CN116096737A - 用于治疗突触核蛋白病的组合物和方法 - Google Patents
用于治疗突触核蛋白病的组合物和方法 Download PDFInfo
- Publication number
- CN116096737A CN116096737A CN202180058141.7A CN202180058141A CN116096737A CN 116096737 A CN116096737 A CN 116096737A CN 202180058141 A CN202180058141 A CN 202180058141A CN 116096737 A CN116096737 A CN 116096737A
- Authority
- CN
- China
- Prior art keywords
- lys
- fusion protein
- ala
- gly
- glu
- 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
- 238000000034 method Methods 0.000 title claims description 49
- 208000032859 Synucleinopathies Diseases 0.000 title claims description 10
- 239000000203 mixture Substances 0.000 title description 20
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 304
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 304
- 108090000185 alpha-Synuclein Proteins 0.000 claims abstract description 251
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 60
- 201000010099 disease Diseases 0.000 claims abstract description 40
- 230000001404 mediated effect Effects 0.000 claims abstract description 20
- 102000003802 alpha-Synuclein Human genes 0.000 claims abstract 32
- 210000004027 cell Anatomy 0.000 claims description 193
- 239000013598 vector Substances 0.000 claims description 99
- 150000007523 nucleic acids Chemical group 0.000 claims description 86
- 102000039446 nucleic acids Human genes 0.000 claims description 68
- 108020004707 nucleic acids Proteins 0.000 claims description 68
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 60
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 42
- 230000003612 virological effect Effects 0.000 claims description 39
- 229920001184 polypeptide Polymers 0.000 claims description 37
- 239000002245 particle Substances 0.000 claims description 35
- 230000008685 targeting Effects 0.000 claims description 33
- 241000282414 Homo sapiens Species 0.000 claims description 30
- 210000000234 capsid Anatomy 0.000 claims description 27
- 108020004414 DNA Proteins 0.000 claims description 23
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 21
- 101710101803 DNA-binding protein J Proteins 0.000 claims description 19
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 15
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 241000701161 unidentified adenovirus Species 0.000 claims description 12
- 230000003013 cytotoxicity Effects 0.000 claims description 11
- 231100000135 cytotoxicity Toxicity 0.000 claims description 11
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 10
- 241000713666 Lentivirus Species 0.000 claims description 10
- 238000009825 accumulation Methods 0.000 claims description 10
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 9
- 210000003169 central nervous system Anatomy 0.000 claims description 9
- 108091034057 RNA (poly(A)) Proteins 0.000 claims description 8
- 230000028327 secretion Effects 0.000 claims description 8
- 241001430294 unidentified retrovirus Species 0.000 claims description 8
- 241000972680 Adeno-associated virus - 6 Species 0.000 claims description 7
- 201000002832 Lewy body dementia Diseases 0.000 claims description 7
- 230000002159 abnormal effect Effects 0.000 claims description 7
- 241000702421 Dependoparvovirus Species 0.000 claims description 6
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 6
- 239000004973 liquid crystal related substance Substances 0.000 claims description 6
- 230000000149 penetrating effect Effects 0.000 claims description 6
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 241000701447 unidentified baculovirus Species 0.000 claims description 5
- 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 4
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 4
- 241000580270 Adeno-associated virus - 4 Species 0.000 claims description 4
- 241001164823 Adeno-associated virus - 7 Species 0.000 claims description 4
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 4
- 108700039691 Genetic Promoter Regions Proteins 0.000 claims description 4
- 101000870166 Homo sapiens DnaJ homolog subfamily C member 14 Proteins 0.000 claims description 4
- 241000649045 Adeno-associated virus 10 Species 0.000 claims description 3
