWFVIIDOC-YEPSODPASA-N 0.000 description 1
- GWNIGUKSRJBIHX-STQMWFEESA-N Gly-Tyr-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)CN)O GWNIGUKSRJBIHX-STQMWFEESA-N 0.000 description 1
- PNUFMLXHOLFRLD-KBPBESRZSA-N Gly-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 PNUFMLXHOLFRLD-KBPBESRZSA-N 0.000 description 1
- GBYYQVBXFVDJPJ-WLTAIBSBSA-N Gly-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)CN)O GBYYQVBXFVDJPJ-WLTAIBSBSA-N 0.000 description 1
- RYAOJUMWLWUGNW-QMMMGPOBSA-N Gly-Val-Gly Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O RYAOJUMWLWUGNW-QMMMGPOBSA-N 0.000 description 1
- YGHSQRJSHKYUJY-SCZZXKLOSA-N Gly-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN YGHSQRJSHKYUJY-SCZZXKLOSA-N 0.000 description 1
- AFMOTCMSEBITOE-YEPSODPASA-N Gly-Val-Thr Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O AFMOTCMSEBITOE-YEPSODPASA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 1
- 206010019468 Hemiplegia Diseases 0.000 description 1
- 102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- KZTLOHBDLMIFSH-XVYDVKMFSA-N His-Ala-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O KZTLOHBDLMIFSH-XVYDVKMFSA-N 0.000 description 1
- TVQGUFGDVODUIF-LSJOCFKGSA-N His-Arg-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC1=CN=CN1)N TVQGUFGDVODUIF-LSJOCFKGSA-N 0.000 description 1
- HDXNWVLQSQFJOX-SRVKXCTJSA-N His-Arg-Gln Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N HDXNWVLQSQFJOX-SRVKXCTJSA-N 0.000 description 1
- LDTJBEOANMQRJE-CIUDSAMLSA-N His-Cys-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N LDTJBEOANMQRJE-CIUDSAMLSA-N 0.000 description 1
- YADRBUZBKHHDAO-XPUUQOCRSA-N His-Gly-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C)C(O)=O YADRBUZBKHHDAO-XPUUQOCRSA-N 0.000 description 1
- FYTCLUIYTYFGPT-YUMQZZPRSA-N His-Gly-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FYTCLUIYTYFGPT-YUMQZZPRSA-N 0.000 description 1
- BZKDJRSZWLPJNI-SRVKXCTJSA-N His-His-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O BZKDJRSZWLPJNI-SRVKXCTJSA-N 0.000 description 1
- 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 1
- XDIVYNSPYBLSME-DCAQKATOSA-N His-Met-Asp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N XDIVYNSPYBLSME-DCAQKATOSA-N 0.000 description 1
- FHKZHRMERJUXRJ-DCAQKATOSA-N His-Ser-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CN=CN1 FHKZHRMERJUXRJ-DCAQKATOSA-N 0.000 description 1
- 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 1
- CUEQQFOGARVNHU-VGDYDELISA-N His-Ser-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O CUEQQFOGARVNHU-VGDYDELISA-N 0.000 description 1
- 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 1
- FWWJVUFXUQOEDM-WDSOQIARSA-N His-Trp-Arg Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC3=CN=CN3)N FWWJVUFXUQOEDM-WDSOQIARSA-N 0.000 description 1
- 108010061805 His-Trp-Arg-Arg Proteins 0.000 description 1
- 101000785776 Homo sapiens Artemin Proteins 0.000 description 1
- 101000899111 Homo sapiens Hemoglobin subunit beta Proteins 0.000 description 1
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 1
- 101001111320 Homo sapiens Nestin Proteins 0.000 description 1
- 101000979333 Homo sapiens Neurofilament light polypeptide Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- WUEIUSDAECDLQO-NAKRPEOUSA-N Ile-Ala-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)O)N WUEIUSDAECDLQO-NAKRPEOUSA-N 0.000 description 1
- UNDGQKWQNSTPPW-CYDGBPFRSA-N Ile-Arg-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCSC)C(=O)O)N UNDGQKWQNSTPPW-CYDGBPFRSA-N 0.000 description 1
- QYZYJFXHXYUZMZ-UGYAYLCHSA-N Ile-Asn-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N QYZYJFXHXYUZMZ-UGYAYLCHSA-N 0.000 description 1
- RSDHVTMRXSABSV-GHCJXIJMSA-N Ile-Asn-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N RSDHVTMRXSABSV-GHCJXIJMSA-N 0.000 description 1
- XENGULNPUDGALZ-ZPFDUUQYSA-N Ile-Asn-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)O)N XENGULNPUDGALZ-ZPFDUUQYSA-N 0.000 description 1
- UDLAWRKOVFDKFL-PEFMBERDSA-N Ile-Asp-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N UDLAWRKOVFDKFL-PEFMBERDSA-N 0.000 description 1
- IDAHFEPYTJJZFD-PEFMBERDSA-N Ile-Asp-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N IDAHFEPYTJJZFD-PEFMBERDSA-N 0.000 description 1
- NKRJALPCDNXULF-BYULHYEWSA-N Ile-Asp-Gly Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O NKRJALPCDNXULF-BYULHYEWSA-N 0.000 description 1
- KUHFPGIVBOCRMV-MNXVOIDGSA-N Ile-Gln-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)O)N KUHFPGIVBOCRMV-MNXVOIDGSA-N 0.000 description 1
- LGMUPVWZEYYUMU-YVNDNENWSA-N Ile-Glu-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N LGMUPVWZEYYUMU-YVNDNENWSA-N 0.000 description 1
- XLCZWMJPVGRWHJ-KQXIARHKSA-N Ile-Glu-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N XLCZWMJPVGRWHJ-KQXIARHKSA-N 0.000 description 1
- JXMSHKFPDIUYGS-SIUGBPQLSA-N Ile-Glu-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N JXMSHKFPDIUYGS-SIUGBPQLSA-N 0.000 description 1
- WUKLZPHVWAMZQV-UKJIMTQDSA-N Ile-Glu-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N WUKLZPHVWAMZQV-UKJIMTQDSA-N 0.000 description 1
- PDTMWFVVNZYWTR-NHCYSSNCSA-N Ile-Gly-Lys Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O PDTMWFVVNZYWTR-NHCYSSNCSA-N 0.000 description 1
- CCYGNFBYUNHFSC-MGHWNKPDSA-N Ile-His-Phe Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O CCYGNFBYUNHFSC-MGHWNKPDSA-N 0.000 description 1
- KYLIZSDYWQQTFM-PEDHHIEDSA-N Ile-Ile-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CCCN=C(N)N KYLIZSDYWQQTFM-PEDHHIEDSA-N 0.000 description 1
- CSQNHSGHAPRGPQ-YTFOTSKYSA-N Ile-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)O)N CSQNHSGHAPRGPQ-YTFOTSKYSA-N 0.000 description 1
- TWYOYAKMLHWMOJ-ZPFDUUQYSA-N Ile-Leu-Asn Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O TWYOYAKMLHWMOJ-ZPFDUUQYSA-N 0.000 description 1
- CIDLJWVDMNDKPT-FIRPJDEBSA-N Ile-Phe-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)N CIDLJWVDMNDKPT-FIRPJDEBSA-N 0.000 description 1
- SVZFKLBRCYCIIY-CYDGBPFRSA-N Ile-Pro-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SVZFKLBRCYCIIY-CYDGBPFRSA-N 0.000 description 1
- VISRCHQHQCLODA-NAKRPEOUSA-N Ile-Pro-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)O)N VISRCHQHQCLODA-NAKRPEOUSA-N 0.000 description 1
- IVXJIMGDOYRLQU-XUXIUFHCSA-N Ile-Pro-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O IVXJIMGDOYRLQU-XUXIUFHCSA-N 0.000 description 1
- CIJLNXXMDUOFPH-HJWJTTGWSA-N Ile-Pro-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 CIJLNXXMDUOFPH-HJWJTTGWSA-N 0.000 description 1
- JZNVOBUNTWNZPW-GHCJXIJMSA-N Ile-Ser-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N JZNVOBUNTWNZPW-GHCJXIJMSA-N 0.000 description 1
- VGSPNSSCMOHRRR-BJDJZHNGSA-N Ile-Ser-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N VGSPNSSCMOHRRR-BJDJZHNGSA-N 0.000 description 1
- JNLSTRPWUXOORL-MMWGEVLESA-N Ile-Ser-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N JNLSTRPWUXOORL-MMWGEVLESA-N 0.000 description 1
- COWHUQXTSYTKQC-RWRJDSDZSA-N Ile-Thr-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N COWHUQXTSYTKQC-RWRJDSDZSA-N 0.000 description 1
- HJDZMPFEXINXLO-QPHKQPEJSA-N Ile-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N HJDZMPFEXINXLO-QPHKQPEJSA-N 0.000 description 1
- KBDIBHQICWDGDL-PPCPHDFISA-N Ile-Thr-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N KBDIBHQICWDGDL-PPCPHDFISA-N 0.000 description 1
- NURNJECQNNCRBK-FLBSBUHZSA-N Ile-Thr-Thr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NURNJECQNNCRBK-FLBSBUHZSA-N 0.000 description 1
- ZUWSVOYKBCHLRR-MGHWNKPDSA-N Ile-Tyr-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZUWSVOYKBCHLRR-MGHWNKPDSA-N 0.000 description 1
- NGKPIPCGMLWHBX-WZLNRYEVSA-N Ile-Tyr-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N NGKPIPCGMLWHBX-WZLNRYEVSA-N 0.000 description 1
- YWCJXQKATPNPOE-UKJIMTQDSA-N Ile-Val-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N YWCJXQKATPNPOE-UKJIMTQDSA-N 0.000 description 1
- WIYDLTIBHZSPKY-HJWJTTGWSA-N Ile-Val-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 WIYDLTIBHZSPKY-HJWJTTGWSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000012355 Integrin beta1 Human genes 0.000 description 1
- 108010022222 Integrin beta1 Proteins 0.000 description 1
- 238000012313 Kruskal-Wallis test Methods 0.000 description 1
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 1
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- RCFDOSNHHZGBOY-UHFFFAOYSA-N L-isoleucyl-L-alanine Natural products CCC(C)C(N)C(=O)NC(C)C(O)=O RCFDOSNHHZGBOY-UHFFFAOYSA-N 0.000 description 1
- 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
- CZCSUZMIRKFFFA-CIUDSAMLSA-N Leu-Ala-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O CZCSUZMIRKFFFA-CIUDSAMLSA-N 0.000 description 1
- 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 1
- XBBKIIGCUMBKCO-JXUBOQSCSA-N Leu-Ala-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XBBKIIGCUMBKCO-JXUBOQSCSA-N 0.000 description 1
- HBJZFCIVFIBNSV-DCAQKATOSA-N Leu-Arg-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(O)=O HBJZFCIVFIBNSV-DCAQKATOSA-N 0.000 description 1
- 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 1
- STAVRDQLZOTNKJ-RHYQMDGZSA-N Leu-Arg-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O STAVRDQLZOTNKJ-RHYQMDGZSA-N 0.000 description 1
- IGUOAYLTQJLPPD-DCAQKATOSA-N Leu-Asn-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IGUOAYLTQJLPPD-DCAQKATOSA-N 0.000 description 1
- 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 1
- KTFHTMHHKXUYPW-ZPFDUUQYSA-N Leu-Asp-Ile 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)CC)C(O)=O KTFHTMHHKXUYPW-ZPFDUUQYSA-N 0.000 description 1
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 1
- RRSLQOLASISYTB-CIUDSAMLSA-N Leu-Cys-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(O)=O RRSLQOLASISYTB-CIUDSAMLSA-N 0.000 description 1
- KWURTLAFFDOTEQ-GUBZILKMSA-N Leu-Cys-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KWURTLAFFDOTEQ-GUBZILKMSA-N 0.000 description 1
- NHHKSOGJYNQENP-SRVKXCTJSA-N Leu-Cys-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N NHHKSOGJYNQENP-SRVKXCTJSA-N 0.000 description 1
- DPWGZWUMUUJQDT-IUCAKERBSA-N Leu-Gln-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O DPWGZWUMUUJQDT-IUCAKERBSA-N 0.000 description 1
- CQGSYZCULZMEDE-UHFFFAOYSA-N Leu-Gln-Pro Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)N1CCCC1C(O)=O CQGSYZCULZMEDE-UHFFFAOYSA-N 0.000 description 1
- GPICTNQYKHHHTH-GUBZILKMSA-N Leu-Gln-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GPICTNQYKHHHTH-GUBZILKMSA-N 0.000 description 1
- 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 1
- PRZVBIAOPFGAQF-SRVKXCTJSA-N Leu-Glu-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O PRZVBIAOPFGAQF-SRVKXCTJSA-N 0.000 description 1
- ZFNLIDNJUWNIJL-WDCWCFNPSA-N Leu-Glu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZFNLIDNJUWNIJL-WDCWCFNPSA-N 0.000 description 1
- HVJVUYQWFYMGJS-GVXVVHGQSA-N Leu-Glu-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVJVUYQWFYMGJS-GVXVVHGQSA-N 0.000 description 1
- VWHGTYCRDRBSFI-ZETCQYMHSA-N Leu-Gly-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)NCC(O)=O VWHGTYCRDRBSFI-ZETCQYMHSA-N 0.000 description 1
- CCQLQKZTXZBXTN-NHCYSSNCSA-N Leu-Gly-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O CCQLQKZTXZBXTN-NHCYSSNCSA-N 0.000 description 1
- KOSWSHVQIVTVQF-ZPFDUUQYSA-N Leu-Ile-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O KOSWSHVQIVTVQF-ZPFDUUQYSA-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
- 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 1
- VULJUQZPSOASBZ-SRVKXCTJSA-N Leu-Pro-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O VULJUQZPSOASBZ-SRVKXCTJSA-N 0.000 description 1
- YRRCOJOXAJNSAX-IHRRRGAJSA-N Leu-Pro-Lys Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)O)N YRRCOJOXAJNSAX-IHRRRGAJSA-N 0.000 description 1
- IZPVWNSAVUQBGP-CIUDSAMLSA-N Leu-Ser-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IZPVWNSAVUQBGP-CIUDSAMLSA-N 0.000 description 1
- SBANPBVRHYIMRR-UHFFFAOYSA-N Leu-Ser-Pro Natural products CC(C)CC(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O SBANPBVRHYIMRR-UHFFFAOYSA-N 0.000 description 1
- SQUFDMCWMFOEBA-KKUMJFAQSA-N Leu-Ser-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 SQUFDMCWMFOEBA-KKUMJFAQSA-N 0.000 description 1
- ICYRCNICGBJLGM-HJGDQZAQSA-N Leu-Thr-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O ICYRCNICGBJLGM-HJGDQZAQSA-N 0.000 description 1
- QWWPYKKLXWOITQ-VOAKCMCISA-N Leu-Thr-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QWWPYKKLXWOITQ-VOAKCMCISA-N 0.000 description 1
- ILDSIMPXNFWKLH-KATARQTJSA-N Leu-Thr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ILDSIMPXNFWKLH-KATARQTJSA-N 0.000 description 1
- YLMIDMSLKLRNHX-HSCHXYMDSA-N Leu-Trp-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O YLMIDMSLKLRNHX-HSCHXYMDSA-N 0.000 description 1
- RDFIVFHPOSOXMW-ACRUOGEOSA-N Leu-Tyr-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RDFIVFHPOSOXMW-ACRUOGEOSA-N 0.000 description 1
- YIRIDPUGZKHMHT-ACRUOGEOSA-N Leu-Tyr-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YIRIDPUGZKHMHT-ACRUOGEOSA-N 0.000 description 1
- WQWZXKWOEVSGQM-DCAQKATOSA-N Lys-Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN WQWZXKWOEVSGQM-DCAQKATOSA-N 0.000 description 1
- 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 1
- SWWCDAGDQHTKIE-RHYQMDGZSA-N Lys-Arg-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWWCDAGDQHTKIE-RHYQMDGZSA-N 0.000 description 1
- LZWNAOIMTLNMDW-NHCYSSNCSA-N Lys-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N LZWNAOIMTLNMDW-NHCYSSNCSA-N 0.000 description 1
- 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 1
- DRCILAJNUJKAHC-SRVKXCTJSA-N Lys-Glu-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DRCILAJNUJKAHC-SRVKXCTJSA-N 0.000 description 1
- ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 description 1
- DCRWPTBMWMGADO-AVGNSLFASA-N Lys-Glu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DCRWPTBMWMGADO-AVGNSLFASA-N 0.000 description 1
- 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 1
- PAMDBWYMLWOELY-SDDRHHMPSA-N Lys-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N)C(=O)O PAMDBWYMLWOELY-SDDRHHMPSA-N 0.000 description 1
- ITWQLSZTLBKWJM-YUMQZZPRSA-N Lys-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCCN ITWQLSZTLBKWJM-YUMQZZPRSA-N 0.000 description 1
- GPJGFSFYBJGYRX-YUMQZZPRSA-N Lys-Gly-Asp Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O GPJGFSFYBJGYRX-YUMQZZPRSA-N 0.000 description 1
- DKTNGXVSCZULPO-YUMQZZPRSA-N Lys-Gly-Cys Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CS)C(O)=O DKTNGXVSCZULPO-YUMQZZPRSA-N 0.000 description 1
- UETQMSASAVBGJY-QWRGUYRKSA-N Lys-Gly-His Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CNC=N1 UETQMSASAVBGJY-QWRGUYRKSA-N 0.000 description 1
- DTUZCYRNEJDKSR-NHCYSSNCSA-N Lys-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN DTUZCYRNEJDKSR-NHCYSSNCSA-N 0.000 description 1
- NKKFVJRLCCUJNA-QWRGUYRKSA-N Lys-Gly-Lys Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN NKKFVJRLCCUJNA-QWRGUYRKSA-N 0.000 description 1
- NNKLKUUGESXCBS-KBPBESRZSA-N Lys-Gly-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NNKLKUUGESXCBS-KBPBESRZSA-N 0.000 description 1
- NCZIQZYZPUPMKY-PPCPHDFISA-N Lys-Ile-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NCZIQZYZPUPMKY-PPCPHDFISA-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
- QKXZCUCBFPEXNK-KKUMJFAQSA-N Lys-Leu-His Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 QKXZCUCBFPEXNK-KKUMJFAQSA-N 0.000 description 1
- YPLVCBKEPJPBDQ-MELADBBJSA-N Lys-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N YPLVCBKEPJPBDQ-MELADBBJSA-N 0.000 description 1
- RIJCHEVHFWMDKD-SRVKXCTJSA-N Lys-Lys-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O RIJCHEVHFWMDKD-SRVKXCTJSA-N 0.000 description 1
- YDDDRTIPNTWGIG-SRVKXCTJSA-N Lys-Lys-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O YDDDRTIPNTWGIG-SRVKXCTJSA-N 0.000 description 1
- PLDJDCJLRCYPJB-VOAKCMCISA-N Lys-Lys-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PLDJDCJLRCYPJB-VOAKCMCISA-N 0.000 description 1
- GZGWILAQHOVXTD-DCAQKATOSA-N Lys-Met-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O GZGWILAQHOVXTD-DCAQKATOSA-N 0.000 description 1
- AZOFEHCPMBRNFD-BZSNNMDCSA-N Lys-Phe-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CC=CC=C1 AZOFEHCPMBRNFD-BZSNNMDCSA-N 0.000 description 1
- MEQLGHAMAUPOSJ-DCAQKATOSA-N Lys-Ser-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O MEQLGHAMAUPOSJ-DCAQKATOSA-N 0.000 description 1
- MDDUIRLQCYVRDO-NHCYSSNCSA-N Lys-Val-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN MDDUIRLQCYVRDO-NHCYSSNCSA-N 0.000 description 1
- 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 1
- 108010059343 MM Form Creatine Kinase Proteins 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- DSWOTZCVCBEPOU-IUCAKERBSA-N Met-Arg-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCNC(N)=N DSWOTZCVCBEPOU-IUCAKERBSA-N 0.000 description 1
- ZEDVFJPQNNBMST-CYDGBPFRSA-N Met-Arg-Ile Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZEDVFJPQNNBMST-CYDGBPFRSA-N 0.000 description 1
- CAODKDAPYGUMLK-FXQIFTODSA-N Met-Asn-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O CAODKDAPYGUMLK-FXQIFTODSA-N 0.000 description 1
- GODBLDDYHFTUAH-CIUDSAMLSA-N Met-Asp-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O GODBLDDYHFTUAH-CIUDSAMLSA-N 0.000 description 1
- OSOLWRWQADPDIQ-DCAQKATOSA-N Met-Asp-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O OSOLWRWQADPDIQ-DCAQKATOSA-N 0.000 description 1
- SDTSLIMYROCDNS-FXQIFTODSA-N Met-Cys-Asn Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O SDTSLIMYROCDNS-FXQIFTODSA-N 0.000 description 1
- SLQDSYZHHOKQSR-QXEWZRGKSA-N Met-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCSC SLQDSYZHHOKQSR-QXEWZRGKSA-N 0.000 description 1
- AFFKUNVPPLQUGA-DCAQKATOSA-N Met-Leu-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O AFFKUNVPPLQUGA-DCAQKATOSA-N 0.000 description 1
- UROWNMBTQGGTHB-DCAQKATOSA-N Met-Leu-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O UROWNMBTQGGTHB-DCAQKATOSA-N 0.000 description 1
- RBGLBUDVQVPTEG-DCAQKATOSA-N Met-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCSC)N RBGLBUDVQVPTEG-DCAQKATOSA-N 0.000 description 1
- HUURTRNKPBHHKZ-JYJNAYRXSA-N Met-Phe-Val Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=CC=C1 HUURTRNKPBHHKZ-JYJNAYRXSA-N 0.000 description 1
- 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 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 101001111315 Mus musculus Nestin Proteins 0.000 description 1
- 208000007379 Muscle Hypotonia Diseases 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 102100037369 Nidogen-1 Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- KIAWKQJTSGRCSA-AVGNSLFASA-N Phe-Asn-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KIAWKQJTSGRCSA-AVGNSLFASA-N 0.000 description 1
- WMGVYPPIMZPWPN-SRVKXCTJSA-N Phe-Asp-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N WMGVYPPIMZPWPN-SRVKXCTJSA-N 0.000 description 1
- CSYVXYQDIVCQNU-QWRGUYRKSA-N Phe-Asp-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O CSYVXYQDIVCQNU-QWRGUYRKSA-N 0.000 description 1
- KKYHKZCMETTXEO-AVGNSLFASA-N Phe-Cys-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKYHKZCMETTXEO-AVGNSLFASA-N 0.000 description 1
- CTNODEMQIKCZGQ-JYJNAYRXSA-N Phe-Gln-His Chemical compound C([C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=CC=C1 CTNODEMQIKCZGQ-JYJNAYRXSA-N 0.000 description 1
- MFQXSDWKUXTOPZ-DZKIICNBSA-N Phe-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=CC=C1)N MFQXSDWKUXTOPZ-DZKIICNBSA-N 0.000 description 1
- KXUZHWXENMYOHC-QEJZJMRPSA-N Phe-Leu-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O KXUZHWXENMYOHC-QEJZJMRPSA-N 0.000 description 1
- SMFGCTXUBWEPKM-KBPBESRZSA-N Phe-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 SMFGCTXUBWEPKM-KBPBESRZSA-N 0.000 description 1
- BNRFQGLWLQESBG-YESZJQIVSA-N Phe-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O BNRFQGLWLQESBG-YESZJQIVSA-N 0.000 description 1
- 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 1
- XOHJOMKCRLHGCY-UNQGMJICSA-N Phe-Pro-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOHJOMKCRLHGCY-UNQGMJICSA-N 0.000 description 1
- IIEOLPMQYRBZCN-SRVKXCTJSA-N Phe-Ser-Cys Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O IIEOLPMQYRBZCN-SRVKXCTJSA-N 0.000 description 1
- QSWKNJAPHQDAAS-MELADBBJSA-N Phe-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O QSWKNJAPHQDAAS-MELADBBJSA-N 0.000 description 1
- IAOZOFPONWDXNT-IXOXFDKPSA-N Phe-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IAOZOFPONWDXNT-IXOXFDKPSA-N 0.000 description 1
- IEIFEYBAYFSRBQ-IHRRRGAJSA-N Phe-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N IEIFEYBAYFSRBQ-IHRRRGAJSA-N 0.000 description 1
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- DRVIASBABBMZTF-GUBZILKMSA-N Pro-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@@H]1CCCN1 DRVIASBABBMZTF-GUBZILKMSA-N 0.000 description 1
- OOLOTUZJUBOMAX-GUBZILKMSA-N Pro-Ala-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O OOLOTUZJUBOMAX-GUBZILKMSA-N 0.000 description 1
- WECYCNFPGZLOOU-FXQIFTODSA-N Pro-Asn-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O WECYCNFPGZLOOU-FXQIFTODSA-N 0.000 description 1
- OLTFZQIYCNOBLI-DCAQKATOSA-N Pro-Cys-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O OLTFZQIYCNOBLI-DCAQKATOSA-N 0.000 description 1
- TUYWCHPXKQTISF-LPEHRKFASA-N Pro-Cys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N2CCC[C@@H]2C(=O)O TUYWCHPXKQTISF-LPEHRKFASA-N 0.000 description 1
- SNIPWBQKOPCJRG-CIUDSAMLSA-N Pro-Gln-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CS)C(=O)O SNIPWBQKOPCJRG-CIUDSAMLSA-N 0.000 description 1
- CMOIIANLNNYUTP-SRVKXCTJSA-N Pro-Gln-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O CMOIIANLNNYUTP-SRVKXCTJSA-N 0.000 description 1
- HJSCRFZVGXAGNG-SRVKXCTJSA-N Pro-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1 HJSCRFZVGXAGNG-SRVKXCTJSA-N 0.000 description 1
- QCARZLHECSFOGG-CIUDSAMLSA-N Pro-Glu-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O QCARZLHECSFOGG-CIUDSAMLSA-N 0.000 description 1
- DMKWYMWNEKIPFC-IUCAKERBSA-N Pro-Gly-Arg Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O DMKWYMWNEKIPFC-IUCAKERBSA-N 0.000 description 1
- FKLSMYYLJHYPHH-UWVGGRQHSA-N Pro-Gly-Leu Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O FKLSMYYLJHYPHH-UWVGGRQHSA-N 0.000 description 1
- XYHMFGGWNOFUOU-QXEWZRGKSA-N Pro-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 XYHMFGGWNOFUOU-QXEWZRGKSA-N 0.000 description 1
- FKVNLUZHSFCNGY-RVMXOQNASA-N Pro-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 FKVNLUZHSFCNGY-RVMXOQNASA-N 0.000 description 1
- AUQGUYPHJSMAKI-CYDGBPFRSA-N Pro-Ile-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 AUQGUYPHJSMAKI-CYDGBPFRSA-N 0.000 description 1
- OFGUOWQVEGTVNU-DCAQKATOSA-N Pro-Lys-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OFGUOWQVEGTVNU-DCAQKATOSA-N 0.000 description 1
- 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 1
- FHZJRBVMLGOHBX-GUBZILKMSA-N Pro-Pro-Asp Chemical compound OC(=O)C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1)C(O)=O FHZJRBVMLGOHBX-GUBZILKMSA-N 0.000 description 1
- RFWXYTJSVDUBBZ-DCAQKATOSA-N Pro-Pro-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RFWXYTJSVDUBBZ-DCAQKATOSA-N 0.000 description 1
- RNEFESSBTOQSAC-DCAQKATOSA-N Pro-Ser-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O RNEFESSBTOQSAC-DCAQKATOSA-N 0.000 description 1
- ITUDDXVFGFEKPD-NAKRPEOUSA-N Pro-Ser-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ITUDDXVFGFEKPD-NAKRPEOUSA-N 0.000 description 1
- BJCXXMGGPHRSHV-GUBZILKMSA-N Pro-Ser-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 BJCXXMGGPHRSHV-GUBZILKMSA-N 0.000 description 1
- MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 1
- PRKWBYCXBBSLSK-GUBZILKMSA-N Pro-Ser-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O PRKWBYCXBBSLSK-GUBZILKMSA-N 0.000 description 1
- MDAWMJUZHBQTBO-XGEHTFHBSA-N Pro-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@@H]1CCCN1)O MDAWMJUZHBQTBO-XGEHTFHBSA-N 0.000 description 1
- 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 1
- AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 1
- VVEQUISRWJDGMX-VKOGCVSHSA-N Pro-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@@H]3CCCN3 VVEQUISRWJDGMX-VKOGCVSHSA-N 0.000 description 1
- CWZUFLWPEFHWEI-IHRRRGAJSA-N Pro-Tyr-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O CWZUFLWPEFHWEI-IHRRRGAJSA-N 0.000 description 1
- BVRBCQBUNGAWFP-KKUMJFAQSA-N Pro-Tyr-Gln Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O BVRBCQBUNGAWFP-KKUMJFAQSA-N 0.000 description 1
- FZXSYIPVAFVYBH-KKUMJFAQSA-N Pro-Tyr-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O FZXSYIPVAFVYBH-KKUMJFAQSA-N 0.000 description 1
- JXVXYRZQIUPYSA-NHCYSSNCSA-N Pro-Val-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JXVXYRZQIUPYSA-NHCYSSNCSA-N 0.000 description 1
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 1
- 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 1
- FHJQROWZEJFZPO-SRVKXCTJSA-N Pro-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FHJQROWZEJFZPO-SRVKXCTJSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 238000001190 Q-PCR Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 1
- 230000010799 Receptor Interactions Effects 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MWMKFWJYRRGXOR-ZLUOBGJFSA-N Ser-Ala-Asn Chemical compound N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)CC(N)=O)C)CO MWMKFWJYRRGXOR-ZLUOBGJFSA-N 0.000 description 1
- SRTCFKGBYBZRHA-ACZMJKKPSA-N Ser-Ala-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SRTCFKGBYBZRHA-ACZMJKKPSA-N 0.000 description 1
- BTKUIVBNGBFTTP-WHFBIAKZSA-N Ser-Ala-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NCC(O)=O BTKUIVBNGBFTTP-WHFBIAKZSA-N 0.000 description 1
- BRKHVZNDAOMAHX-BIIVOSGPSA-N Ser-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N BRKHVZNDAOMAHX-BIIVOSGPSA-N 0.000 description 1
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 1
- HBZBPFLJNDXRAY-FXQIFTODSA-N Ser-Ala-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O HBZBPFLJNDXRAY-FXQIFTODSA-N 0.000 description 1
- NLQUOHDCLSFABG-GUBZILKMSA-N Ser-Arg-Arg Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NLQUOHDCLSFABG-GUBZILKMSA-N 0.000 description 1
- YUSRGTQIPCJNHQ-CIUDSAMLSA-N Ser-Arg-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O YUSRGTQIPCJNHQ-CIUDSAMLSA-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
- WXUBSIDKNMFAGS-IHRRRGAJSA-N Ser-Arg-Tyr Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@H](CO)N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WXUBSIDKNMFAGS-IHRRRGAJSA-N 0.000 description 1
- CNIIKZQXBBQHCX-FXQIFTODSA-N Ser-Asp-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O CNIIKZQXBBQHCX-FXQIFTODSA-N 0.000 description 1
- QPFJSHSJFIYDJZ-GHCJXIJMSA-N Ser-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO QPFJSHSJFIYDJZ-GHCJXIJMSA-N 0.000 description 1
- MMAPOBOTRUVNKJ-ZLUOBGJFSA-N Ser-Asp-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CO)N)C(=O)O MMAPOBOTRUVNKJ-ZLUOBGJFSA-N 0.000 description 1
- BTPAWKABYQMKKN-LKXGYXEUSA-N Ser-Asp-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BTPAWKABYQMKKN-LKXGYXEUSA-N 0.000 description 1
- NJSPTZXVPZDRCU-UBHSHLNASA-N Ser-Asp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N NJSPTZXVPZDRCU-UBHSHLNASA-N 0.000 description 1
- WTPKKLMBNBCCNL-ACZMJKKPSA-N Ser-Cys-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N WTPKKLMBNBCCNL-ACZMJKKPSA-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
- SWIQQMYVHIXPEK-FXQIFTODSA-N Ser-Cys-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O SWIQQMYVHIXPEK-FXQIFTODSA-N 0.000 description 1
- CDVFZMOFNJPUDD-ACZMJKKPSA-N Ser-Gln-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CDVFZMOFNJPUDD-ACZMJKKPSA-N 0.000 description 1
- BQWCDDAISCPDQV-XHNCKOQMSA-N Ser-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N)C(=O)O BQWCDDAISCPDQV-XHNCKOQMSA-N 0.000 description 1
- KJMOINFQVCCSDX-XKBZYTNZSA-N Ser-Gln-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KJMOINFQVCCSDX-XKBZYTNZSA-N 0.000 description 1
- GYXVUTAOICLGKJ-ACZMJKKPSA-N Ser-Glu-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N GYXVUTAOICLGKJ-ACZMJKKPSA-N 0.000 description 1
- 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 1
- WSTIOCFMWXNOCX-YUMQZZPRSA-N Ser-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N WSTIOCFMWXNOCX-YUMQZZPRSA-N 0.000 description 1
- JFWDJFULOLKQFY-QWRGUYRKSA-N Ser-Gly-Phe Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JFWDJFULOLKQFY-QWRGUYRKSA-N 0.000 description 1
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 1
- XXXAXOWMBOKTRN-XPUUQOCRSA-N Ser-Gly-Val Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O XXXAXOWMBOKTRN-XPUUQOCRSA-N 0.000 description 1
- CICQXRWZNVXFCU-SRVKXCTJSA-N Ser-His-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O CICQXRWZNVXFCU-SRVKXCTJSA-N 0.000 description 1
- 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 1
- LQESNKGTTNHZPZ-GHCJXIJMSA-N Ser-Ile-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O LQESNKGTTNHZPZ-GHCJXIJMSA-N 0.000 description 1
- 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 1
- GJFYFGOEWLDQGW-GUBZILKMSA-N Ser-Leu-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GJFYFGOEWLDQGW-GUBZILKMSA-N 0.000 description 1
- 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 1
- GZSZPKSBVAOGIE-CIUDSAMLSA-N Ser-Lys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O GZSZPKSBVAOGIE-CIUDSAMLSA-N 0.000 description 1