- 102100026031 Beta-glucuronidase Human genes 0.000 claims description 3
- 101000933465 Homo sapiens Beta-glucuronidase Proteins 0.000 claims description 3
- 230000001086 cytosolic effect Effects 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 230000001988 toxicity Effects 0.000 claims description 3
- 231100000419 toxicity Toxicity 0.000 claims description 3
- 241001529453 unidentified herpesvirus Species 0.000 claims description 3
- 241000649046 Adeno-associated virus 11 Species 0.000 claims description 2
- 241000649047 Adeno-associated virus 12 Species 0.000 claims description 2
- 241000710929 Alphavirus Species 0.000 claims description 2
- 241000711404 Avian avulavirus 1 Species 0.000 claims description 2
- 102100034114 DnaJ homolog subfamily C member 14 Human genes 0.000 claims description 2
- 238000012286 ELISA Assay Methods 0.000 claims description 2
- 241000710831 Flavivirus Species 0.000 claims description 2
- 201000005505 Measles Diseases 0.000 claims description 2
- 241000702263 Reovirus sp. Species 0.000 claims description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 claims description 2
- 208000009091 myxoma Diseases 0.000 claims description 2
- 208000007089 vaccinia Diseases 0.000 claims description 2
- 108020005345 3' Untranslated Regions Proteins 0.000 claims 1
- 108020003589 5' Untranslated Regions Proteins 0.000 claims 1
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 claims 1
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 claims 1
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 abstract description 91
- 102000004169 proteins and genes Human genes 0.000 abstract description 64
- 108010006519 Molecular Chaperones Proteins 0.000 abstract description 11
- 230000007246 mechanism Effects 0.000 abstract description 9
- 230000004845 protein aggregation Effects 0.000 abstract description 2
- 102100026882 Alpha-synuclein Human genes 0.000 description 219
- 230000014509 gene expression Effects 0.000 description 57
- 108091033319 polynucleotide Proteins 0.000 description 57
- 102000040430 polynucleotide Human genes 0.000 description 57
- 239000002157 polynucleotide Substances 0.000 description 57
- 235000018102 proteins Nutrition 0.000 description 53
- 108010050848 glycylleucine Proteins 0.000 description 45
- 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 35
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 35
- 108010092854 aspartyllysine Proteins 0.000 description 33
- 208000018737 Parkinson disease Diseases 0.000 description 30
- 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 28
- 230000002776 aggregation Effects 0.000 description 28
- 238000004220 aggregation Methods 0.000 description 28
- MTDDMSUUXNQMKK-BPNCWPANSA-N Ala-Tyr-Arg Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N MTDDMSUUXNQMKK-BPNCWPANSA-N 0.000 description 25
- 230000000694 effects Effects 0.000 description 25
- 108020004999 messenger RNA Proteins 0.000 description 25
- 108010093581 aspartyl-proline Proteins 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 22
- ALMIMUZAWTUNIO-BZSNNMDCSA-N Asp-Tyr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ALMIMUZAWTUNIO-BZSNNMDCSA-N 0.000 description 21
- 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 21
- 108010005233 alanylglutamic acid Proteins 0.000 description 21
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 20
- 125000003729 nucleotide group Chemical group 0.000 description 20
- CLNJSLSHKJECME-BQBZGAKWSA-N Pro-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1 CLNJSLSHKJECME-BQBZGAKWSA-N 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 19
- 208000035475 disorder Diseases 0.000 description 19
- 108010057952 lysyl-phenylalanyl-lysine Proteins 0.000 description 19
- 210000002569 neuron Anatomy 0.000 description 19
- 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 18
- 230000006870 function Effects 0.000 description 17
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 17
- WLYPRKLMRIYGPP-JYJNAYRXSA-N Phe-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 WLYPRKLMRIYGPP-JYJNAYRXSA-N 0.000 description 16
- 239000013603 viral vector Substances 0.000 description 16
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 15
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 15
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 15
- 241000700584 Simplexvirus Species 0.000 description 15
- 108010064235 lysylglycine Proteins 0.000 description 15
- 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 14
- 241000701022 Cytomegalovirus Species 0.000 description 14
- LGYZYFFDELZWRS-DCAQKATOSA-N Glu-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O LGYZYFFDELZWRS-DCAQKATOSA-N 0.000 description 14
- UABYBEBXFFNCIR-YDHLFZDLSA-N Tyr-Asp-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UABYBEBXFFNCIR-YDHLFZDLSA-N 0.000 description 14
- OHYQKYUTLIPFOX-ZPFDUUQYSA-N Arg-Glu-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OHYQKYUTLIPFOX-ZPFDUUQYSA-N 0.000 description 13
- NHMRJKKAVMENKJ-WDCWCFNPSA-N Gln-Thr-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NHMRJKKAVMENKJ-WDCWCFNPSA-N 0.000 description 13
- LLZXNUUIBOALNY-QWRGUYRKSA-N Gly-Leu-Lys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN LLZXNUUIBOALNY-QWRGUYRKSA-N 0.000 description 13
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 13
- 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 13
- XKHCJJPNXFBADI-DCAQKATOSA-N Pro-Asp-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O XKHCJJPNXFBADI-DCAQKATOSA-N 0.000 description 13
- 239000013604 expression vector Substances 0.000 description 13
- 108010003700 lysyl aspartic acid Proteins 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 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 12
- AQPVUEJJARLJHB-BQBZGAKWSA-N Arg-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N AQPVUEJJARLJHB-BQBZGAKWSA-N 0.000 description 12
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 12
- SOEATRRYCIPEHA-BQBZGAKWSA-N Gly-Glu-Glu Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SOEATRRYCIPEHA-BQBZGAKWSA-N 0.000 description 12
- 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 12
- 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 12
- MYZMQWHPDAYKIE-SRVKXCTJSA-N Lys-Leu-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O MYZMQWHPDAYKIE-SRVKXCTJSA-N 0.000 description 12
- QSKCKTUQPICLSO-AVGNSLFASA-N Pro-Arg-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O QSKCKTUQPICLSO-AVGNSLFASA-N 0.000 description 12
- 108010070783 alanyltyrosine Proteins 0.000 description 12
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- ILJQISGMGXRZQQ-IHRRRGAJSA-N Asp-Arg-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ILJQISGMGXRZQQ-IHRRRGAJSA-N 0.000 description 11
- 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 11
- 238000002965 ELISA Methods 0.000 description 11
- NZGTYCMLUGYMCV-XUXIUFHCSA-N Ile-Lys-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N NZGTYCMLUGYMCV-XUXIUFHCSA-N 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- VIPDPMHGICREIS-GVXVVHGQSA-N Glu-Val-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O VIPDPMHGICREIS-GVXVVHGQSA-N 0.000 description 10
- GVNNAHIRSDRIII-AJNGGQMLSA-N Ile-Lys-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N GVNNAHIRSDRIII-AJNGGQMLSA-N 0.000 description 10
- 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 10
- JACAKCWAOHKQBV-UWVGGRQHSA-N Met-Gly-Lys Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN JACAKCWAOHKQBV-UWVGGRQHSA-N 0.000 description 10
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 10
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 10
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 10
- 229960003638 dopamine Drugs 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 208000024827 Alzheimer disease Diseases 0.000 description 9
- CDGLBYSAZFIIJO-RCOVLWMOSA-N Ile-Gly-Gly Chemical compound CC[C@H](C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O CDGLBYSAZFIIJO-RCOVLWMOSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- -1 antibodies Substances 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 108010009298 lysylglutamic acid Proteins 0.000 description 9
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 8
- OOWSBIOUKIUWLO-RCOVLWMOSA-N Asn-Gly-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O OOWSBIOUKIUWLO-RCOVLWMOSA-N 0.000 description 8