- LRZLZIUXQBIWTB-KATARQTJSA-N Ser-Lys-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LRZLZIUXQBIWTB-KATARQTJSA-N 0.000 description 1
- XQAPEISNMXNKGE-FXQIFTODSA-N Ser-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CS)C(=O)O XQAPEISNMXNKGE-FXQIFTODSA-N 0.000 description 1
- WNDUPCKKKGSKIQ-CIUDSAMLSA-N Ser-Pro-Gln Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O WNDUPCKKKGSKIQ-CIUDSAMLSA-N 0.000 description 1
- FKYWFUYPVKLJLP-DCAQKATOSA-N Ser-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FKYWFUYPVKLJLP-DCAQKATOSA-N 0.000 description 1
- 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
- GYDFRTRSSXOZCR-ACZMJKKPSA-N Ser-Ser-Glu Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O GYDFRTRSSXOZCR-ACZMJKKPSA-N 0.000 description 1
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 1
- 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 1
- CUXJENOFJXOSOZ-BIIVOSGPSA-N Ser-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CO)N)C(=O)O CUXJENOFJXOSOZ-BIIVOSGPSA-N 0.000 description 1
- SQHKXWODKJDZRC-LKXGYXEUSA-N Ser-Thr-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O SQHKXWODKJDZRC-LKXGYXEUSA-N 0.000 description 1
- PQEQXWRVHQAAKS-SRVKXCTJSA-N Ser-Tyr-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)N)CC1=CC=C(O)C=C1 PQEQXWRVHQAAKS-SRVKXCTJSA-N 0.000 description 1
- GSCVDSBEYVGMJQ-SRVKXCTJSA-N Ser-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](CO)N)O GSCVDSBEYVGMJQ-SRVKXCTJSA-N 0.000 description 1
- PLQWGQUNUPMNOD-KKUMJFAQSA-N Ser-Tyr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O PLQWGQUNUPMNOD-KKUMJFAQSA-N 0.000 description 1
- YXGCIEUDOHILKR-IHRRRGAJSA-N Ser-Tyr-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CO)N YXGCIEUDOHILKR-IHRRRGAJSA-N 0.000 description 1
- OQSQCUWQOIHECT-YJRXYDGGSA-N Ser-Tyr-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OQSQCUWQOIHECT-YJRXYDGGSA-N 0.000 description 1
- 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 1
- JZRYFUGREMECBH-XPUUQOCRSA-N Ser-Val-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O JZRYFUGREMECBH-XPUUQOCRSA-N 0.000 description 1
- ANOQEBQWIAYIMV-AEJSXWLSSA-N Ser-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N ANOQEBQWIAYIMV-AEJSXWLSSA-N 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 238000000692 Student's t-test Methods 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 108090000054 Syndecan-2 Proteins 0.000 description 1
- 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 1
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 1
- CAJFZCICSVBOJK-SHGPDSBTSA-N Thr-Ala-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAJFZCICSVBOJK-SHGPDSBTSA-N 0.000 description 1
- XSLXHSYIVPGEER-KZVJFYERSA-N Thr-Ala-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O XSLXHSYIVPGEER-KZVJFYERSA-N 0.000 description 1
- XYEXCEPTALHNEV-RCWTZXSCSA-N Thr-Arg-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XYEXCEPTALHNEV-RCWTZXSCSA-N 0.000 description 1
- GZYNMZQXFRWDFH-YTWAJWBKSA-N Thr-Arg-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O GZYNMZQXFRWDFH-YTWAJWBKSA-N 0.000 description 1
- WFUAUEQXPVNAEF-ZJDVBMNYSA-N Thr-Arg-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CCCN=C(N)N WFUAUEQXPVNAEF-ZJDVBMNYSA-N 0.000 description 1
- UNURFMVMXLENAZ-KJEVXHAQSA-N Thr-Arg-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O UNURFMVMXLENAZ-KJEVXHAQSA-N 0.000 description 1
- JNQZPAWOPBZGIX-RCWTZXSCSA-N Thr-Arg-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)CCCN=C(N)N JNQZPAWOPBZGIX-RCWTZXSCSA-N 0.000 description 1
- SWIKDOUVROTZCW-GCJQMDKQSA-N Thr-Asn-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C)C(=O)O)N)O SWIKDOUVROTZCW-GCJQMDKQSA-N 0.000 description 1
- IRKWVRSEQFTGGV-VEVYYDQMSA-N Thr-Asn-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IRKWVRSEQFTGGV-VEVYYDQMSA-N 0.000 description 1
- LXWZOMSOUAMOIA-JIOCBJNQSA-N Thr-Asn-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O LXWZOMSOUAMOIA-JIOCBJNQSA-N 0.000 description 1
- PQLXHSACXPGWPD-GSSVUCPTSA-N Thr-Asn-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PQLXHSACXPGWPD-GSSVUCPTSA-N 0.000 description 1
- DCLBXIWHLVEPMQ-JRQIVUDYSA-N Thr-Asp-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 DCLBXIWHLVEPMQ-JRQIVUDYSA-N 0.000 description 1
- DSLHSTIUAPKERR-XGEHTFHBSA-N Thr-Cys-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O DSLHSTIUAPKERR-XGEHTFHBSA-N 0.000 description 1
- VOHWDZNIESHTFW-XKBZYTNZSA-N Thr-Glu-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)O VOHWDZNIESHTFW-XKBZYTNZSA-N 0.000 description 1
- KBLYJPQSNGTDIU-LOKLDPHHSA-N Thr-Glu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O KBLYJPQSNGTDIU-LOKLDPHHSA-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
- YZUWGFXVVZQJEI-PMVVWTBXSA-N Thr-Gly-His Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O YZUWGFXVVZQJEI-PMVVWTBXSA-N 0.000 description 1
- IMULJHHGAUZZFE-MBLNEYKQSA-N Thr-Gly-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IMULJHHGAUZZFE-MBLNEYKQSA-N 0.000 description 1
- MSIYNSBKKVMGFO-BHNWBGBOSA-N Thr-Gly-Pro Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N1CCC[C@@H]1C(=O)O)N)O MSIYNSBKKVMGFO-BHNWBGBOSA-N 0.000 description 1
- JKGGPMOUIAAJAA-YEPSODPASA-N Thr-Gly-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O JKGGPMOUIAAJAA-YEPSODPASA-N 0.000 description 1
- WBCCCPZIJIJTSD-TUBUOCAGSA-N Thr-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H]([C@@H](C)O)N WBCCCPZIJIJTSD-TUBUOCAGSA-N 0.000 description 1
- XOWKUMFHEZLKLT-CIQUZCHMSA-N Thr-Ile-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O XOWKUMFHEZLKLT-CIQUZCHMSA-N 0.000 description 1
- CRZNCABIJLRFKZ-IUKAMOBKSA-N Thr-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N CRZNCABIJLRFKZ-IUKAMOBKSA-N 0.000 description 1
- VTVVYQOXJCZVEB-WDCWCFNPSA-N Thr-Leu-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VTVVYQOXJCZVEB-WDCWCFNPSA-N 0.000 description 1
- 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 1
- SPVHQURZJCUDQC-VOAKCMCISA-N Thr-Lys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O SPVHQURZJCUDQC-VOAKCMCISA-N 0.000 description 1
- WFAUDCSNCWJJAA-KXNHARMFSA-N Thr-Lys-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(O)=O WFAUDCSNCWJJAA-KXNHARMFSA-N 0.000 description 1
- XNTVWRJTUIOGQO-RHYQMDGZSA-N Thr-Met-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O XNTVWRJTUIOGQO-RHYQMDGZSA-N 0.000 description 1
- UGFSAPWZBROURT-IXOXFDKPSA-N Thr-Phe-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)O)N)O UGFSAPWZBROURT-IXOXFDKPSA-N 0.000 description 1
- BIBYEFRASCNLAA-CDMKHQONSA-N Thr-Phe-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 BIBYEFRASCNLAA-CDMKHQONSA-N 0.000 description 1
- ABWNZPOIUJMNKT-IXOXFDKPSA-N Thr-Phe-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O ABWNZPOIUJMNKT-IXOXFDKPSA-N 0.000 description 1
- YGCDFAJJCRVQKU-RCWTZXSCSA-N Thr-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)[C@@H](C)O YGCDFAJJCRVQKU-RCWTZXSCSA-N 0.000 description 1
- FWTFAZKJORVTIR-VZFHVOOUSA-N Thr-Ser-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O FWTFAZKJORVTIR-VZFHVOOUSA-N 0.000 description 1
- WKGAAMOJPMBBMC-IXOXFDKPSA-N Thr-Ser-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O WKGAAMOJPMBBMC-IXOXFDKPSA-N 0.000 description 1
- NDZYTIMDOZMECO-SHGPDSBTSA-N Thr-Thr-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O NDZYTIMDOZMECO-SHGPDSBTSA-N 0.000 description 1
- BGHVVGPELPHRCI-HZTRNQAASA-N Thr-Trp-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)N)O BGHVVGPELPHRCI-HZTRNQAASA-N 0.000 description 1
- RPECVQBNONKZAT-WZLNRYEVSA-N Thr-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H]([C@@H](C)O)N RPECVQBNONKZAT-WZLNRYEVSA-N 0.000 description 1
- KVEWWQRTAVMOFT-KJEVXHAQSA-N Thr-Tyr-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O KVEWWQRTAVMOFT-KJEVXHAQSA-N 0.000 description 1
- KPMIQCXJDVKWKO-IFFSRLJSSA-N Thr-Val-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KPMIQCXJDVKWKO-IFFSRLJSSA-N 0.000 description 1
- BKVICMPZWRNWOC-RHYQMDGZSA-N Thr-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O BKVICMPZWRNWOC-RHYQMDGZSA-N 0.000 description 1
- 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 1
- QNXZCKMXHPULME-ZNSHCXBVSA-N Thr-Val-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O QNXZCKMXHPULME-ZNSHCXBVSA-N 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- XZLHHHYSWIYXHD-XIRDDKMYSA-N Trp-Gln-Arg Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XZLHHHYSWIYXHD-XIRDDKMYSA-N 0.000 description 1
- AIISTODACBDQLW-WDSOQIARSA-N Trp-Leu-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 AIISTODACBDQLW-WDSOQIARSA-N 0.000 description 1
- WMIUTJPFHMMUGY-ZFWWWQNUSA-N Trp-Pro-Gly Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)NCC(=O)O WMIUTJPFHMMUGY-ZFWWWQNUSA-N 0.000 description 1
- QHWMVGCEQAPQDK-UMPQAUOISA-N Trp-Thr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O QHWMVGCEQAPQDK-UMPQAUOISA-N 0.000 description 1
- MBLJBGZWLHTJBH-SZMVWBNQSA-N Trp-Val-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 MBLJBGZWLHTJBH-SZMVWBNQSA-N 0.000 description 1
- DLZKEQQWXODGGZ-KWQFWETISA-N Tyr-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DLZKEQQWXODGGZ-KWQFWETISA-N 0.000 description 1
- OOEUVMFKKZYSRX-LEWSCRJBSA-N Tyr-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OOEUVMFKKZYSRX-LEWSCRJBSA-N 0.000 description 1
- AKXBNSZMYAOGLS-STQMWFEESA-N Tyr-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AKXBNSZMYAOGLS-STQMWFEESA-N 0.000 description 1
- PZXUIGWOEWWFQM-SRVKXCTJSA-N Tyr-Asn-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O PZXUIGWOEWWFQM-SRVKXCTJSA-N 0.000 description 1
- XMNDQSYABVWZRK-BZSNNMDCSA-N Tyr-Asn-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O XMNDQSYABVWZRK-BZSNNMDCSA-N 0.000 description 1
- YGKVNUAKYPGORG-AVGNSLFASA-N Tyr-Asp-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YGKVNUAKYPGORG-AVGNSLFASA-N 0.000 description 1
- VFJIWSJKZJTQII-SRVKXCTJSA-N Tyr-Asp-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O VFJIWSJKZJTQII-SRVKXCTJSA-N 0.000 description 1
- RIJPHPUJRLEOAK-JYJNAYRXSA-N Tyr-Gln-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O RIJPHPUJRLEOAK-JYJNAYRXSA-N 0.000 description 1
- IWRMTNJCCMEBEX-AVGNSLFASA-N Tyr-Glu-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)O IWRMTNJCCMEBEX-AVGNSLFASA-N 0.000 description 1
- QAYSODICXVZUIA-WLTAIBSBSA-N Tyr-Gly-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O QAYSODICXVZUIA-WLTAIBSBSA-N 0.000 description 1
- ARSHSYUZHSIYKR-ACRUOGEOSA-N Tyr-His-Phe 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](CC1=CC=CC=C1)C(O)=O ARSHSYUZHSIYKR-ACRUOGEOSA-N 0.000 description 1
- KSCVLGXNQXKUAR-JYJNAYRXSA-N Tyr-Leu-Glu 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](CCC(O)=O)C(O)=O KSCVLGXNQXKUAR-JYJNAYRXSA-N 0.000 description 1
- BJCILVZEZRDIDR-PMVMPFDFSA-N Tyr-Leu-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=C(O)C=C1 BJCILVZEZRDIDR-PMVMPFDFSA-N 0.000 description 1
- HSBZWINKRYZCSQ-KKUMJFAQSA-N Tyr-Lys-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O HSBZWINKRYZCSQ-KKUMJFAQSA-N 0.000 description 1
- SBLZVFCEOCWRLS-BPNCWPANSA-N Tyr-Met-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=C(C=C1)O)N SBLZVFCEOCWRLS-BPNCWPANSA-N 0.000 description 1
- YSGAPESOXHFTQY-IHRRRGAJSA-N Tyr-Met-Asp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N YSGAPESOXHFTQY-IHRRRGAJSA-N 0.000 description 1
- VBFVQTPETKJCQW-RPTUDFQQSA-N Tyr-Phe-Thr 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@@H](C)O)C(O)=O VBFVQTPETKJCQW-RPTUDFQQSA-N 0.000 description 1
- PYJKETPLFITNKS-IHRRRGAJSA-N Tyr-Pro-Asn Chemical compound N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O PYJKETPLFITNKS-IHRRRGAJSA-N 0.000 description 1
- RWOKVQUCENPXGE-IHRRRGAJSA-N Tyr-Ser-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RWOKVQUCENPXGE-IHRRRGAJSA-N 0.000 description 1
- 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
- ZZDYJFVIKVSUFA-WLTAIBSBSA-N Tyr-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O ZZDYJFVIKVSUFA-WLTAIBSBSA-N 0.000 description 1
- KSGKJSFPWSMJHK-JNPHEJMOSA-N Tyr-Tyr-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KSGKJSFPWSMJHK-JNPHEJMOSA-N 0.000 description 1
- BQASAMYRHNCKQE-IHRRRGAJSA-N Tyr-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N BQASAMYRHNCKQE-IHRRRGAJSA-N 0.000 description 1
- NWEGIYMHTZXVBP-JSGCOSHPSA-N Tyr-Val-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O NWEGIYMHTZXVBP-JSGCOSHPSA-N 0.000 description 1
- OBKOPLHSRDATFO-XHSDSOJGSA-N Tyr-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OBKOPLHSRDATFO-XHSDSOJGSA-N 0.000 description 1
- 101150004676 VGF gene Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- UEOOXDLMQZBPFR-ZKWXMUAHSA-N Val-Ala-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N UEOOXDLMQZBPFR-ZKWXMUAHSA-N 0.000 description 1
- ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 description 1
- REJBPZVUHYNMEN-LSJOCFKGSA-N Val-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N REJBPZVUHYNMEN-LSJOCFKGSA-N 0.000 description 1
- SLLKXDSRVAOREO-KZVJFYERSA-N Val-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N)O SLLKXDSRVAOREO-KZVJFYERSA-N 0.000 description 1
- LABUITCFCAABSV-UHFFFAOYSA-N Val-Ala-Tyr Natural products CC(C)C(N)C(=O)NC(C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LABUITCFCAABSV-UHFFFAOYSA-N 0.000 description 1
- VDPRBUOZLIFUIM-GUBZILKMSA-N Val-Arg-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N VDPRBUOZLIFUIM-GUBZILKMSA-N 0.000 description 1
- UUYCNAXCCDNULB-QXEWZRGKSA-N Val-Arg-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(O)=O UUYCNAXCCDNULB-QXEWZRGKSA-N 0.000 description 1
- HNWQUBBOBKSFQV-AVGNSLFASA-N Val-Arg-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N HNWQUBBOBKSFQV-AVGNSLFASA-N 0.000 description 1
- DCOOGDCRFXXQNW-ZKWXMUAHSA-N Val-Asn-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N DCOOGDCRFXXQNW-ZKWXMUAHSA-N 0.000 description 1
- ZMDCGGKHRKNWKD-LAEOZQHASA-N Val-Asn-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZMDCGGKHRKNWKD-LAEOZQHASA-N 0.000 description 1
- 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 1
- FRUYSSRPJXNRRB-GUBZILKMSA-N Val-Cys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N FRUYSSRPJXNRRB-GUBZILKMSA-N 0.000 description 1
- BWVHQINTNLVWGZ-ZKWXMUAHSA-N Val-Cys-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N BWVHQINTNLVWGZ-ZKWXMUAHSA-N 0.000 description 1
- XIFAHCUNWWKUDE-DCAQKATOSA-N Val-Cys-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N XIFAHCUNWWKUDE-DCAQKATOSA-N 0.000 description 1
- VFOHXOLPLACADK-GVXVVHGQSA-N Val-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N VFOHXOLPLACADK-GVXVVHGQSA-N 0.000 description 1
- NYTKXWLZSNRILS-IFFSRLJSSA-N Val-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N)O NYTKXWLZSNRILS-IFFSRLJSSA-N 0.000 description 1
- GBESYURLQOYWLU-LAEOZQHASA-N Val-Glu-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N GBESYURLQOYWLU-LAEOZQHASA-N 0.000 description 1
- 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 1
- WDIGUPHXPBMODF-UMNHJUIQSA-N Val-Glu-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N WDIGUPHXPBMODF-UMNHJUIQSA-N 0.000 description 1
- 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 1
- BEGDZYNDCNEGJZ-XVKPBYJWSA-N Val-Gly-Gln Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O BEGDZYNDCNEGJZ-XVKPBYJWSA-N 0.000 description 1
- 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 1
- YTPLVNUZZOBFFC-SCZZXKLOSA-N Val-Gly-Pro Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N1CCC[C@@H]1C(O)=O YTPLVNUZZOBFFC-SCZZXKLOSA-N 0.000 description 1
- CPGJELLYDQEDRK-NAKRPEOUSA-N Val-Ile-Ala Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](C)C(O)=O CPGJELLYDQEDRK-NAKRPEOUSA-N 0.000 description 1
- SDUBQHUJJWQTEU-XUXIUFHCSA-N Val-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](C(C)C)N SDUBQHUJJWQTEU-XUXIUFHCSA-N 0.000 description 1
- FEXILLGKGGTLRI-NHCYSSNCSA-N Val-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N FEXILLGKGGTLRI-NHCYSSNCSA-N 0.000 description 1
- SVFRYKBZHUGKLP-QXEWZRGKSA-N Val-Met-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)N)C(=O)O)N SVFRYKBZHUGKLP-QXEWZRGKSA-N 0.000 description 1
- VENKIVFKIPGEJN-NHCYSSNCSA-N Val-Met-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N VENKIVFKIPGEJN-NHCYSSNCSA-N 0.000 description 1
- NZGOVKLVQNOEKP-YDHLFZDLSA-N Val-Phe-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)N)C(=O)O)N NZGOVKLVQNOEKP-YDHLFZDLSA-N 0.000 description 1
- YTNGABPUXFEOGU-SRVKXCTJSA-N Val-Pro-Arg Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O YTNGABPUXFEOGU-SRVKXCTJSA-N 0.000 description 1
- MIKHIIQMRFYVOR-RCWTZXSCSA-N Val-Pro-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C(C)C)N)O MIKHIIQMRFYVOR-RCWTZXSCSA-N 0.000 description 1
- JQTYTBPCSOAZHI-FXQIFTODSA-N Val-Ser-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N JQTYTBPCSOAZHI-FXQIFTODSA-N 0.000 description 1
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 1
- QTPQHINADBYBNA-DCAQKATOSA-N Val-Ser-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN QTPQHINADBYBNA-DCAQKATOSA-N 0.000 description 1
- CEKSLIVSNNGOKH-KZVJFYERSA-N Val-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](C(C)C)N)O CEKSLIVSNNGOKH-KZVJFYERSA-N 0.000 description 1
- GVNLOVJNNDZUHS-RHYQMDGZSA-N Val-Thr-Lys Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O GVNLOVJNNDZUHS-RHYQMDGZSA-N 0.000 description 1
- 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 1
- JXWGBRRVTRAZQA-ULQDDVLXSA-N Val-Tyr-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C(C)C)N JXWGBRRVTRAZQA-ULQDDVLXSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 239000012082 adaptor molecule Substances 0.000 description 1
- 102000035181 adaptor proteins Human genes 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000910 agglutinin Substances 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 1
- 108010066829 alanyl-glutamyl-aspartylprolyine Proteins 0.000 description 1
- 108010069490 alanyl-glycyl-seryl-glutamic acid Proteins 0.000 description 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- 108010070783 alanyltyrosine Proteins 0.000 description 1
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 239000012637 allosteric effector Substances 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 108010008355 arginyl-glutamine Proteins 0.000 description 1
- 108010038850 arginyl-isoleucyl-tyrosine Proteins 0.000 description 1
- 108010029539 arginyl-prolyl-proline Proteins 0.000 description 1
- 108010084758 arginyl-tyrosyl-aspartic acid Proteins 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229940090047 auto-injector Drugs 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000005821 brain abnormality Effects 0.000 description 1
- 210000004781 brain capillary Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000031736 central nervous system myelination Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007881 chronic fibrosis Effects 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 201000006948 congenital merosin-deficient muscular dystrophy 1A Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 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
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 210000000188 diaphragm Anatomy 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 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
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 229940073505 ethyl vanillin Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000004954 familial nephrotic syndrome Diseases 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 108010027668 glycyl-alanyl-valine Proteins 0.000 description 1
- 108010023364 glycyl-histidyl-arginine Proteins 0.000 description 1
- 108010048994 glycyl-tyrosyl-alanine Proteins 0.000 description 1
- 108010059898 glycyl-tyrosyl-lysine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 108010050343 histidyl-alanyl-glutamine Proteins 0.000 description 1
- 102000046949 human MSC Human genes 0.000 description 1
- 102000043377 human NES Human genes 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 108010031424 isoleucyl-prolyl-proline Proteins 0.000 description 1
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 108010028309 kalinin Proteins 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 108010038862 laminin 10 Proteins 0.000 description 1
- 102000025702 laminin binding proteins Human genes 0.000 description 1
- 108091014736 laminin binding proteins Proteins 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 108010076756 leucyl-alanyl-phenylalanine Proteins 0.000 description 1
- 108010091871 leucylmethionine Proteins 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 1
- 108010057952 lysyl-phenylalanyl-lysine Proteins 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 208000037843 metastatic solid tumor Diseases 0.000 description 1
- 108010005942 methionylglycine Proteins 0.000 description 1
- 108010068488 methionylphenylalanine Proteins 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 230000031783 myelination in peripheral nervous system Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 230000008043 neural expression Effects 0.000 description 1
- 230000001123 neurodevelopmental effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000011330 nucleic acid test Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229940090668 parachlorophenol Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 108010012581 phenylalanylglutamate Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 210000003105 phrenic nerve Anatomy 0.000 description 1
- 230000008560 physiological behavior Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920000771 poly (alkylcyanoacrylate) Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000037048 polymerization activity Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000026526 progressive weakness Diseases 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000005451 protein repair Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000013646 rAAV2 vector Substances 0.000 description 1
- 230000003439 radiotherapeutic effect Effects 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 101150066583 rep gene Proteins 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 102200089579 rs786202787 Human genes 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000007847 structural defect Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 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
- 229940044609 sulfur dioxide Drugs 0.000 description 1
- 235000010269 sulphur dioxide Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 230000008427 tissue turnover Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000011820 transgenic animal model Methods 0.000 description 1
- 238000012250 transgenic expression Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 108700004896 tripeptide FEG Proteins 0.000 description 1
- 108010005834 tyrosyl-alanyl-glycine Proteins 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 239000011882 ultra-fine particle Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
- A01K2217/077—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out heterozygous knock out animals displaying phenotype
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14122—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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Abstract
本发明涉及重组层粘连蛋白腺相关病毒载体(AAV)构建体以及用于恢复缺陷型哺乳动物或具有基底膜不稳定性的哺乳动物的层粘连蛋白表达的相关方法。
Description
政府支持声明
本发明是在由美国国立卫生研究院(National Institutes of Health)授予的授权号R01-DK36425下由政府支持进行的。政府在本发明中具有某些权利。
序列表
本申请含有已经以ASCII格式电子提交并且特此通过引用整体并入的序列表。创建于2019年5月8日的所述ASCII副本名称为10491_006542-WO0_V2_ST25.txt并且大小为170KB(174,236字节)。
技术领域
本发明涉及重组层粘连蛋白腺相关病毒载体(AAV)构建体以及用于恢复缺陷型哺乳动物或具有基底膜不稳定性的哺乳动物的层粘连蛋白表达的相关方法。
背景技术
层粘连蛋白是基底膜(BM)及其组装的基本组分。这些大的糖蛋白是由以长卷曲螺旋连接的α-、β-和γ亚基组成的异源三聚体。层粘连蛋白的基础作用是创建主要支架，所述主要支架(1)将胞外基质附着到细胞表面和细胞骨架，并且(2)充当其它胞外基质组分(如巢蛋白、胶原蛋白和基底膜聚糖(perlecan)/集聚蛋白硫酸肝素蛋白聚糖)变得稳定地附着在其上的平台。
许多不同类型的疾病涉及基底膜和层粘连蛋白。转移实体瘤必须穿过基底膜以到达血管系统，并且各种微生物和病毒通过与层粘连蛋白的直接相互作用进入细胞。基于小鼠的基因证据，所述层粘连蛋白中的至少九种层粘连蛋白对于生命是必需的。若干种层粘连蛋白的层粘连蛋白N末端(LN)聚合结构域中的突变是引起肌肉、神经和肾脏疾病的原因。参见Scheele等人,2007《分子医学杂志(J Mol Med)》85(8):825-36。
层粘连蛋白-211(由α2、β1和γ1亚基组成的异源三聚体，缩写为Lm211)是骨骼肌和外周神经许旺细胞(SC)的基底膜的主要层粘连蛋白，并且还发现于脑毛细血管中。参见Aumailley等人,(2005)《基质生物学(Matrix Biol)》24(5):326-32。
在胚胎发生期间，层粘连蛋白α2链从胚胎发育的第11天开始沿着发育中的肌肉表达。在编码层粘连蛋白α2链的LAMA2基因内的LN结构域突变可能导致层粘连蛋白α2蛋白亚基表达的完全或接近完全的损失，以引起层粘连蛋白α2缺陷型肌营养不良(LAMA2-MD)。LAMA2-MD是一种常染色体隐性疾病，其通常表现为非走动性先天性肌营养不良(CMD)，也称为先天性肌营养不良1A型(MDC1A)，是一种在出生或婴儿期开始并且经常伴有外周神经和脑的参与的特别严重的非走动性先天性营养不良。
在英国，最近对249名LAMA2 MD患者进行的研究揭示，LAMA2突变是最常见的(37.4％)，随后是肌营养不良蛋白聚糖病(dystroglycanopathy)和Ullrich-CMD。参见Sframeli等人,(2017)《神经肌肉病症(Neuromuscul Disor)》27(9):793-803。还存在少量的造成更温和的走动性营养不良的错义和框内缺失突变，主要映射到层粘连蛋白α2短臂聚合结构域(LN)。参见Allamand等人,(1997)《人类分子遗传学(Hum Mol Genet)》6(5):747-52；Gavassini等人,(2011)《肌肉神经(Muscle Nerve)》44(5):703-9；Bonnemann等人,(2014)《神经肌肉病症》24(4):289-311；Chan等人,(2014)《神经肌肉病症》24(8):677-83。两者的病理均由肌肉变性、再生、慢性炎症和纤维化组成，伴有白质脑异常和减少的外周神经传导。参见Jimenez-Mallebrera等人,(20025)《细胞与分子生命科学(Cell Mol LifeSci)》62(7-8):809-23。具有无效表达突变的患者从不走动，可能具有外周神经传导缺陷、癫痫和中度精神发育迟缓，并经常在年轻时死于肌肉萎缩和呼吸衰竭。患有缺陷性α2-层粘连蛋白的患者在以后生活中出现不太严重的走动性形式的营养不良(通常是肢带型)，并且还表现出外周和中枢神经系统缺陷。参见Bonnemann等人,(2014)《神经肌肉病症》24(4):289-311。治疗通常集中于管理病症的个体体征和症状。目前无法治愈任何一个。
另一种神经肌肉疾病，皮尔森综合征(Pierson syndrome)，与层粘连蛋白β2链的缺陷相关，所述层粘连蛋白β2链在神经肌肉接点处的肾小球基底膜中以及在眼内肌肉、晶状体和视网膜中显著表达。层粘连蛋白β2链缺陷是由LAMB2基因的错义和框内缺失突变引起的。皮尔森综合征是一种常染色体隐性疾病，主要影响肾脏和眼睛的非常罕见的病症。大多数受影响的儿童患有早期发作、慢性肾衰竭、神经发育问题、明显的眼部异常，其可能包含失明、肌张力减退、精神运动延迟、偏瘫和异常运动。参见Schéele等人,(2007)《分子医学杂志》85:825-836。受影响的婴儿可能无法存活超过生命的最初几周或几个月。那些在婴儿期之后存活的人通常具有神经功能障碍和发育延迟。大多数人需要在生命的前十年内进行肾脏移植来治疗晚期肾脏疾病。长期前景不佳。
持续需要更好的治疗，尤其是用于基因疗法以恢复患者的层粘连蛋白聚合表达和基底膜组装，特别是用于治疗涉及层粘连蛋白α2和层粘连蛋白β2缺陷的疾病。
发明内容
在某些实施例中，本发明涉及一种重组腺相关载体(rAAV)，其包括核酸序列，所述核酸序列包括对alphaLNNdDeltaG2short(αLNNdΔG2')进行编码的转基因。在某些实施例中，αLNNdΔG2'包括SEQ ID NO:1。在某些实施例中，rAAV进一步包括CMV启动子，所述CMV启动子包括SEQ ID NO:12。在某些实施例中，rAAV是AAV8或AAV-DJ。在某些实施例中，rAAV进一步包括末端反向重复序列(ITR)。在某些实施例中，ITR是包括SEQ ID NO:11的5'ITR和包括SEQ ID NO:16的3'ITR。
在某些实施例中，本发明涉及一种组合物，其包括本文所述的重组AAV中的任何重组AAV。在某些实施例中，组合物进一步包括药物载剂。
在某些实施例中，本发明涉及一种试剂盒，其包括容器壳体，所述容器壳体包括本文所述的组合物。在某些实施例中，所述容器是注射器。
在某些实施例中，本发明涉及一种恢复受试者的层粘连蛋白聚合表达和基底膜组装的方法，所述方法包括向所述受试者施用有效量的本文所述的重组AAV载体中的任何重组AAV载体。
在某些实施例中，本发明涉及一种治疗有需要的受试者的层粘连蛋白α-2缺陷的方法，所述方法包括向所述受试者施用有效量的本文所述的重组AAV载体中的任何重组AAV载体。
在某些实施例中，本发明涉及一种减轻受试者的与选自由层粘连蛋白缺陷型肌营养不良和层粘连蛋白α2缺陷型肌营养不良组成的组的层粘连蛋白缺陷相关的症状中的至少一种症状的方法，其中所述方法包括向所述受试者施用有效量的本文所述的重组AAV载体中的任何重组AAV载体。
在某些实施例中，本发明涉及一种减轻受试者的与选自由以下组成的组的层粘连蛋白α2-缺陷相关的症状中的至少一种症状的方法：肌肉变性、再生、慢性炎症、纤维化、白质脑异常、外周神经传导减少、癫痫、中度精神发育迟缓以及呼吸衰竭，其中所述方法包括向所述受试者施用有效量的本文所述的重组AAV载体中的任何重组AAV载体。
在某些方面，本发明的实施例涉及一种用于治疗表征为LAMA2基因的缺陷或单倍体不足的受试者的层粘连蛋白α2缺乏型肌营养不良的方法。所述方法可以包含向受试者施用有效量的携带对alphaLNNdDeltaG2short(αLNNdΔG2')进行编码的核酸序列(即，转基因)的重组腺相关病毒，在所期望的细胞中表达所述αLNNdΔG2'产物的启动子序列的控制下。在某些实施例中，启动子序列提供了αLNNdΔG2'产物在基底膜中的表达。在某些实施例中，转基因的表达向细胞提供了恢复或维持受试者的所期望的层粘连蛋白聚合表达和基底膜组装所必需的产物。在仍另一个实施例中，本发明提供了用于治疗层粘连蛋白α2缺乏型肌营养不良的组合物。此类组合物可以与载剂和适合注射的另外的组分一起调配。
在以下对本发明的优选实施例的详细描述中进一步描述了本发明的其它方面和优点。
附图说明
图1展示了神经肌肉层粘连蛋白与核心基底膜(BM)组分的相互作用。标记相关层粘连蛋白和其它蛋白质结构域。虚线和点线指示结构域结合相互作用。缩略语：层粘连蛋白(Lm)；层粘连蛋白111(Lm111)；层粘连蛋白411(Lm411)；硫酸化糖脂(SGL)；α营养不良聚糖(αDG)；巢蛋白(Nd)；Lmα2短臂聚合结构域(LN)。
图2展示了在肌肉和外周神经中Lm211和Lm411介导的BM组装的模型。缩略语：层粘连蛋白211(Lm211)；层粘连蛋白411(Lm411)；硫酸化糖脂(SGL)；α营养不良聚糖(αDG)；巢蛋白(Nd)；Lmα2短臂聚合结构域(LN)；与层粘连蛋白卷曲螺旋结合的集聚蛋白的N末端结构域(agrin-NtA)；层粘连蛋白G样结构域(LG)。
图3A-E是示出了层粘连蛋白功能的连接子蛋白修复的图示、EM图像和SDS-PAGE图像。图3A示出了αLNNd和mag的结构域结构和功能性活性。源自层粘连蛋白-α1的区域呈绿色；源自巢蛋白-1的区域呈橙色。Mag是具有N末端区域(蓝色)和C末端部分(红色)的集聚蛋白的微型化版本。图3B示出了αLNNd和mag以及与层粘连蛋白的复合物的旋转阴影EM图像。图3C示出了在LAMA2 MD及其dy2J/dy2J小鼠模型的走动性形式中，表达截短版本的Lm-211(“dy2J-Lm-211”)。αLNNd与巢蛋白结合位点结合并创建具有功能性LN结构域的人工短臂。αLNNd和mag的共表达提供了聚合和αDG锚定的必要结构域。图3D示出了缺乏G2结构域±2个EGF样重复序列的聚合连接子蛋白的缩短版本，即αLNNd、αLNNdΔG2和αLNNdΔG2。图3E示出了αLNNdΔG2与Lmα1ΔLN-L4b的连接子-层粘连蛋白复合物形成。
图4示出了缺乏G2结构域±2个EGF样重复序列的αLNNd聚合连接子蛋白的缩短版本，即αLNNd(alphaLNNd，其中α是指层粘连蛋白-α1，LN是指LN结构域，并且Nd是指巢蛋白)、αLNNdΔG2(alphaLNNdDeltaG2)和αLNNdΔG2'(alphaLNNdDeltaG2short)。
图5A-E是SDS-PAGE、免疫荧光图像以及示出了αLNNdΔG2'和mag的与Lm411结合的AAV表达以及αLNNdΔG'-Lm411在许旺细胞上的组装的图。图5A和5B分别示出了表达Lm411的293细胞的αLNNdΔG2'-AAV和mag5myc-AAV感染。通过N末端FLAG标记的Lm411从培养基中免疫沉淀，随后用图5A中的Lmα4的上区段和αLNNdΔG2'或图5B中的mag和αLNNdΔG2'的下区段的免疫印迹切割膜来显示与Lm411的复合物。图5C和5D示出了由AAV产生的αLNNdΔG2'引起的Lm411组装的显著增加。图5E示出了在肌纤维膜中检测来自将AAV-αLNNdΔG2'肌内(i.m.)注射到1周龄的dy3K/dy3K mag Tg小鼠中的抗体染色的αLNNdΔG2'(红色)和层粘连蛋白(绿色)。
图6是pAAV-MCS表达载体的图谱。
图7是pAAV-DJ载体的图谱。
图8是p辅助载体的图谱。
图9是使用蛋白质BLAST比对的αLNNdΔG2'蛋白的小鼠和人氨基酸序列的比较。查询＝人αLNNdΔG2'氨基酸序列。受试者–小鼠αLNNdΔG2'氨基酸序列。
图10提供了如插入AAV中的小鼠αLNNdΔG2'(短-noG2)的开放阅读框的核苷酸和氨基酸序列。信号肽由核苷酸1到51(颜色：绿色)编码。Lma1 LN由核苷酸52到804(颜色：蓝色)编码。LEa1由核苷酸805到975(颜色：品红色)编码。LEa2由核苷酸976到1185(颜色：绿色)编码。LEa3由核苷酸1186到1356(颜色：红色)编码。Lea4由核苷酸1357到1503(颜色：青色)编码。Lma1 LF区段由核苷酸1504到1536(颜色：蓝色)编码。Nd egf-4由核苷酸1537到1668(颜色：红色)编码。Nd egf-5由核苷酸1669到1809(颜色：青色)编码。NdTY由核苷酸1810到2091(颜色：品红色)编码。Nd G3由核苷酸2092到2835(颜色：绿色)编码。Nd egf-6由核苷酸2836到3006(颜色：红色)编码。
图11提供了如插入AAV中的人αLNNdΔG2'(短-noG2)的开放阅读框的核苷酸和氨基酸序列。信号肽由核苷酸1到51(颜色：绿色)编码。Lma1 LN由核苷酸52到804(颜色：蓝色)编码。LEa1由核苷酸805到975(颜色：品红色)编码。LEa2由核苷酸976到1185(颜色：绿色)编码。LEa3由核苷酸1186到1356(颜色：红色)编码。LEa 4由核苷酸1357到1503(颜色：青色)编码。LF片段由核苷酸1504到1536(颜色：蓝色)编码。Nd egf-4由核苷酸1537到1668(颜色：红色)编码。Nd egf-5由核苷酸1669到1809(颜色：青色)编码。NdTY由核苷酸1810到2091(颜色：品红色)编码。Nd G3由核苷酸2092到2835(颜色：绿色)编码。Nd egf-6由核苷酸2836到3006(颜色：红色)编码。
图12提供了如插入AAV中的小鼠αLNNdΔG2'(短-noG2)的开放阅读框的核苷酸序列。
图13提供了小鼠αLNNdΔG2'(短-noG2)的氨基酸序列。
图14提供了如插入AAV中的人αLNNdΔG2'(短-noG2)的开放阅读框的核苷酸序列。
图15提供了人αLNNdΔG2'(短-noG2)的氨基酸序列。
具体实施方式
异源三聚体层粘连蛋白是所有基底膜的限定组分并且自组装成细胞相关网络。在哺乳动物中，所有层粘连蛋白都是由五个α链之一、三个β链之一和三个γ链之一构成的异源三聚体。尽管总共有至少45种潜在的αβγ链组合，但截至2010年仅报道了15种不同的层粘连蛋白同种型。基于体外研究，存在至少16种允许的层粘连蛋白同种型(下表1)。
表1.哺乳动物层粘连蛋白.12
| 名称 | 缩写名称 | 链组合物 |
| 层粘连蛋白-111 | Lm111 | α1β1γ1 |
| 层粘连蛋白-121 | Lm121 | α1β2γ1 |
| 层粘连蛋白-211 | Lm211 | α2β1γ1 |
| 层粘连蛋白-213 | Lm213 | α2β1γ3 |
| 层粘连蛋白-221 | Lm221 | α2β2γ1 |
| 层粘连蛋白-311<sup>3</sup> | Lm311 | α3β1γ1 |
| 层粘连蛋白-312<sup>4</sup> | Lm312 | α3β1γ2 |
| 层粘连蛋白-321 | Lm321 | α3β2γ1 |
| 层粘连蛋白-332 | Lm332 | α3β3γ2 |
| 层粘连蛋白-411 | Lm411 | α4β1γ1 |
| 层粘连蛋白-421 | Lm421 | α4β2γ1 |
| 层粘连蛋白-422<sup>5</sup> | Lm422 | α4β2γ2 |
| 层粘连蛋白-423 | Lm423 | α4β2γ3 |
| 层粘连蛋白-511 | Lm511 | α5β1γ1 |
| 层粘连蛋白-521 | Lm521 | α5β2γ1 |
| 层粘连蛋白-523 | Lm523 | α5β2γ3 |
层粘连蛋白是基底膜的基本中央组织者，这可能是层粘连蛋白与细胞、与自身以及与其它基底膜组分结合的独特能力的结果。组织和分化细胞的出现所需的基底膜在胚胎发育、组织稳态和人类疾病中是很重要的。
十字形层粘连蛋白分子的三个短臂形成网络节点，其中对一个α臂、一个β臂和一个γ臂具有严格要求。同源短臂由远端层粘连蛋白N末端(LN)结构域构成，随后是层粘连蛋白型表皮生长因子样(LE)结构域的串联重复序列并穿插有未知结构的球形结构域。LN结构域对于层粘连蛋白聚合和BM组装是必需的。层粘连蛋白聚合对于髓鞘形成是很重要的。含有α3A、α4和β2亚基的层粘
连蛋白不具有LN结构域的完整补体，并且因此无法聚合(在Hohenester和Yurchenco中进行综述2012.《细胞粘附和迁移(Cell Adh.Migr.)》2013.7(1):56-63)。
所述十字的长臂(长度为75-80nm)是由所有三个链形成的α螺旋状的卷曲螺旋，而三个短臂(35–50nm)各自由一个链构成。在长臂远端处，α链添加了含有层粘连蛋白的主要细胞粘附位点的五个层粘连蛋白G样(LG)结构域。长臂的端处的这个球形结构域与细胞受体结合，包含整联蛋白、α营养不良聚糖、硫酸乙酰肝素和硫酸化糖脂。层粘连蛋白网络的侧枝锚定由蛋白聚糖、基底膜聚糖和集聚蛋白提供。然后，由IV胶原蛋白形成第二网络，所述胶原蛋白通过基底膜聚糖和集聚蛋白的硫酸乙酰肝素链以及通过巢蛋白进行另外连接与层粘连蛋白网络相互作用。通常参见Hohenester等人(2013)《细胞粘附和迁移》7(1):56-63。在胚胎发育的后期，基底膜的这种成熟变得至关重要。在图1中，Lm111，一种在胚胎发生中表达的原型层粘连蛋白(Lm)，与细胞表面硫酸化糖脂(SGL)、整联蛋白、α营养不良聚糖(αDG)、巢蛋白(Nd)、集聚蛋白结合并且通过其LN结构域聚合。胶原蛋白-IV和基底膜聚糖与巢蛋白结合。整联蛋白和αDG通过衔接子蛋白附着到细胞骨架。Lm411，一种不聚合的Lm同种型，表现出非常弱的整联蛋白和αDG结合。
Lm211和Lm411在肌肉和外周神经中介导BM组装。层粘连蛋白通过与硫酸化糖脂(SGL)(如硫苷脂)结合、与整联蛋白α7β1和α营养不良聚糖(αDG)结合并且通过LN相互作用聚合而形成初始的新生支架，如图2所示。巢蛋白(主要是巢蛋白-1)与层粘连蛋白和胶原蛋白-IV结合，充当桥，其中胶原蛋白聚合以形成第二网络。所有组分通过层粘连蛋白直接地或间接地束缚到细胞受体，但可以单独地与其它整联蛋白相互作用。Lm411是与Lm211在神经中共组装的非聚合层粘连蛋白。αLNNd与Lm411结合并赋予聚合活性。微型集聚蛋白(miniagrin)(mag，mA)与Lm411结合并赋予αDG结合。(参见McKee等人,2017.《临床研究杂志(J.Clin.Invest.》127:1075-1089和Reinhard等人2017,《科学转化医学(Sci.Transl.Med.)》28:9(396),pii:eaal4649.doi:10.1126/scitranslmed.aal4649)。
许旺细胞(SC)BM与肌肉BM共享整个架构组织；然而，所述两者在以下若干方面有所不同：(i)β1-整联蛋白是髓鞘形成的主要介质，而在肌肉中，αDG是最重要的受体；(ii)若干SC整联蛋白可用于与BM相互作用(但在肌肉中仅α7β1)，从而允许其它BM组分的整联蛋白连接；(iii)在肌纤维中不存在的Lmα4是有助于髓鞘形成的正常SC亚基；(iv)SC表达可以实现α4-层粘连蛋白粘附的硫苷脂和CD146；并且(v)Dy2J脱髓鞘在坐骨神经和根中最明显，表明层粘连蛋白聚合的特别重要性。α2-层粘连蛋白也在形成血脑屏障的毛细血管中发现。层粘连蛋白亚基的损失使屏障对水渗漏，这很可能解释了几乎所有LAMA2-MD患者中通过MRI检测到的脑白质变化。
层粘连蛋白α2缺陷型肌营养不良(LAMA2-MD)是由LAMA2基因内的突变引起的常染色体隐性疾病，其通常呈现为非走动性先天性肌营养不良(CMD)。营养不良经常伴有外周神经和脑的参与。大多数LAMA2突变导致蛋白质亚基表达(特别是Lm211)的完全或接近完全的损失，从而造成特别严重的非走动性先天性营养不良。还存在少量的造成更温和的走动性营养不良的错义和框内缺失突变，主要映射到Lmα短臂聚合结构域(LN)。在LAMA2-MD中，Lm411的转录和蛋白质积累增加，而Lm511少量增加。Lm411是不寻常的，是因为其与肌肉αDG和整联蛋白弱结合并且缺乏聚合的能力。Lm411不足以进行BM组装，使得细胞表面积累相对于其它层粘连蛋白需要高Lm411浓度，这解释了其拯救LAMA2突变的有限能力。这些组成变化是在不存在层粘连蛋白-α2的情况下观察到的BM的结构衰减的基础。参见综述，Yurchenco等人,2017,《基质生物学》,pii:S0945-053X(17)30333-5.doi:10.1016/j.matbio.2017.11.009。
用于层粘连蛋白α2链缺陷的若干个小鼠模型是可获得的，并且所述若干个小鼠模型还显示肌肉营养不良以及外周和中枢神经系统髓鞘形成缺陷。BM被破坏，并且在LMα2链缺陷型肌肉中LMα2链受体和一些BM相关蛋白的表达被改变，并且结构和信号传导缺陷两者对于正常的肌肉功能可能是有害的。此外，已经证明层粘连蛋白α2链分别在外周神经系统和中枢神经系统中诱导许旺细胞增殖和少突胶质细胞扩散以及髓鞘形成的关键性作用。参见Schéele等人,(2007)《分子医学杂志》85:825-836。层粘连蛋白α2在dyW(dyW/dyW)小鼠中大大减少，而在dy3K(dy3K/dy3K)Lama2-敲除小鼠中则完全不存在。这两个模型表示大多数表达非常低的或根本不表达层粘连蛋白α2亚基的LAMA2-MD患者。dy3K小鼠(受影响最严重的小鼠)是极其虚弱、小的，以及寿命非常短。第三个模型是dy2J(dy2J/dy2J基因型)小鼠，其中层粘连蛋白α2略有减少，而层粘连蛋白α4适度增加。dy2J小鼠中的Lm211由于LN结构域的损失而不能聚合。Dy2J小鼠的特征在于：在约3 1/2周龄时开始进行性虚弱和麻痹，其中后肢首先受影响，并且随后轴向和前肢肌肉受影响，许旺细胞不能分选并包埋轴突，从而导致脱髓鞘。然而，这些小鼠可以存活许多个月。
对于LAMA2-MD的治疗的发展存在挑战。通过Lama1(Lmα1)的种系转基因恢复层粘连蛋白表达的直接方法在其恢复小鼠的正常功能的能力方面是有效的；然而，9.3kb DNA构建体对于可用的递送系统而言太大。药物疗法显示出改进，但重要的是未纠正潜在的结构缺陷。已经发现EHS源性Lm111(肠胃外递送到发炎肌肉)在dyW小鼠中是有益的，但尚未显示这种方法对于治疗所需的重组层粘连蛋白是有效的。尽管纠正框外突变的外显子跳读已经用于治疗肌营养不良蛋白缺陷，但对于层粘连蛋白缺陷是有问题的，因为外显子边界与蛋白质结构域边界不匹配，并且几乎所有LAMA2外显子的跳读将可能导致半胱氨酸错配和结构域错折叠。AAV递送的CRISPR/Cas9已经用于修复剪接缺陷，所述剪接缺陷发现于大约20％的LAMA2-MD受试者中。显示的是，转基因minagrin(mag)表达部分地改善层粘连蛋白-α2缺陷型肌营养不良的小鼠模型的肌肉病理生理，即使在出生之后表达时也是如此。当通过AAV将mag基因引入围产期dyW(dyW/dyW)小鼠时，观察到类似的益处。参见Qiao等人,《美国国家科学院院刊(Proc Natl Acad Sci USA)》(2005)102(34):11999-2004。已经证明用于在人中治疗杜氏肌营养不良的微型肌营养不良蛋白AAV递送。参见Mendell,《神经科学快报(Neurosci Lett)》(2012)。本发明提供了具有改善所有LAMA2-MD的潜力的基底膜的修复。
重组层粘连蛋白和嵌合连接子蛋白可以修复LAMA2-MD的模型中的基底膜缺陷。理解BM组装要求的最新进展已经显示，层粘连蛋白结合蛋白可以提供用于在缺乏LN结构域的层粘连蛋白中聚合的替代性臂。αLNNd、βLNNd和γLNNd连接子蛋白可以使得能够在缺乏对应的αLN、βLN和γLN结构域的层粘连蛋白中聚合。参见McKee等人,《基质生物学》(2018),www.//doi.org/10.1016/j.matbio.2018.01.012,《营养不良的皮尔森和其它层粘连蛋白聚合残基的嵌合蛋白鉴定(Chimeric protein identification of dystrophic,Piersonand other laminin polymerization residues)》。αLNNd由三个球形结构域组成，其中介入杆由Lmα1LN-Lea结构域与巢蛋白-1G2-G3结构域融合产生，如图3A和图4所示。LN球形结构域是聚合结构域。G2与胶原蛋白-IV和基底膜聚糖结合，而G3与Lmγ1-LEb3结构域结合，从而产生附着到短臂十字交叉点附近的基因座的人工臂。当与缺乏α-LN结构域的非聚合层粘连蛋白结合时，αLNNd使得能够聚合并且胶原蛋白-IV募集到BM，而对WT层粘连蛋白没有不利影响。参见McKee等人,《生物化学杂志(J Biol Chem)》,(2009)284(13):8984-8994。
已经显示出αLNNd的转基因表达改善了dy2J肌肉营养不良并且与minagrin(增强受体结合的蛋白质)组合，还改善了更严重的dyW营养不良。参见McKee等人,《临床研究杂志》(2017)127(3)1075-1089；Reinhard等人,《科学转化医学》(2017)9(396)。另外值得注意的是，通过使用βLNNd而不是αLNNd蛋白来恢复聚合到携带β2LN突变的肾小球Lm521，可能治疗患有由层粘连蛋白自组装失败引起的皮尔森综合征的患者。
腺相关病毒(AAV)是最有前景的基因递送系统之一，在所述基因递送系统中可以在肌肉、外周神经和其它组织中实现高表达。潜在风险包含对转基因产物和AAV衣壳的宿主细胞免疫应答，以及随后的蛋白质损失。然而，通过避免转基因新抗原的产生已经减少了这个问题。αLNNdd、βLNNd和γLNNd连接子蛋白的结构域通常表达为更大的基底膜蛋白的部分，甚至在营养不良状态下，并且不太可能是免疫原性的。为了利用其中CMV启动子已经被增强并且具有最大的插入能力的AAV递送的最新改进，本发明的优选的AAV系统是采用具有混合的血清型衣壳的增强的CMV启动子并允许高达3.1kB插入的AAV-DJ系统(加利福尼亚州圣地牙哥的细胞生物实验室公司(Cell Biolabs,Inc.,San Diego,CA))(参见图6-8)。
αLNNd的AAV体细胞基因表达的问题是，尽管αLNNd小到足以由AAV表达，但启动子将必须非常小并且将不可能提供良好的表达。对于这个问题的潜在解决方案是减小αLNNdDNA的大小(4.17kB)，使其可以适合AAV，但关注的是减小大小可能影响蛋白质的用于基膜组装和髓鞘形成的功能。由于N末端和C末端结构域是必需的，因此重点在于减小内部结构域的大小。图3A和4示出了被制备并命名为αLNNdΔG2的第一经过修饰蛋白。G2的去除给出了大部分所需的还原，但是代价是失去聚合层粘连蛋白与胶原蛋白-IV以及基底膜聚糖的直接偶联。用许旺细胞、肌管和背根神经节进行的实验揭示，G2及其侧接3kB的LE/EGF样结构域是可消耗的，只要某个巢蛋白-1存在于测试系统中。用转基因进行的其它实验显示，基本的巢蛋白-1保留在基底膜中，这指示可以追求αLNNd连接子蛋白的大小减小。本发明提供了被命名为αLNNdΔG2'的新的αLNNd连接子蛋白，其中内部G2和两个EGF样的间隔子结构域已经被去除，将核苷酸序列的大小减小到约2.9-3.0kB，使得其足够小以由AAV表达但保留蛋白质的用于基底膜组装和髓鞘形成的功能。
本发明涉及使用AAV-DJ-αLNNdΔG2'构建体来恢复在肌肉、外周神经和其它组织中的层粘连蛋白聚合和基底膜组装，并且改善LAMA2-MD。预期的是，此类方法和AAV-DJ-αLNNdΔG2'构建体可以有效治疗人类疾病。为了便于参考，本文所述的载体构建体被称为各种AAV-DJ-αLNNdΔG2'构建体，其指示包括编码小鼠alphaLNNdDeltaG2short的核酸序列以及其它元件的AAV-DJ构建体。如图9所示，人alphaLLNdDeltaG2short蛋白与小鼠alphaLLNdDeltaG2short蛋白具有87％同一性。预期的是，密码子优化的人构建体将以相同的期望方式发挥作用，以恢复在肌肉、外周神经和其它组织中的层粘连蛋白聚合和基底膜组装，并且改善LAMA2-MD。据信，可以使用相同的AAV-DJ构建体通过用来自βLNNd蛋白的β1区段替代α1区段以便恢复聚合到携带β2LN突变的肾小球Lm521来治疗患有皮尔森综合征的患者。
AAV相容的层粘蛋白—连接子蛋白alphaLNNdDeltaG2short，缩略语：
AAV：腺相关病毒
rAAV重组腺相关病毒或病毒载体
BM：基底膜
αLNNdα层粘连蛋白N末端结构域连接蛋白
αLNNdΔG2'α层粘连蛋白N末端结构域ΔG2短连接蛋白，alphaLNNdDeltaG2short
α-DGα营养不良聚糖
βLNNdΔG2'β层粘连蛋白N末端结构域ΔG2短连接蛋白，betaLNNdDeltaG2short
ECM胞外基质
γLNNdΔG2'γ层粘连蛋白N末端结构域ΔG2短连接蛋白，gammaLNNdDeltaG2short
LE结构域层粘连蛋白型表皮生长因子样结构域
LG结构域层粘连蛋白G样结构域
LM或Lm层粘连蛋白
LN结构域层粘连蛋白N末端结构域
定义
为了可以更容易地理解本发明，下文具体定义了某些技术和科学术语。除非在本文档的其它地方明确定义，否则本文所使用的所有其它技术和科学术语具有与本发明所属领域的普通技术人员通常所理解的含义。
如本文所使用的，包含所附权利要求书，词语的单数形式，如“一个(a)”、“一种(an)”和“所述(the)”包含其对应的复数指代物，除非上下文中清楚地另有指明。
“激活”、“刺激”和“治疗”，在其应用于细胞或受体时，可以具有相同的含义，例如用配体激活、刺激或治疗细胞或受体，除非上下文中明确地另有指明。“配体”涵盖天然和合成的配体，例如细胞因子、细胞因子变体、类似物、突变蛋白以及源自抗体的结合化合物。“配体”还涵盖小分子，例如细胞因子的肽模拟物和抗体的肽模拟物。“激活”可以指代由内部机制以及外部或环境因素调节的细胞激活。例如细胞、组织、器官或生物体的“应答”涵盖生物化学或生理行为的变化，例如生物隔室内的浓度、密度、粘附或迁移、基因表达的速率或分化状态，其中所述变化与激活、刺激或治疗或与内部机制(如基因编程)相关。
分子的“活性”可以描述或指代分子与配体或与受体、与催化活性的结合；刺激基因表达或细胞信号传导、分化或成熟的能力；抗原活性、调节其它分子的活性等。分子的“活性”还可以指代在调节或维持细胞到细胞相互作用(例如，粘附)中的活性或在维持细胞的结构(例如，细胞膜或细胞骨架)中的活性。“活性”还可以意指比活性，例如(催化活性)/(mg蛋白质)或(免疫活性)/(mg蛋白质)、在生物隔室中的浓度等。“活性”可以指代先天性或适应性免疫系统的组分的调节。
“施用”和“治疗”，在其应用于动物、人、实验受试者、细胞、组织、器官或生物流体时，是指外源药物、治疗剂、诊断剂或组合物与动物、人、受试者、细胞、组织，器官或生物流体的接触。“施用”和“治疗”可以指代例如治疗、药代动力学、诊断、研究和实验方法。细胞的治疗涵盖试剂与细胞的接触以及试剂与流体的接触，其中流体与细胞接触。“施用”和“治疗”还意指例如通过试剂、诊断、结合化合物或通过另一细胞进行的细胞的体外和离体治疗。术语“受试者”包含任何生物体，优选地动物，更优选地哺乳动物(例如，大鼠、小鼠、狗、猫、兔子)，并且最优选地人类，包含人类患者。
“alphaLNNd”(αLNNd)是由三个球形结构域组成的连接子蛋白，其中介入杆由Lmα1LN-LEa结构域与巢蛋白-1G2-G3结构域融合产生。LN球形结构域是聚合结构域。G2与胶原蛋白-IV和基底膜聚糖结合，而G3与Lmα1-LEb3结构域结合，从而产生附着到短臂十字交叉点附近的基因座的人工臂。当与缺乏αLN结构域的非聚合层粘连蛋白结合时，αLNNd使得能够聚合并且胶原蛋白-IV募集到BM，而对WT层粘连蛋白没有不利影响。
“治疗(treat)”或“治疗(treating)”意指向患有一种或多种疾病症状或怀疑患有疾病或处于升高的患病风险的受试者或患者内部或外部地施用治疗剂，如含有本发明的任何rAAV构建体的组合物，对于所述疾病药剂具有治疗活性。通常，所述药剂以有效减轻所治疗受试者或群体中的一种或多种疾病症状的量施用，无论是通过以临床上可测量的程度诱导此类一种或多种症状的消退或抑制其的进展。有效减轻任何特定疾病症状的治疗剂的量(也称为“治疗有效量”)可以根据如患者的疾病状态、年龄和体重以及药物能够在受试者中引起期望的应答的能力而变化。疾病症状是否已经减轻可以通过由医师或其它熟练的医疗保健提供者通常用于评估所述症状的严重性或进展状态的任何临床测量来评估。尽管本发明的实施例(例如，治疗方法或制品)可能不能有效地减轻每个受试者的一种或多种靶疾病症状，但是所述实施例应当减轻统计学上显著数量的受试者中的一种或多种靶疾病症状，如通过本领域已知的任何统计学测试(如学生t测试(Student's t-test)、chi2测试、根据Mann和Whitney的U测试、Kruskal-Wallis测试(H测试)、Jonckheere-Terpstra测试和Wilcoxon测试)所确定的。
“治疗”，在其应用于人、兽医或研究受试者时，是指治疗性治疗、预防性(prophylactic或preventative)措施，用于研究和诊断应用。“治疗”，在其应用于人、兽医或研究受试者或细胞、组织或器官时，涵盖在应用于人或动物受试者、细胞、组织、生理隔室或生理流体时，本发明的任何rAAV构建体的转染或相关方法。
“分离的核酸分子”意指基因组、mRNA、cDNA或合成来源的DNA或RNA或其某种组合，其不与在自然界中发现分离的多核苷酸的多核苷酸的全部或一部分相关，或与在自然界中未与其连接的多核苷酸连接。出于本公开的目的，应当理解，“包括”特定核苷酸序列的核酸分子不涵盖完整的染色体。除指定序列之外，“包括”指定核酸序列的分离的核酸分子可以包含多达十个或甚至多达二十个或更多个其它蛋白质或其部分或片段的编码序列，或可以包含控制所列举的核酸序列的编码区的表达的可操作地连接的调节序列，和/或可以包含载体序列。
短语“控制序列”是指在特定宿主生物体中表达可操作地连接的编码序列所必需的DNA序列。适用于原核生物的控制序列例如包含启动子、任选地操纵子序列和核糖体结合位点。已知真核细胞使用启动子、聚腺苷酸化信号和增强子。
当核酸被放置到与另一核酸序列处于功能关系中时，所述核酸是“可操作地连接的”。例如，如果前序列或分泌性前导序列的DNA表达为参与多肽分泌的前蛋白，则其与多肽的DNA可操作地连接；如果启动子或增强子影响序列的转录，则所述启动子或增强子与编码序列可操作地连接；或如果核糖体结合位点被定位以便促进翻译，则所述核糖体结合位点与编码序列可操作地连接。通常，“可操作地连接”意指被连接的DNA序列是连续的，并且在分泌性前导序列的情况下是连续的并且处于阅读相中。然而，增强子不必是连续的。通过在方便的限制性位点处进行连接来完成连接。如果此类位点不存在，则根据常规实践使用合成寡核苷酸衔接子或连接子。
如本文所使用的，表达“细胞”、“细胞系”和“细胞培养物”可互换使用，并且所有此类命名均包含子代。因此，词语“转化体”和“经过转化的细胞”包含原代受试者细胞和源自其的培养物，而不考虑转移的数量。还应理解，由于有意或故意的突变，并非所有子代将具有精确地相同的DNA含量。包含具有与经过原始转化的细胞中筛选的功能或生物活性相同的功能或生物活性的突变体子代。在打算使用不同的命名的情况下，则从上下文将显而易见。
重组AAV
在一些方面，本发明提供了分离的AAV。如本文关于AAV所使用的，术语“分离的”是指已经从其天然的环境(例如，从宿主细胞、组织或受试者)中分离或人工产生的AAV。可以使用重组方法产生分离的AAV。此类AAV在本文中被称为“重组AAV”。重组AAV(rAAV)优选地具有组织特异性靶向能力，使得rAAV的转基因将被特异性地递送到一个或多个预定组织。AAV衣壳是确定这些组织特异性靶向能力的重要元件。因此，可以选择具有适合于被靶向的组织的衣壳的rAAV。
为了在治疗层粘连蛋白α-2缺乏的上下文中靶向期望的组织，优选的rAAV是AAV-DJ衣壳和AAV-2Rep基因主链的组合，从而产生本文所述的各种rAAV(参见序列表)。
已经描述了用于获得具有期望的衣壳蛋白的重组AAV的方法(参见例如US 2003/0138772，所述文献的内容通过引用整体并入本文)。已经描述了许多不同的AAV衣壳蛋白，例如在G.Gao等人,《病毒学杂志(J.Virol)》,78(12):6381-6388(2004年6月)中公开的AAV衣壳蛋白；G.Gao等人,《美国国家科学院院刊》,100(10):6081-6086(2003年5月13日)；US2003-0138772、US 2007/0036760、US 2009/0197338，所述文献涉及AAV衣壳蛋白以及相关的核苷酸和氨基酸序列的内容通过引用并入本文。对于目前描述的构建体和方法的期望包装，AAV-DJ载体和衣壳是优选的(SEQ ID NO:17)。通常，所述方涉及培养宿主细胞，所述宿主细胞含有对AAV衣壳蛋白或其片段进行编码的核酸序列；功能性rep基因；由AAV末端反向重复序列(ITR)和转基因构成的重组AAV载体；以及足够的辅助功能以允许将重组AAV载体包装到AAV衣壳蛋白中。
可以以反式向宿主细胞提供有待在宿主细胞中培养以将rAAV载体包装在AAV衣壳中的组分。可替代地，所需组分(例如，重组AAV载体、rep序列、cap序列和/或辅助功能)中的任何一种或多种组分可以由稳定宿主细胞提供，所述稳定宿主细胞已经使用本领域的技术人员已知的方法被工程化成含有所需组分中的一种或多种组分。最适合的是，此类稳定宿主细胞将含有在诱导型启动子的控制下所需的一种或多种组分。然而，所需的一种或多种组分可以在组成型启动子的控制下。在仍另一个替代方案中，所选的稳定宿主细胞可以含有在组成型启动子控制下的所选的一种或多种组分以及在一个或多个诱导型启动子控制下的其它所选的一种或多种组分。例如，可以产生稳定宿主细胞，所述稳定宿主细胞源自293个细胞(所述细胞在组成型启动子控制下含有E1辅助功能)，但是所述细胞在诱导型启动子控制下含有rep蛋白和/或cap蛋白。
可以使用任何适当的基因元件(载体)将重组AAV载体、rep序列、cap序列和用于产生rAAV的辅助功能递送到包装宿主细胞。可以通过任何适合的方法(包含本文所述的方法)递送所选基因元件。参见例如K.Fisher等人,《病毒学杂志》,70:520-532(1993)和美国专利第5,478,745号。
在一些实施例中，可以使用三重转染方法来产生重组AAV(例如，如在美国专利第6,001,650号中详细描述的，所述美国专利涉及三重转染方法的内容通过引用并入本文)。通常，通过用有待包装成AAV颗粒、AAV辅助功能载体和附属功能(accessory function)载体的重组AAV载体(包括转基因)转染宿主细胞来产生重组AAV。AAV辅助功能载体编码“AAV辅助功能”序列(即，rep和cap)，所述序列以反式作用于生产性AAV复制和衣壳化。优选地，AAV辅助功能载体支持有效的AAV载体产生，而不产生任何可检测的野生型AAV病毒粒子(即，含有功能性rep和cap基因的AAV病毒粒子)。适合与本发明一起使用的载体的非限制性实例包含在美国专利第6,001,650号中描述的pHLP19和在美国专利第6,156,303号中描述的pRep6cap6载体，所述两个美国专利的整体通过引用并入本文。附属功能载体编码非AAV源性病毒和/或细胞功能的核苷酸序列，AAV依赖于所述非AAV源性病毒和/或细胞功能进行复制(即“附属功能”)。附属功能包含AAV复制所需的功能，包含但不限于涉及AAV基因转录的激活、阶段特异性AAV mRNA剪接、AAV DNA复制、cap表达产物的合成以及AAV衣壳组装的那些部分。基于病毒的附属功能可以源自任何已知的辅助病毒，如腺病毒、疱疹病毒(除了单纯疱疹病毒1型)和牛痘病毒。
关于经过转染的宿主细胞，术语“转染”用于指代由细胞摄取外源DNA，并且当外源DNA已经被引入到细胞膜内部时，细胞已经被“转染”。许多转染技术通常是本领域已知的。参见例如Graham等人(1973)《病毒学(Virology)》,52:456；Sambrook等人(1989)《分子克隆，实验室手册(Molecular Cloning,a laboratory manual)》,冷泉港实验室(ColdSpring Harbor Laboratories),纽约；Davis等人(1986)《分子生物学的基本方法(BasicMethods in Molecular Biology)》；Elsevier和Chu等人(1981)《基因(Gene)》13:197。此类技术可以用于将一种或多种外源核酸，如核苷酸整合载体和其它核酸分子引入适合的宿主细胞中。
“宿主细胞”是指包含或能够包含感兴趣的物质的任何细胞。宿主细胞通常是哺乳动物细胞。宿主细胞可以用作AAV辅助构建体、AAV微基因质粒、附属功能载体或与重组AAV的产生相关的其它转移DNA的受体。术语包含已经被转染的原始细胞的子代。因此，如本文所使用的“宿主细胞”可以是指已经用外源DNA序列转染的细胞。应当理解，由于天然的、偶然的或故意的突变，单个亲本细胞的子代在形态学上或在基因组或总DNA互补物上可能不一定与原始亲本细胞完全相同。
关于细胞，术语“分离的”是指已经从其天然环境(例如，从组织或受试者)分离的细胞。术语“细胞系”指代能够在体外连续或延长的生长和分裂的细胞群体。通常，细胞系是源自单个祖细胞的克隆群体。在本领域中进一步已知的是，在此类克隆群体的储存或转移期间，自发或诱导的变化可能在核型中发生。因此，源自所提及的细胞系的细胞可能与祖细胞或培养物不精确地相同，并且所提及的细胞系包含此类变体。如本文所使用的，术语“重组细胞”是指外源DNA区段，如导致生物活性多肽的转录或生物活性核酸(如RNA)的产生的DNA区段已经被引入其中的细胞。
术语“载体”包含任何基因元件，如质粒、噬菌体、转座子、粘粒、染色体、人工染色体、病毒、病毒粒子等，当与合适的控制元件相关时所述基因元件能够进行复制并且可以细胞之间转移基因序列。因此，所述术语包含克隆和表达载体，以及病毒载体。在一些实施例中，有用的载体预期是其中待转录的核酸区段定位在启动子的转录控制下的那些载体。“启动子”是指由细胞的合成机制(synthetic machinery)或引入的合成机制识别的、启动基因的特异性转录所需的DNA序列。短语“可操作地定位”、“可操作地连接”、“在控制下”或“在转录控制下”意指启动子相对于核酸处于正确的位置和朝向，以控制RNA聚合酶启动和基因的表达。术语“表达载体或构建体”意指含有核酸的任何类型的基因构建体，其中部分或全部核酸编码序列能够被转录。在一些实施例中，表达包含核酸的转录，例如以从转录的基因产生生物活性多肽产物或抑制性RNA(例如，shRNA、miRNA)。
重组AAV载体
本文所述的“重组AAV(rAAV)载体”通常至少由转基因(例如，编码αLNNdΔG2')和其调节序列以及5'和3'AAV末端反向重复序列(ITR)构成。正是这种重组AAV载体被包装到衣壳蛋白中并且被递送到所选靶细胞。在一些实施例中，转基因是与载体序列异源的核酸序列，所述核酸序列编码多肽、蛋白质、功能性RNA分子(例如，miRNA、miRNA抑制剂)或其它感兴趣的基因产物(例如，αLNNdΔG2')。核酸编码序列以允许转基因在靶组织的细胞中转录、翻译和/或表达的方式与调节组分可操作地连接。
载体的AAV序列可以包括顺式作用的5'和3'末端反向重复序列(参见例如，B.J.Carter,在《细小病毒手册(Handbook of Parvoviruses)》中,编辑,P.Tijsser,CRC出版社(CRC Press),第155-168页(1990))。ITR序列的长度通常为约145bp。优选地，基本上对ITR进行编码的整个序列用于分子中，但是对这些序列进行一定程度的微小修饰是可允许的。(参见例如，如Sambrook等人,《分子克隆，实验室手册》,第2版,冷泉港实验室,纽约(1989)；以及K.Fisher等人,《病毒学杂志》,70:520 532(1996))的文本。此类分子的实例是含有转基因的“顺式作用”质粒，其中所选转基因序列和相关调节元件的侧接是5'和3'AAVITR序列。AAV ITR序列可以从任何已知的AAV获得，包含目前所鉴定的哺乳动物AAV类型。
除了上文鉴定的用于重组AAV载体的元件之外，载体还可以包含常规控制元件，所述常规控制元件以允许其在用质粒载体转染或用本发明产生的病毒感染的细胞中转录、翻译和/或表达的方式与转基因可操作地连接。如本文所使用的，“可操作地连接的”序列包含与感兴趣的基因邻接的表达控制序列和以反式或在远处起作用以控制感兴趣的基因的表达控制序列。表达控制序列包含适当的转录起始、终止、启动子和增强子序列；有效的RNA加工信号，如剪接和聚腺苷酸化(polyA)信号；使细胞质mRNA稳定的序列；增强翻译效率的序列(即，Kozak共有序列)；增强蛋白质稳定性的序列；以及当需要时，增强所编码产物的分泌的序列。大量表达控制序列(包含天然的、组成型、诱导型和/或组织特异性启动子)是本领域已知的并且可以被利用。
如本文所使用的，当核酸序列(例如，编码序列)和调节序列以将核酸序列的表达或转录放置于调节序列的影响或控制下的方式共价连接时，所述核酸序列和调节序列被认为是可操作地连接。如果期望将核酸序列翻译成功能性蛋白质，如果在5'调节序列中启动子的诱导导致编码序列的转录并且如果在两个DNA序列之间的连接的性质不会(1)导致移码突变的引入；(2)干扰启动子区指导编码序列的转录的能力，或(3)干扰对应的RNA转录物被翻译成蛋白质的能力，则这两个DNA序列被认为是可操作地连接的。因此，如果启动子区能够影响所述DNA序列的转录，使得所得转录物可以翻译成期望的蛋白质或多肽，则所述启动子区将与核酸序列可操作地连接。类似地，当两个或更多个编码区连接方式使得其从共同启动子的转录导致两个或更多个蛋白质的表达已经使用相同读框翻译时，所述两个或更多个编码区是可操作地连接的。在一些实施例中，可操作地连接的编码序列产生融合蛋白。在一些实施例中，可操作地连接的编码序列产生功能性RNA(例如，shRNA、miRNA)。
对于对蛋白质进行编码的核酸，通常在转基因序列之后并且在3'AAV ITR序列之前插入聚腺苷酸化序列。可用于本发明的rAAV构建体还可以含有令人希望地定位在启动子/增强子序列与转基因之间的内含子。一种可能的内含子序列源自SV-40，并且被称为SV-40T内含子序列。可以使用的另一个载体元件是内部核糖体进入位点(IRES)。IRES序列用于从单个基因转录物产生多于一个多肽。IRES序列将用于产生含有多于一个多肽链的蛋白质。这些和其它常见载体元件的选择是常规的，并且许多此类序列是可获得的(参见例如，Sambrook等人以及其中引用的参考文献，例如第3.18 3.26和16.17 16.27页和Ausubel等人,《当前分子生物学实验指南(Current Protocols in Molecular Biology)》,约翰·威立父子出版公司(John Wiley&Sons),纽约,1989)。在一些情况下，口蹄疫病毒2A序列可以包含在多蛋白中；这是已经显示出介导多蛋白裂解的小肽(长度大约为18个氨基酸)(Ryan,M D等人,《欧洲分子生物学组织(EMBO)》,1994；4:928-933；Mattion,N M等人,《病毒学杂志》,1996年11月；第8124-8127页；Furler,S等人,《基因疗法(Gene Therapy)》,2001；8:864-873；以及Halpin,C等人,《植物学杂志(The Plant Journal)》,1999；4:453-459)。先前已经在包含质粒和基因疗法载体(AAV和逆转录病毒)的人工系统中证明了2A序列的裂解活性(Ryan,M D等人,《欧洲分子生物学组织》,1994；4:928-933；Mattion,N M等人,《病毒学杂志》,1996年11月；第8124-8127页；Furler,S等人,《基因疗法》,2001；8:864-873；以及Halpin,C等人,《植物学杂志(The Plant Journal)》,1999；4:453-459；de Felipe,P等人,《基因疗法》,1999；6:198-208；de Felipe,P等人,《人类基因疗法(Human Gene Therapy)》,2000；11:1921-1931；以及Klump,H等人,《基因疗法》,2001；8:811-817)。
宿主细胞中基因表达所需的调节序列的精确性质可能在物种、组织或细胞类型之间有所不同，但如有必要，通常应包含分别涉及转录和翻译的起始的5'非转录序列和5'非翻译序列，如TATA盒、加帽序列、CAAT序列、增强子元件等。特别地，此类5'非转录调节序列将包含启动子区，所述启动子区包含用于可操作地连接的基因的转录控制的启动子序列。调节序列还可以根据需要包含增强子序列或上游激活子序列。载体可以任选地包含5'前导序列或信号序列。
组成型启动子的实例包含但不限于逆转录病毒劳斯氏肉瘤病毒(RSV)LTR启动子(任选地具有RSV增强子)、巨细胞病毒(CMV)启动子(任选地具有CMV增强子)(参见例如Boshart等人,《细胞(Cell)》,41:521-530(1985))、SV40启动子、二氢叶酸还原酶启动子、13-肌动蛋白启动子、磷酸甘油激酶(PGK)启动子和EFla启动子(英杰公司(Invitrogen))。
诱导型启动子允许调节基因表达并且可以通过外源供应的化合物、环境因素如温度或特异性生理状态例如急性期、细胞的特定分化状态、或仅在复制细胞时的存在来调节。诱导型启动子和诱导型系统可从多种商业来源获得，包含但不限于英杰公司、克罗泰克公司(Clontech)和阿瑞雅德公司(Ariad)。通过外源供应的启动子调节的诱导型启动子的实例包含锌诱导型绵羊金属硫蛋白(MT)启动子、地塞米松(Dex)诱导型小鼠乳腺肿瘤病毒(MMTV)启动子、T7聚合酶启动子系统(WO 98/10088)；蜕皮激素昆虫启动子(No等人,《美国国家科学院院刊》,93:3346-3351(1996))、四环素可抑制系统(Gossen等人,《美国国家科学院院刊》,89:5547-5551(1992))、四环素诱导型系统(Gossen等人,《科学(Science)》,268:1766-1769(1995)，还参见Harvey等人,《化学生物当前观点(Curr.Opin.Chem.Biol.)》,2:512-518(1998))、RU486诱导型系统(Wang等人,《自然生物技术(Nat.Biotech.)》,15:239-243(1997)和Wang等人,《基因疗法》,4:432-441(1997))以及雷帕霉素诱导型系统(Magari等人,《临床研究杂志)100:2865-2872(1997))。在此上下文中可能有用的仍其它类型的诱导型启动子是受特定生理状态例如温度、急性期、细胞的特定分化状态、或仅在复制细胞时调节的那些启动子。
在另一个实施例中，将使用转基因的天然启动子或其片段。当期望转基因的表达应模仿天然表达时，天然启动子可能是优选的。当转基因的表达必须在时间上或发育上、或以组织特异性方式、或响应于特异性转录刺激调节时，可以使用天然启动子。在另外的实施例中，还可以使用其它天然表达控制元件，如增强子元件、聚腺苷酸化位点或Kozak共有序列来模仿天然表达。
在一些实施例中，调节序列赋予组织特异性基因表达能力。在某些情况下，组织特异性调节序列与以组织特异性方式诱导转录的组织特异性转录因子结合。此类组织特异性调节序列(例如，启动子、增强子等)是本领域众所周知的。示例性组织特异性调节序列包含但不限于以下组织特异性启动子：神经元如神经元特异性烯醇化酶(NSE)启动子(Andersen等人,《细胞分子神经生物学(CellMol.Neurobiol.)》,13:503-15(1993))，神经丝轻链基因启动子(Piccioli等人,《美国国家科学院院刊》,IDSA,88:5611-5(1991))和神经元特异性vgf基因启动子(Piccioli等人,《神经元(Neuron)》,15:373-84(1995))。在一些实施例中，组织特异性启动子是选自以下的基因的启动子：神经元核(NeuN)、胶质原纤维酸性蛋白(GFAP)、结肠腺瘤样息肉病(APC)和电离钙结合衔接子分子1(Iba-1)。在一些实施例中，启动子是CMV启动子。
转基因编码序列
rAAV载体的转基因序列的组合物将取决于将投入的所得载体的用途。例如，一种类型的转基因序列包含报道序列，所述报道序列在表达时产生可检测的信号。在另一个实例中，所述转基因编码治疗性αLNNdΔG2'蛋白或治疗性功能性RNA。在另一个实例中，所述转基因编码旨在用于研究目的的蛋白质或功能性RNA，例如用于创建包含转基因的体细胞转基因动物模型，例如用于研究转基因产物的功能。在另一个实例中，所述转基因编码旨在用于创建疾病的动物模型的蛋白质或功能性RNA。适当的转基因编码序列对于技术人员将是显而易见的。
在一些方面，本发明提供了用于预防或治疗哺乳动物中的LAMA2基因缺陷(例如，可遗传基因缺陷、体细胞基因改变)的方法中的rAAV载体，例如在受试者中导致层粘连蛋白α-2多肽缺陷的基因缺陷，并且特别是用于治疗或降低表现出层粘连蛋白α-2缺陷的受试者的缺陷的严重程度或程度。在一些实施例中，方法涉及以足以治疗患有或怀疑患有LAMA2病症的受试者的此类病症的量和持续时间段向受试者施用药学上可接受的载剂中的编码一种或多种治疗性肽、多肽、shRNA、微小RNA、反义核苷酸等的rAAV载体。
重组AAV施用
以足够的量施用rAAVS以转染期望的组织的细胞并提供足够水平的基因转移和表达，而没有过度的不利影响。常规的和药学上可接受的施用途径包含但不限于直接递送到所选组织(例如，脑内施用、鞘内施用)、静脉内、口服、吸入(包含鼻内和气管内递送)、眼内、静脉内、肌内、皮下、皮内、瘤内和其它亲本施用途径。如果需要，可以组合施用途径。
向受试者递送某些rAAV可以例如通过向受试者的血流中施用来进行。可以通过注射到静脉、动脉或任何其它血管导管来施用到血液中。此外，在某些情况下，可能期望的是向脑组织、脑膜、神经元细胞、神经胶质细胞、星形胶质细胞、少突胶质细胞、脑脊髓液(CSF)、间隙空间等递送rAAV。在一些实施例中，重组AAV可以使用本领域已知的神经外科技术，如通过立体定向注射用针、导管或相关装置向脊髓或脑直接递送(参见例如Stein等人,《病毒学杂志》,73:3424-3429,1999；Davidson等人,《美国国家科学院院刊(PNAS)》97:3428-3432,2000；Davidson等人,《自然遗传学(Nat.Genet.)》3:219-223,1993；以及Alisky和Davidson,《人类基因疗法》11:2315-2329,2000)。在某些情况下，将期望的是皮下地、胰腺内地、鼻内地、肠胃外地、静脉内地、肌内地、脑内地、鞘内地、脑内地、口服地、腹膜内地或通过吸入递送本文中所公开的适合地调配的药物组合物中的基于rAAV的治疗性构建体。在一些实施例中，如美国专利第5,543,158号；第5,641,515号和第5,399,363号中所描述的施用模式(所述美国专利各自通过引用整体明确地并入本文)可以用于递送rAAV。
重组AAV组合物
rAAV可以根据本领域已知的任何适当的方法在组合物中向受试者递送。可以向受试者，例如人、小鼠、大鼠、猫、狗、绵羊、兔、马、牛、山羊、猪、豚鼠、仓鼠、鸡、火鸡或非人灵长类动物(例如，猕猴)施用优选地悬浮在生理上相容的载剂(例如，在组合物中)的rAAV。在某些实施例中，组合物可以仅包括rAAV，或与一种或多种其它病毒(例如，编码具有一种或多种不同转基因的第二rAAV)组合。
鉴于rAAV针对的适应症(indication)，本领域的技术人员可以容易地选择适合的载剂。例如，一种适合的载剂包含盐水，其可以与多种缓冲溶液(例如，磷酸盐缓冲盐水)一起调配。其它示例性载剂包含无菌盐水、乳糖、蔗糖、磷酸钙、明胶、葡聚糖、琼脂、果胶、花生油、芝麻油和水。载剂的选择不是对本发明的限制。
任选地，除了rAAV和一种或多种载剂之外，本发明的组合物还可以含有其它常规药物成分，如防腐剂或化学稳定剂。适合的示例性防腐剂包含氯丁醇、山梨酸钾、山梨酸、二氧化硫、没食子酸丙酯、对羟基苯甲酸酯、乙基香草醛、甘油、苯酚以及对氯苯酚。适合的化学稳定剂包含明胶和白蛋白。
实现期望效果或“治疗效果”所需的rAAV病毒粒子的剂量(例如，在载体基因组中的剂量单位/每千克体重(vg/kg))将基于若干因素而变化，包含但不限于：rAAV施用的途径、实现治疗效果所需的基因或RNA表达水平、所治疗的特异性疾病或病症以及基因或RNA产物的稳定性。基于上述因素以及本领域众所周知的其它因素，本领域的技术人员可以容易地确定用于治疗患有特定疾病或病症的受试者的rAAV病毒粒子剂量范围。rAAV的有效量通常处于含有约109到1016基因组拷贝每受试者的溶液的约10μl到约100ml的范围内。可以使用其它体积的溶液。除了别的之外，所使用的体积将通常取决于受试者的大小、rAAV的剂量和施用的途径。例如，对于鞘内或脑内施用，可以使用1μl到10μl或10μl到100μl的范围内的体积。对于静脉内施用，可以使用10μl到100μl、100μl到1ml、1ml到10ml或更大的范围内的体积。在一些情况下，约1010到1012个rAAV基因组拷贝每受试者之间的剂量是适当的。在某些实施例中，1012个rAAV基因组拷贝每受试者对于靶向CNS组织是有效的。在一些实施例中，所述rAAV以1010、1011、1012、1013、1014或1015基因组拷贝每受试者的剂量施用。在一些实施例中，所述rAAV以每千克1010、1011、1012、1013或1014基因组拷贝的剂量施用。
在一些实施例中，调配rAAV组合物以减少AAV颗粒在组合物中的聚集，特别是在存在高rAAV浓度(例如，约1013GC/ml或更高)的情况下。用于减少rAAV的聚集的方法是本领域众所周知的，并且包含例如添加表面活性剂、pII调节、盐浓度调节等。(参见例如Wright FR等人,《分子疗法(Molecular Therapy)》(2005)12,171-178，所述文献的内容通过引用并入本文。)
药学上可接受的赋形剂和载剂溶液的调配物是本领域的技术人员众所周知的，同样是用于在多种治疗方案中使用本文所述的特定组合物的适合的给药和治疗方案的开发。通常，这些调配物可以含有至少约0.1％的活性成分或更多，但是一种或多种活性成分的百分比当然可以变化并且可以方便地介于总调配物的重量或体积的约1％或2％与约70％或80％或更多之间。自然地，每种治疗上有用的组合物中的活性成分的量可以是以这样的方式来制备，所述方式使得在化合物的任何给定的单位剂量中将获得适合的剂量。制备此类药物调配物的本领域的技术人员将考虑如溶解度、生物利用度、生物半衰期、施用途径、产品保质期以及其它药理学因素等因素，并且如此，多种剂量和治疗方案可能是期望的。
适用于可注射使用的药物形式包含无菌水溶液或分散体和用于临时制备无菌可注射溶液或分散体的无菌粉末。还可以在甘油、液体聚乙二醇及其混合物中以及在油中制备分散体。在普通储存和使用条件下，这些制剂含有防止微生物生长的防腐剂。在许多情况下，所述形式是无菌的并且具有达到易于注射的程度的流动性。其在制造和储存条件下必须是稳定的并且必须被保存免于如细菌和真菌等微生物的污染作用。载剂可以是含有例如水、乙醇、多元醇(例如，甘油、丙二醇和液体聚乙二醇等)、其适合的混合物和/或植物油的溶剂或分散介质。合适的流动性可以例如通过使用如卵磷脂等包衣、在分散体的情况下通过维持所需的粒径并且通过使用表面活性剂来维持。对微生物的作用的预防可以通过多种抗细菌剂和抗真菌剂，例如对羟基苯甲酸酯、氯丁醇、苯酚、山梨酸、硫柳汞等来提供。在许多情况下，将优选的是包含等渗剂，例如，糖或氯化钠。对可注射组合物的延长吸收可以通过在组合物中使用延迟吸收的药剂，例如单硬脂酸铝和明胶来提供。
对于可注射水溶液的施用，例如，如果需要，所述溶液可以被适合地缓冲，并且液体稀释剂首先用足够的盐水或葡萄糖等渗。这些特定的水溶液特别适合于静脉内、肌内、皮下和腹膜内施用。在此方面，本领域的技术人员将知道可以采用的无菌水性介质。例如，可以将一个剂量溶解于1ml等渗NaCl溶液中，并且添加到1000ml皮下输液液体中或注射在建议的输注部位处(参见例如《雷明顿药物科学(Remington's Pharmaceutical Sciences)》,第15版,第1035-1038页和第1570-1580页)。剂量的一些变化必然会根据宿主的病症而发生。在任何情况下，负责施用的人员将确定用于个体宿主的适当剂量。
通过将活性rAAV以所需的量根据需要与本文枚举的各种其它成分一起并入适当的溶剂中，然后进行过滤灭菌来制备无菌可注射溶液。通常，通过将各种灭菌的活性成分并入无菌媒剂中来制备分散体，所述无菌媒剂含有基础分散介质和来自上文枚举的那些的所需其它成分。在用于制备无菌可注射溶液的无菌粉末的情况下，优选的制备方法是真空干燥和冷冻干燥技术，所述技术从其先前的无菌过滤溶液中产生活性成分加上任何另外的期望成分的粉末。
本文公开的rAAV组合物还可以以中性或盐形式调配。药学上可接受的盐包含酸加成盐(与蛋白质的游离氨基形成)，并且其与例如盐酸或磷酸等无机酸或如乙酸、草酸、酒石酸、扁桃酸等有机酸形成。与游离羧基形成的盐还可以源自如氢氧化钠、氢氧化钾、氢氧化铵、氢氧化钙或氢氧化铁等无机碱和如异丙胺、三甲胺、组氨酸、普鲁卡因(procaine)等有机碱。在调配后，溶液将以与剂量调配物相容的方式并以治疗上有效的量施用。调配物容易地以多种剂型施用，如可注射溶液、药物释放胶囊等。
如本文所使用的，“载剂”包含任何和所有溶剂、分散介质、媒剂、涂层、稀释剂、抗细菌剂和抗真菌剂、等渗剂和吸收延迟剂、缓冲剂、载剂溶液、悬浮液、胶体等。将这种培养基和药剂用于药物活性物质在本领域中是众所周知的。还可以将补充性活性成分并入到组合物中。短语“药学上可接受的”是指当向宿主施用时不产生过敏或类似不良反应的分子实体和组合物。
递送媒剂，如脂质体、纳米胶囊、微粒、微球、脂质颗粒、囊泡等可以用于将本发明的组合物引入到适合的宿主细胞中。具体地，rAAV载体递送的转基因可以被调配成用于递送或包封在脂质颗粒、脂质体、囊泡、纳米球或纳米颗粒等中。
此类调配物对于引入本文公开的核酸或rAAV构建体的药学上可接受的调配物可能是优选的。脂质体的形成和使用通常是本领域的技术人员已知的。最近，开发具有改进的血清稳定性和循环半衰期的脂质体(美国专利第5,741,516号)。进一步地，已经描述了脂质体和脂质体样制剂作为潜在的药物载剂的各种方法(美国专利第5,567,434号；第5,552,157号；第5,565,213号；第5,738,868号和第5,795,587号)。
脂质体已经成功地与通常对通过其它程序的转染具有抗性的许多细胞类型一起使用。另外，脂质体没有典型的基于病毒的递送系统的DNA长度限制。已经将脂质体有效地用于将基因、药物、放射治疗剂、病毒、转录因子和变构效应子引入到各种培养的细胞系和动物中。另外，已经完成了检查脂质体介导的药物递送的有效性的若干成功的临床试验。
脂质体由分散在水性介质中的磷脂形成并且自发地形成多层同心双层囊泡(也称为多层囊泡(MLV))。MLV的直径通常为25nm到4μm。MLV的超声处理导致形成直径在200到
范围内的小单层囊泡(SUV)，从而在核心中含有水溶液。
可替代地，可以使用rAAV的纳米胶囊调配物。纳米胶囊通常可以以稳定且可再现的方式截留物质。为了避免由于胞内聚合物超载引起的副作用，应使用能够在体内降解的聚合物来设计此类超细颗粒(尺寸约为0.1μm)。考虑使用满足这些要求的可生物降解的聚烷基-氰基丙烯酸酯纳米颗粒。
除了上述递送方法之外，还考虑以下技术作为向宿主递送rAAV组合物的替代性方法。超声促渗(即，超声)已经在美国专利第5,656,016号中使用并且描述为用于增强药物渗透进入和通过循环系统的速率和功效的装置。考虑的其它药物递送替代方案是骨内注射(美国专利第5,779,708号)、微芯片装置(美国专利第5,797,898号)、眼科调配物(Bourlais等人,1998)、经皮基质(美国专利第5,770,219号和第5,783,208号)和反馈控制递送(美国专利第5,697,899号)。
涉及rAAV组合物的递送的一般方法
本发明提供了包括rAAV病毒粒子的稳定的药物组合物。即使在经受冷冻/解冻循环时并且当储存在由包含玻璃的各种材料制成的容器中时，组合物仍保持稳定和活性。
含有感兴趣的异源核苷酸序列的重组AAV病毒粒子可以用于基因递送，如在基因疗法应用中、用于产生转基因动物、在核酸疫苗接种中、核酶和反义疗法以及用于向各种细胞类型体外递送基因。
通常，使用体内或体外转导技术将rAAV病毒粒子引入到受试者的细胞中。如果体外转导，则将从受试者中取出期望的受体细胞，用rAAV病毒粒子转导并重新引入到受试者体内中。可替代地，可以使用同基因细胞或异基因细胞，其中那些细胞将不会在受试者中产生不适当的免疫应答。
已经描述了用于将经过转导的细胞递送和引入到受试者中的适合方法。例如，可以通过将重组AAV病毒粒子与细胞(例如，在适当的培养基中)组合并使用常规技术(如Southern印迹和/或PCR)或通过使用可选标志物筛选包含感兴趣的DNA的那些细胞来在体外转导细胞。如下文更全面描述的，然后可以将经过转导的细胞调配成药物组合物，并且通过各种途径将组合物引入到受试者中，如通过肌内、静脉内、动脉内、皮下和腹膜内注射或通过使用例如导管注射到平滑肌中或直接注射到器官中。
对于体内递送，将rAAV病毒粒子调配成药物组合物，并且通常将通过肠胃外施用，例如通过肌内直接注射到骨骼肌、关节内、静脉内或直接注射到器官中。
适当的剂量将取决于待治疗的受试者(例如，人或非人灵长类动物或其它哺乳动物)、待治疗的受试者的年龄和一般状况、待治疗的病症的严重程度、rAAV病毒粒子的施用模式以及其它因素。适当的有效量可以由本领域的技术人员容易地确定。
因此，“治疗有效量”将落在可以通过临床试验确定的相对较宽的范围内。例如，对于体内注射，即直接向受试者注射，治疗有效剂量将为约105到1016个rAAV病毒粒子，更优选地108到1014个rAAV病毒粒子。对于体外转导，向细胞待递送的rAAV病毒粒子的有效量将为105到1013个rAAV病毒粒子，优选地108到1013个rAAV病毒粒子。如果组合物包括待递送回到受试者的经过转导的细胞，则药物组合物中的经过转导的细胞的量将为约104到1010个细胞，更优选地105到108个细胞。当然，剂量取决于转导的效率、启动子强度、信息的稳定性和由其编码的蛋白质等。本领域的普通技术人员可以通过建立剂量反应曲线的常规试验容易地确定有效剂量。
剂量治疗可以是单剂量方案或多剂量方案，以最终递送上文指定的量。此外，受试者可以施用尽可能多的剂量。因此，可以例如以单一剂量将例如105到1016个rAAV病毒粒子给予受试者或以共同导致递送例如105到1016个rAAV病毒粒子的两个、四个、五个、六个或更多个剂量给予受试者。本领域的技术人员可以容易地确定待施用的剂量的适当数量。
因此，药物组合物将包括足够的遗传物质以产生治疗有效量的感兴趣的蛋白质，即足以减少或改善所讨论的疾病状态的症状的量或足以赋予所期望的益处的量。因此，当以一个或多个剂量给予时，rAAV病毒粒子将以足以提供治疗效果的量存在于本发明组合物中。rAAV病毒粒子可以被提供为冻干的制剂，并在病毒粒子稳定组合物中稀释以供立即使用或将来使用。可替代地，rAAV病毒粒子可以在产生之后立即提供，并储存以供将来使用。
药物组合物还将含有药学上可接受的赋形剂。此类赋形剂包含本身不诱导对接受组合物的个体有害的抗体的产生的任何药物制剂，并且所述任何药物制剂可以在没有过度毒性的情况下施用。药学上可接受的赋形剂包含但不限于液体，如水、盐水、甘油和乙醇。药学上可接受的盐可以包含在其中，例如无机酸盐，如盐酸盐、氢溴酸盐、磷酸盐、硫酸盐等；和有机酸的盐，如乙酸盐、丙酸盐、丙二酸盐、苯甲酸盐等。另外，此类媒剂中可以存在辅助物质，如润湿剂或乳化剂、pH缓冲物质等。对药学上可接受的赋形剂的详尽讨论可在《雷明顿药物科学》(新泽西州麦克出版公司(Mack Pub.Co.),1991)中获得。
如本文所使用的，“聚合酶链反应”或“PCR”是指程序或技术，其中特异性核酸序列、RNA和/或DNA如在例如美国专利第4,683,195号中所描述的进行扩增。通常，使用来自感兴趣的区域的末端或以外的序列信息来设计寡核苷酸引物。这些引物在序列上与待扩增的模板的相反链相同或类似。两个引物的5'末端核苷酸可以与经过扩增的材料的末端一致。PCR可以用于扩增特异性RNA序列、来自总基因组DNA的特异性DNA序列以及从总细胞RNA转录的cDNA、噬菌体或质粒序列等。通常参见Mullis等人,(1987)《冷泉港生物学季度讨论会(Cold Spring Harbor Symp.Quant.Biol.)》51:263；Erlich编辑,(1989)《PCR技术(PCRTECHNOLOGY)》(斯托克顿出版社(Stockton Press),纽约)。如本文所使用的，PCR被认为是用于扩增核酸测试样本的核酸聚合酶反应方法的一个但不是唯一的实例，所述方法包括使用已知的核酸作为引物和核酸聚合酶来扩增或产生核酸的特异性片段。
核酸
本发明还包括对本文所述的αLNNdΔG2'蛋白进行编码的某些构建体和核酸。包含在序列表中列出的包含SEQ ID NO:1和SEQ ID NO:24的所选序列的某些构建体和序列可以用于本发明的实施例中。
优选地，核酸在低、中或高严格性条件下杂交，并且编码维持生物功能的αLNNdΔG2'蛋白。当第一核酸分子的单链形式可以在适当的温度和溶液离子强度条件下退火到第二核酸分子时，第一核酸分子与第二核酸分子是“可杂交”(参见Sambrook等人,同上)。温度和离子强度的条件确定了杂交的“严格性”。典型的低严格性杂交条件包含55℃、5X SSC、0.1％SDS和无甲酰胺；或30％甲酰胺、5X SSC、0.5％SDS，在42℃下。典型的中等严格性杂交条件是40％甲酰胺，与5X或6X SSC和0.1％SDS，在42℃下。高严格性杂交条件是50％甲酰胺，5X或6X SSC，在42℃下，或任选地在更高温度(例如，57℃、59℃、60℃、62℃、63℃、65℃或68℃)下。通常，SSC是0.15M NaCl和0.015M柠檬酸钠。杂交要求两个核酸含有互补序列，但是取决于杂交的严格性，并且碱基之间的错配是可能的。用于杂交核酸的适当严格性取决于核酸的长度和互补的程度，本领域众所周知的变量。两个核苷酸序列之间的相似性或同源性程度越高，核酸可以杂交的严格性越高。对于长度大于100个核苷酸的杂合体，已经得出用于计算熔解温度的方程(参见Sambrook等人,同上,9.50-9.51)。为了与较短的核酸(例如,寡核苷酸)杂交，错配的位置变得更加重要，并且寡核苷酸的长度确定了其特异性(参见Sambrook等人,同上,11.7-11.8)。
αLNNdΔG2'小鼠多肽包括SEQ ID NO:21的氨基酸序列。αLNNdΔG2'人多肽包括SEQ ID NO:22的氨基酸序列，并且与小鼠多肽具有87％同一性，如图9所示。当通过BLAST算法进行比较时，关于恢复层粘连蛋白聚合功能，考虑到包括与本文提供的αLNNdΔG2'氨基酸序列(例如，SEQ ID NO:21-22)至少约90％相同并且最优选地至少约95％相同(例如,95％、96％、97％、98％、99％、100％)的氨基酸序列的αLNNdΔG2'多肽，其中选择所述算法的参数以在相应的参考序列的整个长度上在相应的序列之间给出最大匹配。当使用BLAST算法进行比较时，包括与任何参考αLNNdΔG2'氨基酸序列至少约90％相似并且最优选地至少约95％相似(例如，95％、96％、97％、98％、99％、100％)的氨基酸序列的多肽也包含在本发明的构建体和方法中，其中选择所述算法的参数以在相应的参考序列的整个长度上在相应的序列之间给出最大匹配。
序列同一性是指当两个序列进行最佳比对时，两个多肽的氨基酸在等效位置处相同的程度。序列相似性包含相同的残基和不相同的、生物化学相关的氨基酸。上文讨论了共享相似性质并且可以是可互换的生物化学相关氨基酸。
“同源性”是指当进行最佳比对时，两个多核苷酸序列之间或两个多肽序列之间的序列相似性。当所述两个比较序列中的一个位置被同一碱基或氨基酸单体亚基占据时，例如如果两个DNA分子中的每个分子中的一个位置被腺嘌呤占据，则所述分子在那个位置处是同源的。同源性的百分比是由两个序列共享的同源位置的数量除以所比较的位置的总数量×100。例如，如果当两个序列进行最佳比对时，所述两个序列中的10个位置中的6个位置是匹配的或同源的，则这两个序列是60％同源的。通常，当两个序列被比对以给出最大百分比同源性时进行比较。
以下参考文献涉及通常用于序列分析的BLAST算法：BLAST算法：Altschul,S.F.等人,(1990)《分子生物学杂志(J.Mol.Biol.)》215:403-410；Gish,W.等人,(1993)《自然遗传学》3:266-272；Madden,T.L.等人,(1996)《酶学方法(Meth.Enzymol.)》266:131-141；Altschul,S.F.等人,(1997)《核酸研究(Nucleic Acids Res.)》25:3389-3402；Zhang,J.等人,(1997)《基因组研究(Genome Res.)》7:649-656；Wootton,J.C.等人,(1993)《计算化学(Comput.Chem.)》17:149-163；Hancock,J.M.等人,(1994)《计算机应用生物科学(Comput.Appl.Biosci.)》10:67-70；比对评分系统：Dayhoff,M.O.等人,《蛋白质序列和结构图谱学(Atlas of Protein Sequence and Structure)》中的“蛋白质中演化变化的模型(A model of evolutionary change in proteins.)”(1978)第5卷,第3增刊。M.O.Dayhoff(编辑),第345-352页,《美国国家生物医学研究基金会(Natl.Biomed.Res.Found.)》,华盛顿特区；Schwartz,R.M.等人,《蛋白质序列和结构图谱学》中的“用于检测距离关系的基质(Matrices for detecting distant relationships.)”(1978)第5卷,第3增刊”。M.O.Dayhoff(编辑),第353-358页,《美国国家生物医学研究基金会》,华盛顿特区；Altschul,S.F.(1991)《分子生物学杂志》219:555-565；States,D.J.等人,(1991)《方法(Methods)》3:66-70；Henikoff,S.等人,(1992)《美国国家科学院院刊》89:10915-10919；Altschul,S.F.等人,(1993)《分子进化杂志(J.Mol.Evol.)》36:290-300；比对统计：Karlin,S.等人,(1990)《美国国家科学院院刊》87:2264-2268；Karlin,S.等人,(1993)《美国国家科学院院刊》90:5873-5877；Dembo,A.等人,(1994)《概率年报(Ann.Prob.)》22:2022-2039；以及Altschul,S.F.《基因组研究中的理论和计算方法(Theoretical andComputational Methods in Genome Research)》中的“评估多个不同的局部比对的统计显著性(Evaluating the statistical significance of multiple distinct localalignments)”(S.Suhai编辑),(1997),第1-14页,普莱南出版公司(Plenum),纽约。
本发明还提供了包括各种核酸的表达载体，其中当用载体转染宿主细胞时，核酸与由宿主细胞识别的控制序列可操作地连接。还提供了包括重组AAV-DJ和某些AAV-2序列的病毒粒子，以及用于在CMV启动子和CMV增强子的指导下表达αLNNdΔG2'的核酸序列。可以使用替代性启动子，条件是所述替代性启动子的大小是小的并且具有高活性和良好表达。在这些构建体中，rAAV2序列与5'和3'ITR序列相对应，例如SEQ ID NO:11和16以及序列表中所述的其它序列。在本发明中，将这些序列与AAV-DJ衣壳一起包装以形成对层粘连蛋白α-2缺陷是治疗性的病毒粒子。
药物组合物和施用
为了制备本发明的组合物的药物组合物或无菌组合物，可以将AAV-DJ载体或相关组合物与药学上可接受的载剂或赋形剂混合。参见例如《雷明顿药物科学》和《美国药典国家处方集(U.S.Pharmacopeia:National Formulary)》,麦克出版公司,伊斯顿,宾夕法尼亚州(1984)。
治疗剂和诊断剂的调配物可以通过与呈例如冻干粉末、浆料、水溶液或悬浮剂的形式的可接受载剂、赋形剂或稳定剂混合来制备(参见例如，Hardman等人,(2001)Goodman和Gilman的《治疗学的药理学基础(The Pharmacological Basis of Therapeutics)》,麦格劳-希尔出版公司(McGraw-Hill),纽约市,纽约州；Gennaro(2000)《雷明顿：药物科学与实践(Remington:The Science and Practice of Pharmacy)》,利平科特·威廉斯·威尔金斯出版公司(Lippincott,Williams,and Wilkins),纽约市,纽约州；Avis等人(编辑)(1993)《药物剂型：肠胃外药物(Pharmaceutical Dosage Forms:ParenteralMedications)》,马塞尔德克尔公司(Marcel Dekker),纽约；Lieberman等人(编辑)(1990)《药物剂型：片剂(Pharmaceutical Dosage Forms:Tablets)》,马塞尔德克尔公司,纽约；Lieberman等人(编辑)(1990)《药物剂型：分散系统(Pharmaceutical Dosage Forms:Disperse Systems)》,马塞尔德克尔公司,纽约；Weiner和Kotkoskie(2000),《赋形剂毒性和安全性(Excipient Toxicity and Safety)》,马塞尔德克尔公司,纽约市,纽约州)。
单独施用或与另一种药剂组合施用的治疗组合物的毒性和治疗功效可以通过在细胞培养物或实验动物中的标准药学程序来确定，例如用于确定LD50(使50％的群体致死的剂量)和ED50(对50％的群体具有治疗有效性的剂量)。毒性与治疗效果之间的剂量比是治疗指数(LD50/ED50)。在特定方面，表现出高治疗指数的治疗组合物是令人期望的。从这些细胞培养测定和动物研究获得的数据可以用于调配用于在人类中使用的剂量范围。此类化合物的剂量优选地处于包含ED50的具有很小毒性或没有毒性的循环浓度范围内。剂量可以根据所采用的剂型和施用途径而在这个范围内变化。
在本发明的实施例中，根据医师案头参考(Physicians'Desk Reference)2003(汤姆森医疗保健(Thomson Healthcare)；第57版(2002年11月1日))向受试者施用本发明的组合物。
施用模式可以变化。适合的施用途径包含口服、直肠、经粘膜、肠、肠胃外；肌内、皮下、皮内、髓内、鞘内、直接心室内、静脉内、腹膜内、鼻内、眼内、吸入、吹入、局部、皮肤、经皮或动脉内。
在特定实施例中，可以通过侵入性途径，如通过注射(参见上文)施用组合物或治疗剂。在本发明的另外的实施例中，静脉内、皮下、肌内、动脉内、关节内(例如，在关节炎关节中)、瘤内或通过吸入、气雾剂递送施用所述组合物、其治疗剂或药物组合物。通过非侵入性途径(例如，口服地；例如，以丸剂、胶囊或片剂的形式)的施用也处于本发明的范围内。
组合物可以用本领域已知的医疗装置施用。例如，可以通过用包含例如预填充注射器或自动注射器的皮下注射针注射来施用本发明的药物组合物。
本发明的药物组合物还可以用无针皮下注射装置施用；如美国专利第6,620,135号；第6,096,002号；第5,399,163号；第5,383,851号；第5,312,335号；第5,064,413号；第4,941,880号；第4,790,824号或第4,596,556号中公开的装置。
可替代地，可以以局部而非全身性方式施用AAV-DJ载体或相关化合物，例如通过通常以长效调配物或持续释放调配物的形式直接注射到所期望的靶位点。此外，可以在靶向药物递送系统中，例如在用靶向例如脑的组织特异性抗体包被的脂质体中施用组合物。脂质体靶向于所期望的组织并被其选择性地摄取。
施用方案取决于若干因素，包含治疗组合物的血清或组织周转率、症状水平以及生物基质中的靶细胞的可及性。优选地，施用方案递送足够的治疗组合物以实现靶疾病状态的改善，而同时使不期望的副作用最小化。因此，所递送的生物剂的量部分取决于特定治疗组合物和所治疗病症的严重性。
对适当剂量的确定是由临床医生例如使用本领域已知或怀疑影响治疗的参数或因素进行的。通常，剂量开始的量略微小于最佳剂量并且其随后以小增量增加，直到相对于任何负性副作用达到期望的或最佳效应。重要的诊断措施包含例如所产生的炎症或炎性细胞因子水平的症状中的那些症状。通常，令人期望的是将使用的生物剂源自与靶向治疗的动物相同的物种，从而使对所述试剂的任何免疫应答最小化。
如本文所使用的，“抑制”或“治疗”或“治疗”包含延缓与病症相关的症状的发展和/或降低此类病症的症状的严重程度。所述术语进一步包含改善现有的不受控制或不想要的症状、预防另外的症状以及改善或预防此类症状的潜在原因。因此，所述术语表示已经向患有病症、疾病或症状或具有可能发展成这种病症、疾病或症状的脊椎动物受试者赋予了有益结果。
如本文所使用的，术语“治疗有效量”、“治疗有效剂量”和“有效量”是指当向细胞、组织或受试者单独施用或与另外的治疗剂组合施用时，有效地引起疾病或病状的一种或多种症状或此类疾病或病状的进展的重大改善的本发明的基于rAAV-DJ-αLNNdΔG2'的化合物的量。治疗有效剂量进一步是指足以导致症状的至少部分改善(例如，相关医学病状的治疗、治愈、预防或改善或此类病状的治疗、治愈、预防或改善的速率的增加)的化合物的量。当应用于单独施用的个体活性成分时，治疗有效剂量单独是指所述个体活性成分。当应用于组合时，治疗有效剂量是指导致治疗效果的活性成分的组合量，无论是以组合方式连续施用还是同时施用。有效量的治疗剂将导致诊断措施或参数提高至少10％；通常至少20％；优选地至少约30％；更优选地至少约40％，并且最优选地至少约50％。在使用主观量度来评估疾病严重程度的情况下，有效量也可以导致主观量度的改善。
试剂盒
本发明还提供了试剂盒，所述试剂盒包括试剂盒形式的本发明的组合的组分。本发明的试剂盒包含一种或多种组分，包含但不限于如本文所讨论的基于rAAV-DJ-αLNNdΔG2'的化合物与一种或多种另外的组分，包含但不限于如本文所讨论的药学上可接受的载剂和/或化学治疗剂的联合。基于rAAV-DJ-αLNNdΔG2'的化合物或组合物和/或治疗剂可以在药物组合物中调配成纯组合物或与药学上可接受的载剂组合。
在一个实施例中，试剂盒包含在一个容器(例如，在无菌玻璃或塑料小瓶中)中的本发明的基于rAAV-DJ-αLNNdΔG2'的化合物/组合物或其药物组合物，以及在另一容器(例如，在无菌玻璃或塑料小瓶中)中的其药物组合物和/或化学治疗剂。
在本发明的另一个实施例中，所述试剂盒包括本发明的组合，包含任选地在药物组合物中在单个共同容器中一起调配的基于rAAV-DJ-αLNNdΔG2'的化合物连同药学上可接受的载剂，任选地与一种或多种化学治疗剂组分组合。