- 108020004635 Complementary DNA Proteins 0.000 description 8
- 239000004971 Cross linker Substances 0.000 description 8
- OHUKZZYSJBKFRR-WHFBIAKZSA-N Gly-Ser-Asp Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O OHUKZZYSJBKFRR-WHFBIAKZSA-N 0.000 description 8
- 241000880493 Leptailurus serval Species 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- ZUGXSSFMTXKHJS-ZLUOBGJFSA-N Ser-Ala-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O ZUGXSSFMTXKHJS-ZLUOBGJFSA-N 0.000 description 8
- 102000019355 Synuclein Human genes 0.000 description 8
- 108050006783 Synuclein Proteins 0.000 description 8
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 8
- 108010077245 asparaginyl-proline Proteins 0.000 description 8
- XDHNQDDQEHDUTM-JQWOJBOSSA-N bafilomycin A1 Chemical compound CO[C@H]1\C=C\C=C(C)\C[C@H](C)[C@H](O)[C@H](C)\C=C(/C)\C=C(OC)\C(=O)O[C@@H]1[C@@H](C)[C@@H](O)[C@H](C)[C@]1(O)O[C@H](C(C)C)[C@@H](C)[C@H](O)C1 XDHNQDDQEHDUTM-JQWOJBOSSA-N 0.000 description 8
- XDHNQDDQEHDUTM-ZGOPVUMHSA-N bafilomycin A1 Natural products CO[C@H]1C=CC=C(C)C[C@H](C)[C@H](O)[C@H](C)C=C(C)C=C(OC)C(=O)O[C@@H]1[C@@H](C)[C@@H](O)[C@H](C)[C@]1(O)O[C@H](C(C)C)[C@@H](C)[C@H](O)C1 XDHNQDDQEHDUTM-ZGOPVUMHSA-N 0.000 description 8
- XDHNQDDQEHDUTM-UHFFFAOYSA-N bafliomycin A1 Natural products COC1C=CC=C(C)CC(C)C(O)C(C)C=C(C)C=C(OC)C(=O)OC1C(C)C(O)C(C)C1(O)OC(C(C)C)C(C)C(O)C1 XDHNQDDQEHDUTM-UHFFFAOYSA-N 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
- 239000013592 cell lysate Substances 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 108010073969 valyllysine Proteins 0.000 description 8
- 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 7
- BGGAIXWIZCIFSG-XDTLVQLUSA-N Ala-Tyr-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O BGGAIXWIZCIFSG-XDTLVQLUSA-N 0.000 description 7
- 201000011240 Frontotemporal dementia Diseases 0.000 description 7
- 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 7
- 241000725303 Human immunodeficiency virus Species 0.000 description 7
- 102100037935 Polyubiquitin-C Human genes 0.000 description 7
- 241000714474 Rous sarcoma virus Species 0.000 description 7
- 108010056354 Ubiquitin C Proteins 0.000 description 7
- 108010068265 aspartyltyrosine Proteins 0.000 description 7
- 238000010804 cDNA synthesis Methods 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 108010078144 glutaminyl-glycine Proteins 0.000 description 7
- 108010049041 glutamylalanine Proteins 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 230000006798 recombination Effects 0.000 description 7
- 238000005215 recombination Methods 0.000 description 7
- 230000010076 replication Effects 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- BZMWJLLUAKSIMH-FXQIFTODSA-N Asn-Glu-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BZMWJLLUAKSIMH-FXQIFTODSA-N 0.000 description 6
- XWSIYTYNLKCLJB-CIUDSAMLSA-N Asp-Lys-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O XWSIYTYNLKCLJB-CIUDSAMLSA-N 0.000 description 6
- 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 6
- FNXSYBOHALPRHV-ONGXEEELSA-N Gly-Val-Lys Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN FNXSYBOHALPRHV-ONGXEEELSA-N 0.000 description 6
- FZWVCYCYWCLQDH-NHCYSSNCSA-N Ile-Leu-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)O)N FZWVCYCYWCLQDH-NHCYSSNCSA-N 0.000 description 6
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 6
- KPYAOIVPJKPIOU-KKUMJFAQSA-N Leu-Lys-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O KPYAOIVPJKPIOU-KKUMJFAQSA-N 0.000 description 6
- 102000005431 Molecular Chaperones Human genes 0.000 description 6
- 241000713869 Moloney murine leukemia virus Species 0.000 description 6
- 108010008355 arginyl-glutamine Proteins 0.000 description 6
- 108010038633 aspartylglutamate Proteins 0.000 description 6
- 230000004186 co-expression Effects 0.000 description 6
- 238000001415 gene therapy Methods 0.000 description 6
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 6
- 108010089804 glycyl-threonine Proteins 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 6
- 108010034529 leucyl-lysine Proteins 0.000 description 6