如果试剂盒包含用于向受试者进行肠胃外施用的药物组合物，则所述试剂盒可以包含用于进行此类施用的装置。例如，试剂盒可以包含一个或多个皮下注射针或如上文所讨论的其它注射装置。
试剂盒可以包含包装插入物(package insert)，所述包装插入物包含关于试剂盒中的药物组合物和剂型的信息。通常，此类信息帮助患者和医师有效地且安全地使用包封的药物组合物和剂型。例如，可以在插入物中提供关于本发明的组合的以下信息：药代动力学、药效学、临床研究、功效参数、适应症和用法、禁忌症、警告、注意事项、不良反应、过剂量、合适的剂量和施用、如何供应、合适的储存条件、参考资料、制造商/经销商信息和专利信息。
一般方法
在以下文献中描述了分子生物学的标准方法：Sambrook、Fritsch和Maniatis(1982和1989,第2版,2001,第3版)《分子克隆，实验室手册》,冷泉港实验室出版社,冷泉港,纽约)；Sambrook和Russell(2001)《分子克隆(Molecular Cloning)》,第3版,冷泉港实验室出版社,冷泉港,纽约；Wu(1993)《重组DNA(Recombinant DNA)》,第217卷,学术出版社(Academic Press),圣地亚哥,加利福尼亚州)。标准方法还出现在以下文献中：Ausbel等人(2001)《当前分子生物学实验指南》第1-4卷,约翰·威利父子出版公司,纽约市,纽约州，所述文献描述了细菌细胞和DNA诱变中的克隆(第1卷)、哺乳动物细胞和酵母中的克隆(第2卷)、糖缀合物和蛋白质表达(第3卷)以及生物信息学(第4卷)。
描述了用于蛋白质纯化的方法，包含免疫沉淀、色谱、电泳、离心和结晶(Coligan等人,(2000)《当代蛋白质科学实验指南(Current Protocols in Protein Science)》,第1卷,约翰·威利父子出版公司,纽约)。描述了化学分析、化学修饰、翻译后修饰、融合蛋白的产生、蛋白质的糖基化(参见例如Coligan等人(2000)《当代蛋白质科学实验指南》第2卷,约翰·威利父子出版公司,纽约；Ausubel等人,(2001)《当代分子生物学实验指南》,第3卷,约翰·威利父子出版公司,纽约市,纽约州,第16.0.5-16.22.17页；西格玛奥德里奇公司(Sigma-Aldrich,Co.)(2001)《生命科学研究产物(Products for Life ScienceResearch)》,圣路易斯,密苏里州；第45-89页；安玛西亚法玛西亚生物技术公司(AmershamPharmacia Biotech)(2001)《生物目录(BioDirectory)》,皮斯卡塔韦,新泽西州,第384-391页。描述了多克隆和单克隆抗体的产生、纯化和片段化(Coligan等人,(2001)《当代免疫学实验指南(Current Protcols in Immunology)》,第1卷,约翰·威利父子出版公司,纽约)；Harlow和Lane(1999)《使用抗体(Using Antibodies)》,冷泉港实验室出版社,冷泉港,纽约；Harlow和Lane,同上)。用于表征配体/受体相互作用的标准技术是可获得的(参见例如Coligan等人(2001)《当代免疫学实验指南》,第4卷,约翰·威利父子出版公司,纽约)。
实例
实例1
AlphaLNNdDeltaG2short(αLNNdΔG2')构建体开发
用重叠的PCR完成αLNNd pcDNA3.1 Zeo中的G2巢蛋白-1结构域的去除。在第一轮PCR中，1.2Kb-5'(F1noG2 1F 5'-ctgggtcactgtcaccctgg-3'(SEQ ID NO:2)和noG2 2R 5'-atggattctgaagacagacaccagagacac-3'(SEQ ID NO:3))和1.8Kb-3'(no G2 2F 5'-ctggtgtctgtcttcagaatccatgctac-3'(SEQ ID NO:4)和F1 no G2 1R 5'-gaaggcacagtcgaggctgatcag-3'(SEQ ID NO:5))产物产生于αLNNd的G2巢蛋白-1结构域的任一侧上。将其与第二轮PCR(F1noG2 1Fand F1 no G2 1R)一起缝合到3Kb产物中，然后将所述产物用2.4Kb的EcoRI消化并连接到5.85Kb EcoRIαLNNd pcDNA 3.1zeo载体(产生8.25Kb noG2 αLNNd pcDNA3.1 zeo质粒)。用重叠的PCR引物(Bam shnoG2 1F 5'-cggcagcctgaatgaggatccatgcataga-3'(SEQ ID NO:6)和shnoG2 2R 5'-cacagtagttgatgggacagacacc-3'(SEQ ID NO:7))以及3'(shnoG2 2F 5'-gtctctggtgtctgtcccatcaacta-3'(SEQ ID NO:8)和sse shnoG2 1R 5'-gaggcacaaacatcccctgcagggtgggcc-3'(SEQ ID NO:9)执行noG2 αLNND的另外的2EGF(270bp)缺失以分别产生160bp和357bp产物。在第二轮PCR之后，将485bp BamHI-SbfI消化的插入物连接到同样消化的noG2 αLNNd pcDNA3.1 zeo载体(7.5Kb)中。为了去除短的noG2 αLNNd开放阅读框(ORF)上的N末端Myc标签，将1.5Kb BamHI插入物从F3-8 mck-pA构建体移动到MCS-AAV载体(4.6Kb，细胞生物学实验室(Cell Biolabs)，VPK-410-DJ)，从而产生6.1Kb AAV-5'F1无标签-10质粒。用FseI和XhoI消化短的noG2 αLNND pcDNA3.1 zeo质粒，以产生将其连接到类似消化的AAV-5'F1无标签-10载体(4.9Kb)中的2.8Kb插入物。最终的载体大小为7.7Kb，其中alphaLNNdDeltaG2short(αLNNdΔG2')的ORF为3009bp(SEQ ID NO:1)。
实例2
AAV病毒的产生
使用磷酸钙瞬时转染的常用方法，将αLNNdΔG2'-MCS质粒与AAV-DJ p辅助p辅助质粒(分别是SEQ ID NO:1、17、20；图6-8)(加利福尼亚州圣地亚哥细胞实验室有限公司(Cell Biolabs,Inc.))以1:1:1的比率一起三重转染到粘附的HEK293中。简而言之，根据制造商的说明书(密苏里州圣路易斯西格玛奥德里奇公司，目录号CAPHOS)，将12.5ug每/150mm培养皿(每次制备10-150mm培养皿)添加到75％汇合的HEK293细胞中过夜。96小时后，用AAVpro纯化试剂盒(加利福尼亚州山景城美国塔卡拉生物公司(Takara Bio USA,Inc.)，目录号6666)从培养物收获病毒。替代性纯化方法是可获得的，其包含细胞冷冻-解冻或Triton-100裂解，然后进行PEG8000和/或氯化铯离心。用实时PCR(AAVpro滴定试剂盒，加利福尼亚州山景城美国塔卡拉生物公司，目录号6233)测定病毒滴度。
实例3
AAV产生的αLNNdΔG2'蛋白的表达和分析
用约6×10vg/6孔培养皿感染稳定转染的411HEK293细胞。四天后，通过用a-flag琼脂糖珠在室温下免疫沉淀1小时，然后进行蛋白质印迹分析来评估条件培养基。将蛋白质印迹切割并用1μg/ml的抗-flag(上图)或抗G2-G2巢蛋白(下图)对其进行染色。结果示出在图5A中。可替代地，向高传代大鼠许旺细胞中添加条件化AAV 411HEK293培养基持续1小时，并且使用1ug/ml鸡抗α4和1:100抗鸡Alexa Fluor 647通过免疫荧光对411层粘连蛋白组装进行分析(加利福尼亚州卡尔斯巴德生命技术公司(Life Technologies)，目录号A-21449)。Lm411组装的显著增加是由图5C和5D所示的AAV产生的αLNNdΔG2'蛋白引起的。
将AAVαLNNdΔG2'(病毒，含1010vg的～25μl)或PBS缓冲液腹膜内注射到1周龄的dy3K/dy3K mag小鼠中。两周后，收获股四头肌，对其进行切片，并且用抗体染色以检测αLNNdΔG2'(红色)和层粘连蛋白(绿色)，如图5E所示。在股四头肌肌肉组织中检测到αLNNdΔG2'的∞1LN表位，这指示连接子被并入肌肉肌膜中。
实例4
使有症状的小鼠恢复层粘连蛋白α2
在表达mag转基因的dy3K/dy3K小鼠中注射AAV-DJ-αLNNdΔG2'构建体，在表达αLNNd转基因的dy3K/dy3K小鼠中完成集聚蛋白图3B(SEQ ID NO:23)的微小型化版本以及AAV-DJ-αLNNdΔG2'构建体的注射，以结合稳定且已经表征的配对连接子蛋白的表达来评估一次一种病毒感染，并且分别地验证每种连接子蛋白，从而使可变性最小化。使用免疫荧光显微镜，用以下文献中所描述的特异性连接子和层粘连蛋白抗体，对肌肉进行初始分析以确定哪些肌肉在神经表达的程度之后填充有αLNNdΔG2'和mag，并且在注射后持续表达：McKee等人,(2017)《临床研究杂志》127(3):1075-1089；Reinhard等人,(2017)《科学转化医学》9(396)。
在评估初始分析后，将dy3K/dy3K小鼠与病毒制剂两者共感染。注射将在出生后第1天或第2天给予，考虑到髓鞘形成的围产期时间过程(在出生前通过基本上在出生后第一周发生的径向分选开始SC增殖)。待进行的表型和组织学分析包含：(1)测量存活率、体重、肌肉重量、垂直网格上的时间、握力和不同年龄的整体行为的测量结果；(2)隔膜、肋间肌和膈神经的检查；(3)通过H&E和天狼星红(Sirius Red)(胶原蛋白)染色的在不同年龄的前肢桡侧腕伸肌(extensor carpi radialis)和隔膜/肋间肌的组织学的骨骼肌分析，其中对纤维大小、数量、再生(具有中央核的肌纤维的部分)、炎症和纤维化进行形态学定量；(4)通过检查免疫染色的神经和根来评估连接子-蛋白7表达的程度和检测层粘连蛋白亚基的相对变化的外周神经分析；使用电子显微镜检查亚甲蓝染色的半薄切片，以定量地评估轴突分选的程度、髓鞘形成、髓鞘脂厚度和裸轴突的部分；从EdU/dapi比率确定SC增殖，并且使用qRT-PCR来评估髓鞘形成的成熟(例如，Oct6、Sox2、cJun)。
分析的结果用于优化递送并评估可以进一步改善功能的αLNNdΔG2'和mag连接子蛋白的变体。
实例5
具有变体血清型衣壳的AAV的αLNNdΔG2'的表达
出于改变组织特异性的目的，例如仅骨骼肌加上心脏或主要是肝脏，将αLNNdΔG2'DNA插入具有编码不同衣壳血清型或复合血清型的AAV载体中。注意：αLNNdΔG2'是可溶的分泌蛋白，其中合成位点不需要是靶细胞类型。
实例6
被修饰以减少泛素化的AAV衣壳序列
与其它AAV一样，AAV-DJ在衣壳上含有若干磷酸化位点和泛素化位点。发现在K137R、S503A和T251A处的rep/cap质粒上的点突变显著增加体外和体内蛋白质表达(如Mao,Wang,Yan,Li,Wang和Li中所描述的,2016,“腺相关病毒载体-DJ衣壳中的单点突变导致体内基因递送的改善(Single point mutation in adeno-associated viral vectors–DJ capsid leads to improvement for gene delivery in vivo)”《BMC生物技术(BMCBiotechnology)》16:1-8)。可以容易地修饰AAV质粒以引入这种改善。
实例7
使用特异性启动子用AAV表达αLNNdΔG2'
将αLNNdΔG2'DNA插入具有不同启动子/增强子的AAV载体中，其作用是(a)改变特异性和/或(b)增加插入物的可允许的开放阅读框。用于驱动骨骼肌和心脏中微肌营养不良蛋白的表达的一个实例是已经从肌肉肌酸激酶基因基础启动子和上游增强子修饰的436bpCK8e启动子/增强子。CK8e启动子/增强子描述于J.N.Ramos等人,2019,《分子疗法》,27:623-635。
实例8
用替代性信号序列表达Lmα1LNNdΔG2'
已经使用BM-40信号序列在体外和小鼠中表达了蛋白质αLNNdΔG2'和相关蛋白，所述信号序列具有SEQ ID NO:25中的核苷酸序列并且已经在下表2中给出了字母代码A。替代方案是表达具有内源性α1亚基信号肽的蛋白质，所述亚基信号肽具有SEQ ID NO:27中的核苷酸序列并且已经在表2中给出了字母代码A'。
表2提供了所有具有指定字母代码的变体蛋白质序列的列表，所述字母代码可以与BM-40信号肽或通常在层粘连蛋白N末端亚基之前的层粘连蛋白内源性信号肽一起使用。这些结构域可以用于产生实现层粘连蛋白聚合的连接子蛋白。可以实现聚合的层粘连蛋白结合连接子蛋白和内部大小减小的连接子蛋白的小鼠结构域已经被指定为核苷酸和氨基酸序列两者的字母代码A、A'到P(SEQ ID NOS:25-58)。替代性N末端结构域(小鼠和人)已经被指定为核苷酸和氨基酸序列两者的字母代码Q到Z和a到b(SEQ ID NOS:59-106)。另外的C末端结构域，可以与聚合连接子蛋白的巢蛋白层粘连蛋白结合G3结构域C末端(5'到)融合的小鼠和人非神经集聚蛋白营养不良聚糖(non-neural agrin dystroglycan)-结合结构域，已经被指定为核苷酸和氨基酸序列两者的字母代码c到j(SEQ ID NOS:107-138)。
表3提供了表2中列出的变体蛋白序列中的每个变体蛋白序列的小鼠和人核苷酸和氨基酸序列，并且提供了指定给序列表中的这些序列的SEQ ID NO。
表2.结构域单字母代码
| 字母代码 | 基因 | 蛋白质 | 结构域 | DNA大小，bp<sup>6</sup> |
| A | LAMA1 | 层粘连蛋白-α1 | BM-40信号肽 | 51 |
| A' | LAMA1 | 层粘连蛋白-α1 | 内源性信号肽 | 72 |
| B | LAMA1 | 层粘连蛋白-α1 | LN | 753 |
表3.结构域序列
实例9
功能性增强的LmαLNNdΔG2'的简化和修饰
当前评估的AAV-DJ构建体允许包含表示开放阅读框的3.1kB DNA。现有或计划的其它构建体可以允许更大的内含物。基于AAV-DJ极限的允许的蛋白质大小，注意到LmαLNNdΔG2'的巢蛋白G3结构域的大小可以减少到螺旋桨结构域的大小(～270个残基，810bp)，保留如J.Takagi等人,2003,《自然(Nature)》424:963-974中所描述的层粘连蛋白结合。393bp的减少允许结构域重排，使得可以包含G2型IV胶原蛋白和基底膜聚糖结合结构域。新的布置允许层粘连蛋白聚合与胶原蛋白/基底膜聚糖结合偶联。实例是(a)αLNNdG2Propeller(3.08kB)和(b)αLNNdG2Propeller-2(3.02kB)。下表4中示出了使用表2中提供的字母结构域编码的结构域中的每个结构域的结构域组合物。表3和序列表中提供了结构域组合物中使用的结构域的核苷酸和蛋白质序列。另一种布置允许层粘连蛋白聚合与营养不良聚糖结合偶联，所述营养不良聚糖结合的实例是αLNNdPropellerAgrinLG(3.6kB)。下表4中示出了使用表2中提供的字母结构域编码的αLNNdPropellerAgrinLG的结构域组合物。表3和序列表中提供了结构域组合物中使用的结构域的核苷酸和蛋白质序列。
表4
具有字母代码的结构域组合物的层粘连蛋白连接子蛋白7
实例10
具有聚合缺陷的其它层粘连蛋白的修复
皮尔森综合征是具有眼部异常的先天性肾病综合征，导致早期终末期肾脏疾病、失明和死亡。原因是编码层粘连蛋白β2亚基的LAMB2基因中的无效、框内缺失或错义突变。这些突变阻止亚基表达或改变亚基性质。所述错义突变中的若干错义突变聚类在β2LN结构域中(参见Maatejas等人,2010,《人突变(Hum Mutat.)》38:992-1002和K.K.McKee,M.Aleksandrova和P.D.Yurchenco,2018,《基质生物学》67:32-46)。LN结构域介导层粘连蛋白的聚合。这些突变的可能作用是可能是低分泌者/非分泌者的结构域的折叠失败以及聚合突变失败。在将皮尔森综合征中的两个高度保守的突变(S80R和H147R)放置到β1亚基(S68R和H135R)中之后对其进行评估。两种突变大大降低了聚合，并且发现βLNNd(β1LN-LEa结构域在与巢蛋白G3融合时交换为α1LN-LEa)能够拯救不能聚合的重组层粘连蛋白，因为层粘连蛋白缺乏βLN结构域(描述于K.K.McKee,M.Aleksandrova和P.D.Yurchenco,2018,《基质生物学》67:32-46)。由于βLNNd可以在体外修复皮尔森缺陷，因此推断较短的βLNNdΔG2可以用于治疗疾病。类似地，预期可通过表达相关的层粘连蛋白连接子蛋白来治疗由于影响聚合的层粘连蛋白LN突变引起的其它疾病，其中其对应的LN-LEa区段已经替代了融合蛋白中的α1LN-LEa区段。这些蛋白质(βLNNdΔG2'、βLNNdG2Propeller、γLNNdΔG2'和γLNNdG2Propeller)通过表2和表4中的结构域组合物以及表3和序列表中提供的结构域组合物中使用的结构域的序列来描述。
实例11
向αLNNdΔG2直接添加营养不良聚糖结合活性
采用巢蛋白螺旋桨结构域而不是完整的G3结构域复合物产生了用于添加营养不良聚糖结合结构域的空间(在允许的AAV插入物大小的上下文中)。所述蛋白质被指定为αLNNdΔG2PropellerAgrinLG。在表2和4中示出了结构域组合物，其中表3和序列表中提供了结构域组合物中使用的结构域的序列。此处的大小增加阻止了在标准AAV-DJ病毒中的使用，并且需要允许更大插入物的病毒，如含有较小CK8e启动子的插入物。
实例12
通过肠胃外注射递送蛋白质
LmαLNNdΔG2'蛋白及其任何替代性形式均可以肠胃外(腹膜内、血管内、肌内途径)注射，以将所述蛋白质递送到其预期的组织靶标，作为病毒递送的体细胞基因疗法的替代方案。
构建体的密码子优化
为了优化本文所述的测试构建体的表达，不仅作为在制造过程期间降低病毒滴度的手段，而且为了解决与高浓度的病毒相关的安全问题，将使用密码子优化方法使用自由可获得的软件对αLNNdΔG2'转基因进行评估(https://www.idtdna.com/CodonOpt)。另外，根据需要将共有Kozak序列引入到构建体中。因此，可以以这种方式对本文所述的构建体或元件中的任何构建体或元件进行密码子优化。在小鼠中，将与亲本构建体平行地测试经过修饰的构建体中的每个经过修饰的构建体。简而言之，将通过颞静脉向小鼠幼崽全身性地施用构建体。然后在两周或三周后使动物安乐死，并且通过Q-PCR和蛋白质印迹来测定所述构建体中的每个构建体的蛋白质水平。递送最快和高水平表达的构建体将被考虑用于最终用于非人灵长类动物研究中，并且最终用于人类患者的临床试验中。
参考文献
1.Donnelly,M.L.等人(2001).口蹄疫病毒2A定点突变体和天然存在的“2A样”序列的“裂解”活性(The‘cleavage’activities of foot-and-mouth disease virus 2Asite directed mutants and naturally occurring‘2A-like’sequences)《普通病毒学杂志(J.Gen.Virol.)》82,1027-1041。
2.Foust,K.D、Nurre,E、Montgomery,C.L、Hernandez,A、Chan,C.M.和Kaspar,B.K.(2009).血管内AAV9优选地靶向新生神经元和成年星形胶质细胞(Intravascular AAV9preferentially targets neonatal neurons and adult astrocytes)《自然生物技术(Nat.Biotech.)》27,59-65。
3.Grieger JC、Samulski RJ(2005),腺相关病毒作为基因疗法载体：载体开发、生产和临床应用(Adeno-associated virus as a gene therapy vector:vectordevelopment,production and clinical applications)《生物化学工程技术进展(AdvBiochem Eng Biotechnol.)》99,119-145。
4.Grieger JC、Samulski RJ(2012),腺相关病毒载体学、制造和临床应用(Adeno-associated virus vectorology,manufacturing,and clinical applications)《酶学方法(Methods Enzymol)》507,229-254。
5.Kariya S、Re DB、Jacquier A、Nelson K、Przedborski S、Monani UR(2012),突变体超氧化物歧化酶1(SOD1)，肌萎缩性脊髓侧索硬化症的原因，破坏SMN(脊髓性肌肉萎缩蛋白)向核酸Cajal体的募集(Mutant superoxide dismutase 1(SOD1),a cause ofamyotrophic lateral sclerosis,disrupts the recruitment of SMN,the spinalmuscular atrophy protein to nuclear Cajal bodies)《人类分子遗传学(Hum MolGenet)》21,3421-3434。
6.Foust KD、Wang X、McGovern VL、Braun L、Bevan AK、Haidet AM、Le TT、Morales PR、Rich MM、Burghes AH、Kaspar BK(2010),通过早期出生后递送SMN来拯救小鼠模型的脊髓性肌萎缩表型(Rescue of the spinal muscular atrophy phenotype in amouse model by early postnatal delivery of SMN)《自然生物技术(Nat.Biotech.)》28,271-274。
7.Fleming JO、Ting JY、Stohlman SA、Weiner LP(1983),在获得和表征小鼠脑脊髓液方面的改进(Improvements in obtaining and characterizing mousecerebrospinal fluid)应用于小鼠肝炎病毒诱导的脑脊髓炎(Application to mousehepatitis virus-induced encephalomyelitis)《神经免疫学杂志(J Neuroimmunol.)》4,129-140。
8.Gao,G.P.和Sena-Esteves,M.(2012).将基因引入到哺乳动物细胞中：病毒载体(Introducing Genes into Mammalian Cells:Viral Vectors)在《分子克隆(MolecularCloning)》,第2卷：实验室手册(A Laboratory Manual)(M.R.Green和J.Sambrook编辑),第1209-1313页,冷泉港实验室出版社(Cold Spring Harbor Laboratory Press),纽约。
9.Rapti K、Louis-Jeune V、Kohlbrenner E、Ishikawa K、Ladage D、ZolotukhinS、Hajjar RJ、Weber(2012),在大量常用动物模型中针对AAV血清型1、2、6和9的中和抗体(Neutralizing antibodies against AAV serotypes 1,2,6,and 9in sea of commonlyused animal models)《分子疗法(Mol.Ther.)》20,73-83。
10.Goulder PJ、Addo MM、Altfeld MA、Rosenberg ES、Tang Y、Govender U、Mngqundaniso N、Annamalai K、Vogel TU、Hammond M、Bunce M、Coovadia HM、Walker BD(2001),通过酶联免疫斑点测定法和胞内细胞因子染色测定法快速定义五种新颖的HLA-A*3002限制的人免疫缺陷病毒特异性细胞毒性T淋巴细胞表位(Rapid definition of fivenovel HLA-A*3002-restricted human immunodeficiency virus-specific cytotoxicT-lymphocyte epitopes by elispot and intracellular cytokine staining assays)《病毒学杂志(J.Virol.)》75,1339-1347。
11.Aumailley,M、L.Bruckner-Tuderman、W.G.Carter、R.Deutzmann、D.Edgar、P.Ekblom、J.Engel、E.Engvall、E.Hohenester、J.C.Jones、H.K.Kleinman、M.P.Marinkovich、G.R.Martin、U.Mayer、G.Meneguzzi、J.H.Miner、K.Miyazaki,M。
12.Patarroyo、M.Paulsson、V.Quaranta、J.R.Sanes、T.Sasaki、K.Sekiguchi、L.M.Sorokin、J.F.Talts、K.Tryggvason、J.Uitto,I.Virtanen、K.von der Mark、U.M.Wewer、Y.Yamada和P.D.Yurchenco,简化的层粘连蛋白命名法(A simplified lamininnomenclature)《基质生物学(Matrix Biol)》,2005.24(5):第326-32页。
13.Jimenez-Mallebrera,C、S.C.Brown、C.A.Sewry和F.Muntoni,先天性肌营养不良：分子和细胞方面(Congenital musculardystrophy:molecular and cellularaspects)《细胞与分子生命科学(Cell Mol Life Sci.)》2005.62(7-8):第809-23页。
14.Sframeli,M、A.Sarkozy、M.Bertoli、G.Astrea、J.Hudson、M.Scoto、R.Mein、M.Yau、R.Phadke、L.Feng、C.Sewry、A.N.S.Fen、C.Longman、G.McCullagh、V.Straub、S.Robb、A.Manzur、K.Bushby和F.Muntoni,英国群体中的先天性肌营养不良：在12年时间段内诊断的大群的临床和分子谱(Congenital muscular dystrophies in the UKpopulation:Clinical and molecular spectrum of a large cohort diagnosed over a12-year period)《神经肌肉病症(Neuromuscul Disord)》,2017.27(9):第793-803页。
15.Allamand,V、Y.Sunada、M.A.Salih、V.Straub,C.O.Ozo、M.H.Al-Turaiki、M.Akbar、T.Kolo,H.Colognato、X.Zhang、L.M.Sorokin、P.D.Yurchenco、K.Tryggvason和K.P.Campbell,在具有内部缺失层粘连蛋白α2-链的两个患者的轻度先天性肌营养不良(Mild congenital muscular dystrophy in two patients with an internallydeleted laminin alpha2-chain)《人类分子遗传学(Hum Mol Genet)》,1997.6(5):第747-52页。
16.Gavassini,B.F.、N.Carboni、J.E.Nielsen、E.R.Danielsen、C.Thomsen、K.Svenstrup、L.Bello、M.A.Maioli、G.Marrosu、A.F.Ticca、M.Mura、M.G.Marrosu、G.Soraru、C.Angelini、J.Vissing和E.Pegoraro,由于LAMA2突变引起的肢带型肌营养不良的临床和分子表征(Clinical and molecular characterization of limb girdlemuscular dystrophy due to LAMA2 mutations)《肌肉神经(Muscle Nerve)》,2011.44(5):第703-9页。
17.Bonnemann,C.G、C.H.Wang、S.Quijano-Roy、N.Deconinck、E.Bertini、A.Ferreiro、F.Muntoni、C.Sewry、C.Beroud、K.D.Mathews、S.A.Moore、J.Bellini、A.Rutkowski和K.N.North,先天性肌营养不良的诊断方法(Diagnostic approach to thecongenital muscular dystrophies)《神经肌肉病症(Neuromuscul Disord)》,2014.24(4):第289-311页。
18.Chan,S.H、A.R.Foley、R.Phadke、A.A.Mathew、M.Pitt、C.Sewry和F.Muntoni,由于LAMA2突变引起的肢带型肌营养不良：由于相关的外周神经病引起的诊断困难(Limbgirdle muscular dystrophy due to LAMA2 mutations:diagnostic difficulties dueto associated peripheral neuropathy)《神经肌肉病症(Neuromuscul Disord)》,2014.24(8):第677-83页。
19.McKee,K.K、D.Harrison、S.Capizzi和P.D.Yurchenco,层粘连蛋白末端球形结构域在基底膜组装中的作用(Role of laminin terminal globular domains inbasement membrane assembly)《生物化学杂志(J Biol Chem)》,2007.282(29):第21437-47页。
20.McKee,K.K、D.H.Yang、R.Patel、Z.L.Chen、S.Strickland、J.Takagi、K.Sekiguchi和P.D.Yurchenco,许旺细胞髓鞘形成需要层粘连蛋白活性的整合(SchwannCell Myelination Requires Integration of Laminin Activities)《细胞科学杂志(JCell Sci)》,2012.125(19):第4609-4619页。PMC3500866
21.McKee,K.K、S.Capizzi和P.D.Yurchenco,合成的层粘连蛋白结合蛋白对基底膜组装的支架形成和粘附作用(Scaffold-forming and adhesive contributions ofsynthetic laminin-binding proteins to basement membrane assembly)《生物化学杂志(J Biol Chem)》,2009.284(13):第8984-8994页。PMC2659255
22.Smirnov,S.P、P.Barzaghi、K.K.McKee、M.A.Ruegg和P.D.Yurchenco,集聚蛋白和基底膜聚糖的LG结构域与层粘连蛋白-2的缀合促进乙酰胆碱受体的聚簇(Conjugationof LG domains of agrins and perlecan to polymerizing laminin-2 promotesacetylcholine receptor clustering)《生物化学杂志(J Biol Chem)》,2005.280(50):第41449-57页。
23.Chang,C.、H.L.Goel、H.Gao、B.Pursell、L.D.Shultz、D.L.Greiner、S.Ingerpuu、M.Patarroyo、S.Cao、E.Lim、J.Mao、K.K.McKee、P.D.Yurchenco和A.M.Mercurio,层粘连蛋白511基质由TAZ调节，并且充当α6Bβ1整联蛋白的配体以维持乳腺癌干细胞(Alaminin 511matrix is regulated by TAZ and functions as the ligandfor the alpha6Bbeta1 integrin to sustain breast cancer stem cells)《基因与发育(Genes Dev)》,2015.29(1):第1-6页。PMC4281560
24.Colombelli,C、M.Palmisano、Y.Eshed-Eisenbach、D.Zambroni、E.Pavoni、C.Ferri、S.Saccucci、S.Nicole、R.Soininen、K.K.McKee、P.D.Yurchenco、E.Peles、L.Wrabetz和M.L.Feltri,基底膜聚糖由营养不良聚糖募集到Ranvier的节点，并且结合聚类分子胶质蛋白(Perlecan is recruited by dystroglycan to nodes of Ranvier andbinds the clustering molecule gliomedin)《细胞生物学杂志(J Cell Biol)》,2015.208(3):第313-29页。PMC4315246
25.Yazlovitskaya、E.M、H.Y.Tseng、O.Viquez、T.Tu、G.Mernaugh、K.K.McKee、K.Riggins、V.Quaranta、A.Pathak、B.D.Carter、P.Yurchenco、A.Sonnenberg、R.T.Bottcher、A.Pozzi和R.Zent,整联蛋白α3β1通过Akt的TRAF6依赖性K63连接的蛋白激酶的聚泛素化调节肾脏的收集管发育(Integrin alpha3beta1 regulates kidneycollecting duct development via TRAF6-dependent K63-linked polyubiquitinationof Akt)《分子细胞生物学(Mol Biol Cell)》,2015.26(10):第1857-74页。PMC4436831
26.Reuten,R.、T.R.Patel、M.McDougall、N.Rama、D.Nikodemus、B.Gibert、J.G.Delcros、C.Prein、M.Meier、S.Metzger、Z.Zhou、J.Kaltenberg、K.K.McKee、T.Bald、T.Tuting、P.Zigrino、V.Djonov、W.Bloch、H.Clausen-Schaumann、E.Poschl、P.D.Yurchenco、M.Ehrbar、P.Mehlen、J.Stetefeld和M.Koch,神经突起生长导向因子-4的结构解码揭示了对成熟基底膜的调节功能(Structural decoding of netrin-4reveals aregulatory function towards mature basement membranes)《自然通讯(Nat Commun)》,2016.7:第13515页。PMC514367
在不脱离本发明的精神和范围的情况下，可以对本发明进行许多修改和变化，如对本领域的技术人员来说是显而易见的。本发明由所附权利要求的条款连同此类权利要求有权获得的等效物的全部范围限定。本文所述的具体实施例(包含以下实例)仅以实例的方式提供，并且不通过其细节限制本发明的范围。
本文引用的所有参考文献均通过引用并入，达到如同每个单独的出版物、数据库条目(例如，Genbank序列或GeneID条目)、专利申请或专利被专门且单独地指示通过引用并入的相同程度。根据37 C.F.R.§1.57(b)(1)，申请人旨在通过引用并入本说明以涉及每个单独的出版物、数据库条目(例如，Genbank序列或GeneID条目)、专利申请或专利，所述文献中的每一个根据37 C.F.R.§1.57(b)(2)明确鉴定，即使此类引用不与通过引用并入的专有说明紧密相邻。在说明书中包含通过引用并入的专有说明(如果有的话)并不以任何方式削弱通过引用并入的此一般性声明。本文引用参考文献并非旨在承认所述参考文献是相关的现有技术，也不构成对这些出版物或文献的内容或日期的任何承认。
本发明不限于本文所述的具体实施例的范围。事实上，除了本文所述的那些之外，本发明的各种修改对于本领域的技术人员来说将从前面的描述和附图中变得显而易见。此类修改旨在落入所附权利要求书的范围内。
前述书面说明书被认为足以使本领域的技术人员能够实践本发明。除了本文所示出和所描述的那些之外，本发明的各种修改对于本领域的技术人员来说将从前面的描述中变得显而易见，并且落入所附权利要求的范围内。
序列表
<110> 罗特格斯新泽西州立大学（Rutgers, The State University of New Jersey）
<120> AAV相容的层粘连蛋白—连接子聚合蛋白
<130> 10491/006542-WO0
<150> 62/668,664
<151> 2018-05-08
<160> 170
<170> PatentIn版本3.5
<210> 1
<211> 3009
<212> DNA
<213> 人工序列
<220>
<223> 在AAV构建体中未使用标签的alphaLNNdDeltaG2开放阅读框
<400> 1
atgagggcct ggatcttctt tctcctttgc ctggccggga gggctctggc acagcagaga 60
ggcttgttcc ctgccattct caacctggcc accaatgccc acatcagcgc caatgctacc 120
tgtggagaga aggggcctga gatgttctgc aaactcgtgg agcacgtgcc gggccggcct 180
gttcgacacg cccaatgccg ggtctgtgac ggtaacagta cgaatcctag agagcgccat 240
ccgatatcac acgcaatcga tggcaccaac aactggtggc agagccccag tattcagaat 300
gggagagagt atcactgggt cactgtcacc ctggacttac ggcaggtctt tcaagttgca 360
tacatcatca ttaaagctgc caatgcccct cggcctggaa actggatttt ggagcgctcc 420
gtggatggcg tcaagttcaa accctggcag tactatgccg tcagcgatac agagtgtttg 480
acccgctaca aaataactcc acggcgggga cctcccactt acagagcaga caacgaagtc 540
atctgcacct cgtattattc aaagctggtg ccacttgaac atggagagat tcacacatca 600
ctcatcaatg gcagacccag cgctgacgac ccctcacccc agttgctgga attcacctca 660
gcacggtaca ttcgccttcg tcttcagcgc atcagaacac tcaacgcaga cctcatgacc 720
cttagccatc gggacctcag agaccttgac cccattgtca caagacgtta ttactattcg 780
ataaaagaca tttccgttgg aggcatgtgc atttgctacg gccatgccag cagctgcccg 840
tgggatgaag aagcaaagca actacagtgt cagtgtgaac acaatacgtg tggcgagagc 900
tgcgacaggt gctgtcctgg ctaccatcag cagccctgga ggcccggaac catttcctcc 960
ggcaacgagt gtgaggaatg caactgtcac aacaaagcca aagattgtta ctatgacagc 1020
agtgttgcaa aggagaggag aagcctgaac actgccgggc agtacagtgg aggaggggtt 1080
tgtgtcaact gctcgcagaa taccacaggg atcaactgtg aaacctgtat cgaccagtat 1140
tacagacctc acaaggtatc tccttatgat gaccaccctt gccgtccctg taactgtgac 1200
cctgtggggt ctctgagttc tgtctgtatc aaggatgacc gccatgccga tttagccaat 1260
ggaaagtggc caggtcagtg tccatgtagg aaaggttatg ctggagataa atgtgaccgc 1320
tgccagtttg gctaccgggg tttcccaaat tgcatcccct gtgactgcag gactgtcggc 1380
agcctgaatg aggatccatg catagagccg tgtctttgta agaaaaatgt tgagggtaag 1440
aactgtgatc gctgcaagcc aggattctac aacttgaagg aacgaaaccc cgagggctgc 1500
tccgagtgct tctgcttcgg tgtctctggt gtctgtccca tcaactactg tgaaactggt 1560
ctccacaact gtgatatccc ccagcgagcc cagtgcatct atatgggtgg ttcctcctac 1620
acctgctcct gtctgcctgg cttctctggg gatggcagag cctgccgaga cgtggatgaa 1680
tgccagcaca gccgatgtca ccccgatgcc ttctgctaca acacaccagg ctctttcaca 1740
tgtcagtgca agcctggcta tcagggggat ggcttccgat gcatgcccgg agaggtgagc 1800
aaaacccggt gtcaactgga acgagagcac atccttggag cagccggcgg ggcagatgca 1860
cagcggccca ccctgcaggg gatgtttgtg cctcagtgtg atgaatatgg acactatgta 1920
cccacccagt gtcaccacag cactggctac tgctggtgtg tggaccgaga tggtcgggag 1980
ctggagggta gccgtacccc acctgggatg aggcccccgt gtctgagtac agtggctcct 2040
cctattcacc agggaccagt agtacctaca gctgtcatcc ccctgcctcc agggacacac 2100
ttactctttg ctcagactgg aaagattgaa cgcctgcccc tggaaagaaa caccatgaag 2160
aagacagaac gcaaggcctt tctccatatc cctgcaaaag tcatcattgg actggccttt 2220
gactgcgtgg acaaggtggt ttactggaca gacatcagcg agccttccat tgggagagcc 2280
agcctccacg gtggagagcc aaccaccatc attcgacaag atcttggaag ccctgaaggc 2340
attgcccttg accatcttgg tcgaaccatc ttctggacgg actctcagtt ggatcgaata 2400
gaagttgcaa agatggatgg cacccagcgc cgagtgctgt ttgacacggg tttggtgaat 2460
cccagaggca ttgtgacaga ccccgtaaga gggaaccttt attggacaga ttggaacaga 2520
gataatccca aaattgagac ttctcacatg gatggcacca accggaggat tctcgcacag 2580
gacaacctgg gcttgcccaa tggtctgacc tttgatgcat tctcatctca gctttgctgg 2640
gtggatgcag gcacccatag ggcagaatgc ctgaacccag ctcagcctgg cagacgcaaa 2700
gttctcgaag ggctccagta tcctttcgct gtgactagct atgggaagaa tttgtactac 2760
acagactgga agacgaattc agtgattgcc atggaccttg ctatatccaa agagatggat 2820
accttccacc cacacaagca gacccggcta tatggcatca ccatcgccct gtcccagtgt 2880
ccccaaggcc acaattactg ctcagtgaat aatggtggat gtacccacct ctgcttgccc 2940
actccaggga gcaggacctg ccgatgtcct gacaacaccc tgggagttga ctgcattgaa 3000
cggaaatga 3009
<210> 2
<211> 20
<212> DNA
<213> 人工序列
<220>
<223> F1noG2 1F
<400> 2
ctgggtcact gtcaccctgg 20
<210> 3
<211> 30
<212> DNA
<213> 人工序列
<220>
<223> noG2 2R
<400> 3
atggattctg aagacagaca ccagagacac 30
<210> 4
<211> 29
<212> DNA
<213> 人工序列
<220>
<223> no G2 2F
<400> 4
ctggtgtctg tcttcagaat ccatgctac 29
<210> 5
<211> 24
<212> DNA
<213> 人工序列
<220>
<223> F1 no G2 1R
<400> 5
gaaggcacag tcgaggctga tcag 24
<210> 6
<211> 30
<212> DNA
<213> 人工序列
<220>
<223> Bam shnoG2 1F
<400> 6
cggcagcctg aatgaggatc catgcataga 30
<210> 7
<211> 25
<212> DNA
<213> 人工序列
<220>
<223> shnoG2 2R
<400> 7
cacagtagtt gatgggacag acacc 25
<210> 8
<211> 26
<212> DNA
<213> 人工序列
<220>
<223> shnoG2 2F
<400> 8
gtctctggtg tctgtcccat caacta 26
<210> 9
<211> 30
<212> DNA
<213> 人工序列
<220>
<223> sse shnoG2 1R
<400> 9
gaggcacaaa catcccctgc agggtgggcc 30
<210> 10
<211> 4639
<212> DNA
<213> 人工序列
<220>
<223> pAAV-MCS表达载体
<400> 10
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt 60
ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact 120
aggggttcct gcggccgcac gcgtggagct agttattaat agtaatcaat tacggggtca 180
ttagttcata gcccatatat ggagttccgc gttacataac ttacggtaaa tggcccgcct 240
ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcccatagta 300
acgtcaatag ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac 360
ttggcagtac atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt 420
aaatggcccg cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag 480
tacatctacg tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat 540
gggcgtggat agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgtcaat 600
gggagtttgt tttgcaccaa aatcaacggg actttccaaa atgtcgtaac aactccgccc 660
cattgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc agagctcgtt 720
tagtgaaccg tcagatcgcc tggagacgcc atccacgctg ttttgacctc catagaagac 780
accgggaccg atccagcctc cgcggattcg aatcccggcc gggaacggtg cattggaacg 840
cggattcccc gtgccaagag tgacgtaagt accgcctata gagtctatag gcccacaaaa 900
aatgctttct tcttttaata tacttttttg tttatcttat ttctaatact ttccctaatc 960
tctttctttc agggcaataa tgatacaatg tatcatgcct ctttgcacca ttctaaagaa 1020
taacagtgat aatttctggg ttaaggcaat agcaatattt ctgcatataa atatttctgc 1080
atataaattg taactgatgt aagaggtttc atattgctaa tagcagctac aatccagcta 1140
ccattctgct tttattttat ggttgggata aggctggatt attctgagtc caagctaggc 1200
ccttttgcta atcatgttca tacctcttat cttcctccca cagctcctgg gcaacgtgct 1260
ggtctgtgtg ctggcccatc actttggcaa agaattggga ttcgaacatc gattgaattc 1320
cccggggatc ctctagagtc gacctgcaga agcttgcctc gagcagcgct gctcgagaga 1380
tctacgggtg gcatccctgt gacccctccc cagtgcctct cctggccctg gaagttgcca 1440
ctccagtgcc caccagcctt gtcctaataa aattaagttg catcattttg tctgactagg 1500
tgtccttcta taatattatg gggtggaggg gggtggtatg gagcaagggg caagttggga 1560
agacaacctg tagggcctgc ggggtctatt gggaaccaag ctggagtgca gtggcacaat 1620
cttggctcac tgcaatctcc gcctcctggg ttcaagcgat tctcctgcct cagcctcccg 1680
agttgttggg attccaggca tgcatgacca ggctcagcta atttttgttt ttttggtaga 1740
gacggggttt caccatattg gccaggctgg tctccaactc ctaatctcag gtgatctacc 1800
caccttggcc tcccaaattg ctgggattac aggcgtgaac cactgctccc ttccctgtcc 1860
ttctgatttt gtaggtaacc acgtgcggac cgagcggccg caggaacccc tagtgatgga 1920
gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc 1980
ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gctgcctgca 2040
ggggcgcctg atgcggtatt ttctccttac gcatctgtgc ggtatttcac accgcatacg 2100
tcaaagcaac catagtacgc gccctgtagc ggcgcattaa gcgcggcggg tgtggtggtt 2160
acgcgcagcg tgaccgctac acttgccagc gccctagcgc ccgctccttt cgctttcttc 2220
ccttcctttc tcgccacgtt cgccggcttt ccccgtcaag ctctaaatcg ggggctccct 2280
ttagggttcc gatttagtgc tttacggcac ctcgacccca aaaaacttga tttgggtgat 2340
ggttcacgta gtgggccatc gccctgatag acggtttttc gccctttgac gttggagtcc 2400
acgttcttta atagtggact cttgttccaa actggaacaa cactcaaccc tatctcgggc 2460
tattcttttg atttataagg gattttgccg atttcggcct attggttaaa aaatgagctg 2520
atttaacaaa aatttaacgc gaattttaac aaaatattaa cgtttacaat tttatggtgc 2580
actctcagta caatctgctc tgatgccgca tagttaagcc agccccgaca cccgccaaca 2640
cccgctgacg cgccctgacg ggcttgtctg ctcccggcat ccgcttacag acaagctgtg 2700
accgtctccg ggagctgcat gtgtcagagg ttttcaccgt catcaccgaa acgcgcgaga 2760
cgaaagggcc tcgtgatacg cctattttta taggttaatg tcatgataat aatggtttct 2820
tagacgtcag gtggcacttt tcggggaaat gtgcgcggaa cccctatttg tttatttttc 2880
taaatacatt caaatatgta tccgctcatg agacaataac cctgataaat gcttcaataa 2940
tattgaaaaa ggaagagtat gagtattcaa catttccgtg tcgcccttat tccctttttt 3000
gcggcatttt gccttcctgt ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct 3060
gaagatcagt tgggtgcacg agtgggttac atcgaactgg atctcaacag cggtaagatc 3120
cttgagagtt ttcgccccga agaacgtttt ccaatgatga gcacttttaa agttctgcta 3180
tgtggcgcgg tattatcccg tattgacgcc gggcaagagc aactcggtcg ccgcatacac 3240
tattctcaga atgacttggt tgagtactca ccagtcacag aaaagcatct tacggatggc 3300
atgacagtaa gagaattatg cagtgctgcc ataaccatga gtgataacac tgcggccaac 3360
ttacttctga caacgatcgg aggaccgaag gagctaaccg cttttttgca caacatgggg 3420
gatcatgtaa ctcgccttga tcgttgggaa ccggagctga atgaagccat accaaacgac 3480
gagcgtgaca ccacgatgcc tgtagcaatg gcaacaacgt tgcgcaaact attaactggc 3540
gaactactta ctctagcttc ccggcaacaa ttaatagact ggatggaggc ggataaagtt 3600
gcaggaccac ttctgcgctc ggcccttccg gctggctggt ttattgctga taaatctgga 3660
gccggtgagc gtgggtctcg cggtatcatt gcagcactgg ggccagatgg taagccctcc 3720
cgtatcgtag ttatctacac gacggggagt caggcaacta tggatgaacg aaatagacag 3780
atcgctgaga taggtgcctc actgattaag cattggtaac tgtcagacca agtttactca 3840
tatatacttt agattgattt aaaacttcat ttttaattta aaaggatcta ggtgaagatc 3900
ctttttgata atctcatgac caaaatccct taacgtgagt tttcgttcca ctgagcgtca 3960
gaccccgtag aaaagatcaa aggatcttct tgagatcctt tttttctgcg cgtaatctgc 4020
tgcttgcaaa caaaaaaacc accgctacca gcggtggttt gtttgccgga tcaagagcta 4080
ccaactcttt ttccgaaggt aactggcttc agcagagcgc agataccaaa tactgtcctt 4140
ctagtgtagc cgtagttagg ccaccacttc aagaactctg tagcaccgcc tacatacctc 4200
gctctgctaa tcctgttacc agtggctgct gccagtggcg ataagtcgtg tcttaccggg 4260
ttggactcaa gacgatagtt accggataag gcgcagcggt cgggctgaac ggggggttcg 4320
tgcacacagc ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag 4380
ctatgagaaa gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc 4440
agggtcggaa caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat 4500
agtcctgtcg ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg 4560
gggcggagcc tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc 4620
tggccttttg ctcacatgt 4639
<210> 11
<211> 130
<212> DNA
<213> 人工序列
<220>
<223> 5' ITR
<400> 11
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt 60
ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact 120
aggggttcct 130
<210> 12
<211> 663
<212> DNA
<213> 人工序列
<220>
<223> CMV启动子
<400> 12
acgcgtggag ctagttatta atagtaatca attacggggt cattagttca tagcccatat 60
atggagttcc gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac 120
ccccgcccat tgacgtcaat aatgacgtat gttcccatag taacgtcaat agggactttc 180
cattgacgtc aatgggtgga gtatttacgg taaactgccc acttggcagt acatcaagtg 240
tatcatatgc caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat 300
tatgcccagt acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc 360
atcgctatta ccatggtgat gcggttttgg cagtacatca atgggcgtgg atagcggttt 420
gactcacggg gatttccaag tctccacccc attgacgtca atgggagttt gttttgcacc 480
aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 540
gtaggcgtgt acggtgggag gtctatataa gcagagctcg tttagtgaac cgtcagatcg 600
cctggagacg ccatccacgc tgttttgacc tccatagaag acaccgggac cgatccagcc 660
tcc 663
<210> 13
<211> 493
<212> DNA
<213> 人工序列
<220>
<223> 人β球蛋白内含子
<400> 13
cgaatcccgg ccgggaacgg tgcattggaa cgcggattcc ccgtgccaag agtgacgtaa 60
gtaccgccta tagagtctat aggcccacaa aaaatgcttt cttcttttaa tatacttttt 120
tgtttatctt atttctaata ctttccctaa tctctttctt tcagggcaat aatgatacaa 180
tgtatcatgc ctctttgcac cattctaaag aataacagtg ataatttctg ggttaaggca 240
atagcaatat ttctgcatat aaatatttct gcatataaat tgtaactgat gtaagaggtt 300
tcatattgct aatagcagct acaatccagc taccattctg cttttatttt atggttggga 360
taaggctgga ttattctgag tccaagctag gcccttttgc taatcatgtt catacctctt 420
atcttcctcc cacagctcct gggcaacgtg ctggtctgtg tgctggccca tcactttggc 480
aaagaattgg gat 493
<210> 14
<211> 76
<212> DNA
<213> 人工序列
<220>
<223> MCS
<400> 14
atcgattgaa ttccccgggg atcctctaga gtcgacctgc agaagcttgc ctcgagcagc 60
gctgctcgag agatct 76
<210> 15
<211> 479
<212> DNA
<213> 人工序列
<220>
<223> PolyA
<400> 15
acgggtggca tccctgtgac ccctccccag tgcctctcct ggccctggaa gttgccactc 60
cagtgcccac cagccttgtc ctaataaaat taagttgcat cattttgtct gactaggtgt 120
ccttctataa tattatgggg tggagggggg tggtatggag caaggggcaa gttgggaaga 180
caacctgtag ggcctgcggg gtctattggg aaccaagctg gagtgcagtg gcacaatctt 240
ggctcactgc aatctccgcc tcctgggttc aagcgattct cctgcctcag cctcccgagt 300
tgttgggatt ccaggcatgc atgaccaggc tcagctaatt tttgtttttt tggtagagac 360
ggggtttcac catattggcc aggctggtct ccaactccta atctcaggtg atctacccac 420
cttggcctcc caaattgctg ggattacagg cgtgaaccac tgctcccttc cctgtcctt 479
<210> 16
<211> 141
<212> DNA
<213> 人工序列
<220>
<223> 3' ITR
<400> 16
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg 60
ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc 120
gagcgcgcag ctgcctgcag g 141
<210> 17
<211> 7333
<212> DNA
<213> 人工序列
<220>
<223> pAAV-DJ载体
<400> 17
ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt gacgagcatc 60
tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg gagttgccgc 120
cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg gccgagaagc 180
tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag gcccttttct 240
ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg gaaaccaccg 300
gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa ctgattcaga 360
gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca aagaccagaa 420
atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat tacttgctcc 480
ccaaaaccca gcctgagctc cagtgggcgt ggactaatat ggaacagtat ttaagcgcct 540
gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac gtgtcgcaga 600
cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg atcagatcaa 660
aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg attacctcgg 720
agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg gcctccaact 780
cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc ctgactaaaa 840
ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc aatcggattt 900
ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc tttctgggat 960
gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct gcaactaccg 1020
ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg tgcgtaaact 1080
ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc tggtgggagg 1140
aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctcgga ggaagcaagg 1200
tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc gtgatcgtca 1260
cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc gaacaccagc 1320
agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat catgactttg 1380
ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat cacgtggttg 1440
aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc gcccccagtg 1500
acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca tcgacgtcag 1560
acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct cgtcacgtgg 1620
gcatgaatct gatgctgttt ccctgcagac aatgcgagag aatgaatcag aattcaaata 1680
tctgcttcac tcacggacag aaagactgtt tagagtgctt tcccgtgtca gaatctcaac 1740
ccgtttctgt cgtcaaaaag gcgtatcaga aactgtgcta cattcatcat atcatgggaa 1800
aggtgccaga cgcttgcact gcctgcgatc tggtcaatgt ggatttggat gactgcatct 1860
ttgaacaata aatgatttaa atcaggtatg gctgccgatg gttatcttcc agattggctc 1920
gaggacactc tctctgaagg aataagacag tggtggaagc tcaaacctgg cccaccacca 1980
ccaaagcccg cagagcggca taaggacgac agcaggggtc ttgtgcttcc tgggtacaag 2040
tacctcggac ccttcaacgg actcgacaag ggagagccgg tcaacgaggc agacgccgcg 2100
gccctcgagc acgacaaagc ctacgaccgg cagctcgaca gcggagacaa cccgtacctc 2160
aagtacaacc acgccgacgc cgagttccag gagcggctca aagaagatac gtcttttggg 2220
ggcaacctcg ggcgagcagt cttccaggcc aaaaagaggc ttcttgaacc tcttggtctg 2280
gttgaggaag cggctaagac ggctcctgga aagaagaggc ctgtagagca ctctcctgtg 2340
gagccagact cctcctcggg aaccggaaag gcgggccagc agcctgcaag aaaaagattg 2400
aattttggtc agactggaga cgcagactca gtcccagacc ctcaaccaat cggagaacct 2460
cccgcagccc cctcaggtgt gggatctctt acaatggctg caggcggtgg cgcaccaatg 2520
gcagacaata acgagggcgc cgacggagtg ggtaattcct cgggaaattg gcattgcgat 2580
tccacatgga tgggcgacag agtcatcacc accagcaccc gaacctgggc cctgcccacc 2640
tacaacaacc acctctacaa gcaaatctcc aacagcacat ctggaggatc ttcaaatgac 2700
aacgcctact tcggctacag caccccctgg gggtattttg actttaacag attccactgc 2760
cacttttcac cacgtgactg gcagcgactc atcaacaaca actggggatt ccggcccaag 2820
agactcagct tcaagctctt caacatccag gtcaaggagg tcacgcagaa tgaaggcacc 2880
aagaccatcg ccaataacct caccagcacc atccaggtgt ttacggactc ggagtaccag 2940
ctgccgtacg ttctcggctc tgcccaccag ggctgcctgc ctccgttccc ggcggacgtg 3000
ttcatgattc cccagtacgg ctacctaaca ctcaacaacg gtagtcaggc cgtgggacgc 3060
tcctccttct actgcctgga atactttcct tcgcagatgc tgagaaccgg caacaacttc 3120
cagtttactt acaccttcga ggacgtgcct ttccacagca gctacgccca cagccagagc 3180
ttggaccggc tgatgaatcc tctgattgac cagtacctgt actacttgtc tcggactcaa 3240
acaacaggag gcacgacaaa tacgcagact ctgggcttca gccaaggtgg gcctaataca 3300
atggccaatc aggcaaagaa ctggctgcca ggaccctgtt accgccagca gcgagtatca 3360
aagacatctg cggataacaa caacagtgaa tactcgtgga ctggagctac caagtaccac 3420
ctcaatggca gagactctct ggtgaatccg ggcccggcca tggcaagcca caaggacgat 3480
gaagaaaagt tttttcctca gagcggggtt ctcatctttg ggaagcaagg ctcagagaaa 3540
acaaatgtgg acattgaaaa ggtcatgatt acagacgaag aggaaatcag gacaaccaat 3600
cccgtggcta cggagcagta tggttctgta tctaccaacc tccagagagg caacagacaa 3660
gcagctaccg cagatgtcaa cacacaaggc gttcttccag gcatggtctg gcaggacaga 3720
gatgtgtacc ttcaggggcc catctgggca aagattccac acacggacgg acattttcac 3780
ccctctcccc tcatgggtgg attcggactt aaacaccctc cgcctcagat cctgatcaag 3840
aacacgcctg tacctgcgga tcctccgacc accttcaacc agtcaaagct gaactctttc 3900
atcacccagt attctactgg ccaagtcagc gtggagatcg agtgggagct gcagaaggaa 3960
aacagcaagc gctggaaccc cgagatccag tacacctcca actactacaa atctacaagt 4020
gtggactttg ctgttaatac agaaggcgtg tactctgaac cccgccccat tggcacccgt 4080
tacctcaccc gtaatctgta attgcctgtt aatcaataaa ccggttgatt cgtttcagtt 4140
gaactttggt ctctgcgaag ggcgaattcg tttaaacctg caggactaga ggtcctgtat 4200
tagaggtcac gtgagtgttt tgcgacattt tgcgacacca tgtggtcacg ctgggtattt 4260
aagcccgagt gagcacgcag ggtctccatt ttgaagcggg aggtttgaac gcgcagccgc 4320
caagccgaat tctgcagata tccatcacac tggcggccgc tcgactagag cggccgccac 4380
cgcggtggag ctccagcttt tgttcccttt agtgagggtt aattgcgcgc ttggcgtaat 4440
catggtcata gctgtttcct gtgtgaaatt gttatccgct cacaattcca cacaacatac 4500
gagccggaag cataaagtgt aaagcctggg gtgcctaatg agtgagctaa ctcacattaa 4560
ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat 4620
gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc 4680
tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg 4740
cggtaatacg gttatccaca gaatcagggg ataacgcagg aaagaacatg tgagcaaaag 4800
gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc 4860
gcccccctga cgagcatcac aaaaatcgac gctcaagtca gaggtggcga aacccgacag 4920
gactataaag ataccaggcg tttccccctg gaagctccct cgtgcgctct cctgttccga 4980
ccctgccgct taccggatac ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc 5040
atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg 5100
tgcacgaacc ccccgttcag cccgaccgct gcgccttatc cggtaactat cgtcttgagt 5160
ccaacccggt aagacacgac ttatcgccac tggcagcagc cactggtaac aggattagca 5220
gagcgaggta tgtaggcggt gctacagagt tcttgaagtg gtggcctaac tacggctaca 5280
ctagaagaac agtatttggt atctgcgctc tgctgaagcc agttaccttc ggaaaaagag 5340
ttggtagctc ttgatccggc aaacaaacca ccgctggtag cggtggtttt tttgtttgca 5400
agcagcagat tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg 5460
ggtctgacgc tcagtggaac gaaaactcac gttaagggat tttggtcatg agattatcaa 5520
aaaggatctt cacctagatc cttttaaatt aaaaatgaag ttttaaatca atctaaagta 5580
tatatgagta aacttggtct gacagttacc aatgcttaat cagtgaggca cctatctcag 5640
cgatctgtct atttcgttca tccatagttg cctgactccc cgtcgtgtag ataactacga 5700
tacgggaggg cttaccatct ggccccagtg ctgcaatgat accgcgagac ccacgctcac 5760
cggctccaga tttatcagca ataaaccagc cagccggaag ggccgagcgc agaagtggtc 5820
ctgcaacttt atccgcctcc atccagtcta ttaattgttg ccgggaagct agagtaagta 5880
gttcgccagt taatagtttg cgcaacgttg ttgccattgc tacaggcatc gtggtgtcac 5940
gctcgtcgtt tggtatggct tcattcagct ccggttccca acgatcaagg cgagttacat 6000
gatcccccat gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc gttgtcagaa 6060
gtaagttggc cgcagtgtta tcactcatgg ttatggcagc actgcataat tctcttactg 6120
tcatgccatc cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag tcattctgag 6180
aatagtgtat gcggcgaccg agttgctctt gcccggcgtc aatacgggat aataccgcgc 6240
cacatagcag aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg cgaaaactct 6300
caaggatctt accgctgttg agatccagtt cgatgtaacc cactcgtgca cccaactgat 6360
cttcagcatc ttttactttc accagcgttt ctgggtgagc aaaaacagga aggcaaaatg 6420
ccgcaaaaaa gggaataagg gcgacacgga aatgttgaat actcatactc ttcctttttc 6480
aatattattg aagcatttat cagggttatt gtctcatgag cggatacata tttgaatgta 6540
tttagaaaaa taaacaaata ggggttccgc gcacatttcc ccgaaaagtg ccacctaaat 6600
tgtaagcgtt aatattttgt taaaattcgc gttaaatttt tgttaaatca gctcattttt 6660
taaccaatag gccgaaatcg gcaaaatccc ttataaatca aaagaataga ccgagatagg 6720
gttgagtgtt gttccagttt ggaacaagag tccactatta aagaacgtgg actccaacgt 6780
caaagggcga aaaaccgtct atcagggcga tggcccacta cgtgaaccat caccctaatc 6840
aagttttttg gggtcgaggt gccgtaaagc actaaatcgg aaccctaaag ggagcccccg 6900
atttagagct tgacggggaa agccggcgaa cgtggcgaga aaggaaggga agaaagcgaa 6960
aggagcgggc gctagggcgc tggcaagtgt agcggtcacg ctgcgcgtaa ccaccacacc 7020
cgccgcgctt aatgcgccgc tacagggcgc gtcccattcg ccattcaggc tgcgcaactg 7080
ttgggaaggg cgatcggtgc gggcctcttc gctattacgc cagctggcga aagggggatg 7140
tgctgcaagg cgattaagtt gggtaacgcc agggttttcc cagtcacgac gttgtaaaac 7200
gacggccagt gagcgcgcgt aatacgactc actatagggc gaattgggta ccgggccccc 7260
cctcgatcga ggtcgacggt atcgggggag ctcgcagggt ctccattttg aagcgggagg 7320
tttgaacgcg cag 7333
<210> 18
<211> 1866
<212> DNA
<213> 人工序列
<220>
<223> AAV-2 Rep基因
<400> 18
atgccggggt tttacgagat tgtgattaag gtccccagcg accttgacga gcatctgccc 60
ggcatttctg acagctttgt gaactgggtg gccgagaagg aatgggagtt gccgccagat 120
tctgacatgg atctgaatct gattgagcag gcacccctga ccgtggccga gaagctgcag 180
cgcgactttc tgacggaatg gcgccgtgtg agtaaggccc cggaggccct tttctttgtg 240
caatttgaga agggagagag ctacttccac atgcacgtgc tcgtggaaac caccggggtg 300
aaatccatgg ttttgggacg tttcctgagt cagattcgcg aaaaactgat tcagagaatt 360
taccgcggga tcgagccgac tttgccaaac tggttcgcgg tcacaaagac cagaaatggc 420
gccggaggcg ggaacaaggt ggtggatgag tgctacatcc ccaattactt gctccccaaa 480
acccagcctg agctccagtg ggcgtggact aatatggaac agtatttaag cgcctgtttg 540
aatctcacgg agcgtaaacg gttggtggcg cagcatctga cgcacgtgtc gcagacgcag 600
gagcagaaca aagagaatca gaatcccaat tctgatgcgc cggtgatcag atcaaaaact 660
tcagccaggt acatggagct ggtcgggtgg ctcgtggaca aggggattac ctcggagaag 720
cagtggatcc aggaggacca ggcctcatac atctccttca atgcggcctc caactcgcgg 780
tcccaaatca aggctgcctt ggacaatgcg ggaaagatta tgagcctgac taaaaccgcc 840
cccgactacc tggtgggcca gcagcccgtg gaggacattt ccagcaatcg gatttataaa 900
attttggaac taaacgggta cgatccccaa tatgcggctt ccgtctttct gggatgggcc 960
acgaaaaagt tcggcaagag gaacaccatc tggctgtttg ggcctgcaac taccgggaag 1020
accaacatcg cggaggccat agcccacact gtgcccttct acgggtgcgt aaactggacc 1080
aatgagaact ttcccttcaa cgactgtgtc gacaagatgg tgatctggtg ggaggagggg 1140
aagatgaccg ccaaggtcgt ggagtcggcc aaagccattc tcggaggaag caaggtgcgc 1200
gtggaccaga aatgcaagtc ctcggcccag atagacccga ctcccgtgat cgtcacctcc 1260
aacaccaaca tgtgcgccgt gattgacggg aactcaacga ccttcgaaca ccagcagccg 1320
ttgcaagacc ggatgttcaa atttgaactc acccgccgtc tggatcatga ctttgggaag 1380
gtcaccaagc aggaagtcaa agactttttc cggtgggcaa aggatcacgt ggttgaggtg 1440
gagcatgaat tctacgtcaa aaagggtgga gccaagaaaa gacccgcccc cagtgacgca 1500
gatataagtg agcccaaacg ggtgcgcgag tcagttgcgc agccatcgac gtcagacgcg 1560
gaagcttcga tcaactacgc agacaggtac caaaacaaat gttctcgtca cgtgggcatg 1620
aatctgatgc tgtttccctg cagacaatgc gagagaatga atcagaattc aaatatctgc 1680
ttcactcacg gacagaaaga ctgtttagag tgctttcccg tgtcagaatc tcaacccgtt 1740
tctgtcgtca aaaaggcgta tcagaaactg tgctacattc atcatatcat gggaaaggtg 1800
ccagacgctt gcactgcctg cgatctggtc aatgtggatt tggatgactg catctttgaa 1860
caataa 1866
<210> 19
<211> 2214
<212> DNA
<213> 人工序列
<220>
<223> AAV-DJ Cap基因
<400> 19
atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60
cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120
gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180
aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa agcctacgac 240
cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgccgagttc 300
caggagcggc tcaaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360
gccaaaaaga ggcttcttga acctcttggt ctggttgagg aagcggctaa gacggctcct 420
ggaaagaaga ggcctgtaga gcactctcct gtggagccag actcctcctc gggaaccgga 480
aaggcgggcc agcagcctgc aagaaaaaga ttgaattttg gtcagactgg agacgcagac 540
tcagtcccag accctcaacc aatcggagaa cctcccgcag ccccctcagg tgtgggatct 600
cttacaatgg ctgcaggcgg tggcgcacca atggcagaca ataacgaggg cgccgacgga 660
gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc 720
accaccagca cccgaacctg ggccctgccc acctacaaca accacctcta caagcaaatc 780
tccaacagca catctggagg atcttcaaat gacaacgcct acttcggcta cagcaccccc 840
tgggggtatt ttgactttaa cagattccac tgccactttt caccacgtga ctggcagcga 900
ctcatcaaca acaactgggg attccggccc aagagactca gcttcaagct cttcaacatc 960
caggtcaagg aggtcacgca gaatgaaggc accaagacca tcgccaataa cctcaccagc 1020
accatccagg tgtttacgga ctcggagtac cagctgccgt acgttctcgg ctctgcccac 1080
cagggctgcc tgcctccgtt cccggcggac gtgttcatga ttccccagta cggctaccta 1140
acactcaaca acggtagtca ggccgtggga cgctcctcct tctactgcct ggaatacttt 1200
ccttcgcaga tgctgagaac cggcaacaac ttccagttta cttacacctt cgaggacgtg 1260
cctttccaca gcagctacgc ccacagccag agcttggacc ggctgatgaa tcctctgatt 1320
gaccagtacc tgtactactt gtctcggact caaacaacag gaggcacgac aaatacgcag 1380
actctgggct tcagccaagg tgggcctaat acaatggcca atcaggcaaa gaactggctg 1440
ccaggaccct gttaccgcca gcagcgagta tcaaagacat ctgcggataa caacaacagt 1500
gaatactcgt ggactggagc taccaagtac cacctcaatg gcagagactc tctggtgaat 1560
ccgggcccgg ccatggcaag ccacaaggac gatgaagaaa agttttttcc tcagagcggg 1620
gttctcatct ttgggaagca aggctcagag aaaacaaatg tggacattga aaaggtcatg 1680
attacagacg aagaggaaat caggacaacc aatcccgtgg ctacggagca gtatggttct 1740
gtatctacca acctccagag aggcaacaga caagcagcta ccgcagatgt caacacacaa 1800
ggcgttcttc caggcatggt ctggcaggac agagatgtgt accttcaggg gcccatctgg 1860
gcaaagattc cacacacgga cggacatttt cacccctctc ccctcatggg tggattcgga 1920
cttaaacacc ctccgcctca gatcctgatc aagaacacgc ctgtacctgc ggatcctccg 1980
accaccttca accagtcaaa gctgaactct ttcatcaccc agtattctac tggccaagtc 2040
agcgtggaga tcgagtggga gctgcagaag gaaaacagca agcgctggaa ccccgagatc 2100
cagtacacct ccaactacta caaatctaca agtgtggact ttgctgttaa tacagaaggc 2160
gtgtactctg aaccccgccc cattggcacc cgttacctca cccgtaatct gtaa 2214
<210> 20
<211> 11635
<212> DNA
<213> 人工序列
<220>
<223> p辅助载体
<400> 20
ggtacccaac tccatgctta acagtcccca ggtacagccc accctgcgtc gcaaccagga 60
acagctctac agcttcctgg agcgccactc gccctacttc cgcagccaca gtgcgcagat 120
taggagcgcc acttcttttt gtcacttgaa aaacatgtaa aaataatgta ctaggagaca 180
ctttcaataa aggcaaatgt ttttatttgt acactctcgg gtgattattt accccccacc 240
cttgccgtct gcgccgttta aaaatcaaag gggttctgcc gcgcatcgct atgcgccact 300
ggcagggaca cgttgcgata ctggtgttta gtgctccact taaactcagg cacaaccatc 360
cgcggcagct cggtgaagtt ttcactccac aggctgcgca ccatcaccaa cgcgtttagc 420
aggtcgggcg ccgatatctt gaagtcgcag ttggggcctc cgccctgcgc gcgcgagttg 480
cgatacacag ggttgcagca ctggaacact atcagcgccg ggtggtgcac gctggccagc 540
acgctcttgt cggagatcag atccgcgtcc aggtcctccg cgttgctcag ggcgaacgga 600
gtcaactttg gtagctgcct tcccaaaaag ggtgcatgcc caggctttga gttgcactcg 660
caccgtagtg gcatcagaag gtgaccgtgc ccggtctggg cgttaggata cagcgcctgc 720
atgaaagcct tgatctgctt aaaagccacc tgagcctttg cgccttcaga gaagaacatg 780
ccgcaagact tgccggaaaa ctgattggcc ggacaggccg cgtcatgcac gcagcacctt 840
gcgtcggtgt tggagatctg caccacattt cggccccacc ggttcttcac gatcttggcc 900
ttgctagact gctccttcag cgcgcgctgc ccgttttcgc tcgtcacatc catttcaatc 960
acgtgctcct tatttatcat aatgctcccg tgtagacact taagctcgcc ttcgatctca 1020
gcgcagcggt gcagccacaa cgcgcagccc gtgggctcgt ggtgcttgta ggttacctct 1080
gcaaacgact gcaggtacgc ctgcaggaat cgccccatca tcgtcacaaa ggtcttgttg 1140
ctggtgaagg tcagctgcaa cccgcggtgc tcctcgttta gccaggtctt gcatacggcc 1200
gccagagctt ccacttggtc aggcagtagc ttgaagtttg cctttagatc gttatccacg 1260
tggtacttgt ccatcaacgc gcgcgcagcc tccatgccct tctcccacgc agacacgatc 1320
ggcaggctca gcgggtttat caccgtgctt tcactttccg cttcactgga ctcttccttt 1380
tcctcttgcg tccgcatacc ccgcgccact gggtcgtctt cattcagccg ccgcaccgtg 1440
cgcttacctc ccttgccgtg cttgattagc accggtgggt tgctgaaacc caccatttgt 1500
agcgccacat cttctctttc ttcctcgctg tccacgatca cctctgggga tggcgggcgc 1560
tcgggcttgg gagaggggcg cttctttttc tttttggacg caatggccaa atccgccgtc 1620
gaggtcgatg gccgcgggct gggtgtgcgc ggcaccagcg catcttgtga cgagtcttct 1680
tcgtcctcgg actcgagacg ccgcctcagc cgcttttttg ggggcgcgcg gggaggcggc 1740
ggcgacggcg acggggacga cacgtcctcc atggttggtg gacgtcgcgc cgcaccgcgt 1800
ccgcgctcgg gggtggtttc gcgctgctcc tcttcccgac tggccatttc cttctcctat 1860
aggcagaaaa agatcatgga gtcagtcgag aaggaggaca gcctaaccgc cccctttgag 1920
ttcgccacca ccgcctccac cgatgccgcc aacgcgccta ccaccttccc cgtcgaggca 1980
cccccgcttg aggaggagga agtgattatc gagcaggacc caggttttgt aagcgaagac 2040
gacgaggatc gctcagtacc aacagaggat aaaaagcaag accaggacga cgcagaggca 2100
aacgaggaac aagtcgggcg gggggaccaa aggcatggcg actacctaga tgtgggagac 2160
gacgtgctgt tgaagcatct gcagcgccag tgcgccatta tctgcgacgc gttgcaagag 2220
cgcagcgatg tgcccctcgc catagcggat gtcagccttg cctacgaacg ccacctgttc 2280
tcaccgcgcg taccccccaa acgccaagaa aacggcacat gcgagcccaa cccgcgcctc 2340
aacttctacc ccgtatttgc cgtgccagag gtgcttgcca cctatcacat ctttttccaa 2400
aactgcaaga tacccctatc ctgccgtgcc aaccgcagcc gagcggacaa gcagctggcc 2460
ttgcggcagg gcgctgtcat acctgatatc gcctcgctcg acgaagtgcc aaaaatcttt 2520
gagggtcttg gacgcgacga gaaacgcgcg gcaaacgctc tgcaacaaga aaacagcgaa 2580
aatgaaagtc actgtggagt gctggtggaa cttgagggtg acaacgcgcg cctagccgtg 2640
ctgaaacgca gcatcgaggt cacccacttt gcctacccgg cacttaacct accccccaag 2700
gttatgagca cagtcatgag cgagctgatc gtgcgccgtg cacgacccct ggagagggat 2760
gcaaacttgc aagaacaaac cgaggagggc ctacccgcag ttggcgatga gcagctggcg 2820
cgctggcttg agacgcgcga gcctgccgac ttggaggagc gacgcaagct aatgatggcc 2880
gcagtgcttg ttaccgtgga gcttgagtgc atgcagcggt tctttgctga cccggagatg 2940
cagcgcaagc tagaggaaac gttgcactac acctttcgcc agggctacgt gcgccaggcc 3000
tgcaaaattt ccaacgtgga gctctgcaac ctggtctcct accttggaat tttgcacgaa 3060
aaccgcctcg ggcaaaacgt gcttcattcc acgctcaagg gcgaggcgcg ccgcgactac 3120
gtccgcgact gcgtttactt atttctgtgc tacacctggc aaacggccat gggcgtgtgg 3180
cagcaatgcc tggaggagcg caacctaaag gagctgcaga agctgctaaa gcaaaacttg 3240
aaggacctat ggacggcctt caacgagcgc tccgtggccg cgcacctggc ggacattatc 3300
ttccccgaac gcctgcttaa aaccctgcaa cagggtctgc cagacttcac cagtcaaagc 3360
atgttgcaaa actttaggaa ctttatccta gagcgttcag gaattctgcc cgccacctgc 3420
tgtgcgcttc ctagcgactt tgtgcccatt aagtaccgtg aatgccctcc gccgctttgg 3480
ggtcactgct accttctgca gctagccaac taccttgcct accactccga catcatggaa 3540
gacgtgagcg gtgacggcct actggagtgt cactgtcgct gcaacctatg caccccgcac 3600
cgctccctgg tctgcaattc gcaactgctt agcgaaagtc aaattatcgg tacctttgag 3660
ctgcagggtc cctcgcctga cgaaaagtcc gcggctccgg ggttgaaact cactccgggg 3720
ctgtggacgt cggcttacct tcgcaaattt gtacctgagg actaccacgc ccacgagatt 3780
aggttctacg aagaccaatc ccgcccgcca aatgcggagc ttaccgcctg cgtcattacc 3840
cagggccaca tccttggcca attgcaagcc atcaacaaag cccgccaaga gtttctgcta 3900
cgaaagggac ggggggttta cctggacccc cagtccggcg aggagctcaa cccaatcccc 3960
ccgccgccgc agccctatca gcagccgcgg gcccttgctt cccaggatgg cacccaaaaa 4020
gaagctgcag ctgccgccgc cgccacccac ggacgaggag gaatactggg acagtcaggc 4080
agaggaggtt ttggacgagg aggaggagat gatggaagac tgggacagcc tagacgaagc 4140
ttccgaggcc gaagaggtgt cagacgaaac accgtcaccc tcggtcgcat tcccctcgcc 4200
ggcgccccag aaattggcaa ccgttcccag catcgctaca acctccgctc ctcaggcgcc 4260
gccggcactg cctgttcgcc gacccaaccg tagatgggac accactggaa ccagggccgg 4320
taagtctaag cagccgccgc cgttagccca agagcaacaa cagcgccaag gctaccgctc 4380
gtggcgcggg cacaagaacg ccatagttgc ttgcttgcaa gactgtgggg gcaacatctc 4440
cttcgcccgc cgctttcttc tctaccatca cggcgtggcc ttcccccgta acatcctgca 4500
ttactaccgt catctctaca gcccctactg caccggcggc agcggcagcg gcagcaacag 4560
cagcggtcac acagaagcaa aggcgaccgg atagcaagac tctgacaaag cccaagaaat 4620
ccacagcggc ggcagcagca ggaggaggag cgctgcgtct ggcgcccaac gaacccgtat 4680
cgacccgcga gcttagaaat aggatttttc ccactctgta tgctatattt caacaaagca 4740
ggggccaaga acaagagctg aaaataaaaa acaggtctct gcgctccctc acccgcagct 4800
gcctgtatca caaaagcgaa gatcagcttc ggcgcacgct ggaagacgcg gaggctctct 4860
tcagcaaata ctgcgcgctg actcttaagg actagtttcg cgccctttct caaatttaag 4920
cgcgaaaact acgtcatctc cagcggccac acccggcgcc agcacctgtc gtcagcgcca 4980
ttatgagcaa ggaaattccc acgccctaca tgtggagtta ccagccacaa atgggacttg 5040
cggctggagc tgcccaagac tactcaaccc gaataaacta catgagcgcg ggaccccaca 5100
tgatatcccg ggtcaacgga atccgcgccc accgaaaccg aattctcctc gaacaggcgg 5160
ctattaccac cacacctcgt aataacctta atccccgtag ttggcccgct gccctggtgt 5220
accaggaaag tcccgctccc accactgtgg tacttcccag agacgcccag gccgaagttc 5280
agatgactaa ctcaggggcg cagcttgcgg gcggctttcg tcacagggtg cggtcgcccg 5340
ggcgttttag ggcggagtaa cttgcatgta ttgggaattg tagttttttt aaaatgggaa 5400
gtgacgtatc gtgggaaaac ggaagtgaag atttgaggaa gttgtgggtt ttttggcttt 5460
cgtttctggg cgtaggttcg cgtgcggttt tctgggtgtt ttttgtggac tttaaccgtt 5520
acgtcatttt ttagtcctat atatactcgc tctgtacttg gcccttttta cactgtgact 5580
gattgagctg gtgccgtgtc gagtggtgtt ttttaatagg tttttttact ggtaaggctg 5640
actgttatgg ctgccgctgt ggaagcgctg tatgttgttc tggagcggga gggtgctatt 5700
ttgcctaggc aggagggttt ttcaggtgtt tatgtgtttt tctctcctat taattttgtt 5760
atacctccta tgggggctgt aatgttgtct ctacgcctgc gggtatgtat tcccccgggc 5820
tatttcggtc gctttttagc actgaccgat gttaaccaac ctgatgtgtt taccgagtct 5880
tacattatga ctccggacat gaccgaggaa ctgtcggtgg tgctttttaa tcacggtgac 5940
cagttttttt acggtcacgc cggcatggcc gtagtccgtc ttatgcttat aagggttgtt 6000
tttcctgttg taagacaggc ttctaatgtt taaatgtttt tttttttgtt attttatttt 6060
gtgtttaatg caggaacccg cagacatgtt tgagagaaaa atggtgtctt tttctgtggt 6120
ggttccggaa cttacctgcc tttatctgca tgagcatgac tacgatgtgc ttgctttttt 6180
gcgcgaggct ttgcctgatt ttttgagcag caccttgcat tttatatcgc cgcccatgca 6240
acaagcttac ataggggcta cgctggttag catagctccg agtatgcgtg tcataatcag 6300
tgtgggttct tttgtcatgg ttcctggcgg ggaagtggcc gcgctggtcc gtgcagacct 6360
gcacgattat gttcagctgg ccctgcgaag ggacctacgg gatcgcggta tttttgttaa 6420
tgttccgctt ttgaatctta tacaggtctg tgaggaacct gaatttttgc aatcatgatt 6480
cgctgcttga ggctgaaggt ggagggcgct ctggagcaga tttttacaat ggccggactt 6540
aatattcggg atttgcttag agacatattg ataaggtggc gagatgaaaa ttatttgggc 6600
atggttgaag gtgctggaat gtttatagag gagattcacc ctgaagggtt tagcctttac 6660
gtccacttgg acgtgagggc agtttgcctt ttggaagcca ttgtgcaaca tcttacaaat 6720
gccattatct gttctttggc tgtagagttt gaccacgcca ccggagggga gcgcgttcac 6780
ttaatagatc ttcattttga ggttttggat aatcttttgg aataaaaaaa aaaaaacatg 6840
gttcttccag ctcttcccgc tcctcccgtg tgtgactcgc agaacgaatg tgtaggttgg 6900
ctgggtgtgg cttattctgc ggtggtggat gttatcaggg cagcggcgca tgaaggagtt 6960
tacatagaac ccgaagccag ggggcgcctg gatgctttga gagagtggat atactacaac 7020
tactacacag agcgagctaa gcgacgagac cggagacgca gatctgtttg tcacgcccgc 7080
acctggtttt gcttcaggaa atatgactac gtccggcgtt ccatttggca tgacactacg 7140
accaacacga tctcggttgt ctcggcgcac tccgtacagt agggatcgcc tacctccttt 7200
tgagacagag acccgcgcta ccatactgga ggatcatccg ctgctgcccg aatgtaacac 7260
tttgacaatg cacaacgtga gttacgtgcg aggtcttccc tgcagtgtgg gatttacgct 7320
gattcaggaa tgggttgttc cctgggatat ggttctgacg cgggaggagc ttgtaatcct 7380
gaggaagtgt atgcacgtgt gcctgtgttg tgccaacatt gatatcatga cgagcatgat 7440
gatccatggt tacgagtcct gggctctcca ctgtcattgt tccagtcccg gttccctgca 7500
gtgcatagcc ggcgggcagg ttttggccag ctggtttagg atggtggtgg atggcgccat 7560
gtttaatcag aggtttatat ggtaccggga ggtggtgaat tacaacatgc caaaagaggt 7620
aatgtttatg tccagcgtgt ttatgagggg tcgccactta atctacctgc gcttgtggta 7680
tgatggccac gtgggttctg tggtccccgc catgagcttt ggatacagcg ccttgcactg 7740
tgggattttg aacaatattg tggtgctgtg ctgcagttac tgtgctgatt taagtgagat 7800
cagggtgcgc tgctgtgccc ggaggacaag gcgtctcatg ctgcgggcgg tgcgaatcat 7860
cgctgaggag accactgcca tgttgtattc ctgcaggacg gagcggcggc ggcagcagtt 7920
tattcgcgcg ctgctgcagc accaccgccc tatcctgatg cacgattatg actctacccc 7980
catgtaggcg tggacttccc cttcgccgcc cgttgagcaa ccgcaagttg gacagcagcc 8040
tgtggctcag cagctggaca gcgacatgaa cttaagcgag ctgcccgggg agtttattaa 8100
tatcactgat gagcgtttgg ctcgacagga aaccgtgtgg aatataacac ctaagaatat 8160
gtctgttacc catgatatga tgctttttaa ggccagccgg ggagaaagga ctgtgtactc 8220
tgtgtgttgg gagggaggtg gcaggttgaa tactagggtt ctgtgagttt gattaaggta 8280
cggtgatcaa tataagctat gtggtggtgg ggctatacta ctgaatgaaa aatgacttga 8340
aattttctgc aattgaaaaa taaacacgtt gaaacataac atgcaacagg ttcacgattc 8400
tttattcctg ggcaatgtag gagaaggtgt aagagttggt agcaaaagtt tcagtggtgt 8460
attttccact ttcccaggac catgtaaaag acatagagta agtgcttacc tcgctagttt 8520
ctgtggattc actagaatcg atgtaggatg ttgcccctcc tgacgcggta ggagaagggg 8580
agggtgccct gcatgtctgc cgctgctctt gctcttgccg ctgctgagga ggggggcgca 8640
tctgccgcag caccggatgc atctgggaaa agcaaaaaag gggctcgtcc ctgtttccgg 8700
aggaatttgc aagcggggtc ttgcatgacg gggaggcaaa cccccgttcg ccgcagtccg 8760
gccggcccga gactcgaacc gggggtcctg cgactcaacc cttggaaaat aaccctccgg 8820
ctacagggag cgagccactt aatgctttcg ctttccagcc taaccgctta cgccgcgcgc 8880
ggccagtggc caaaaaagct agcgcagcag ccgccgcgcc tggaaggaag ccaaaaggag 8940
cgctcccccg ttgtctgacg tcgcacacct gggttcgaca cgcgggcggt aaccgcatgg 9000
atcacggcgg acggccggat ccggggttcg aaccccggtc gtccgccatg atacccttgc 9060
gaatttatcc accagaccac ggaagagtgc ccgcttacag gctctccttt tgcacggtct 9120
agagcgtcaa cgactgcgca cgcctcaccg gccagagcgt cccgaccatg gagcactttt 9180
tgccgctgcg caacatctgg aaccgcgtcc gcgactttcc gcgcgcctcc accaccgccg 9240
ccggcatcac ctggatgtcc aggtacatct acggattacg tcgacgttta aaccatatga 9300
tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa cgcaggaaag 9360
aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg 9420
tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc aagtcagagg 9480
tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag ctccctcgtg 9540
cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct cccttcggga 9600
agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc 9660
tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc cttatccggt 9720
aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc agcagccact 9780
ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt gaagtggtgg 9840
cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct gaagccagtt 9900
accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc tggtagcggt 9960
ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca agaagatcct 10020
ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta agggattttg 10080
gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa atgaagtttt 10140
aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg cttaatcagt 10200
gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg actccccgtc 10260
gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc aatgataccg 10320
cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc cggaagggcc 10380
gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa ttgttgccgg 10440
gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc cattgctaca 10500
ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg ttcccaacga 10560
tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc cttcggtcct 10620
ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat ggcagcactg 10680
cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg tgagtactca 10740
accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata 10800
cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg aaaacgttct 10860
tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat gtaacccact 10920
cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg gtgagcaaaa 10980
acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg ttgaatactc 11040
atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct catgagcgga 11100
tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac atttccccga 11160
aaagtgccac ctaaattgta agcgttaata ttttgttaaa attcgcgtta aatttttgtt 11220
aaatcagctc attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag 11280
aatagaccga gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga 11340
acgtggactc caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg 11400
aaccatcacc ctaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc 11460
ctaaagggag cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg 11520
aagggaagaa agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc 11580
gcgtaaccac cacacccgcc gcgcttaatg cgccgctaca gggcgcgatg gatcc 11635
<210> 21
<211> 1002
<212> PRT
<213> 人工序列
<220>
<223> 小鼠alphaLNNdDeltaG2
<400> 21
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Gln Arg Gly Leu Phe Pro Ala Ile Leu Asn Leu Ala Thr Asn
20 25 30
Ala His Ile Ser Ala Asn Ala Thr Cys Gly Glu Lys Gly Pro Glu Met
35 40 45
Phe Cys Lys Leu Val Glu His Val Pro Gly Arg Pro Val Arg His Ala
50 55 60
Gln Cys Arg Val Cys Asp Gly Asn Ser Thr Asn Pro Arg Glu Arg His
65 70 75 80
Pro Ile Ser His Ala Ile Asp Gly Thr Asn Asn Trp Trp Gln Ser Pro
85 90 95
Ser Ile Gln Asn Gly Arg Glu Tyr His Trp Val Thr Val Thr Leu Asp
100 105 110
Leu Arg Gln Val Phe Gln Val Ala Tyr Ile Ile Ile Lys Ala Ala Asn
115 120 125
Ala Pro Arg Pro Gly Asn Trp Ile Leu Glu Arg Ser Val Asp Gly Val
130 135 140
Lys Phe Lys Pro Trp Gln Tyr Tyr Ala Val Ser Asp Thr Glu Cys Leu
145 150 155 160
Thr Arg Tyr Lys Ile Thr Pro Arg Arg Gly Pro Pro Thr Tyr Arg Ala
165 170 175
Asp Asn Glu Val Ile Cys Thr Ser Tyr Tyr Ser Lys Leu Val Pro Leu
180 185 190
Glu His Gly Glu Ile His Thr Ser Leu Ile Asn Gly Arg Pro Ser Ala
195 200 205
Asp Asp Pro Ser Pro Gln Leu Leu Glu Phe Thr Ser Ala Arg Tyr Ile
210 215 220
Arg Leu Arg Leu Gln Arg Ile Arg Thr Leu Asn Ala Asp Leu Met Thr
225 230 235 240
Leu Ser His Arg Asp Leu Arg Asp Leu Asp Pro Ile Val Thr Arg Arg
245 250 255
Tyr Tyr Tyr Ser Ile Lys Asp Ile Ser Val Gly Gly Met Cys Ile Cys
260 265 270
Tyr Gly His Ala Ser Ser Cys Pro Trp Asp Glu Glu Ala Lys Gln Leu
275 280 285
Gln Cys Gln Cys Glu His Asn Thr Cys Gly Glu Ser Cys Asp Arg Cys
290 295 300
Cys Pro Gly Tyr His Gln Gln Pro Trp Arg Pro Gly Thr Ile Ser Ser
305 310 315 320
Gly Asn Glu Cys Glu Glu Cys Asn Cys His Asn Lys Ala Lys Asp Cys
325 330 335
Tyr Tyr Asp Ser Ser Val Ala Lys Glu Arg Arg Ser Leu Asn Thr Ala
340 345 350
Gly Gln Tyr Ser Gly Gly Gly Val Cys Val Asn Cys Ser Gln Asn Thr
355 360 365
Thr Gly Ile Asn Cys Glu Thr Cys Ile Asp Gln Tyr Tyr Arg Pro His
370 375 380
Lys Val Ser Pro Tyr Asp Asp His Pro Cys Arg Pro Cys Asn Cys Asp
385 390 395 400
Pro Val Gly Ser Leu Ser Ser Val Cys Ile Lys Asp Asp Arg His Ala
405 410 415
Asp Leu Ala Asn Gly Lys Trp Pro Gly Gln Cys Pro Cys Arg Lys Gly
420 425 430
Tyr Ala Gly Asp Lys Cys Asp Arg Cys Gln Phe Gly Tyr Arg Gly Phe
435 440 445
Pro Asn Cys Ile Pro Cys Asp Cys Arg Thr Val Gly Ser Leu Asn Glu
450 455 460
Asp Pro Cys Ile Glu Pro Cys Leu Cys Lys Lys Asn Val Glu Gly Lys
465 470 475 480
Asn Cys Asp Arg Cys Lys Pro Gly Phe Tyr Asn Leu Lys Glu Arg Asn
485 490 495
Pro Glu Gly Cys Ser Glu Cys Phe Cys Phe Gly Val Ser Gly Val Cys