- 108010054155 lysyllysine Proteins 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 239000002105 nanoparticle Substances 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 230000008488 polyadenylation Effects 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 6
- AWZKCUCQJNTBAD-SRVKXCTJSA-N Ala-Leu-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN AWZKCUCQJNTBAD-SRVKXCTJSA-N 0.000 description 5
- VCSABYLVNWQYQE-UHFFFAOYSA-N Ala-Lys-Lys Natural products NCCCCC(NC(=O)C(N)C)C(=O)NC(CCCCN)C(O)=O VCSABYLVNWQYQE-UHFFFAOYSA-N 0.000 description 5
- YUOXLJYVSZYPBJ-CIUDSAMLSA-N Asn-Pro-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O YUOXLJYVSZYPBJ-CIUDSAMLSA-N 0.000 description 5
- YGHSQRJSHKYUJY-SCZZXKLOSA-N Gly-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN YGHSQRJSHKYUJY-SCZZXKLOSA-N 0.000 description 5
- SBVMXEZQJVUARN-XPUUQOCRSA-N Gly-Val-Ser Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O SBVMXEZQJVUARN-XPUUQOCRSA-N 0.000 description 5
- JRHFQUPIZOYKQP-KBIXCLLPSA-N Ile-Ala-Glu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O JRHFQUPIZOYKQP-KBIXCLLPSA-N 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- GFZQWWDXJVGEMW-ULQDDVLXSA-N Tyr-Arg-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N)O GFZQWWDXJVGEMW-ULQDDVLXSA-N 0.000 description 5
- UNUZEBFXGWVAOP-DZKIICNBSA-N Tyr-Glu-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UNUZEBFXGWVAOP-DZKIICNBSA-N 0.000 description 5
- UMPVMAYCLYMYGA-ONGXEEELSA-N Val-Leu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O UMPVMAYCLYMYGA-ONGXEEELSA-N 0.000 description 5
- 108010047495 alanylglycine Proteins 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000021615 conjugation Effects 0.000 description 5
- 239000003431 cross linking reagent Substances 0.000 description 5
- 108010037850 glycylvaline Proteins 0.000 description 5
- 108010085325 histidylproline Proteins 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 108010047926 leucyl-lysyl-tyrosine Proteins 0.000 description 5
- 210000004558 lewy body Anatomy 0.000 description 5
- 108010051242 phenylalanylserine Proteins 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 108010031719 prolyl-serine Proteins 0.000 description 5
- 108010026333 seryl-proline Proteins 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 108010051110 tyrosyl-lysine Proteins 0.000 description 5
- 102100028626 4-hydroxyphenylpyruvate dioxygenase Human genes 0.000 description 4
- 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 4
- FJVAQLJNTSUQPY-CIUDSAMLSA-N Ala-Ala-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN FJVAQLJNTSUQPY-CIUDSAMLSA-N 0.000 description 4
- JTXVXGXTRXMOFJ-FXQIFTODSA-N Asn-Pro-Asn Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O JTXVXGXTRXMOFJ-FXQIFTODSA-N 0.000 description 4
- YRTOMUMWSTUQAX-FXQIFTODSA-N Asn-Pro-Asp Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O YRTOMUMWSTUQAX-FXQIFTODSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 4
- KBKGRMNVKPSQIF-XDTLVQLUSA-N Glu-Ala-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KBKGRMNVKPSQIF-XDTLVQLUSA-N 0.000 description 4
- 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 4
- 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 4
- 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 4
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 4
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 4
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 4
- ZXFRGTAIIZHNHG-AJNGGQMLSA-N Lys-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N ZXFRGTAIIZHNHG-AJNGGQMLSA-N 0.000 description 4
- XOQMURBBIXRRCR-SRVKXCTJSA-N Lys-Lys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN XOQMURBBIXRRCR-SRVKXCTJSA-N 0.000 description 4
- ZJWIXBZTAAJERF-IHRRRGAJSA-N Lys-Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N ZJWIXBZTAAJERF-IHRRRGAJSA-N 0.000 description 4
- 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 4
- YKBSXQFZWFXFIB-VOAKCMCISA-N Lys-Thr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O YKBSXQFZWFXFIB-VOAKCMCISA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 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 4
- 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 4
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 4
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 4
- 229940079156 Proteasome inhibitor Drugs 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 description 4
- IMYTYAWRKBYTSX-YTQUADARSA-N Trp-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)N)C(=O)O IMYTYAWRKBYTSX-YTQUADARSA-N 0.000 description 4
- FMOSEWZYZPMJAL-KKUMJFAQSA-N Tyr-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N FMOSEWZYZPMJAL-KKUMJFAQSA-N 0.000 description 4
- HPYDSVWYXXKHRD-VIFPVBQESA-N Tyr-Gly Chemical compound [O-]C(=O)CNC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 HPYDSVWYXXKHRD-VIFPVBQESA-N 0.000 description 4
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 4
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 4
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 4
- 108010068380 arginylarginine Proteins 0.000 description 4
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 4
- 230000004900 autophagic degradation Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 4
- 108010092114 histidylphenylalanine Proteins 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 108010017391 lysylvaline Proteins 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 108010029020 prolylglycine Proteins 0.000 description 4
- 239000003207 proteasome inhibitor Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 102220177745 rs200250962 Human genes 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000000527 sonication Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- 230000002463 transducing effect Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 108010029384 tryptophyl-histidine Proteins 0.000 description 4
- NWVVKQZOVSTDBQ-CIUDSAMLSA-N Ala-Glu-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NWVVKQZOVSTDBQ-CIUDSAMLSA-N 0.000 description 3
- GGNHBHYDMUDXQB-KBIXCLLPSA-N Ala-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)N GGNHBHYDMUDXQB-KBIXCLLPSA-N 0.000 description 3
- VNYMOTCMNHJGTG-JBDRJPRFSA-N Ala-Ile-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O VNYMOTCMNHJGTG-JBDRJPRFSA-N 0.000 description 3
- 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 3
- DCVYRWFAMZFSDA-ZLUOBGJFSA-N Ala-Ser-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O DCVYRWFAMZFSDA-ZLUOBGJFSA-N 0.000 description 3
- 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 3
- KXOPYFNQLVUOAQ-FXQIFTODSA-N Arg-Ser-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KXOPYFNQLVUOAQ-FXQIFTODSA-N 0.000 description 3
- VLIJAPRTSXSGFY-STQMWFEESA-N Arg-Tyr-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 VLIJAPRTSXSGFY-STQMWFEESA-N 0.000 description 3
- FTSAJSADJCMDHH-CIUDSAMLSA-N Asn-Lys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N FTSAJSADJCMDHH-CIUDSAMLSA-N 0.000 description 3
- LRCIOEVFVGXZKB-BZSNNMDCSA-N Asn-Tyr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LRCIOEVFVGXZKB-BZSNNMDCSA-N 0.000 description 3
- SEMWSADZTMJELF-BYULHYEWSA-N Asp-Ile-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O SEMWSADZTMJELF-BYULHYEWSA-N 0.000 description 3
- YFSLJHLQOALGSY-ZPFDUUQYSA-N Asp-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N YFSLJHLQOALGSY-ZPFDUUQYSA-N 0.000 description 3
- KESWRFKUZRUTAH-FXQIFTODSA-N Asp-Pro-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O KESWRFKUZRUTAH-FXQIFTODSA-N 0.000 description 3
- OZBXOELNJBSJOA-UBHSHLNASA-N Asp-Ser-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N OZBXOELNJBSJOA-UBHSHLNASA-N 0.000 description 3
- GIKOVDMXBAFXDF-NHCYSSNCSA-N Asp-Val-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GIKOVDMXBAFXDF-NHCYSSNCSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 102100035966 DnaJ homolog subfamily A member 2 Human genes 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HYPVLWGNBIYTNA-GUBZILKMSA-N Gln-Leu-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HYPVLWGNBIYTNA-GUBZILKMSA-N 0.000 description 3
- OACQOWPRWGNKTP-AVGNSLFASA-N Gln-Tyr-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O OACQOWPRWGNKTP-AVGNSLFASA-N 0.000 description 3