500 505 510
Pro Ile Asn Tyr Cys Glu Thr Gly Leu His Asn Cys Asp Ile Pro Gln
515 520 525
Arg Ala Gln Cys Ile Tyr Met Gly Gly Ser Ser Tyr Thr Cys Ser Cys
530 535 540
Leu Pro Gly Phe Ser Gly Asp Gly Arg Ala Cys Arg Asp Val Asp Glu
545 550 555 560
Cys Gln His Ser Arg Cys His Pro Asp Ala Phe Cys Tyr Asn Thr Pro
565 570 575
Gly Ser Phe Thr Cys Gln Cys Lys Pro Gly Tyr Gln Gly Asp Gly Phe
580 585 590
Arg Cys Met Pro Gly Glu Val Ser Lys Thr Arg Cys Gln Leu Glu Arg
595 600 605
Glu His Ile Leu Gly Ala Ala Gly Gly Ala Asp Ala Gln Arg Pro Thr
610 615 620
Leu Gln Gly Met Phe Val Pro Gln Cys Asp Glu Tyr Gly His Tyr Val
625 630 635 640
Pro Thr Gln Cys His His Ser Thr Gly Tyr Cys Trp Cys Val Asp Arg
645 650 655
Asp Gly Arg Glu Leu Glu Gly Ser Arg Thr Pro Pro Gly Met Arg Pro
660 665 670
Pro Cys Leu Ser Thr Val Ala Pro Pro Ile His Gln Gly Pro Val Val
675 680 685
Pro Thr Ala Val Ile Pro Leu Pro Pro Gly Thr His Leu Leu Phe Ala
690 695 700
Gln Thr Gly Lys Ile Glu Arg Leu Pro Leu Glu Arg Asn Thr Met Lys
705 710 715 720
Lys Thr Glu Arg Lys Ala Phe Leu His Ile Pro Ala Lys Val Ile Ile
725 730 735
Gly Leu Ala Phe Asp Cys Val Asp Lys Val Val Tyr Trp Thr Asp Ile
740 745 750
Ser Glu Pro Ser Ile Gly Arg Ala Ser Leu His Gly Gly Glu Pro Thr
755 760 765
Thr Ile Ile Arg Gln Asp Leu Gly Ser Pro Glu Gly Ile Ala Leu Asp
770 775 780
His Leu Gly Arg Thr Ile Phe Trp Thr Asp Ser Gln Leu Asp Arg Ile
785 790 795 800
Glu Val Ala Lys Met Asp Gly Thr Gln Arg Arg Val Leu Phe Asp Thr
805 810 815
Gly Leu Val Asn Pro Arg Gly Ile Val Thr Asp Pro Val Arg Gly Asn
820 825 830
Leu Tyr Trp Thr Asp Trp Asn Arg Asp Asn Pro Lys Ile Glu Thr Ser
835 840 845
His Met Asp Gly Thr Asn Arg Arg Ile Leu Ala Gln Asp Asn Leu Gly
850 855 860
Leu Pro Asn Gly Leu Thr Phe Asp Ala Phe Ser Ser Gln Leu Cys Trp
865 870 875 880
Val Asp Ala Gly Thr His Arg Ala Glu Cys Leu Asn Pro Ala Gln Pro
885 890 895
Gly Arg Arg Lys Val Leu Glu Gly Leu Gln Tyr Pro Phe Ala Val Thr
900 905 910
Ser Tyr Gly Lys Asn Leu Tyr Tyr Thr Asp Trp Lys Thr Asn Ser Val
915 920 925
Ile Ala Met Asp Leu Ala Ile Ser Lys Glu Met Asp Thr Phe His Pro
930 935 940
His Lys Gln Thr Arg Leu Tyr Gly Ile Thr Ile Ala Leu Ser Gln Cys
945 950 955 960
Pro Gln Gly His Asn Tyr Cys Ser Val Asn Asn Gly Gly Cys Thr His
965 970 975
Leu Cys Leu Pro Thr Pro Gly Ser Arg Thr Cys Arg Cys Pro Asp Asn
980 985 990
Thr Leu Gly Val Asp Cys Ile Glu Arg Lys
995 1000
<210> 22
<211> 1002
<212> PRT
<213> 人工序列
<220>
<223> 人shNoG2氨基酸序列；人alphaLNNDdDeltaG2
<400> 22
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Arg Gln Arg Gly Leu Phe Pro Ala Ile Leu Asn Leu Ala Ser Asn
20 25 30
Ala His Ile Ser Thr Asn Ala Thr Cys Gly Glu Lys Gly Pro Glu Met
35 40 45
Phe Cys Lys Leu Val Glu His Val Pro Gly Arg Pro Val Arg Asn Pro
50 55 60
Gln Cys Arg Ile Cys Asp Gly Asn Ser Ala Asn Pro Arg Glu Arg His
65 70 75 80
Pro Ile Ser His Ala Ile Asp Gly Thr Asn Asn Trp Trp Gln Ser Pro
85 90 95
Ser Ile Gln Asn Gly Arg Glu Tyr His Trp Val Thr Ile Thr Leu Asp
100 105 110
Leu Arg Gln Val Phe Gln Val Ala Tyr Val Ile Ile Lys Ala Ala Asn
115 120 125
Ala Pro Arg Pro Gly Asn Trp Ile Leu Glu Arg Ser Leu Asp Gly Thr
130 135 140
Thr Phe Ser Pro Trp Gln Tyr Tyr Ala Val Ser Asp Ser Glu Cys Leu
145 150 155 160
Ser Arg Tyr Asn Ile Thr Pro Arg Arg Gly Pro Pro Thr Tyr Arg Ala
165 170 175
Asp Asp Glu Val Ile Cys Thr Ser Tyr Tyr Ser Arg Leu Val Pro Leu
180 185 190
Glu His Gly Glu Ile His Thr Ser Leu Ile Asn Gly Arg Pro Ser Ala
195 200 205
Asp Asp Leu Ser Pro Lys Leu Leu Glu Phe Thr Ser Ala Arg Tyr Ile
210 215 220
Arg Leu Arg Leu Gln Arg Ile Arg Thr Leu Asn Ala Asp Leu Met Thr
225 230 235 240
Leu Ser His Arg Glu Pro Lys Glu Leu Asp Pro Ile Val Thr Arg Arg
245 250 255
Tyr Tyr Tyr Ser Ile Lys Asp Ile Ser Val Gly Gly Met Cys Ile Cys
260 265 270
Tyr Gly His Ala Ser Ser Cys Pro Trp Asp Glu Thr Thr Lys Lys Leu
275 280 285
Gln Cys Gln Cys Glu His Asn Thr Cys Gly Glu Ser Cys Asn Arg Cys
290 295 300
Cys Pro Gly Tyr His Gln Gln Pro Trp Arg Pro Gly Thr Val Ser Ser
305 310 315 320
Gly Asn Thr Cys Glu Ala Cys Asn Cys His Asn Lys Ala Lys Asp Cys
325 330 335
Tyr Tyr Asp Glu Ser Val Ala Lys Gln Lys Lys Ser Leu Asn Thr Ala
340 345 350
Gly Gln Phe Arg Gly Gly Gly Val Cys Ile Asn Cys Leu Gln Asn Thr
355 360 365
Met Gly Ile Asn Cys Glu Thr Cys Ile Asp Gly Tyr Tyr Arg Pro His
370 375 380
Lys Val Ser Pro Tyr Glu Asp Glu Pro Cys Arg Pro Cys Asn Cys Asp
385 390 395 400
Pro Val Gly Ser Leu Ser Ser Val Cys Ile Lys Asp Asp Leu His Ser
405 410 415
Asp Leu His Asn Gly Lys Gln Pro Gly Gln Cys Pro Cys Lys Glu Gly
420 425 430
Tyr Thr Gly Glu Lys Cys Asp Arg Cys Gln Leu Gly Tyr Lys Asp Tyr
435 440 445
Pro Thr Cys Val Ser Cys Gly Cys Asn Pro Val Gly Ser Ala Ser Asp
450 455 460
Glu Pro Cys Thr Gly Pro Cys Val Cys Lys Glu Asn Val Glu Gly Lys
465 470 475 480
Ala Cys Asp Arg Cys Lys Pro Gly Phe Tyr Asn Leu Lys Glu Lys Asn
485 490 495
Pro Arg Gly Cys Ser Glu Cys Phe Cys Phe Gly Val Ser Asp Val Cys
500 505 510
Pro Ile Asn Tyr Cys Glu Thr Gly Leu His Asn Cys Asp Ile Pro Gln
515 520 525
Arg Ala Gln Cys Ile Tyr Thr Gly Gly Ser Ser Tyr Thr Cys Ser Cys
530 535 540
Leu Pro Gly Phe Ser Gly Asp Gly Gln Ala Cys Gln Asp Val Asp Glu
545 550 555 560
Cys Gln Pro Ser Arg Cys His Pro Asp Ala Phe Cys Tyr Asn Thr Pro
565 570 575
Gly Ser Phe Thr Cys Gln Cys Lys Pro Gly Tyr Gln Gly Asp Gly Phe
580 585 590
Arg Cys Val Pro Gly Glu Val Glu Lys Thr Arg Cys Gln His Glu Arg
595 600 605
Glu His Ile Leu Gly Ala Ala Gly Ala Thr Asp Pro Gln Arg Pro Ile
610 615 620
Pro Pro Gly Leu Phe Val Pro Glu Cys Asp Ala His Gly His Tyr Ala
625 630 635 640
Pro Thr Gln Cys His Gly Ser Thr Gly Tyr Cys Trp Cys Val Asp Arg
645 650 655
Asp Gly Arg Glu Val Glu Gly Thr Arg Thr Arg Pro Gly Met Thr Pro
660 665 670
Pro Cys Leu Ser Thr Val Ala Pro Pro Ile His Gln Gly Pro Ala Val
675 680 685
Pro Thr Ala Val Ile Pro Leu Pro Pro Gly Thr His Leu Leu Phe Ala
690 695 700
Gln Thr Gly Lys Ile Glu Arg Leu Pro Leu Glu Gly Asn Thr Met Arg
705 710 715 720
Lys Thr Glu Ala Lys Ala Phe Leu His Val Pro Ala Lys Val Ile Ile
725 730 735
Gly Leu Ala Phe Asp Cys Val Asp Lys Met Val Tyr Trp Thr Asp Ile
740 745 750
Thr Glu Pro Ser Ile Gly Arg Ala Ser Leu His Gly Gly Glu Pro Thr
755 760 765
Thr Ile Ile Arg Gln Asp Leu Gly Ser Pro Glu Gly Ile Ala Val Asp
770 775 780
His Leu Gly Arg Asn Ile Phe Trp Thr Asp Ser Asn Leu Asp Arg Ile
785 790 795 800
Glu Val Ala Lys Leu Asp Gly Thr Gln Arg Arg Val Leu Phe Glu Thr
805 810 815
Asp Leu Val Asn Pro Arg Gly Ile Val Thr Asp Ser Val Arg Gly Asn
820 825 830
Leu Tyr Trp Thr Asp Trp Asn Arg Asp Asn Pro Lys Ile Glu Thr Ser
835 840 845
Tyr Met Asp Gly Thr Asn Arg Arg Ile Leu Val Gln Asp Asp Leu Gly
850 855 860
Leu Pro Asn Gly Leu Thr Phe Asp Ala Phe Ser Ser Gln Leu Cys Trp
865 870 875 880
Val Asp Ala Gly Thr Asn Arg Ala Glu Cys Leu Asn Pro Ser Gln Pro
885 890 895
Ser Arg Arg Lys Ala Leu Glu Gly Leu Gln Tyr Pro Phe Ala Val Thr
900 905 910
Ser Tyr Gly Lys Asn Leu Tyr Phe Thr Asp Trp Lys Met Asn Ser Val
915 920 925
Val Ala Leu Asp Leu Ala Ile Ser Lys Glu Thr Asp Ala Phe Gln Pro
930 935 940
His Lys Gln Thr Arg Leu Tyr Gly Ile Thr Thr Ala Leu Ser Gln Cys
945 950 955 960
Pro Gln Gly His Asn Tyr Cys Ser Val Asn Asn Gly Gly Cys Thr His
965 970 975
Leu Cys Leu Ala Thr Pro Gly Ser Arg Thr Cys Arg Cys Pro Asp Asn
980 985 990
Thr Leu Gly Val Asp Cys Ile Glu Gln Lys
995 1000
<210> 23
<211> 969
<212> PRT
<213> 人工序列
<220>
<223> AAV的小鼠微型集聚蛋白序列
<400> 23
Met Val Arg Pro Arg Leu Ser Phe Pro Ala Pro Leu Leu Pro Leu Leu
1 5 10 15
Leu Leu Leu Ala Ala Ala Ala Pro Ala Val Pro Gly Ala Ser Gly Thr
20 25 30
Cys Pro Glu Arg Ala Leu Glu Arg Arg Glu Glu Glu Ala Asn Val Val
35 40 45
Leu Thr Gly Thr Val Glu Glu Ile Leu Asn Val Asp Pro Val Gln His
50 55 60
Thr Tyr Ser Cys Lys Val Arg Val Trp Arg Tyr Leu Lys Gly Lys Asp
65 70 75 80
Val Val Ala Gln Glu Ser Leu Leu Asp Gly Gly Asn Lys Val Val Ile
85 90 95
Gly Gly Phe Gly Asp Pro Leu Ile Cys Asp Asn Gln Val Ser Thr Gly
100 105 110
Asp Thr Arg Ile Phe Phe Val Asn Pro Ala Pro Pro Tyr Leu Trp Pro
115 120 125
Ala His Lys Asn Glu Leu Met Leu Asn Ser Ser Leu Met Arg Ile Thr
130 135 140
Leu Arg Asn Leu Glu Glu Val Glu Phe Cys Val Glu Asp Lys Pro Gly
145 150 155 160
Ile His Phe Thr Ala Ala Pro Ser Met Pro Pro Asp Val Cys Arg Gly
165 170 175
Met Leu Cys Gly Phe Gly Ala Val Cys Glu Pro Ser Val Glu Asp Pro
180 185 190
Gly Arg Ala Ser Cys Val Cys Lys Lys Asn Val Cys Pro Ala Met Val
195 200 205
Ala Pro Val Cys Gly Ser Asp Ala Ser Thr Tyr Ser Asn Glu Cys Glu
210 215 220
Leu Gln Arg Ala Gln Cys Asn Gln Gln Arg Arg Ile Arg Leu Leu Arg
225 230 235 240
Gln Gly Pro Cys Pro Pro Lys Ser Cys Asp Ser Gln Pro Cys Leu His
245 250 255
Gly Gly Thr Cys Gln Asp Leu Asp Ser Gly Lys Gly Phe Ser Cys Ser
260 265 270
Cys Thr Ala Gly Arg Ala Gly Thr Val Cys Glu Lys Val Gln Leu Pro
275 280 285
Ser Val Pro Ala Phe Lys Gly His Ser Phe Leu Ala Phe Pro Thr Leu
290 295 300
Arg Ala Tyr His Thr Leu Arg Leu Ala Leu Glu Phe Arg Ala Leu Glu
305 310 315 320
Thr Glu Gly Leu Leu Leu Tyr Asn Gly Asn Ala Arg Gly Lys Asp Phe
325 330 335
Leu Ala Leu Ala Leu Leu Asp Gly His Val Gln Phe Arg Phe Asp Thr
340 345 350
Gly Ser Gly Pro Ala Val Leu Thr Ser Leu Val Pro Val Glu Pro Gly
355 360 365
Arg Trp His Arg Leu Glu Leu Ser Arg His Trp Arg Gln Gly Thr Leu
370 375 380
Ser Val Asp Gly Glu Ala Pro Val Val Gly Glu Ser Pro Ser Gly Thr
385 390 395 400
Asp Gly Leu Asn Leu Asp Thr Lys Leu Tyr Val Gly Gly Leu Pro Glu
405 410 415
Glu Gln Val Ala Thr Val Leu Asp Arg Thr Ser Val Gly Ile Gly Leu
420 425 430
Lys Gly Cys Ile Arg Met Leu Asp Ile Asn Asn Gln Gln Leu Glu Leu
435 440 445
Ser Asp Trp Gln Arg Ala Val Val Gln Ser Ser Gly Val Gly Glu Cys
450 455 460
Gly Asp His Pro Cys Ser Pro Asn Pro Cys His Gly Gly Ala Leu Cys
465 470 475 480
Gln Ala Leu Glu Ala Gly Val Phe Leu Cys Gln Cys Pro Pro Gly Arg
485 490 495
Phe Gly Pro Thr Cys Ala Asp Glu Lys Asn Pro Cys Gln Pro Asn Pro
500 505 510
Cys His Gly Ser Ala Pro Cys His Val Leu Ser Arg Gly Gly Ala Lys
515 520 525
Cys Ala Cys Pro Leu Gly Arg Ser Gly Ser Phe Cys Glu Thr Val Leu
530 535 540
Glu Asn Ala Gly Ser Arg Pro Phe Leu Ala Asp Phe Asn Gly Phe Ser
545 550 555 560
Tyr Leu Glu Leu Lys Gly Leu His Thr Phe Glu Arg Asp Leu Gly Glu
565 570 575
Lys Met Ala Leu Glu Met Val Phe Leu Ala Arg Gly Pro Ser Gly Leu
580 585 590
Leu Leu Tyr Asn Gly Gln Lys Thr Asp Gly Lys Gly Asp Phe Val Ser
595 600 605
Leu Ala Leu His Asn Arg His Leu Glu Phe Arg Tyr Asp Leu Gly Lys
610 615 620
Gly Ala Ala Ile Ile Arg Ser Lys Glu Pro Ile Ala Leu Gly Thr Trp
625 630 635 640
Val Arg Val Phe Leu Glu Arg Asn Gly Arg Lys Gly Ala Leu Gln Val
645 650 655
Gly Asp Gly Pro Arg Val Leu Gly Glu Ser Pro Val Pro His Thr Met
660 665 670
Leu Asn Leu Lys Glu Pro Leu Tyr Val Gly Gly Ala Pro Asp Phe Ser
675 680 685
Lys Leu Ala Arg Gly Ala Ala Val Ala Ser Gly Phe Asp Gly Ala Ile
690 695 700
Gln Leu Val Ser Leu Arg Gly His Gln Leu Leu Thr Gln Glu His Val
705 710 715 720
Leu Arg Ala Val Asp Val Ala Pro Phe Ala Gly His Pro Cys Thr Gln
725 730 735
Ala Val Asp Asn Pro Cys Leu Asn Gly Gly Ser Cys Ile Pro Arg Glu
740 745 750
Ala Thr Tyr Glu Cys Leu Cys Pro Gly Gly Phe Ser Gly Leu His Cys
755 760 765
Glu Lys Gly Ile Val Glu Lys Ser Val Gly Asp Leu Glu Thr Leu Ala
770 775 780
Phe Asp Gly Arg Thr Tyr Ile Glu Tyr Leu Asn Ala Val Thr Glu Ser
785 790 795 800
Glu Lys Ala Leu Gln Ser Asn His Phe Glu Leu Ser Leu Arg Thr Glu
805 810 815
Ala Thr Gln Gly Leu Val Leu Trp Ile Gly Lys Val Gly Glu Arg Ala
820 825 830
Asp Tyr Met Ala Leu Ala Ile Val Asp Gly His Leu Gln Leu Ser Tyr
835 840 845
Asp Leu Gly Ser Gln Pro Val Val Leu Arg Ser Thr Val Lys Val Asn
850 855 860
Thr Asn Arg Trp Leu Arg Val Arg Ala His Arg Glu His Arg Glu Gly
865 870 875 880
Ser Leu Gln Val Gly Asn Glu Ala Pro Val Thr Gly Ser Ser Pro Leu
885 890 895
Gly Ala Thr Gln Leu Asp Thr Asp Gly Ala Leu Trp Leu Gly Gly Leu
900 905 910
Gln Lys Leu Pro Val Gly Gln Ala Leu Pro Lys Ala Tyr Gly Thr Gly
915 920 925
Phe Val Gly Cys Leu Arg Asp Val Val Val Gly His Arg Gln Leu His
930 935 940
Leu Leu Glu Asp Ala Val Thr Lys Pro Glu Leu Arg Pro Cys Pro Thr
945 950 955 960
Leu Ile Asp Gly Ser Gly Lys Ala Met
965
<210> 24
<211> 3009
<212> DNA
<213> 人工序列
<220>
<223> 人shNoG2核苷酸序列
<400> 24
atgagggcct ggatcttctt tctcctttgc ctggccggga gggctctggc acggcagaga 60
ggcctgtttc ctgccattct caatcttgcc agcaatgctc acatcagcac caatgccacc 120
tgtggcgaga aggggccgga gatgttctgc aaacttgtgg agcatgtgcc aggtcggccc 180
gtccgaaacc cacagtgccg gatctgtgat ggcaacagcg caaaccccag agaacgccat 240
ccaatatcac atgccataga tggcaccaat aactggtggc aaagtcccag cattcagaat 300
gggagagaat atcactgggt cacaatcact ctggacttaa gacaggtctt tcaagttgca 360
tatgtcatca ttaaagctgc caatgcccct cgacctggaa actggatttt ggagcgttct 420
ctggatggca ccacgttcag cccctggcag tattatgcag tcagcgactc agagtgtttg 480
tctcgttaca atataactcc aagacgaggg ccacccacct acagggctga tgatgaagtg 540
atctgcacct cctattattc cagattggtg ccacttgagc atggagagat tcatacatca 600
ctcatcaatg gcagaccaag cgctgacgat ctttcaccca agttgttgga attcacttct 660
gcacgatata ttcgccttcg cttgcaacgc attagaacgc tcaatgcaga tctcatgacc 720
cttagccacc gggaacctaa agaactggat cctattgtta ccagacgcta ttattattca 780
ataaaggaca tttctgttgg aggcatgtgt atctgctatg gccatgctag tagctgccca 840
tgggatgaaa ctacaaagaa actgcagtgt caatgtgagc ataatacttg cggggagagc 900
tgtaacaggt gctgtcctgg gtaccatcag cagccctgga ggccgggaac cgtgtcctcc 960
ggcaatacat gtgaagcatg taattgtcac aataaagcca aagactgtta ctatgatgaa 1020
agtgttgcaa agcagaagaa aagtttgaat actgctggac agttcagagg aggaggggtt 1080
tgcataaatt gcttgcagaa caccatggga atcaactgtg aaacctgtat tgatggatat 1140
tatagaccac acaaagtgtc tccttatgag gatgagcctt gccgcccctg taattgtgac 1200
cctgtggggt ccctcagttc tgtctgtatt aaggatgacc tccattctga cttacacaat 1260
gggaagcagc caggtcagtg cccatgtaag gaaggttata caggagaaaa atgtgatcgc 1320
tgccaacttg gctataagga ttacccgacc tgtgtctcct gtgggtgcaa cccagtgggc 1380
agtgccagtg atgagccctg cacagggccc tgtgtttgta aggaaaacgt tgaggggaag 1440
gcctgtgatc gctgcaagcc aggattctat aacttgaagg aaaaaaaccc ccggggctgc 1500
tccgagtgct tctgctttgg cgtttctgat gtctgcccca tcaactactg tgaaactggc 1560
cttcataact gcgacatacc ccagcgggcc cagtgtatct acacaggagg ctcctcctac 1620
acctgttcct gcttgccagg cttttctggg gatggccaag cctgccaaga tgtagatgaa 1680
tgccagccaa gccgatgtca ccctgacgcc ttctgctaca acactccagg ctctttcacg 1740
tgccagtgca aacctggtta tcagggagac ggcttccgtt gcgtgcccgg agaggtggag 1800
aaaacccggt gccagcacga gcgagaacac attctcgggg cagcgggggc gacagaccca 1860
cagcgaccca ttcctccggg gctgttcgtt cctgagtgcg atgcgcacgg gcactacgcg 1920
cccacccagt gccacggcag caccggctac tgctggtgcg tggatcgcga cggccgcgag 1980
gtggagggca ccaggaccag gcccgggatg acgcccccgt gtctgagtac agtggctccc 2040
ccgattcacc aaggacctgc ggtgcctacc gccgtgatcc ccttgcctcc tgggacccat 2100
ttactctttg cccagactgg gaagattgag cgcctgcccc tggagggaaa taccatgagg 2160
aagacagaag caaaggcgtt ccttcatgtc ccggctaaag tcatcattgg actggccttt 2220
gactgcgtgg acaagatggt ttactggacg gacatcactg agccttccat tgggagagct 2280
agtctacatg gtggagagcc aaccaccatc attagacaag atcttggaag tccagaaggt 2340
atcgctgttg atcaccttgg ccgcaacatc ttctggacag actctaacct ggatcgaata 2400
gaagtggcga agctggacgg cacgcagcgc cgggtgctct ttgagactga cttggtgaat 2460
cccagaggca ttgtaacgga ttccgtgaga gggaaccttt actggacaga ctggaacaga 2520
gataacccca agattgaaac ttcctacatg gacggcacga accggaggat ccttgtgcag 2580
gatgacctgg gcttgcccaa tggactgacc ttcgatgcgt tctcatctca gctctgctgg 2640
gtggatgcag gcaccaatcg ggcggaatgc ctgaacccca gtcagcccag cagacgcaag 2700
gctctcgaag ggctccagta tccttttgct gtgacgagct acgggaagaa tctgtatttc 2760
acagactgga agatgaattc cgtggttgct ctcgatcttg caatttccaa ggagacggat 2820
gctttccaac cccacaagca gacccggctg tatggcatca ccacggccct gtctcagtgt 2880
ccgcaaggcc ataactactg ctcagtgaac aatggcggct gcacccacct atgcttggcc 2940
accccaggga gcaggacctg ccgttgccct gacaacacct tgggagttga ctgtatcgaa 3000
cagaaatga 3009
<210> 25
<211> 51
<212> DNA
<213> 人工序列
<220>
<223> 小鼠BM-40（Sparc）信号序列[DNA, 51 bp)
<400> 25
atgagggcct ggatcttctt tctcctttgc ctggccggga gggctctggc a 51
<210> 26
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 小鼠BM-40（Sparc）信号肽
<400> 26
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala
<210> 27
<211> 72
<212> DNA
<213> 人工序列
<220>
<223> 小鼠Lm 1内源性信号序列[DNA, 72 bp]
<400> 27
atgcgcggca gcggcacggg agccgcgctc ctggtgctcc tggcctcggt gctctgggtc 60
accgtgcgga gc 72
<210> 28
<211> 24
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1内源性信号肽
<400> 28
Met Arg Gly Ser Gly Thr Gly Ala Ala Leu Leu Val Leu Leu Ala Ser
1 5 10 15
Val Leu Trp Val Thr Val Arg Ser
20
<210> 29
<211> 51
<212> DNA
<213> 人工序列
<220>
<223> 层粘连蛋白（Lm）1信号肽[DNA, 51 bp]
<400> 29
atgagggcct ggatcttctt tctcctttgc ctggccggga gggctctggc a 51
<210> 30
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1信号肽
<400> 30
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala
<210> 31
<211> 753
<212> DNA
<213> 人工序列
<220>
<223> 小鼠Lm 1 LN结构域[DNA, 753 bp]
<400> 31
cagcagagag gcttgttccc tgccattctc aacctggcca ccaatgccca catcagcgcc 60
aatgctacct gtggagagaa ggggcctgag atgttctgca aactcgtgga gcacgtgccg 120
ggccggcctg ttcgacacgc ccaatgccgg gtctgtgacg gtaacagtac gaatcctaga 180
gagcgccatc cgatatcaca cgcaatcgat ggcaccaaca actggtggca gagccccagt 240
attcagaatg ggagagagta tcactgggtc actgtcaccc tggacttacg gcaggtcttt 300
caagttgcat acatcatcat taaagctgcc aatgcccctc ggcctggaaa ctggattttg 360
gagcgctccg tggatggcgt caagttcaaa ccctggcagt actatgccgt cagcgataca 420
gagtgtttga cccgctacaa aataactcca cggcggggac ctcccactta cagagcagac 480
aacgaagtca tctgcacctc gtattattca aagctggtgc cacttgaaca tggagagatt 540
cacacatcac tcatcaatgg cagacccagc gctgacgacc cctcacccca gttgctggaa 600
ttcacctcag cacggtacat tcgccttcgt cttcagcgca tcagaacact caacgcagac 660
ctcatgaccc ttagccatcg ggacctcaga gaccttgacc ccattgtcac aagacgttat 720
tactattcga taaaagacat ttccgttgga ggc 753
<210> 32
<211> 251
<212> PRT
<213> 人工序列
<220>
<223> 小鼠Lm 1 LN [聚合结构域]
<400> 32
Gln Gln Arg Gly Leu Phe Pro Ala Ile Leu Asn Leu Ala Thr Asn Ala
1 5 10 15
His Ile Ser Ala Asn Ala Thr Cys Gly Glu Lys Gly Pro Glu Met Phe
20 25 30
Cys Lys Leu Val Glu His Val Pro Gly Arg Pro Val Arg His Ala Gln
35 40 45
Cys Arg Val Cys Asp Gly Asn Ser Thr Asn Pro Arg Glu Arg His Pro
50 55 60
Ile Ser His Ala Ile Asp Gly Thr Asn Asn Trp Trp Gln Ser Pro Ser
65 70 75 80
Ile Gln Asn Gly Arg Glu Tyr His Trp Val Thr Val Thr Leu Asp Leu
85 90 95
Arg Gln Val Phe Gln Val Ala Tyr Ile Ile Ile Lys Ala Ala Asn Ala
100 105 110
Pro Arg Pro Gly Asn Trp Ile Leu Glu Arg Ser Val Asp Gly Val Lys
115 120 125
Phe Lys Pro Trp Gln Tyr Tyr Ala Val Ser Asp Thr Glu Cys Leu Thr
130 135 140
Arg Tyr Lys Ile Thr Pro Arg Arg Gly Pro Pro Thr Tyr Arg Ala Asp
145 150 155 160
Asn Glu Val Ile Cys Thr Ser Tyr Tyr Ser Lys Leu Val Pro Leu Glu
165 170 175
His Gly Glu Ile His Thr Ser Leu Ile Asn Gly Arg Pro Ser Ala Asp
180 185 190
Asp Pro Ser Pro Gln Leu Leu Glu Phe Thr Ser Ala Arg Tyr Ile Arg
195 200 205
Leu Arg Leu Gln Arg Ile Arg Thr Leu Asn Ala Asp Leu Met Thr Leu
210 215 220
Ser His Arg Asp Leu Arg Asp Leu Asp Pro Ile Val Thr Arg Arg Tyr
225 230 235 240
Tyr Tyr Ser Ile Lys Asp Ile Ser Val Gly Gly
245 250
<210> 33
<211> 1020
<212> DNA
<213> 人工序列
<220>
<223> 人Lm 1 LN [DNA, 753 bp]
<400> 33
cggcagagag gcctgtttcc tgccattctc aatcttgcca gcaatgctca catcagcacc 60
aatgccacct gtggcgagaa ggggccggag atgttctgca aacttgtgga gcatgtgcca 120
ggtcggcccg tccgaaaccc acagtgccgg atctgtgatg gcaacagcgc aaaccccaga 180
gaacgccatc caatatcaca tgccatagat ggcaccaata actggtggca aagtcccagc 240
attcagaatg ggagagaata tcactggcgg cagagaggcc tgtttcctgc cattctcaat 300
cttgccagca atgctcacat cagcaccaat gccacctgtg gcgagaaggg gccggagatg 360
ttctgcaaac ttgtggagca tgtgccaggt cggcccgtcc gaaacccaca gtgccggatc 420
tgtgatggca acagcgcaaa ccccagagaa cgccatccaa tatcacatgc catagatggc 480
accaataact ggtggcaaag tcccagcatt cagaatggga gagaatatca ctgggtcaca 540
atcactctgg acttaagaca ggtctttcaa gttgcatatg tcatcattaa agctgccaat 600
gcccctcgac ctggaaactg gattttggag cgttctctgg atggcaccac gttcagcccc 660
tggcagtatt atgcagtcag cgactcagag tgtttgtctc gttacaatat aactccaaga 720
cgagggccac ccacctacag ggctgatgat gaagtgatct gcacctccta ttattccaga 780
ttggtgccac ttgagcatgg agagattcat acatcactca tcaatggcag accaagcgct 840
gacgatcttt cacccaagtt gttggaattc acttctgcac gatatattcg ccttcgcttg 900
caacgcatta gaacgctcaa tgcagatctc atgaccctta gccaccggga acctaaagaa 960
ctggatccta ttgttaccag acgctattat tattcaataa aggacatttc tgttggaggc 1020
<210> 34
<211> 251
<212> PRT
<213> 人工序列
<220>
<223> 人Lm 1 LN
<400> 34
Arg Gln Arg Gly Leu Phe Pro Ala Ile Leu Asn Leu Ala Ser Asn Ala
1 5 10 15
His Ile Ser Thr Asn Ala Thr Cys Gly Glu Lys Gly Pro Glu Met Phe
20 25 30
Cys Lys Leu Val Glu His Val Pro Gly Arg Pro Val Arg Asn Pro Gln
35 40 45
Cys Arg Ile Cys Asp Gly Asn Ser Ala Asn Pro Arg Glu Arg His Pro
50 55 60
Ile Ser His Ala Ile Asp Gly Thr Asn Asn Trp Trp Gln Ser Pro Ser
65 70 75 80
Ile Gln Asn Gly Arg Glu Tyr His Trp Val Thr Ile Thr Leu Asp Leu
85 90 95
Arg Gln Val Phe Gln Val Ala Tyr Val Ile Ile Lys Ala Ala Asn Ala
100 105 110
Pro Arg Pro Gly Asn Trp Ile Leu Glu Arg Ser Leu Asp Gly Thr Thr
115 120 125
Phe Ser Pro Trp Gln Tyr Tyr Ala Val Ser Asp Ser Glu Cys Leu Ser
130 135 140
Arg Tyr Asn Ile Thr Pro Arg Arg Gly Pro Pro Thr Tyr Arg Ala Asp
145 150 155 160
Asp Glu Val Ile Cys Thr Ser Tyr Tyr Ser Arg Leu Val Pro Leu Glu
165 170 175
His Gly Glu Ile His Thr Ser Leu Ile Asn Gly Arg Pro Ser Ala Asp
180 185 190
Asp Leu Ser Pro Lys Leu Leu Glu Phe Thr Ser Ala Arg Tyr Ile Arg
195 200 205
Leu Arg Leu Gln Arg Ile Arg Thr Leu Asn Ala Asp Leu Met Thr Leu
210 215 220
Ser His Arg Glu Pro Lys Glu Leu Asp Pro Ile Val Thr Arg Arg Tyr
225 230 235 240
Tyr Tyr Ser Ile Lys Asp Ile Ser Val Gly Gly
245 250
<210> 35
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-1结构域[DNA, 171 bp]
<400> 35
atgtgcattt gctacggcca tgccagcagc tgcccgtggg atgaagaagc aaagcaacta 60
cagtgtcagt gtgaacacaa tacgtgtggc gagagctgcg acaggtgctg tcctggctac 120
catcagcagc cctggaggcc cggaaccatt tcctccggca acgagtgtga g 171
<210> 36
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-1 [LN折叠所需的；间隔子结构域]
<400> 36
Met Cys Ile Cys Tyr Gly His Ala Ser Ser Cys Pro Trp Asp Glu Glu
1 5 10 15
Ala Lys Gln Leu Gln Cys Gln Cys Glu His Asn Thr Cys Gly Glu Ser
20 25 30
Cys Asp Arg Cys Cys Pro Gly Tyr His Gln Gln Pro Trp Arg Pro Gly
35 40 45
Thr Ile Ser Ser Gly Asn Glu Cys Glu
50 55
<210> 37
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> 人Lm 1 LEa-1 [DNA, 171 bp]
<400> 37
atgtgtatct gctatggcca tgctagtagc tgcccatggg atgaaactac aaagaaactg 60
cagtgtcaat gtgagcataa tacttgcggg gagagctgta acaggtgctg tcctgggtac 120
catcagcagc cctggaggcc gggaaccgtg tcctccggca atacatgtga a 171
<210> 38
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 人Lm 1 LEa-1
<400> 38
Met Cys Ile Cys Tyr Gly His Ala Ser Ser Cys Pro Trp Asp Glu Thr
1 5 10 15
Thr Lys Lys Leu Gln Cys Gln Cys Glu His Asn Thr Cys Gly Glu Ser
20 25 30
Cys Asn Arg Cys Cys Pro Gly Tyr His Gln Gln Pro Trp Arg Pro Gly
35 40 45
Thr Val Ser Ser Gly Asn Thr Cys Glu
50 55
<210> 39
<211> 210
<212> DNA
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-2结构域[DNA, 210 bp]
<400> 39
gaatgcaact gtcacaacaa agccaaagat tgttactatg acagcagtgt tgcaaaggag 60
aggagaagcc tgaacactgc cgggcagtac agtggaggag gggtttgtgt caactgctcg 120
cagaatacca cagggatcaa ctgtgaaacc tgtatcgacc agtattacag acctcacaag 180
gtatctcctt atgatgacca cccttgccgt 210
<210> 40
<211> 70
<212> PRT
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-2 [LN折叠所需的；间隔子结构域]
<400> 40
Glu Cys Asn Cys His Asn Lys Ala Lys Asp Cys Tyr Tyr Asp Ser Ser
1 5 10 15
Val Ala Lys Glu Arg Arg Ser Leu Asn Thr Ala Gly Gln Tyr Ser Gly
20 25 30
Gly Gly Val Cys Val Asn Cys Ser Gln Asn Thr Thr Gly Ile Asn Cys
35 40 45
Glu Thr Cys Ile Asp Gln Tyr Tyr Arg Pro His Lys Val Ser Pro Tyr
50 55 60
Asp Asp His Pro Cys Arg
65 70
<210> 41
<211> 210
<212> DNA
<213> 人工序列
<220>
<223> 人Lm 1 LEa-2 [DNA, 210 bp]
<400> 41
gcatgtaatt gtcacaataa agccaaagac tgttactatg atgaaagtgt tgcaaagcag 60
aagaaaagtt tgaatactgc tggacagttc agaggaggag gggtttgcat aaattgcttg 120
cagaacacca tgggaatcaa ctgtgaaacc tgtattgatg gatattatag accacacaaa 180
gtgtctcctt atgaggatga gccttgccgc 210
<210> 42
<211> 70
<212> PRT
<213> 人工序列
<220>
<223> 人Lm 1 LEa-2
<400> 42
Ala Cys Asn Cys His Asn Lys Ala Lys Asp Cys Tyr Tyr Asp Glu Ser
1 5 10 15
Val Ala Lys Gln Lys Lys Ser Leu Asn Thr Ala Gly Gln Phe Arg Gly
20 25 30
Gly Gly Val Cys Ile Asn Cys Leu Gln Asn Thr Met Gly Ile Asn Cys
35 40 45
Glu Thr Cys Ile Asp Gly Tyr Tyr Arg Pro His Lys Val Ser Pro Tyr
50 55 60
Glu Asp Glu Pro Cys Arg
65 70
<210> 43
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-3结构域[DNA, 171 bp]
<400> 43
ccctgtaact gtgaccctgt ggggtctctg agttctgtct gtatcaagga tgaccgccat 60
gccgatttag ccaatggaaa gtggccaggt cagtgtccat gtaggaaagg ttatgctgga 120
gataaatgtg accgctgcca gtttggctac cggggtttcc caaattgcat c 171
<210> 44
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-3 [用作间隔子的结构域]
<400> 44
Pro Cys Asn Cys Asp Pro Val Gly Ser Leu Ser Ser Val Cys Ile Lys
1 5 10 15
Asp Asp Arg His Ala Asp Leu Ala Asn Gly Lys Trp Pro Gly Gln Cys
20 25 30
Pro Cys Arg Lys Gly Tyr Ala Gly Asp Lys Cys Asp Arg Cys Gln Phe
35 40 45
Gly Tyr Arg Gly Phe Pro Asn Cys Ile
50 55
<210> 45
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> 人Lm 1 LEa-3 [DNA, 171 bp]
<400> 45
ccctgtaatt gtgaccctgt ggggtccctc agttctgtct gtattaagga tgacctccat 60
tctgacttac acaatgggaa gcagccaggt cagtgcccat gtaaggaagg ttatacagga 120
gaaaaatgtg atcgctgcca acttggctat aaggattacc cgacctgtgt c 171
<210> 46
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 人Lm 1 LEa-3
<400> 46
Pro Cys Asn Cys Asp Pro Val Gly Ser Leu Ser Ser Val Cys Ile Lys
1 5 10 15
Asp Asp Leu His Ser Asp Leu His Asn Gly Lys Gln Pro Gly Gln Cys
20 25 30
Pro Cys Lys Glu Gly Tyr Thr Gly Glu Lys Cys Asp Arg Cys Gln Leu
35 40 45
Gly Tyr Lys Asp Tyr Pro Thr Cys Val
50 55
<210> 47
<211> 147
<212> DNA
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-4结构域[DNA, 147 bp]
<400> 47
ccctgtgact gcaggactgt cggcagcctg aatgaggatc catgcataga gccgtgtctt 60
tgtaagaaaa atgttgaggg taagaactgt gatcgctgca agccaggatt ctacaacttg 120
aaggaacgaa accccgaggg ctgctcc 147
<210> 48
<211> 49
<212> PRT
<213> 人工序列
<220>
<223> 小鼠Lm 1 LEa-4 [间隔子结构域]
<400> 48
Pro Cys Asp Cys Arg Thr Val Gly Ser Leu Asn Glu Asp Pro Cys Ile
1 5 10 15
Glu Pro Cys Leu Cys Lys Lys Asn Val Glu Gly Lys Asn Cys Asp Arg
20 25 30
Cys Lys Pro Gly Phe Tyr Asn Leu Lys Glu Arg Asn Pro Glu Gly Cys
35 40 45
Ser
<210> 49
<211> 147
<212> DNA
<213> 人工序列
<220>
<223> 人Lm 1 LEa-4 [DNA, 147 bp]
<400> 49
tcctgtgggt gcaacccagt gggcagtgcc agtgatgagc cctgcacagg gccctgtgtt 60
tgtaaggaaa acgttgaggg gaaggcctgt gatcgctgca agccaggatt ctataacttg 120
aaggaaaaaa acccccgggg ctgctcc 147
<210> 50
<211> 49
<212> PRT
<213> 人工序列
<220>
<223> 人Lm 1 LEa-4
<400> 50
Ser Cys Gly Cys Asn Pro Val Gly Ser Ala Ser Asp Glu Pro Cys Thr
1 5 10 15
Gly Pro Cys Val Cys Lys Glu Asn Val Glu Gly Lys Ala Cys Asp Arg
20 25 30
Cys Lys Pro Gly Phe Tyr Asn Leu Lys Glu Lys Asn Pro Arg Gly Cys
35 40 45
Ser
<210> 51
<211> 33
<212> DNA
<213> 人工序列
<220>
<223> 具有3个cys的小鼠Lm 1 LF结构域LE型片段[DNA, 33 bp]
<400> 51
gagtgcttct gcttcggtgt ctctggtgtc tgt 33
<210> 52
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 小鼠Lm 1 LF片段（具有3个cys）[间隔子区段]
<400> 52
Glu Cys Phe Cys Phe Gly Val Ser Gly Val Cys
1 5 10
<210> 53
<211> 33
<212> DNA
<213> 人工序列
<220>
<223> 人Lm 1 LF片段（具有3个cys）[DNA, 33 bp]
<400> 53
gagtgcttct gctttggcgt ttctgatgtc tgc 33
<210> 54
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 人Lm 1 LF片段（具有3个cys）
<400> 54
Cys Phe Cys Phe Gly Val Ser Asp Val Cys
1 5 10
<210> 55
<211> 843
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 G2结构域[DNA, 843 bp]
<400> 55
cagcagactt gtgccaacaa tagacaccag tgctccgtgc atgcagagtg cagagactat 60
gctactggct tctgctgcag gtgtgtggcc aactacacag gcaatggcag acagtgcgtg 120
gcagaaggct ctccacaacg ggtcaatggc aaggtgaagg gaaggatctt cgtggggagc 180
agccaggtcc ccgtggtgtt tgagaacact gacctgcact cctatgtggt gatgaaccac 240
gggcgctctt acacagccat cagcaccatc cctgaaaccg tcggctactc tctgctcccc 300
ctggcaccca ttggaggcat catcggatgg atgtttgcag tggagcagga tgggttcaag 360
aatgggttta gcatcactgg gggcgagttt acccggcaag ctgaggtgac cttcctgggg 420
cacccaggca agctggtcct gaagcagcag ttcagcggta ttgatgaaca tggacacctg 480
accatcagca cggagctgga gggccgcgtg ccgcagatcc cctatggagc ctcggtgcac 540
attgagccct acaccgaact gtaccactac tccagctcag tgatcacttc ctcctccacc 600
cgggagtaca cggtgatgga gcctgatcag gacggcgctg caccctcaca cacccatatt 660
taccagtggc gtcagaccat caccttccag gagtgtgccc acgatgacgc caggccagcc 720
ctgcccagca cccagcagct ctctgtggac agcgtgtttg tcctgtacaa caaggaggag 780
aggatcttgc gctatgccct cagcaactcc atcgggcctg tgagggatgg ctcccctgat 840
gcc 843
<210> 56
<211> 281
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 G2结构域[直接胶原蛋白-IV，基底膜聚糖结合]
<400> 56
Gln Gln Thr Cys Ala Asn Asn Arg His Gln Cys Ser Val His Ala Glu
1 5 10 15
Cys Arg Asp Tyr Ala Thr Gly Phe Cys Cys Arg Cys Val Ala Asn Tyr
20 25 30
Thr Gly Asn Gly Arg Gln Cys Val Ala Glu Gly Ser Pro Gln Arg Val
35 40 45
Asn Gly Lys Val Lys Gly Arg Ile Phe Val Gly Ser Ser Gln Val Pro
50 55 60
Val Val Phe Glu Asn Thr Asp Leu His Ser Tyr Val Val Met Asn His
65 70 75 80
Gly Arg Ser Tyr Thr Ala Ile Ser Thr Ile Pro Glu Thr Val Gly Tyr
85 90 95
Ser Leu Leu Pro Leu Ala Pro Ile Gly Gly Ile Ile Gly Trp Met Phe
100 105 110
Ala Val Glu Gln Asp Gly Phe Lys Asn Gly Phe Ser Ile Thr Gly Gly
115 120 125
Glu Phe Thr Arg Gln Ala Glu Val Thr Phe Leu Gly His Pro Gly Lys
130 135 140
Leu Val Leu Lys Gln Gln Phe Ser Gly Ile Asp Glu His Gly His Leu
145 150 155 160
Thr Ile Ser Thr Glu Leu Glu Gly Arg Val Pro Gln Ile Pro Tyr Gly
165 170 175
Ala Ser Val His Ile Glu Pro Tyr Thr Glu Leu Tyr His Tyr Ser Ser
180 185 190
Ser Val Ile Thr Ser Ser Ser Thr Arg Glu Tyr Thr Val Met Glu Pro
195 200 205
Asp Gln Asp Gly Ala Ala Pro Ser His Thr His Ile Tyr Gln Trp Arg
210 215 220
Gln Thr Ile Thr Phe Gln Glu Cys Ala His Asp Asp Ala Arg Pro Ala
225 230 235 240
Leu Pro Ser Thr Gln Gln Leu Ser Val Asp Ser Val Phe Val Leu Tyr
245 250 255