- RDPOETHPAQEGDP-ACZMJKKPSA-N Glu-Asp-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O RDPOETHPAQEGDP-ACZMJKKPSA-N 0.000 description 3
- JRDYDYXZKFNNRQ-XPUUQOCRSA-N Gly-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN JRDYDYXZKFNNRQ-XPUUQOCRSA-N 0.000 description 3
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 3
- DBJYVKDPGIFXFO-BQBZGAKWSA-N Gly-Met-Ala Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O DBJYVKDPGIFXFO-BQBZGAKWSA-N 0.000 description 3
- IRJWAYCXIYUHQE-WHFBIAKZSA-N Gly-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CN IRJWAYCXIYUHQE-WHFBIAKZSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102000004447 HSP40 Heat-Shock Proteins Human genes 0.000 description 3
- 108010042283 HSP40 Heat-Shock Proteins Proteins 0.000 description 3
- 108700003968 Human immunodeficiency virus 1 tat peptide (49-57) Proteins 0.000 description 3
- 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 3
- ZYVTXBXHIKGZMD-QSFUFRPTSA-N Ile-Val-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ZYVTXBXHIKGZMD-QSFUFRPTSA-N 0.000 description 3
- 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 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- HRTRLSRYZZKPCO-BJDJZHNGSA-N Leu-Ile-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O HRTRLSRYZZKPCO-BJDJZHNGSA-N 0.000 description 3
- FIICHHJDINDXKG-IHPCNDPISA-N Leu-Lys-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O FIICHHJDINDXKG-IHPCNDPISA-N 0.000 description 3
- ONPJGOIVICHWBW-BZSNNMDCSA-N Leu-Lys-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 ONPJGOIVICHWBW-BZSNNMDCSA-N 0.000 description 3
- KZZCOWMDDXDKSS-CIUDSAMLSA-N Leu-Ser-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KZZCOWMDDXDKSS-CIUDSAMLSA-N 0.000 description 3
- 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 3
- 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 3
- JGAMUXDWYSXYLM-SRVKXCTJSA-N Lys-Arg-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O JGAMUXDWYSXYLM-SRVKXCTJSA-N 0.000 description 3
- SJNZALDHDUYDBU-IHRRRGAJSA-N Lys-Arg-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(O)=O SJNZALDHDUYDBU-IHRRRGAJSA-N 0.000 description 3
- NCTDKZKNBDZDOL-GARJFASQSA-N Lys-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N)C(=O)O NCTDKZKNBDZDOL-GARJFASQSA-N 0.000 description 3
- AAORVPFVUIHEAB-YUMQZZPRSA-N Lys-Asp-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O AAORVPFVUIHEAB-YUMQZZPRSA-N 0.000 description 3
- PBIPLDMFHAICIP-DCAQKATOSA-N Lys-Glu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PBIPLDMFHAICIP-DCAQKATOSA-N 0.000 description 3
- ULUQBUKAPDUKOC-GVXVVHGQSA-N Lys-Glu-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O ULUQBUKAPDUKOC-GVXVVHGQSA-N 0.000 description 3
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 3
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 3
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 3
- XWBJLKDCHJVKAK-KKUMJFAQSA-N Phe-Arg-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N XWBJLKDCHJVKAK-KKUMJFAQSA-N 0.000 description 3
- LHALYDBUDCWMDY-CIUDSAMLSA-N Pro-Glu-Ala Chemical compound C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1)C(O)=O LHALYDBUDCWMDY-CIUDSAMLSA-N 0.000 description 3
- DWGFLKQSGRUQTI-IHRRRGAJSA-N Pro-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1 DWGFLKQSGRUQTI-IHRRRGAJSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 108010003201 RGH 0205 Proteins 0.000 description 3
- 108010091086 Recombinases Proteins 0.000 description 3
- 102000018120 Recombinases Human genes 0.000 description 3
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
- FTVRVZNYIYWJGB-ACZMJKKPSA-N Ser-Asp-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FTVRVZNYIYWJGB-ACZMJKKPSA-N 0.000 description 3
- GHPQVUYZQQGEDA-BIIVOSGPSA-N Ser-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N)C(=O)O GHPQVUYZQQGEDA-BIIVOSGPSA-N 0.000 description 3
- UOLGINIHBRIECN-FXQIFTODSA-N Ser-Glu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UOLGINIHBRIECN-FXQIFTODSA-N 0.000 description 3
- 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 3
- 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 3
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 3