Asn Lys Glu Glu Arg Ile Leu Arg Tyr Ala Leu Ser Asn Ser Ile Gly
260 265 270
Pro Val Arg Asp Gly Ser Pro Asp Ala
275 280
<210> 57
<211> 843
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白-1 G2结构域（直接胶原蛋白-IV，基底膜聚糖结合）[DNA, 843 bp]
<400> 57
cgccagacgt gtgctaacaa cagacaccag tgctcggtgc acgcagagtg cagggactac 60
gccacgggct tctgctgcag ctgtgtcgct ggctatacgg gcaatggcag gcaatgtgtt 120
gcagaaggtt ccccccagcg agtcaatggc aaggtgaaag gaaggatctt tgtggggagc 180
agccaggtcc ccattgtctt tgagaacact gacctccact cttacgtagt aatgaaccac 240
gggcgctcct acacagccat cagcaccatt cccgagaccg ttggatattc tctgcttcca 300
ctggccccag ttggaggcat cattggatgg atgtttgcag tggagcagga cggattcaag 360
aatgggttca gcatcaccgg gggtgagttc actcgccagg ctgaggtgac cttcgtgggg 420
cacccgggca atctggtcat taagcagcgg ttcagcggca tcgatgagca tgggcacctg 480
accatcgaca cggagctgga gggccgcgtg ccgcagattc cgttcggctc ctccgtgcac 540
attgagccct acacggagct gtaccactac tccacctcag tgatcacttc ctcctccacc 600
cgggagtaca cggtgactga gcccgagcga gatggggcat ctccttcacg catctacact 660
taccagtggc gccagaccat caccttccag gaatgcgtcc acgatgactc ccggccagcc 720
ctgcccagca cccagcagct ctcggtggac agcgtgttcg tcctgtacaa ccaggaggag 780
aagatcttgc gctatgctct cagcaactcc attgggcctg tgagggaagg ctcccctgat 840
gct 843
<210> 58
<211> 281
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 G2结构域（直接胶原蛋白-IV，基底膜聚糖结合）
<400> 58
Arg Gln Thr Cys Ala Asn Asn Arg His Gln Cys Ser Val His Ala Glu
1 5 10 15
Cys Arg Asp Tyr Ala Thr Gly Phe Cys Cys Ser Cys Val Ala Gly Tyr
20 25 30
Thr Gly Asn Gly Arg Gln Cys Val Ala Glu Gly Ser Pro Gln Arg Val
35 40 45
Asn Gly Lys Val Lys Gly Arg Ile Phe Val Gly Ser Ser Gln Val Pro
50 55 60
Ile Val Phe Glu Asn Thr Asp Leu His Ser Tyr Val Val Met Asn His
65 70 75 80
Gly Arg Ser Tyr Thr Ala Ile Ser Thr Ile Pro Glu Thr Val Gly Tyr
85 90 95
Ser Leu Leu Pro Leu Ala Pro Val Gly Gly Ile Ile Gly Trp Met Phe
100 105 110
Ala Val Glu Gln Asp Gly Phe Lys Asn Gly Phe Ser Ile Thr Gly Gly
115 120 125
Glu Phe Thr Arg Gln Ala Glu Val Thr Phe Val Gly His Pro Gly Asn
130 135 140
Leu Val Ile Lys Gln Arg Phe Ser Gly Ile Asp Glu His Gly His Leu
145 150 155 160
Thr Ile Asp Thr Glu Leu Glu Gly Arg Val Pro Gln Ile Pro Phe Gly
165 170 175
Ser Ser Val His Ile Glu Pro Tyr Thr Glu Leu Tyr His Tyr Ser Thr
180 185 190
Ser Val Ile Thr Ser Ser Ser Thr Arg Glu Tyr Thr Val Thr Glu Pro
195 200 205
Glu Arg Asp Gly Ala Ser Pro Ser Arg Ile Tyr Thr Tyr Gln Trp Arg
210 215 220
Gln Thr Ile Thr Phe Gln Glu Cys Val His Asp Asp Ser Arg Pro Ala
225 230 235 240
Leu Pro Ser Thr Gln Gln Leu Ser Val Asp Ser Val Phe Val Leu Tyr
245 250 255
Asn Gln Glu Glu Lys Ile Leu Arg Tyr Ala Leu Ser Asn Ser Ile Gly
260 265 270
Pro Val Arg Glu Gly Ser Pro Asp Ala
275 280
<210> 59
<211> 126
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样2结构域[126 bp]
<400> 59
cttcagaatc catgctacat tggcacccat gggtgtgaca gcaatgctgc ctgtcgccct 60
ggccctggaa cacagttcac ctgcgaatgc tccatcggct tccgaggaga cgggcagact 120
tgctat 126
<210> 60
<211> 42
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样2 [间隔子]
<400> 60
Leu Gln Asn Pro Cys Tyr Ile Gly Thr His Gly Cys Asp Ser Asn Ala
1 5 10 15
Ala Cys Arg Pro Gly Pro Gly Thr Gln Phe Thr Cys Glu Cys Ser Ile
20 25 30
Gly Phe Arg Gly Asp Gly Gln Thr Cys Tyr
35 40
<210> 61
<211> 126
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白-1 EGF样2结构域[DNA, 126 bp]
<400> 61
cttcagaatc cctgctacat cggcactcat gggtgtgaca ccaacgcggc ctgtcgccct 60
ggtcccagga cacagttcac ctgcgagtgc tccatcggct tccgaggaga cgggcgaacc 120
tgctat 126
<210> 62
<211> 42
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 EGF样2结构域
<400> 62
Leu Gln Asn Pro Cys Tyr Ile Gly Thr His Gly Cys Asp Thr Asn Ala
1 5 10 15
Ala Cys Arg Pro Gly Pro Arg Thr Gln Phe Thr Cys Glu Cys Ser Ile
20 25 30
Gly Phe Arg Gly Asp Gly Arg Thr Cys Tyr
35 40
<210> 63
<211> 126
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样3结构域[126 bp]：
<400> 63
gatattgatg agtgttcaga gcagccttcc cgctgtggga accatgcggt ctgcaacaac 60
ctcccaggaa ccttccgctg cgagtgtgta gagggctacc acttctcaga caggggaaca 120
tgcgtg 126
<210> 64
<211> 42
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样3
<400> 64
Asp Ile Asp Glu Cys Ser Glu Gln Pro Ser Arg Cys Gly Asn His Ala
1 5 10 15
Val Cys Asn Asn Leu Pro Gly Thr Phe Arg Cys Glu Cys Val Glu Gly
20 25 30
Tyr His Phe Ser Asp Arg Gly Thr Cys Val
35 40
<210> 65
<211> 126
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白1 EGF样3结构域DNA 126 bp
<400> 65
cttcagaatc cctgctacat cggcactcat gggtgtgaca ccaacgcggc ctgtcgccct 60
ggtcccagga cacagttcac ctgcgagtgc tccatcggct tccgaggaga cgggcgaacc 120
tgctat 126
<210> 66
<211> 42
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 EGF样3结构域
<400> 66
Leu Gln Asn Pro Cys Tyr Ile Gly Thr His Gly Cys Asp Thr Asn Ala
1 5 10 15
Ala Cys Arg Pro Gly Pro Arg Thr Gln Phe Thr Cys Glu Cys Ser Ile
20 25 30
Gly Phe Arg Gly Asp Gly Arg Thr Cys Tyr
35 40
<210> 67
<211> 18
<212> DNA
<213> 人工序列
<220>
<223> EGF-3与-4之间的小鼠巢蛋白-1间隔子区段[DNA, 18 bp]
<400> 67
gctgccgagg accaacgt 18
<210> 68
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> EGF-3与-4之间的小鼠巢蛋白-1间隔子区段
<400> 68
Ala Ala Glu Asp Gln Arg
1 5
<210> 69
<211> 18
<212> DNA
<213> 人工序列
<220>
<223> EGF-3与-4之间的人巢蛋白-1间隔子区段[DNA, 18 bp]
<400> 69
gctgtcgtgg accagcgc 18
<210> 70
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> EGF-3与-4之间的人巢蛋白-1间隔子区段
<400> 70
Ala Val Val Asp Gln Arg
1 5
<210> 71
<211> 132
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样4结构域[132 bp]
<400> 71
cccatcaact actgtgaaac tggtctccac aactgtgata tcccccagcg agcccagtgc 60
atctatatgg gtggttcctc ctacacctgc tcctgtctgc ctggcttctc tggggatggc 120
agagcctgcc ga 132
<210> 72
<211> 44
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样4
<400> 72
Pro Ile Asn Tyr Cys Glu Thr Gly Leu His Asn Cys Asp Ile Pro Gln
1 5 10 15
Arg Ala Gln Cys Ile Tyr Met Gly Gly Ser Ser Tyr Thr Cys Ser Cys
20 25 30
Leu Pro Gly Phe Ser Gly Asp Gly Arg Ala Cys Arg
35 40
<210> 73
<211> 132
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白-1 EGF样4结构域[DNA, 132 bp]
<400> 73
cccatcaact actgtgaaac tggccttcat aactgcgaca taccccagcg ggcccagtgt 60
atctacacag gaggctcctc ctacacctgt tcctgcttgc caggcttttc tggggatggc 120
caagcctgcc aa 132
<210> 74
<211> 44
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 EGF样4结构域
<400> 74
Pro Ile Asn Tyr Cys Glu Thr Gly Leu His Asn Cys Asp Ile Pro Gln
1 5 10 15
Arg Ala Gln Cys Ile Tyr Thr Gly Gly Ser Ser Tyr Thr Cys Ser Cys
20 25 30
Leu Pro Gly Phe Ser Gly Asp Gly Gln Ala Cys Gln
35 40
<210> 75
<211> 141
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样5结构域[DNA, 141 bp]
<400> 75
gacgtggatg aatgccagca cagccgatgt caccccgatg ccttctgcta caacacacca 60
ggctctttca catgtcagtg caagcctggc tatcaggggg atggcttccg atgcatgccc 120
ggagaggtga gcaaaacccg g 141
<210> 76
<211> 47
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 EGF样5 [间隔子]
<400> 76
Asp Val Asp Glu Cys Gln His Ser Arg Cys His Pro Asp Ala Phe Cys
1 5 10 15
Tyr Asn Thr Pro Gly Ser Phe Thr Cys Gln Cys Lys Pro Gly Tyr Gln
20 25 30
Gly Asp Gly Phe Arg Cys Met Pro Gly Glu Val Ser Lys Thr Arg
35 40 45
<210> 77
<211> 141
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白-1 EGF样5结构域[DNA, 141 bp]
<400> 77
gatgtagatg aatgccagcc aagccgatgt caccctgacg ccttctgcta caacactcca 60
ggctctttca cgtgccagtg caaacctggt tatcagggag acggcttccg ttgcgtgccc 120
ggagaggtgg agaaaacccg g 141
<210> 78
<211> 47
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 EGF样5结构域
<400> 78
Asp Val Asp Glu Cys Gln Pro Ser Arg Cys His Pro Asp Ala Phe Cys
1 5 10 15
Tyr Asn Thr Pro Gly Ser Phe Thr Cys Gln Cys Lys Pro Gly Tyr Gln
20 25 30
Gly Asp Gly Phe Arg Cys Val Pro Gly Glu Val Glu Lys Thr Arg
35 40 45
<210> 79
<211> 282
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 G3 TY（甲状腺球蛋白样）结构域[DNA, 282 bp]
<400> 79
tgtcaactgg aacgagagca catccttgga gcagccggcg gggcagatgc acagcggccc 60
accctgcagg ggatgtttgt gcctcagtgt gatgaatatg gacactatgt acccacccag 120
tgtcaccaca gcactggcta ctgctggtgt gtggaccgag atggtcggga gctggagggt 180
agccgtaccc cacctgggat gaggcccccg tgtctgagta cagtggctcc tcctattcac 240
cagggaccag tagtacctac agctgtcatc cccctgcctc ca 282
<210> 80
<211> 94
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白“G3”TY（甲状腺球蛋白样）结构域
<400> 80
Cys Gln Leu Glu Arg Glu His Ile Leu Gly Ala Ala Gly Gly Ala Asp
1 5 10 15
Ala Gln Arg Pro Thr Leu Gln Gly Met Phe Val Pro Gln Cys Asp Glu
20 25 30
Tyr Gly His Tyr Val Pro Thr Gln Cys His His Ser Thr Gly Tyr Cys
35 40 45
Trp Cys Val Asp Arg Asp Gly Arg Glu Leu Glu Gly Ser Arg Thr Pro
50 55 60
Pro Gly Met Arg Pro Pro Cys Leu Ser Thr Val Ala Pro Pro Ile His
65 70 75 80
Gln Gly Pro Val Val Pro Thr Ala Val Ile Pro Leu Pro Pro
85 90
<210> 81
<211> 282
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白-1 G3 TY（甲状腺球蛋白样）结构域[DNA, 282 bp]
<400> 81
tgccagcacg agcgagaaca cattctcggg gcagcggggg cgacagaccc acagcgaccc 60
attcctccgg ggctgttcgt tcctgagtgc gatgcgcacg ggcactacgc gcccacccag 120
tgccacggca gcaccggcta ctgctggtgc gtggatcgcg acggccgcga ggtggagggc 180
accaggacca ggcccgggat gacgcccccg tgtctgagta cagtggctcc cccgattcac 240
caaggacctg cggtgcctac cgccgtgatc cccttgcctc ct 282
<210> 82
<211> 94
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 G3 TY（甲状腺球蛋白样）结构域
<400> 82
Cys Gln His Glu Arg Glu His Ile Leu Gly Ala Ala Gly Ala Thr Asp
1 5 10 15
Pro Gln Arg Pro Ile Pro Pro Gly Leu Phe Val Pro Glu Cys Asp Ala
20 25 30
His Gly His Tyr Ala Pro Thr Gln Cys His Gly Ser Thr Gly Tyr Cys
35 40 45
Trp Cys Val Asp Arg Asp Gly Arg Glu Val Glu Gly Thr Arg Thr Arg
50 55 60
Pro Gly Met Thr Pro Pro Cys Leu Ser Thr Val Ala Pro Pro Ile His
65 70 75 80
Gln Gly Pro Ala Val Pro Thr Ala Val Ile Pro Leu Pro Pro
85 90
<210> 83
<211> 744
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 G3-螺旋桨结构域[DNA, 744 bp]
<400> 83
gggacacact tactctttgc tcagactgga aagattgaac gcctgcccct ggaaagaaac 60
accatgaaga agacagaacg caaggccttt ctccatatcc ctgcaaaagt catcattgga 120
ctggcctttg actgcgtgga caaggtggtt tactggacag acatcagcga gccttccatt 180
gggagagcca gcctccacgg tggagagcca accaccatca ttcgacaaga tcttggaagc 240
cctgaaggca ttgcccttga ccatcttggt cgaaccatct tctggacgga ctctcagttg 300
gatcgaatag aagttgcaaa gatggatggc acccagcgcc gagtgctgtt tgacacgggt 360
ttggtgaatc ccagaggcat tgtgacagac cccgtaagag ggaaccttta ttggacagat 420
tggaacagag ataatcccaa aattgagact tctcacatgg atggcaccaa ccggaggatt 480
ctcgcacagg acaacctggg cttgcccaat ggtctgacct ttgatgcatt ctcatctcag 540
ctttgctggg tggatgcagg cacccatagg gcagaatgcc tgaacccagc tcagcctggc 600
agacgcaaag ttctcgaagg gctccagtat cctttcgctg tgactagcta tgggaagaat 660
ttgtactaca cagactggaa gacgaattca gtgattgcca tggaccttgc tatatccaaa 720
gagatggata ccttccaccc acac 744
<210> 84
<211> 248
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白“G3”-螺旋桨[层粘连蛋白结合结构域]
<400> 84
Gly Thr His Leu Leu Phe Ala Gln Thr Gly Lys Ile Glu Arg Leu Pro
1 5 10 15
Leu Glu Arg Asn Thr Met Lys Lys Thr Glu Arg Lys Ala Phe Leu His
20 25 30
Ile Pro Ala Lys Val Ile Ile Gly Leu Ala Phe Asp Cys Val Asp Lys
35 40 45
Val Val Tyr Trp Thr Asp Ile Ser Glu Pro Ser Ile Gly Arg Ala Ser
50 55 60
Leu His Gly Gly Glu Pro Thr Thr Ile Ile Arg Gln Asp Leu Gly Ser
65 70 75 80
Pro Glu Gly Ile Ala Leu Asp His Leu Gly Arg Thr Ile Phe Trp Thr
85 90 95
Asp Ser Gln Leu Asp Arg Ile Glu Val Ala Lys Met Asp Gly Thr Gln
100 105 110
Arg Arg Val Leu Phe Asp Thr Gly Leu Val Asn Pro Arg Gly Ile Val
115 120 125
Thr Asp Pro Val Arg Gly Asn Leu Tyr Trp Thr Asp Trp Asn Arg Asp
130 135 140
Asn Pro Lys Ile Glu Thr Ser His Met Asp Gly Thr Asn Arg Arg Ile
145 150 155 160
Leu Ala Gln Asp Asn Leu Gly Leu Pro Asn Gly Leu Thr Phe Asp Ala
165 170 175
Phe Ser Ser Gln Leu Cys Trp Val Asp Ala Gly Thr His Arg Ala Glu
180 185 190
Cys Leu Asn Pro Ala Gln Pro Gly Arg Arg Lys Val Leu Glu Gly Leu
195 200 205
Gln Tyr Pro Phe Ala Val Thr Ser Tyr Gly Lys Asn Leu Tyr Tyr Thr
210 215 220
Asp Trp Lys Thr Asn Ser Val Ile Ala Met Asp Leu Ala Ile Ser Lys
225 230 235 240
Glu Met Asp Thr Phe His Pro His
245
<210> 85
<211> 744
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白-1 G3-螺旋桨结构域[DNA, 744 bp]
<400> 85
gggacccatt tactctttgc ccagactggg aagattgagc gcctgcccct ggagggaaat 60
accatgagga agacagaagc aaaggcgttc cttcatgtcc cggctaaagt catcattgga 120
ctggcctttg actgcgtgga caagatggtt tactggacgg acatcactga gccttccatt 180
gggagagcta gtctacatgg tggagagcca accaccatca ttagacaaga tcttggaagt 240
ccagaaggta tcgctgttga tcaccttggc cgcaacatct tctggacaga ctctaacctg 300
gatcgaatag aagtggcgaa gctggacggc acgcagcgcc gggtgctctt tgagactgac 360
ttggtgaatc ccagaggcat tgtaacggat tccgtgagag ggaaccttta ctggacagac 420
tggaacagag ataaccccaa gattgaaact tcctacatgg acggcacgaa ccggaggatc 480
cttgtgcagg atgacctggg cttgcccaat ggactgacct tcgatgcgtt ctcatctcag 540
ctctgctggg tggatgcagg caccaatcgg gcggaatgcc tgaaccccag tcagcccagc 600
agacgcaagg ctctcgaagg gctccagtat ccttttgctg tgacgagcta cgggaagaat 660
ctgtatttca cagactggaa gatgaattcc gtggttgctc tcgatcttgc aatttccaag 720
gagacggatg ctttccaacc ccac 744
<210> 86
<211> 248
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 G3-螺旋桨结构域
<400> 86
Gly Thr His Leu Leu Phe Ala Gln Thr Gly Lys Ile Glu Arg Leu Pro
1 5 10 15
Leu Glu Gly Asn Thr Met Arg Lys Thr Glu Ala Lys Ala Phe Leu His
20 25 30
Val Pro Ala Lys Val Ile Ile Gly Leu Ala Phe Asp Cys Val Asp Lys
35 40 45
Met Val Tyr Trp Thr Asp Ile Thr Glu Pro Ser Ile Gly Arg Ala Ser
50 55 60
Leu His Gly Gly Glu Pro Thr Thr Ile Ile Arg Gln Asp Leu Gly Ser
65 70 75 80
Pro Glu Gly Ile Ala Val Asp His Leu Gly Arg Asn Ile Phe Trp Thr
85 90 95
Asp Ser Asn Leu Asp Arg Ile Glu Val Ala Lys Leu Asp Gly Thr Gln
100 105 110
Arg Arg Val Leu Phe Glu Thr Asp Leu Val Asn Pro Arg Gly Ile Val
115 120 125
Thr Asp Ser Val Arg Gly Asn Leu Tyr Trp Thr Asp Trp Asn Arg Asp
130 135 140
Asn Pro Lys Ile Glu Thr Ser Tyr Met Asp Gly Thr Asn Arg Arg Ile
145 150 155 160
Leu Val Gln Asp Asp Leu Gly Leu Pro Asn Gly Leu Thr Phe Asp Ala
165 170 175
Phe Ser Ser Gln Leu Cys Trp Val Asp Ala Gly Thr Asn Arg Ala Glu
180 185 190
Cys Leu Asn Pro Ser Gln Pro Ser Arg Arg Lys Ala Leu Glu Gly Leu
195 200 205
Gln Tyr Pro Phe Ala Val Thr Ser Tyr Gly Lys Asn Leu Tyr Phe Thr
210 215 220
Asp Trp Lys Met Asn Ser Val Val Ala Leu Asp Leu Ala Ile Ser Lys
225 230 235 240
Glu Thr Asp Ala Phe Gln Pro His
245
<210> 87
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> 小鼠巢蛋白-1 G3 EGF样6结构域[DNA, 171 bp]
<400> 87
aagcagaccc ggctatatgg catcaccatc gccctgtccc agtgtcccca aggccacaat 60
tactgctcag tgaataatgg tggatgtacc cacctctgct tgcccactcc agggagcagg 120
acctgccgat gtcctgacaa caccctggga gttgactgca ttgaacggaa a 171
<210> 88
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 小鼠巢蛋白“G3”EGF样6[接触层粘连蛋白LE表面]
<400> 88
Lys Gln Thr Arg Leu Tyr Gly Ile Thr Ile Ala Leu Ser Gln Cys Pro
1 5 10 15
Gln Gly His Asn Tyr Cys Ser Val Asn Asn Gly Gly Cys Thr His Leu
20 25 30
Cys Leu Pro Thr Pro Gly Ser Arg Thr Cys Arg Cys Pro Asp Asn Thr
35 40 45
Leu Gly Val Asp Cys Ile Glu Arg Lys
50 55
<210> 89
<211> 162
<212> DNA
<213> 人工序列
<220>
<223> 人巢蛋白-1 G3 EGF样6结构域[DNA, 162 bp]
<400> 89
aagcagaccc ggctgtatgg catcaccacg gccctgtctc agtgtccgca aggccataac 60
tactgctcag tgaacaatgg cggctgcacc cacctatgct tggccacccc agggagcagg 120
acctgccgtt gccctgacaa caccttggga gttgactgta tc 162
<210> 90
<211> 54
<212> PRT
<213> 人工序列
<220>
<223> 人巢蛋白-1 G3 EGF样6结构域
<400> 90
Lys Gln Thr Arg Leu Tyr Gly Ile Thr Thr Ala Leu Ser Gln Cys Pro
1 5 10 15
Gln Gly His Asn Tyr Cys Ser Val Asn Asn Gly Gly Cys Thr His Leu
20 25 30
Cys Leu Ala Thr Pro Gly Ser Arg Thr Cys Arg Cys Pro Asp Asn Thr
35 40 45
Leu Gly Val Asp Cys Ile
50
<210> 91
<211> 63
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1信号肽[63 bp]：
<400> 91
atggggctgc tccaggtgtt cgcctttggt gtcctagccc tatggggcac ccgagtgtgc 60
gct 63
<210> 92
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1信号肽
<400> 92
Met Gly Leu Leu Gln Val Phe Ala Phe Gly Val Leu Ala Leu Trp Gly
1 5 10 15
Thr Arg Val Cys Ala
20
<210> 93
<211> 63
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1信号[63 bp]
<400> 93
atggggcttc tccagttgct agctttcagt ttcttagccc tgtgcagagc ccgagtgcgc 60
gct 63
<210> 94
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1信号肽
<400> 94
Met Gly Leu Leu Gln Leu Leu Ala Phe Ser Phe Leu Ala Leu Cys Arg
1 5 10 15
Ala Arg Val Arg Ala
20
<210> 95
<211> 744
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LN结构域[744 bp]
<400> 95
caggaaccgg agttcagcta tggctgcgca gaaggcagct gctaccctgc cactggcgac 60
cttctcatcg gccgagcgca aaagctctcc gtgacttcga catgtggact gcacaaacca 120
gagccctact gtattgttag ccacctgcag gaggacaaga aatgcttcat atgtgactcc 180
cgagaccctt atcacgagac cctcaacccc gacagccatc tcattgagaa cgtggtcacc 240
acatttgctc caaaccgcct taagatctgg tggcaatcgg aaaatggtgt ggagaacgtg 300
accatccaac tggacctgga agcagaattc catttcactc atctcatcat gaccttcaag 360
acattccgcc cagccgccat gctgatcgag cggtcttctg actttgggaa gacttggggc 420
gtgtacagat acttcgccta cgactgtgag agctcgttcc caggcatttc aactggaccc 480
atgaagaaag tggatgacat catctgtgac tctcgatatt ctgacattga gccctcgaca 540
gaaggagagg taatatttcg tgctttagat cctgctttca aaattgaaga cccttatagt 600
ccaaggatac agaatctatt aaaaatcacc aacttgagaa tcaagtttgt gaaactgcac 660
accttggggg ataacctttt ggactccaga atggaaatcc gagagaagta ctattacgct 720
gtttatgata tggtggttcg aggg 744
<210> 96
<211> 248
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LN
<400> 96
Gln Glu Pro Glu Phe Ser Tyr Gly Cys Ala Glu Gly Ser Cys Tyr Pro
1 5 10 15
Ala Thr Gly Asp Leu Leu Ile Gly Arg Ala Gln Lys Leu Ser Val Thr
20 25 30
Ser Thr Cys Gly Leu His Lys Pro Glu Pro Tyr Cys Ile Val Ser His
35 40 45
Leu Gln Glu Asp Lys Lys Cys Phe Ile Cys Asp Ser Arg Asp Pro Tyr
50 55 60
His Glu Thr Leu Asn Pro Asp Ser His Leu Ile Glu Asn Val Val Thr
65 70 75 80
Thr Phe Ala Pro Asn Arg Leu Lys Ile Trp Trp Gln Ser Glu Asn Gly
85 90 95
Val Glu Asn Val Thr Ile Gln Leu Asp Leu Glu Ala Glu Phe His Phe
100 105 110
Thr His Leu Ile Met Thr Phe Lys Thr Phe Arg Pro Ala Ala Met Leu
115 120 125
Ile Glu Arg Ser Ser Asp Phe Gly Lys Thr Trp Gly Val Tyr Arg Tyr
130 135 140
Phe Ala Tyr Asp Cys Glu Ser Ser Phe Pro Gly Ile Ser Thr Gly Pro
145 150 155 160
Met Lys Lys Val Asp Asp Ile Ile Cys Asp Ser Arg Tyr Ser Asp Ile
165 170 175
Glu Pro Ser Thr Glu Gly Glu Val Ile Phe Arg Ala Leu Asp Pro Ala
180 185 190
Phe Lys Ile Glu Asp Pro Tyr Ser Pro Arg Ile Gln Asn Leu Leu Lys
195 200 205
Ile Thr Asn Leu Arg Ile Lys Phe Val Lys Leu His Thr Leu Gly Asp
210 215 220
Asn Leu Leu Asp Ser Arg Met Glu Ile Arg Glu Lys Tyr Tyr Tyr Ala
225 230 235 240
Val Tyr Asp Met Val Val Arg Gly
245
<210> 97
<211> 744
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LN结构域[DNA, 744 bp]
<400> 97
caggaacccg agttcagcta cggctgcgca gaaggcagct gctatcccgc cacgggcgac 60
cttctcatcg gccgagcaca gaagctttcg gtgacctcga cgtgcgggct gcacaagccc 120
gaaccctact gtatcgtcag ccacttgcag gaggacaaaa aatgcttcat atgcaattcc 180
caagatcctt atcatgagac cctgaatcct gacagccatc tcattgaaaa tgtggtcact 240
acatttgctc caaaccgcct taagatttgg tggcaatctg aaaatggtgt ggaaaatgta 300
actatccaac tggatttgga agcagaattc cattttactc atctcataat gactttcaag 360
acattccgtc cagctgctat gctgatagaa cgatcgtccg actttgggaa aacctggggt 420
gtgtatagat acttcgccta tgactgtgag gcctcgtttc caggcatttc aactggcccc 480
atgaaaaaag tcgatgacat aatttgtgat tctcgatatt ctgacattga accctcaact 540
gaaggagagg tgatatttcg tgctttagat cctgctttca aaatagaaga tccttatagc 600
ccaaggatac agaatttatt aaaaattacc aacttgagaa tcaagtttgt gaaactgcat 660
actttgggag ataaccttct ggattccagg atggaaatca gagaaaagta ttattatgca 720
gtttatgata tggtggttcg agga 744
<210> 98
<211> 248
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LN
<400> 98
Gln Glu Pro Glu Phe Ser Tyr Gly Cys Ala Glu Gly Ser Cys Tyr Pro
1 5 10 15
Ala Thr Gly Asp Leu Leu Ile Gly Arg Ala Gln Lys Leu Ser Val Thr
20 25 30
Ser Thr Cys Gly Leu His Lys Pro Glu Pro Tyr Cys Ile Val Ser His
35 40 45
Leu Gln Glu Asp Lys Lys Cys Phe Ile Cys Asn Ser Gln Asp Pro Tyr
50 55 60
His Glu Thr Leu Asn Pro Asp Ser His Leu Ile Glu Asn Val Val Thr
65 70 75 80
Thr Phe Ala Pro Asn Arg Leu Lys Ile Trp Trp Gln Ser Glu Asn Gly
85 90 95
Val Glu Asn Val Thr Ile Gln Leu Asp Leu Glu Ala Glu Phe His Phe
100 105 110
Thr His Leu Ile Met Thr Phe Lys Thr Phe Arg Pro Ala Ala Met Leu
115 120 125
Ile Glu Arg Ser Ser Asp Phe Gly Lys Thr Trp Gly Val Tyr Arg Tyr
130 135 140
Phe Ala Tyr Asp Cys Glu Ala Ser Phe Pro Gly Ile Ser Thr Gly Pro
145 150 155 160
Met Lys Lys Val Asp Asp Ile Ile Cys Asp Ser Arg Tyr Ser Asp Ile
165 170 175
Glu Pro Ser Thr Glu Gly Glu Val Ile Phe Arg Ala Leu Asp Pro Ala
180 185 190
Phe Lys Ile Glu Asp Pro Tyr Ser Pro Arg Ile Gln Asn Leu Leu Lys
195 200 205
Ile Thr Asn Leu Arg Ile Lys Phe Val Lys Leu His Thr Leu Gly Asp
210 215 220
Asn Leu Leu Asp Ser Arg Met Glu Ile Arg Glu Lys Tyr Tyr Tyr Ala
225 230 235 240
Val Tyr Asp Met Val Val Arg Gly
245
<210> 99
<211> 192
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-1结构域[DNA, 192 bp]
<400> 99
aactgcttct gctatggcca cgccagtgaa tgcgcccctg tggatggagt caatgaagaa 60
gtggaaggaa tggttcacgg gcactgcatg tgcagacaca acaccaaagg cctgaactgt 120
gagctgtgca tggatttcta ccacgatttg ccgtggagac ctgctgaagg ccggaacagc 180
aacgcctgca aa 192
<210> 100
<211> 64
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-1
<400> 100
Asn Cys Phe Cys Tyr Gly His Ala Ser Glu Cys Ala Pro Val Asp Gly
1 5 10 15
Val Asn Glu Glu Val Glu Gly Met Val His Gly His Cys Met Cys Arg
20 25 30
His Asn Thr Lys Gly Leu Asn Cys Glu Leu Cys Met Asp Phe Tyr His
35 40 45
Asp Leu Pro Trp Arg Pro Ala Glu Gly Arg Asn Ser Asn Ala Cys Lys
50 55 60
<210> 101
<211> 192
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-1 [DNA, 192 bp]
<400> 101
aattgcttct gctatggtca tgccagcgaa tgtgcccctg tggatggatt caatgaagaa 60
gtggaaggaa tggttcacgg acactgcatg tgcaggcata acaccaaggg cttaaactgt 120
gaactctgca tggatttcta ccatgattta ccttggagac ctgctgaagg ccgaaacagc 180
aacgcctgta aa 192
<210> 102
<211> 64
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-1
<400> 102
Asn Cys Phe Cys Tyr Gly His Ala Ser Glu Cys Ala Pro Val Asp Gly
1 5 10 15
Phe Asn Glu Glu Val Glu Gly Met Val His Gly His Cys Met Cys Arg
20 25 30
His Asn Thr Lys Gly Leu Asn Cys Glu Leu Cys Met Asp Phe Tyr His
35 40 45
Asp Leu Pro Trp Arg Pro Ala Glu Gly Arg Asn Ser Asn Ala Cys Lys
50 55 60
<210> 103
<211> 189
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-2结构域[DNA, 189 bp]
<400> 103
aaatgtaact gcaatgaaca ttccagctcg tgtcactttg acatggcagt cttcctggct 60
actggcaacg tcagcggggg agtgtgtgat aactgtcagc acaacaccat ggggcgcaac 120
tgtgaacagt gcaaaccgtt ctacttccag caccctgaga gggacatccg ggaccccaat 180
ctctgtgaa 189
<210> 104
<211> 63
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-2
<400> 104
Lys Cys Asn Cys Asn Glu His Ser Ser Ser Cys His Phe Asp Met Ala
1 5 10 15
Val Phe Leu Ala Thr Gly Asn Val Ser Gly Gly Val Cys Asp Asn Cys
20 25 30
Gln His Asn Thr Met Gly Arg Asn Cys Glu Gln Cys Lys Pro Phe Tyr
35 40 45
Phe Gln His Pro Glu Arg Asp Ile Arg Asp Pro Asn Leu Cys Glu
50 55 60
<210> 105
<211> 189
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-2 [DNA, 189 bp]
<400> 105
aaatgtaact gcaatgaaca ttccatctct tgtcactttg acatggctgt ttacctggcc 60
acggggaacg tcagcggagg cgtgtgtgat gactgtcagc acaacaccat ggggcgcaac 120
tgtgagcagt gcaagccgtt ttactaccag cacccagaga gggacatccg agatcctaat 180
ttctgtgaa 189
<210> 106
<211> 63
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-
<400> 106
Lys Cys Asn Cys Asn Glu His Ser Ile Ser Cys His Phe Asp Met Ala
1 5 10 15
Val Tyr Leu Ala Thr Gly Asn Val Ser Gly Gly Val Cys Asp Asp Cys
20 25 30
Gln His Asn Thr Met Gly Arg Asn Cys Glu Gln Cys Lys Pro Phe Tyr
35 40 45
Tyr Gln His Pro Glu Arg Asp Ile Arg Asp Pro Asn Phe Cys Glu
50 55 60
<210> 107
<211> 180
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-3结构域[DNA, 180 bp]
<400> 107
ccatgtacct gtgacccagc tggttctgag aatggcggga tctgtgatgg gtacactgat 60
ttttctgtgg gtctcattgc tggtcagtgt cggtgcaaat tgcacgtgga gggagagcgc 120
tgtgatgttt gtaaagaagg cttctacgac ttaagtgctg aagacccgta tggttgtaaa 180
<210> 108
<211> 60
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-3
<400> 108
Pro Cys Thr Cys Asp Pro Ala Gly Ser Glu Asn Gly Gly Ile Cys Asp
1 5 10 15
Gly Tyr Thr Asp Phe Ser Val Gly Leu Ile Ala Gly Gln Cys Arg Cys
20 25 30
Lys Leu His Val Glu Gly Glu Arg Cys Asp Val Cys Lys Glu Gly Phe
35 40 45
Tyr Asp Leu Ser Ala Glu Asp Pro Tyr Gly Cys Lys
50 55 60
<210> 109
<211> 180
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-3 [DNA, 180 bp]
<400> 109
cgatgtacgt gtgacccagc tggctctcaa aatgagggaa tttgtgacag ctatactgat 60
ttttctactg gtctcattgc tggccagtgt cggtgtaaat taaatgtgga aggagaacat 120
tgtgatgttt gcaaagaagg cttctatgat ttaagcagtg aagatccatt tggttgtaaa 180
<210> 110
<211> 60
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-3
<400> 110
Arg Cys Thr Cys Asp Pro Ala Gly Ser Gln Asn Glu Gly Ile Cys Asp
1 5 10 15
Ser Tyr Thr Asp Phe Ser Thr Gly Leu Ile Ala Gly Gln Cys Arg Cys
20 25 30
Lys Leu Asn Val Glu Gly Glu His Cys Asp Val Cys Lys Glu Gly Phe
35 40 45
Tyr Asp Leu Ser Ser Glu Asp Pro Phe Gly Cys Lys
50 55 60
<210> 111
<211> 156
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-4结构域[DNA, 156 bp]
<400> 111
tcatgtgctt gcaatcctct gggaacaatt cctggtggga atccttgtga ttctgagact 60
ggctactgct actgtaagcg cctggtgaca ggacagcgct gtgaccagtg cctgccgcag 120
cactggggtt taagcaatga tttggatggg tgtcga 156
<210> 112
<211> 52
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-4
<400> 112
Ser Cys Ala Cys Asn Pro Leu Gly Thr Ile Pro Gly Gly Asn Pro Cys
1 5 10 15
Asp Ser Glu Thr Gly Tyr Cys Tyr Cys Lys Arg Leu Val Thr Gly Gln
20 25 30
Arg Cys Asp Gln Cys Leu Pro Gln His Trp Gly Leu Ser Asn Asp Leu
35 40 45
Asp Gly Cys Arg
50
<210> 113
<211> 156
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-4 [DNA, 156 bp]
<400> 113
tcttgtgctt gcaatcctct gggaacaatt cctggaggga atccttgtga ttccgagaca 60
ggtcactgct actgcaagcg tctggtgaca ggacagcatt gtgaccagtg cctgccagag 120
cactggggct taagcaatga tttggatgga tgtcga 156
<210> 114
<211> 52
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-4
<400> 114
Ser Cys Ala Cys Asn Pro Leu Gly Thr Ile Pro Gly Gly Asn Pro Cys
1 5 10 15
Asp Ser Glu Thr Gly His Cys Tyr Cys Lys Arg Leu Val Thr Gly Gln
20 25 30
His Cys Asp Gln Cys Leu Pro Glu His Trp Gly Leu Ser Asn Asp Leu
35 40 45
Asp Gly Cys Arg
50
<210> 115
<211> 99
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1信号肽[DNA, 99 bp]
<400> 115
atgacgggcg gcgggcgggc cgcgctggcc ctgcagcccc gggggcggct gtggccgctg 60
ttggctgtgc tggcggctgt ggcgggctgt gtccgggcg 99
<210> 116
<211> 33
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1信号肽
<400> 116
Met Thr Gly Gly Gly Arg Ala Ala Leu Ala Leu Gln Pro Arg Gly Arg
1 5 10 15
Leu Trp Pro Leu Leu Ala Val Leu Ala Ala Val Ala Gly Cys Val Arg
20 25 30
Ala
<210> 117
<211> 99
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1信号肽[DNA, 99 bp]
<400> 117
atgagaggga gccatcgggc cgcgccggcc ctgcggcccc gggggcggct ctggcccgtg 60
ctggccgtgc tggcggcggc cgccgcggcg ggctgtgcc 99
<210> 118
<211> 33
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1信号肽：
<400> 118
Met Arg Gly Ser His Arg Ala Ala Pro Ala Leu Arg Pro Arg Gly Arg
1 5 10 15
Leu Trp Pro Val Leu Ala Val Leu Ala Ala Ala Ala Ala Ala Gly Cys
20 25 30
Ala
<210> 119
<211> 768
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LN结构域[DNA, 768 bp]（注释：人1中的E/GAG（2）
相对于小鼠I中的D/GAC（1）为D或E，但在小鼠LN-LEa的晶体结构中为E）
<400> 119
gccatggact acaaggacga cgatgacaag gagtgcgcgg atgagggcgg gcggccgcag 60
cgctgcatgc cggagtttgt taatgccgcc ttcaatgtga ccgtggtggc taccaacacg 120
tgtgggactc cgcccgagga gtactgcgtg cagactgggg tgaccggagt cactaagtcc 180
tgtcacctgt gcgacgccgg ccagcagcac ctgcaacacg gggcagcctt cctgaccgac 240
tacaacaacc aggccgacac cacctggtgg caaagccaga ctatgctggc cggggtgcag 300
taccccaact ccatcaacct cacgctgcac ctgggaaagg cttttgacat cacttacgtg 360
cgcctcaagt tccacaccag ccgtccagag agcttcgcca tctataagcg cactcgggaa 420
gacgggccct ggattcctta tcagtactac agtgggtcct gtgagaacac gtactcaaag 480
gctaaccgtg gcttcatcag gaccggaggg gacgagcagc aggccttgtg tactgatgaa 540
ttcagtgaca tttcccccct caccggtggc aacgtggcct tttcaaccct ggaaggacgg 600
ccgagtgcct acaactttga caacagccct gtgctccagg aatgggtaac tgccactgac 660
atcagagtga cgctcaatcg cctgaacacc tttggagatg aagtgtttaa cgagcccaaa 720
gttctcaagt cttactatta cgcaatctca gactttgctg tgggcggc 768
<210> 120
<211> 249
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LN结构域
<400> 120
Ala Met Asp Glu Cys Ala Asp Glu Gly Gly Arg Pro Gln Arg Cys Met
1 5 10 15
Pro Glu Phe Val Asn Ala Ala Phe Asn Val Thr Val Val Ala Thr Asn
20 25 30
Thr Cys Gly Thr Pro Pro Glu Glu Tyr Cys Val Gln Thr Gly Val Thr
35 40 45
Gly Val Thr Lys Ser Cys His Leu Cys Asp Ala Gly Gln Gln His Leu
50 55 60
Gln His Gly Ala Ala Phe Leu Thr Asp Tyr Asn Asn Gln Ala Asp Thr
65 70 75 80
Thr Trp Trp Gln Ser Gln Thr Met Leu Ala Gly Val Gln Tyr Pro Asn
85 90 95
Ser Ile Asn Leu Thr Leu His Leu Gly Lys Ala Phe Asp Ile Thr Tyr
100 105 110
Val Arg Leu Lys Phe His Thr Ser Arg Pro Glu Ser Phe Ala Ile Tyr
115 120 125
Lys Arg Thr Arg Glu Asp Gly Pro Trp Ile Pro Tyr Gln Tyr Tyr Ser
130 135 140
Gly Ser Cys Glu Asn Thr Tyr Ser Lys Ala Asn Arg Gly Phe Ile Arg
145 150 155 160
Thr Gly Gly Asp Glu Gln Gln Ala Leu Cys Thr Asp Glu Phe Ser Asp
165 170 175
Ile Ser Pro Leu Thr Gly Gly Asn Val Ala Phe Ser Thr Leu Glu Gly
180 185 190
Arg Pro Ser Ala Tyr Asn Phe Asp Asn Ser Pro Val Leu Gln Glu Trp
195 200 205
Val Thr Ala Thr Asp Ile Arg Val Thr Leu Asn Arg Leu Asn Thr Phe
210 215 220
Gly Asp Glu Val Phe Asn Glu Pro Lys Val Leu Lys Ser Tyr Tyr Tyr
225 230 235 240
Ala Ile Ser Asp Phe Ala Val Gly Gly
245
<210> 121
<211> 753
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LN结构域[DNA, 753 bp]
<400> 121
caggcagcca tggacgagtg cacggacgag ggcgggcggc cgcaacgctg catgcccgag 60
ttcgtcaacg ccgctttcaa cgtgactgtg gtggccacca acacgtgtgg gactccgccc 120
gaggaatact gtgtgcagac cggggtgacc ggggtcacca agtcctgtca cctgtgcgac 180
gccgggcagc cccacctgca gcacggggca gccttcctga ccgactacaa caaccaggcc 240
gacaccacct ggtggcaaag ccagaccatg ctggccgggg tgcagtaccc cagctccatc 300
aacctcacgc tgcacctggg aaaagctttt gacatcacct atgtgcgtct caagttccac 360
accagccgcc cggagagctt tgccatttac aagcgcacat gggaagacgg gccctggatt 420
ccttaccagt actacagtgg ttcctgcgag aacacctact ccaaggcaaa ccgcggcttc 480
atcaggacag gaggggacga gcagcaggcc ttgtgtactg atgaattcag tgacatttct 540
cccctcactg ggggcaacgt ggccttttct accctggaag gaaggcccag cgcctataac 600
tttgacaata gccctgtgct gcaggaatgg gtaactgcca ctgacatcag tgtaactctt 660
aatcgcctga acacttttgg agatgaagtg tttaacgatc ccaaagttct caagtcctat 720
tattatgcca tctctgattt tgctgtaggt ggc 753
<210> 122
<211> 251
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LN结构域
<400> 122
Gln Ala Ala Met Asp Glu Cys Thr Asp Glu Gly Gly Arg Pro Gln Arg
1 5 10 15
Cys Met Pro Glu Phe Val Asn Ala Ala Phe Asn Val Thr Val Val Ala
20 25 30
Thr Asn Thr Cys Gly Thr Pro Pro Glu Glu Tyr Cys Val Gln Thr Gly
35 40 45
Val Thr Gly Val Thr Lys Ser Cys His Leu Cys Asp Ala Gly Gln Pro
50 55 60
His Leu Gln His Gly Ala Ala Phe Leu Thr Asp Tyr Asn Asn Gln Ala
65 70 75 80
Asp Thr Thr Trp Trp Gln Ser Gln Thr Met Leu Ala Gly Val Gln Tyr
85 90 95
Pro Ser Ser Ile Asn Leu Thr Leu His Leu Gly Lys Ala Phe Asp Ile
100 105 110
Thr Tyr Val Arg Leu Lys Phe His Thr Ser Arg Pro Glu Ser Phe Ala
115 120 125
Ile Tyr Lys Arg Thr Trp Glu Asp Gly Pro Trp Ile Pro Tyr Gln Tyr
130 135 140
Tyr Ser Gly Ser Cys Glu Asn Thr Tyr Ser Lys Ala Asn Arg Gly Phe
145 150 155 160
Ile Arg Thr Gly Gly Asp Glu Gln Gln Ala Leu Cys Thr Asp Glu Phe
165 170 175
Ser Asp Ile Ser Pro Leu Thr Gly Gly Asn Val Ala Phe Ser Thr Leu
180 185 190
Glu Gly Arg Pro Ser Ala Tyr Asn Phe Asp Asn Ser Pro Val Leu Gln
195 200 205
Glu Trp Val Thr Ala Thr Asp Ile Ser Val Thr Leu Asn Arg Leu Asn
210 215 220
Thr Phe Gly Asp Glu Val Phe Asn Asp Pro Lys Val Leu Lys Ser Tyr
225 230 235 240
Tyr Tyr Ala Ile Ser Asp Phe Ala Val Gly Gly
245 250
<210> 123
<211> 168
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa 1结构域DNA 68 bp
注释：用于cys的TGC，Durkin等人, 《生物化学（Biochemistry）》 27 14
<400> 123
aggtgtaaat gtaacggaca tgccagcgag tgtgtaaaga acgagtttga caaactcatg 60
tgcaactgca aacataacac atacggagtt gactgtgaaa agtgcctgcc tttcttcaat 120
gaccggccgt ggaggagggc gactgctgag agcgccagcg agtgcctt 168
<210> 124
<211> 56
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-1
<400> 124
Arg Cys Lys Cys Asn Gly His Ala Ser Glu Cys Val Lys Asn Glu Phe
1 5 10 15
Asp Lys Leu Met Cys Asn Cys Lys His Asn Thr Tyr Gly Val Asp Cys
20 25 30
Glu Lys Cys Leu Pro Phe Phe Asn Asp Arg Pro Trp Arg Arg Ala Thr
35 40 45
Ala Glu Ser Ala Ser Glu Cys Leu
50 55
<210> 125
<211> 168
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-1 [DNA, 168 bp]
<400> 125
agatgtaaat gtaatggaca cgcaagcgag tgtatgaaga acgaatttga taagctggtg 60
tgtaattgca aacataacac atatggagta gactgtgaaa agtgtcttcc tttcttcaat 120
gaccggccgt ggaggagggc aactgcggaa agtgccagtg aatgcctg 168
<210> 126
<211> 56
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-1
<400> 126
Arg Cys Lys Cys Asn Gly His Ala Ser Glu Cys Met Lys Asn Glu Phe
1 5 10 15
Asp Lys Leu Val Cys Asn Cys Lys His Asn Thr Tyr Gly Val Asp Cys
20 25 30
Glu Lys Cys Leu Pro Phe Phe Asn Asp Arg Pro Trp Arg Arg Ala Thr
35 40 45
Ala Glu Ser Ala Ser Glu Cys Leu
50 55
<210> 127
<211> 168
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-2结构域[DNA, 168 bp]
<400> 127
ccttgtgact gcaatggccg atcccaagag tgctactttg atcctgaact ataccgttcc 60
actggacatg gtggccactg taccaactgc cgggataaca cagatggtgc caagtgcgag 120
aggtgccggg agaatttctt ccgcctgggg aacactgaag cctgctct 168
<210> 128
<211> 56
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-2
<400> 128
Pro Cys Asp Cys Asn Gly Arg Ser Gln Glu Cys Tyr Phe Asp Pro Glu
1 5 10 15
Leu Tyr Arg Ser Thr Gly His Gly Gly His Cys Thr Asn Cys Arg Asp
20 25 30
Asn Thr Asp Gly Ala Lys Cys Glu Arg Cys Arg Glu Asn Phe Phe Arg
35 40 45
Leu Gly Asn Thr Glu Ala Cys Ser
50 55
<210> 129
<211> 168
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-2 [DNA, 168 bp]
<400> 129
ccctgtgatt gcaatggtcg atcccaggaa tgctacttcg accctgaact ctatcgttcc 60
actggccatg ggggccactg taccaactgc caggataaca cagatggcgc ccactgtgag 120
aggtgccgag agaacttctt ccgccttggc aacaatgaag cctgctct 168
<210> 130
<211> 56
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-2
<400> 130
Pro Cys Asp Cys Asn Gly Arg Ser Gln Glu Cys Tyr Phe Asp Pro Glu
1 5 10 15
Leu Tyr Arg Ser Thr Gly His Gly Gly His Cys Thr Asn Cys Gln Asp
20 25 30
Asn Thr Asp Gly Ala His Cys Glu Arg Cys Arg Glu Asn Phe Phe Arg
35 40 45
Leu Gly Asn Asn Glu Ala Cys Ser
50 55
<210> 131
<211> 141
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-3结构域[DNA, 141 bp]
<400> 131
ccgtgccact gcagccctgt tggttctctc agcacacagt gtgacagtta cggcagatgc 60
agctgtaagc caggagtgat gggtgacaag tgtgaccgtt gtcagcctgg gttccattcc 120
ctcactgagg caggatgcag g 141
<210> 132
<211> 47
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-3
<400> 132
Pro Cys His Cys Ser Pro Val Gly Ser Leu Ser Thr Gln Cys Asp Ser
1 5 10 15
Tyr Gly Arg Cys Ser Cys Lys Pro Gly Val Met Gly Asp Lys Cys Asp
20 25 30
Arg Cys Gln Pro Gly Phe His Ser Leu Thr Glu Ala Gly Cys Arg
35 40 45
<210> 133
<211> 141
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-3 [DNA, 141 bp]
<400> 133
tcatgccact gtagtcctgt gggctctcta agcacacagt gtgatagtta cggcagatgc 60
agctgtaagc caggagtgat gggggacaaa tgtgaccgtt gccagcctgg attccattct 120
ctcactgaag caggatgcag g 141
<210> 134
<211> 47
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-3
<400> 134
Ser Cys His Cys Ser Pro Val Gly Ser Leu Ser Thr Gln Cys Asp Ser
1 5 10 15
Tyr Gly Arg Cys Ser Cys Lys Pro Gly Val Met Gly Asp Lys Cys Asp
20 25 30
Arg Cys Gln Pro Gly Phe His Ser Leu Thr Glu Ala Gly Cys Arg
35 40 45
<210> 135
<211> 150
<212> DNA
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-4 [DNA, 150 bp]
<400> 135
ccatgctcct gcgatcttcg gggcagcaca gacgagtgta atgttgaaac aggaagatgc 60
gtttgcaaag acaatgttga aggcttcaac tgtgagagat gcaaacctgg attttttaat 120
ctggagtcat ctaatcctaa gggctgcaca 150
<210> 136
<211> 50
<212> PRT
<213> 人工序列
<220>
<223> 小鼠层粘连蛋白1 LEa-4
<400> 136
Pro Cys Ser Cys Asp Leu Arg Gly Ser Thr Asp Glu Cys Asn Val Glu
1 5 10 15
Thr Gly Arg Cys Val Cys Lys Asp Asn Val Glu Gly Phe Asn Cys Glu
20 25 30
Arg Cys Lys Pro Gly Phe Phe Asn Leu Glu Ser Ser Asn Pro Lys Gly
35 40 45
Cys Thr
50
<210> 137
<211> 150
<212> DNA
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-4 [DNA, 150 bp]
<400> 137
ccatgctctt gtgatccctc tggcagcata gatgaatgta atgttgaaac aggaagatgt 60
gtttgcaaag acaatgtcga aggcttcaat tgtgaaagat gcaaacctgg attttttaat 120
ctggaatcat ctaatcctcg gggttgcaca 150
<210> 138
<211> 50
<212> PRT
<213> 人工序列
<220>
<223> 人层粘连蛋白1 LEa-4
<400> 138
Pro Cys Ser Cys Asp Pro Ser Gly Ser Ile Asp Glu Cys Asn Val Glu
1 5 10 15
Thr Gly Arg Cys Val Cys Lys Asp Asn Val Glu Gly Phe Asn Cys Glu
20 25 30
Arg Cys Lys Pro Gly Phe Phe Asn Leu Glu Ser Ser Asn Pro Arg Gly
35 40 45
Cys Thr
50
<210> 139
<211> 531
<212> DNA
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG1结构域[DNA, 531 bp]
<400> 139
ccctctgtgc cagcttttaa gggccactcc ttcttggcct tccccaccct ccgagcctac 60
cacacgctgc gtctggcact agaattccgg gcgctggaga cagagggact gctgctctac 120
aatggcaatg cacgtggcaa agatttcctg gctctggctc tgttggatgg tcatgtacag 180
ttcaggttcg acacgggctc agggccggcg gtgctaacaa gcttagtgcc agtggaaccg 240
ggacggtggc accgcctcga gttgtcacgg cattggcggc agggcacact ttctgtggat 300
ggcgaggctc ctgttgtagg tgaaagtccg agtggcactg atggcctcaa cttggacacg 360
aagctctatg tgggtggtct cccagaagaa caagttgcca cggtgcttga tcggacctct 420
gtgggcatcg gcctgaaagg atgcattcgt atgttggaca tcaacaacca gcagctggag 480
ctgagcgatt ggcagagggc tgtggttcaa agctctggtg tgggggaatg c 531
<210> 140
<211> 177
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG1结构域
<400> 140
Pro Ser Val Pro Ala Phe Lys Gly His Ser Phe Leu Ala Phe Pro Thr
1 5 10 15
Leu Arg Ala Tyr His Thr Leu Arg Leu Ala Leu Glu Phe Arg Ala Leu
20 25 30
Glu Thr Glu Gly Leu Leu Leu Tyr Asn Gly Asn Ala Arg Gly Lys Asp
35 40 45
Phe Leu Ala Leu Ala Leu Leu Asp Gly His Val Gln Phe Arg Phe Asp
50 55 60
Thr Gly Ser Gly Pro Ala Val Leu Thr Ser Leu Val Pro Val Glu Pro
65 70 75 80
Gly Arg Trp His Arg Leu Glu Leu Ser Arg His Trp Arg Gln Gly Thr
85 90 95
Leu Ser Val Asp Gly Glu Ala Pro Val Val Gly Glu Ser Pro Ser Gly
100 105 110
Thr Asp Gly Leu Asn Leu Asp Thr Lys Leu Tyr Val Gly Gly Leu Pro
115 120 125
Glu Glu Gln Val Ala Thr Val Leu Asp Arg Thr Ser Val Gly Ile Gly
130 135 140
Leu Lys Gly Cys Ile Arg Met Leu Asp Ile Asn Asn Gln Gln Leu Glu
145 150 155 160
Leu Ser Asp Trp Gln Arg Ala Val Val Gln Ser Ser Gly Val Gly Glu
165 170 175
Cys
<210> 141
<211> 531
<212> DNA
<213> 人工序列
<220>
<223> 人集聚蛋白LG1 [DNA, 531 bp]
<400> 141
gcccctgtgc cggccttcga gggccgctcc ttcctggcct tccccactct ccgcgcctac 60
cacacgctgc gcctggcact ggaattccgg gcgctggagc ctcaggggct gctgctgtac 120
aatggcaacg cccggggcaa ggacttcctg gcattggcgc tgctagatgg ccgcgtgcag 180
ctcaggtttg acacaggttc ggggccggcg gtgctgacca gtgccgtgcc ggtagagccg 240
ggccagtggc accgcctgga gctgtcccgg cactggcgcc ggggcaccct ctcggtggat 300
ggtgagaccc ctgttctggg cgagagtccc agtggcaccg acggcctcaa cctggacaca 360
gacctctttg tgggcggcgt acccgaggac caggctgccg tggcgctgga gcggaccttc 420
gtgggcgccg gcctgagggg gtgcatccgt ttgctggacg tcaacaacca gcgcctggag 480
cttggcattg ggccgggggc tgccacccga ggctctggcg tgggcgagtg c 531
<210> 142
<211> 177
<212> PRT
<213> 人工序列
<220>
<223> 人集聚蛋白LG1
<400> 142
Ala Pro Val Pro Ala Phe Glu Gly Arg Ser Phe Leu Ala Phe Pro Thr
1 5 10 15
Leu Arg Ala Tyr His Thr Leu Arg Leu Ala Leu Glu Phe Arg Ala Leu
20 25 30
Glu Pro Gln Gly Leu Leu Leu Tyr Asn Gly Asn Ala Arg Gly Lys Asp
35 40 45
Phe Leu Ala Leu Ala Leu Leu Asp Gly Arg Val Gln Leu Arg Phe Asp
50 55 60
Thr Gly Ser Gly Pro Ala Val Leu Thr Ser Ala Val Pro Val Glu Pro
65 70 75 80
Gly Gln Trp His Arg Leu Glu Leu Ser Arg His Trp Arg Arg Gly Thr
85 90 95
Leu Ser Val Asp Gly Glu Thr Pro Val Leu Gly Glu Ser Pro Ser Gly
100 105 110
Thr Asp Gly Leu Asn Leu Asp Thr Asp Leu Phe Val Gly Gly Val Pro
115 120 125
Glu Asp Gln Ala Ala Val Ala Leu Glu Arg Thr Phe Val Gly Ala Gly
130 135 140
Leu Arg Gly Cys Ile Arg Leu Leu Asp Val Asn Asn Gln Arg Leu Glu
145 150 155 160
Leu Gly Ile Gly Pro Gly Ala Ala Thr Arg Gly Ser Gly Val Gly Glu
165 170 175
Cys
<210> 143
<211> 114
<212> DNA
<213> 人工序列
<220>
<223> 小鼠集聚蛋白EGF样结构域2 [DNA, 114 bp]
<400> 143
ggagaccatc cctgctcacc taacccctgc catggcgggg ccctctgcca ggccctggag 60
gctggcgtgt tcctctgtca gtgcccacct ggccgctttg gcccaacttg tgca 114
<210> 144
<211> 38
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白EGF样结构域2
<400> 144
Gly Asp His Pro Cys Ser Pro Asn Pro Cys His Gly Gly Ala Leu Cys
1 5 10 15
Gln Ala Leu Glu Ala Gly Val Phe Leu Cys Gln Cys Pro Pro Gly Arg
20 25 30
Phe Gly Pro Thr Cys Ala
35
<210> 145
<211> 114
<212> DNA
<213> 人工序列
<220>
<223> 人聚集蛋白EGF样结构域2 [DNA, 114 bp]
<400> 145
ggggaccacc cctgcctgcc caacccctgc catggcgggg ccccatgcca gaacctggag 60
gctggaaggt tccattgcca gtgcccgccc ggccgcgtcg gaccaacctg tgcc 114
<210> 146
<211> 38
<212> PRT
<213> 人工序列
<220>
<223> 人聚集蛋白EGF样2
<400> 146
Gly Asp His Pro Cys Leu Pro Asn Pro Cys His Gly Gly Ala Pro Cys
1 5 10 15
Gln Asn Leu Glu Ala Gly Arg Phe His Cys Gln Cys Pro Pro Gly Arg
20 25 30
Val Gly Pro Thr Cys Ala
35
<210> 147
<211> 117
<212> DNA
<213> 人工序列
<220>
<223> 小鼠聚集蛋白EGF样结构域3 [DNA, 117 bp]
<400> 147
gatgaaaaga acccctgcca accgaacccc tgccacgggt cagccccctg ccatgtgctt 60
tccaggggtg gggccaagtg tgcgtgcccc ctgggacgca gtggttcctt ctgtgag 117
<210> 148
<211> 39
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白EGF样结构域3
<400> 148
Asp Glu Lys Asn Pro Cys Gln Pro Asn Pro Cys His Gly Ser Ala Pro
1 5 10 15
Cys His Val Leu Ser Arg Gly Gly Ala Lys Cys Ala Cys Pro Leu Gly
20 25 30
Arg Ser Gly Ser Phe Cys Glu
35
<210> 149
<211> 117
<212> DNA
<213> 人工序列
<220>
<223> 人集聚蛋白EGF样3 [DNA, 117 bp]
<400> 149
gatgagaaga gcccctgcca gcccaacccc tgccatgggg cggcgccctg ccgtgtgctg 60
cccgagggtg gtgctcagtg cgagtgcccc ctggggcgtg agggcacctt ctgccag 117
<210> 150
<211> 39
<212> PRT
<213> 人工序列
<220>
<223> 人集聚蛋白EGF样3
<400> 150
Asp Glu Lys Ser Pro Cys Gln Pro Asn Pro Cys His Gly Ala Ala Pro
1 5 10 15
Cys Arg Val Leu Pro Glu Gly Gly Ala Gln Cys Glu Cys Pro Leu Gly
20 25 30
Arg Glu Gly Thr Phe Cys Gln
35
<210> 151
<211> 27
<212> DNA
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG间隔子1 [DNA, 27 bp]
<400> 151
acagtcctgg agaatgctgg ctcccgg 27
<210> 152
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白间隔子结构域1
<400> 152
Thr Val Leu Glu Asn Ala Gly Ser Arg
1 5
<210> 153
<211> 27
<212> DNA
<213> 人工序列
<220>
<223> 人间隔子[DNA, 27 bp]
<400> 153
acagcctcgg ggcaggacgg ctctggg 27
<210> 154
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人间隔子
<400> 154
Thr Ala Ser Gly Gln Asp Gly Ser Gly
1 5
<210> 155
<211> 537
<212> DNA
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG2结构域[DNA, 537 bp]
<400> 155
cccttcctgg ctgactttaa tggcttctcc tacctggaac tgaaaggctt gcacaccttc 60
gagagagacc taggggagaa gatggcgctg gagatggtgt tcttggctcg tgggcccagt 120
ggcttactcc tctacaatgg gcagaagacg gatggcaagg gggactttgt atccctggcc 180
ctgcataacc ggcacctaga gttccgctat gaccttggca agggggctgc aatcatcagg 240
agcaaagagc ccatagccct gggcacctgg gttagggtat tcctggaacg aaatggccgc 300
aagggtgccc ttcaagtggg tgatgggccc cgtgtgctag gggaatctcc ggtcccgcac 360
accatgctca acctcaagga gcccctctat gtggggggag ctcctgactt cagcaagctg 420
gctcggggcg ctgcagtggc ctccggcttt gatggtgcca tccagctggt gtctctaaga 480
ggccatcagc tgctgactca ggagcatgtg ttgcgggcag tagatgtagc gcctttt 537
<210> 156
<211> 179
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG2结构域
<400> 156
Pro Phe Leu Ala Asp Phe Asn Gly Phe Ser Tyr Leu Glu Leu Lys Gly
1 5 10 15
Leu His Thr Phe Glu Arg Asp Leu Gly Glu Lys Met Ala Leu Glu Met
20 25 30
Val Phe Leu Ala Arg Gly Pro Ser Gly Leu Leu Leu Tyr Asn Gly Gln
35 40 45
Lys Thr Asp Gly Lys Gly Asp Phe Val Ser Leu Ala Leu His Asn Arg
50 55 60
His Leu Glu Phe Arg Tyr Asp Leu Gly Lys Gly Ala Ala Ile Ile Arg
65 70 75 80
Ser Lys Glu Pro Ile Ala Leu Gly Thr Trp Val Arg Val Phe Leu Glu
85 90 95
Arg Asn Gly Arg Lys Gly Ala Leu Gln Val Gly Asp Gly Pro Arg Val
100 105 110
Leu Gly Glu Ser Pro Val Pro His Thr Met Leu Asn Leu Lys Glu Pro
115 120 125
Leu Tyr Val Gly Gly Ala Pro Asp Phe Ser Lys Leu Ala Arg Gly Ala
130 135 140
Ala Val Ala Ser Gly Phe Asp Gly Ala Ile Gln Leu Val Ser Leu Arg
145 150 155 160
Gly His Gln Leu Leu Thr Gln Glu His Val Leu Arg Ala Val Asp Val
165 170 175
Ala Pro Phe
<210> 157
<211> 537
<212> DNA
<213> 人工序列
<220>
<223> 人集聚蛋白G2 [DNA, 537 bp]
<400> 157
cccttcctgg ctgacttcaa cggcttctcc cacctggagc tgagaggcct gcacaccttt 60
gcacgggacc tgggggagaa gatggcgctg gaggtcgtgt tcctggcacg aggccccagc 120
ggcctcctgc tctacaacgg gcagaagacg gacggcaagg gggacttcgt gtcgctggca 180
ctgcgggacc gccgcctgga gttccgctac gacctgggca agggggcagc ggtcatcagg 240
agcagggagc cagtcaccct gggagcctgg accagggtct cactggagcg aaacggccgc 300
aagggtgccc tgcgtgtggg cgacggcccc cgtgtgttgg gggagtcccc ggttccgcac 360
accgtcctca acctgaagga gccgctctac gtagggggcg ctcccgactt cagcaagctg 420
gcccgtgctg ctgccgtgtc ctctggcttc gacggtgcca tccagctggt ctccctcgga 480
ggccgccagc tgctgacccc ggagcacgtg ctgcggcagg tggacgtcac gtccttt 537
<210> 158
<211> 179
<212> PRT
<213> 人工序列
<220>
<223> 人集聚蛋白LG2
<400> 158
Pro Phe Leu Ala Asp Phe Asn Gly Phe Ser His Leu Glu Leu Arg Gly
1 5 10 15
Leu His Thr Phe Ala Arg Asp Leu Gly Glu Lys Met Ala Leu Glu Val
20 25 30
Val Phe Leu Ala Arg Gly Pro Ser Gly Leu Leu Leu Tyr Asn Gly Gln
35 40 45
Lys Thr Asp Gly Lys Gly Asp Phe Val Ser Leu Ala Leu Arg Asp Arg
50 55 60
Arg Leu Glu Phe Arg Tyr Asp Leu Gly Lys Gly Ala Ala Val Ile Arg
65 70 75 80
Ser Arg Glu Pro Val Thr Leu Gly Ala Trp Thr Arg Val Ser Leu Glu
85 90 95
Arg Asn Gly Arg Lys Gly Ala Leu Arg Val Gly Asp Gly Pro Arg Val
100 105 110
Leu Gly Glu Ser Pro Val Pro His Thr Val Leu Asn Leu Lys Glu Pro
115 120 125
Leu Tyr Val Gly Gly Ala Pro Asp Phe Ser Lys Leu Ala Arg Ala Ala
130 135 140
Ala Val Ser Ser Gly Phe Asp Gly Ala Ile Gln Leu Val Ser Leu Gly
145 150 155 160
Gly Arg Gln Leu Leu Thr Pro Glu His Val Leu Arg Gln Val Asp Val
165 170 175
Thr Ser Phe
<210> 159
<211> 120
<212> DNA
<213> 人工序列
<220>
<223> 小鼠集聚蛋白EGF样结构域4 [DNA, 120 bp]
<400> 159
gcaggccacc cttgtaccca ggccgtggac aacccctgcc ttaatggggg ctcctgtatc 60
ccgagggaag ccacttatga gtgcctgtgt cctgggggct tctctgggct gcactgcgag 120
<210> 160
<211> 40
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白EGF样结构域4
<400> 160
Ala Gly His Pro Cys Thr Gln Ala Val Asp Asn Pro Cys Leu Asn Gly
1 5 10 15
Gly Ser Cys Ile Pro Arg Glu Ala Thr Tyr Glu Cys Leu Cys Pro Gly
20 25 30
Gly Phe Ser Gly Leu His Cys Glu
35 40
<210> 161
<211> 120
<212> DNA
<213> 人工序列
<220>
<223> 人聚集蛋白Egf样4 [DNA, 120 bp]
<400> 161
gcaggtcacc cctgcacccg ggcctcaggc cacccctgcc tcaatggggc ctcctgcgtc 60
ccgagggagg ctgcctatgt gtgcctgtgt cccgggggat tctcaggacc gcactgcgag 120
<210> 162
<211> 40
<212> PRT
<213> 人工序列
<220>
<223> 人集聚蛋白EGF样4
<400> 162
Ala Gly His Pro Cys Thr Arg Ala Ser Gly His Pro Cys Leu Asn Gly
1 5 10 15
Ala Ser Cys Val Pro Arg Glu Ala Ala Tyr Val Cys Leu Cys Pro Gly
20 25 30
Gly Phe Ser Gly Pro His Cys Glu
35 40
<210> 163
<211> 30
<212> DNA
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG间隔子2 [DNA, 30 bp]
<400> 163
aaggggatag ttgagaagtc agtgggggac 30
<210> 164
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG间隔子2
<400> 164
Lys Gly Ile Val Glu Lys Ser Val Gly Asp
1 5 10
<210> 165
<211> 30
<212> DNA
<213> 人工序列
<220>
<223> 人间隔子[30 bp]
<400> 165
aaggggctgg tggagaagtc agcgggggac 30
<210> 166
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 人间隔子
<400> 166
Lys Gly Leu Val Glu Lys Ser Ala Gly Asp
1 5 10
<210> 167
<211> 537
<212> DNA
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG3结构域[DNA, 537 bp]
<400> 167
ctagaaacac tggcctttga tgggcggacc tacatcgagt acctcaatgc tgtgactgag 60
agtgagaaag cgctgcagag caaccacttt gagctgagct tacgcactga ggccacgcag 120
gggctggtgc tgtggattgg aaaggttgga gaacgtgcag actacatggc tctggccatt 180
gtggatgggc acctacaact gagctatgac ctaggctccc agccagttgt gctgcgctcc 240
actgtgaagg tcaacaccaa ccgctggctt cgagtcaggg ctcacaggga gcacagggaa 300
ggttcccttc aggtgggcaa tgaagcccct gtgactggct cttccccgct gggtgccaca 360
caattggaca cagatggagc cctgtggctt ggaggcctac agaagcttcc tgtggggcag 420
gctctcccca aggcctatgg cacgggtttt gtgggctgtc tgcgggacgt ggtagtgggc 480
catcgccagc tgcatctgct ggaggacgct gtcaccaaac cagagctaag accctgc 537
<210> 168
<211> 179
<212> PRT
<213> 人工序列
<220>
<223> 小鼠集聚蛋白LG3结构域
<400> 168
Leu Glu Thr Leu Ala Phe Asp Gly Arg Thr Tyr Ile Glu Tyr Leu Asn
1 5 10 15
Ala Val Thr Glu Ser Glu Lys Ala Leu Gln Ser Asn His Phe Glu Leu
20 25 30
Ser Leu Arg Thr Glu Ala Thr Gln Gly Leu Val Leu Trp Ile Gly Lys
35 40 45
Val Gly Glu Arg Ala Asp Tyr Met Ala Leu Ala Ile Val Asp Gly His
50 55 60
Leu Gln Leu Ser Tyr Asp Leu Gly Ser Gln Pro Val Val Leu Arg Ser
65 70 75 80
Thr Val Lys Val Asn Thr Asn Arg Trp Leu Arg Val Arg Ala His Arg
85 90 95
Glu His Arg Glu Gly Ser Leu Gln Val Gly Asn Glu Ala Pro Val Thr
100 105 110
Gly Ser Ser Pro Leu Gly Ala Thr Gln Leu Asp Thr Asp Gly Ala Leu
115 120 125
Trp Leu Gly Gly Leu Gln Lys Leu Pro Val Gly Gln Ala Leu Pro Lys
130 135 140
Ala Tyr Gly Thr Gly Phe Val Gly Cys Leu Arg Asp Val Val Val Gly
145 150 155 160
His Arg Gln Leu His Leu Leu Glu Asp Ala Val Thr Lys Pro Glu Leu
165 170 175
Arg Pro Cys
<210> 169
<211> 537
<212> DNA
<213> 人工序列
<220>
<223> 人集聚蛋白LG3 [DNA, 537 bp]
<400> 169
gtggatacct tggcctttga cgggcggacc tttgtcgagt acctcaacgc tgtgaccgag 60
agcgagaagg cactgcagag caaccacttt gaactgagcc tgcgcactga ggccacgcag 120
gggctggtgc tctggagtgg caaggccacg gagcgggcag actatgtggc actggccatt 180
gtggacgggc acctgcaact gagctacaac ctgggctccc agcccgtggt gctgcgttcc 240
accgtgcccg tcaacaccaa ccgctggttg cgggtcgtgg cacataggga gcagagggaa 300
ggttccctgc aggtgggcaa tgaggcccct gtgaccggct cctccccgct gggcgccacg 360
cagctggaca ctgatggagc cctgtggctt gggggcctgc cggagctgcc cgtgggccca 420
gcactgccca aggcctacgg cacaggcttt gtgggctgct tgcgggacgt ggtggtgggc 480
cggcacccgc tgcacctgct ggaggacgcc gtcaccaagc cagagctgcg gccctgc 537
<210> 170
<211> 179
<212> PRT
<213> 人工序列
<220>
<223> 人集聚蛋白LG3
<400> 170
Val Asp Thr Leu Ala Phe Asp Gly Arg Thr Phe Val Glu Tyr Leu Asn
1 5 10 15
Ala Val Thr Glu Ser Glu Lys Ala Leu Gln Ser Asn His Phe Glu Leu
20 25 30
Ser Leu Arg Thr Glu Ala Thr Gln Gly Leu Val Leu Trp Ser Gly Lys
35 40 45
Ala Thr Glu Arg Ala Asp Tyr Val Ala Leu Ala Ile Val Asp Gly His
50 55 60
Leu Gln Leu Ser Tyr Asn Leu Gly Ser Gln Pro Val Val Leu Arg Ser
65 70 75 80
Thr Val Pro Val Asn Thr Asn Arg Trp Leu Arg Val Val Ala His Arg
85 90 95
Glu Gln Arg Glu Gly Ser Leu Gln Val Gly Asn Glu Ala Pro Val Thr
100 105 110
Gly Ser Ser Pro Leu Gly Ala Thr Gln Leu Asp Thr Asp Gly Ala Leu
115 120 125
Trp Leu Gly Gly Leu Pro Glu Leu Pro Val Gly Pro Ala Leu Pro Lys
130 135 140
Ala Tyr Gly Thr Gly Phe Val Gly Cys Leu Arg Asp Val Val Val Gly
145 150 155 160
Arg His Pro Leu His Leu Leu Glu Asp Ala Val Thr Lys Pro Glu Leu
165 170 175
Arg Pro Cys
Claims (26)
1.一种重组腺相关载体(rAAV)，其包括核酸序列，所述核酸序列包括对alphaLNNdDeltaG2short进行编码的转基因。
2.根据权利要求1所述的重组AAV，其中所述alphaLNNdDeltaG2short包括SEQ ID NO:1或SEQ ID NO:24。
3.根据权利要求1所述的重组AAV，其中所述AAV是AAV8或AAV-DJ。
4.根据权利要求1所述的重组AAV，其进一步包括CMV启动子。
5.根据权利要求4所述的重组AAV，其中所述CMV启动子包括SEQ ID NO:12。
6.根据权利要求1所述的重组AAV，其中所述重组载体进一步包括末端反向重复序列(ITR)。
7.根据权利要求6所述的重组AAV，其中所述末端反向重复序列(ITR)是包括SEQ IDNO:11的5'ITR。
8.根据权利要求6所述的重组AAV，其中所述末端反向重复序列(ITR)是包括SEQ IDNO:16的3'ITR。
9.一种重组腺相关载体(rAAV)，其包括核酸序列，所述核酸序列包括对alphaLNNdDeltaG2Propeller进行编码的转基因，其中所述核酸序列包括：(a)SEQ ID NO:25、29、31、33、35、41、45和55；(b)SEQ ID NO:25、29、31、33、35、41、47和55；或(c)SEQ IDNO:25、29、31、33、35、41、51和55。
10.一种重组腺相关载体(rAAV)，其包括核酸序列，所述核酸序列包括对alphaLNNdDeltaG2Propeller-2进行编码的转基因，其中所述核酸序列包括SEQ ID NO:25、29、31、33、41、43、45和55。
11.一种重组腺相关载体(rAAV)，其包括核酸序列，所述核酸序列包括对betaLNNdDeltaG2short进行编码的转基因，其中所述核酸序列包括SEQ ID NO:59、63、67、71、75、79、49、51、53、55和57。
12.一种重组腺相关载体(rAAV)，其包括核酸序列，所述核酸序列包括对gammaLNNdDeltaG2short进行编码的转基因，其中所述核酸序列包括SEQ ID NO:83、87、91、95、99、103、49、51、53、55和57。
13.一种药物组合物，其包括根据权利要求1、2、9、10、11或12所述的重组AAV以及药物载剂。
14.一种试剂盒，其包括容器壳体，所述容器壳体包括根据权利要求13所述的组合物。
15.一种恢复受试者的层粘连蛋白聚合表达和基底膜组装的方法，所述方法包括向所述受试者施用有效量的根据权利要求1、2、9、10、11或12所述的重组AAV载体。
16.一种治疗有需要的受试者的层粘连蛋白α-2缺陷综合征的方法，其中所述方法包括向所述受试者施用有效量的根据权利要求1所述的重组AAV载体。
17.一种减轻受试者的与选自由层粘连蛋白缺陷型肌营养不良和层粘连蛋白α2缺陷型肌营养不良组成的组的层粘连蛋白缺陷相关的症状中的至少一种症状的方法，其中所述方法包括向所述受试者施用有效量的根据权利要求1所述的重组AAV载体。
18.一种减轻受试者的与选自由以下组成的组的层粘连蛋白α2-缺陷相关的症状中的至少一种症状的方法：肌肉变性、再生、慢性炎症、纤维化、白质脑异常、外周神经传导减少、癫痫、中度精神发育迟缓以及呼吸衰竭，其中所述方法包括向所述受试者施用有效量的根据权利要求1所述的重组AAV载体。
19.根据权利要求16、17或18所述的方法，其中所述alphaLNNdDeltaG2short包括SEQID NO:1或SEQ ID NO:24。
20.根据权利要求16、17或18所述的方法，其中所述AAV是AAV8或AAV-DJ。
21.根据权利要求16、17或18所述的方法，其中所述重组AAV进一步包括CMV启动子。
22.根据权利要求21所述的方法，其中其中所述CMV启动子包括SEQ ID NO:12。
23.根据权利要求16、17或18所述的方法，其中所述重组载体进一步包括末端反向重复序列(ITR)。
24.根据权利要求23所述的方法，其中所述末端反向重复序列(ITR)是包括SEQ ID NO:11的5'ITR。
25.根据权利要求23所述的方法，其中所述末端反向重复序列(ITR)是包括SEQ ID NO:16的3'ITR。
26.根据权利要求16、17或18所述的方法，其中所述重组AAV包括在药物组合物内，所述药物组合物进一步包括药物载剂。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862668664P | 2018-05-08 | 2018-05-08 | |
| US62/668,664 | 2018-05-08 | ||
| PCT/US2019/031369 WO2019217582A1 (en) | 2018-05-08 | 2019-05-08 | Aav-compatible laminin-linker polymerization proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112154209A true CN112154209A (zh) | 2020-12-29 |
Family
ID=68468357
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980029037.8A Pending CN112154209A (zh) | 2018-05-08 | 2019-05-08 | Aav相容的层粘连蛋白—连接子聚合蛋白 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20210207168A1 (zh) |
| EP (1) | EP3790394A4 (zh) |
| JP (1) | JP7253274B2 (zh) |
| KR (1) | KR20210006352A (zh) |
| CN (1) | CN112154209A (zh) |
| AU (1) | AU2019265663A1 (zh) |
| CA (1) | CA3098871A1 (zh) |
| IL (1) | IL278393B2 (zh) |
| SG (1) | SG11202009914SA (zh) |
| WO (1) | WO2019217582A1 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114555814A (zh) * | 2019-09-13 | 2022-05-27 | 罗特格斯新泽西州立大学 | Aav相容的层粘连蛋白-连接子聚合蛋白 |
| EP3842452A1 (en) * | 2019-12-26 | 2021-06-30 | Universitat Autònoma de Barcelona | Scaffold proteins and therapeutic nanoconjugates based on nidogen |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160304904A1 (en) * | 2008-04-30 | 2016-10-20 | The University Of North Carolina At Chapel Hill | Directed Evolution and In Vivo Panning of Virus Vectors |
| CN107635575A (zh) * | 2015-03-10 | 2018-01-26 | 纽约市哥伦比亚大学理事会 | 重组glut1腺相关病毒载体构建体以及用于恢复glut1表达的相关方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| US5543158A (en) | 1993-07-23 | 1996-08-06 | Massachusetts Institute Of Technology | Biodegradable injectable nanoparticles |
| IE80468B1 (en) | 1995-04-04 | 1998-07-29 | Elan Corp Plc | Controlled release biodegradable nanoparticles containing insulin |
| US6001650A (en) | 1995-08-03 | 1999-12-14 | Avigen, Inc. | High-efficiency wild-type-free AAV helper functions |
| EP0931158A1 (en) | 1996-09-06 | 1999-07-28 | The Trustees Of The University Of Pennsylvania | An inducible method for production of recombinant adeno-associated viruses utilizing t7 polymerase |
| US6156303A (en) | 1997-06-11 | 2000-12-05 | University Of Washington | Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom |
| NZ521625A (en) * | 2000-03-29 | 2004-09-24 | Beth Israel Hospital | Anti-angiogenic and anti-tumor properties of matin and other laminin domains |
| NZ532635A (en) | 2001-11-13 | 2007-05-31 | Univ Pennsylvania | A method of identifying unknown adeno-associated virus (AAV) sequences and a kit for the method |
| CN1856576B (zh) | 2003-09-30 | 2011-05-04 | 宾夕法尼亚州立大学托管会 | 腺伴随病毒(aav)进化支、序列、含有这些序列的载体及它们的应用 |
| WO2006043354A1 (ja) * | 2004-10-20 | 2006-04-27 | National Institute Of Radiological Sciences | 組込型の低線量放射線誘導性ベクター |
| CN104293835B (zh) | 2005-04-07 | 2017-07-04 | 宾夕法尼亚大学托管会 | 增强腺相关病毒载体功能的方法 |
| EP2500434A1 (en) * | 2011-03-12 | 2012-09-19 | Association Institut de Myologie | Capsid-free AAV vectors, compositions, and methods for vector production and gene delivery |
| TWI775096B (zh) * | 2012-05-15 | 2022-08-21 | 澳大利亞商艾佛蘭屈澳洲私營有限公司 | 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd) |
| CA2876293C (en) * | 2012-06-27 | 2023-10-10 | Arthrogen B.V. | Combination for treating an inflammatory disorder |
| EP3097197B1 (en) * | 2014-01-21 | 2020-12-16 | Vrije Universiteit Brussel | Muscle-specific nucleic acid regulatory elements and methods and use thereof |
-
2019
- 2019-05-08 SG SG11202009914SA patent/SG11202009914SA/en unknown
- 2019-05-08 IL IL278393A patent/IL278393B2/en unknown
- 2019-05-08 CN CN201980029037.8A patent/CN112154209A/zh active Pending
- 2019-05-08 KR KR1020207031675A patent/KR20210006352A/ko unknown
- 2019-05-08 EP EP19799178.9A patent/EP3790394A4/en active Pending
- 2019-05-08 WO PCT/US2019/031369 patent/WO2019217582A1/en active Application Filing
- 2019-05-08 JP JP2020561690A patent/JP7253274B2/ja active Active
- 2019-05-08 US US17/058,625 patent/US20210207168A1/en active Pending
- 2019-05-08 CA CA3098871A patent/CA3098871A1/en active Pending
- 2019-05-08 AU AU2019265663A patent/AU2019265663A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160304904A1 (en) * | 2008-04-30 | 2016-10-20 | The University Of North Carolina At Chapel Hill | Directed Evolution and In Vivo Panning of Virus Vectors |
| CN107635575A (zh) * | 2015-03-10 | 2018-01-26 | 纽约市哥伦比亚大学理事会 | 重组glut1腺相关病毒载体构建体以及用于恢复glut1表达的相关方法 |
Non-Patent Citations (2)
| Title |
|---|
| JUDITH R. REINHARD ET AL: "Linker proteins restore basement membrane and correct LAMA2-related muscular dystrophy in mice", 《SCI TRANSL MED.》 * |
| 孙兆增等: "鼠层粘蛋白α5链G结构域E3和E8基因在毕赤酵母中的表达", 《中国兽医学报》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2019265663A1 (en) | 2020-10-29 |
| JP2021522791A (ja) | 2021-09-02 |
| US20210207168A1 (en) | 2021-07-08 |
| EP3790394A4 (en) | 2022-07-27 |
| JP7253274B2 (ja) | 2023-04-06 |
| EP3790394A1 (en) | 2021-03-17 |
| KR20210006352A (ko) | 2021-01-18 |
| CA3098871A1 (en) | 2019-11-14 |
| SG11202009914SA (en) | 2020-11-27 |
| IL278393A (zh) | 2020-12-31 |
| IL278393B1 (en) | 2023-07-01 |
| IL278393B2 (en) | 2023-11-01 |
| WO2019217582A1 (en) | 2019-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7361737B2 (ja) | 修飾された第ｉｘ因子、並びに、細胞、器官及び組織への遺伝子導入のための組成物、方法及び使用 | |
| JP6683691B2 (ja) | 高効率ゲノム編集のためのアデノ随伴ウイルスベクターバリアント及びその方法 | |
| US20190127424A1 (en) | Capsid-modified raav vector compositions and methods therefor | |
| AU704391B2 (en) | Improved adenovirus and methods of use thereof | |
| AU2020200041A1 (en) | Capsid-modified, rAAV3 vector compositions and uses in gene therapy of human liver cancer | |
| JP7196104B2 (ja) | 増強された改変ウイルスカプシドタンパク質 | |
| CA3054711A1 (en) | Polyploid adeno-associated virus vectors and methods of making and using the same | |
| KR20180113990A (ko) | 가족성 고콜레스테롤혈증을 치료하기 위한 유전자 요법 | |
| KR20190118163A (ko) | 가족성 고콜레스테롤혈증을 치료하기 위한 유전자 요법 | |
| JP2019533434A (ja) | ファンコニ貧血患者に対する遺伝子療法 | |
| CN111448321A (zh) | Sod1双表达载体及其用途 | |
| CN113966400A (zh) | 用于使神经元细胞兴奋性正常化和治疗德拉韦综合征的中间神经元特异性治疗剂 | |
| CN112154209A (zh) | Aav相容的层粘连蛋白—连接子聚合蛋白 | |
| CA3187353A1 (en) | Adeno-associated virus vector delivery for muscular dystrophies | |
| CN114555814A (zh) | Aav相容的层粘连蛋白-连接子聚合蛋白 | |
| JP2023065516A (ja) | 結節性硬化症の遺伝子治療 | |
| WO2009071679A1 (en) | Novel aav vector and uses thereof | |
| US20230346977A1 (en) | Treatment of neuromuscular diseases via gene therapy that expresses klotho protein | |
| US20230136849A1 (en) | Capsid-modified raav vector compositions and methods therefor | |
| KR20210106489A (ko) | 가족성 고콜레스테롤혈증을 치료하기 위한 유전자 요법 | |
| CA3170657A1 (en) | Gene therapy | |
| Class et al. | Patent application title: CAPSID-MODIFIED RAAV VECTOR COMPOSITIONS AND METHODS THEREFOR Inventors: Arun Srivastava (Gainesville, FL, US) Arun Srivastava (Gainesville, FL, US) George V. Aslanidi (Gainesville, FL, US) Sergei Zolotukhin (Gainesville, FL, US) Sergei Zolotukhin (Gainesville, FL, US) Mavis Agbandje-Mckenna (Gainesville, FL, US) Kim M. Van Vliet (Gainesville, FL, US) Li Zhong (Boxborough, MA, US) Lakshmanan Govindasamy (Gainesville, FL, US) Assignees: University of Florida Research Foundation Inc. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40035051 Country of ref document: HK |