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 3
- 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 3
- 239000007983 Tris buffer Substances 0.000 description 3
- IXTQGBGHWQEEDE-AVGNSLFASA-N Tyr-Asp-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 IXTQGBGHWQEEDE-AVGNSLFASA-N 0.000 description 3
- QOIKZODVIPOPDD-AVGNSLFASA-N Tyr-Cys-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O QOIKZODVIPOPDD-AVGNSLFASA-N 0.000 description 3
- IMXAAEFAIBRCQF-SIUGBPQLSA-N Tyr-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N IMXAAEFAIBRCQF-SIUGBPQLSA-N 0.000 description 3
- ANHVRCNNGJMJNG-BZSNNMDCSA-N Tyr-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CS)C(=O)O)N)O ANHVRCNNGJMJNG-BZSNNMDCSA-N 0.000 description 3
- JQOMHZMWQHXALX-FHWLQOOXSA-N Tyr-Tyr-Glu 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](CCC(O)=O)C(O)=O JQOMHZMWQHXALX-FHWLQOOXSA-N 0.000 description 3
- 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 3
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 108010013835 arginine glutamate Proteins 0.000 description 3
- 108010084758 arginyl-tyrosyl-aspartic acid Proteins 0.000 description 3
- 108010062796 arginyllysine Proteins 0.000 description 3
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000001066 destructive effect Effects 0.000 description 3
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 3
- 108010027668 glycyl-alanyl-valine Proteins 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 210000003000 inclusion body Anatomy 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000007917 intracranial administration Methods 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 238000007913 intrathecal administration Methods 0.000 description 3
- 238000007914 intraventricular administration Methods 0.000 description 3
- 108010053037 kyotorphin Proteins 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 108010056582 methionylglutamic acid Proteins 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 108010070409 phenylalanyl-glycyl-glycine Proteins 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 108010040003 polyglutamine Proteins 0.000 description 3
- 229920000155 polyglutamine Polymers 0.000 description 3
- 108010030799 polyglutamine-binding protein 1 Proteins 0.000 description 3
- 108010070643 prolylglutamic acid Proteins 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 230000003362 replicative effect Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- 239000012096 transfection reagent Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 108010038745 tryptophylglycine Proteins 0.000 description 3
- 108010003137 tyrosyltyrosine Proteins 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 2
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
- BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 description 2
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 description 2
- JARGNLJYKBUKSJ-KGZKBUQUSA-N (2r)-2-amino-5-[[(2r)-1-(carboxymethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid;hydrobromide Chemical compound Br.OC(=O)[C@H](N)CCC(=O)N[C@H](CO)C(=O)NCC(O)=O JARGNLJYKBUKSJ-KGZKBUQUSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 239000013607 AAV vector Substances 0.000 description 2
- 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 2
- HMRWQTHUDVXMGH-GUBZILKMSA-N Ala-Glu-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN HMRWQTHUDVXMGH-GUBZILKMSA-N 0.000 description 2
- BLIMFWGRQKRCGT-YUMQZZPRSA-N Ala-Gly-Lys Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN BLIMFWGRQKRCGT-YUMQZZPRSA-N 0.000 description 2
- 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 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
- AJBVYEYZVYPFCF-CIUDSAMLSA-N Ala-Lys-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O AJBVYEYZVYPFCF-CIUDSAMLSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- HOVPGJUNRLMIOZ-CIUDSAMLSA-N Ala-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N HOVPGJUNRLMIOZ-CIUDSAMLSA-N 0.000 description 2
- LSMDIAAALJJLRO-XQXXSGGOSA-N Ala-Thr-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O LSMDIAAALJJLRO-XQXXSGGOSA-N 0.000 description 2
- TVUFMYKTYXTRPY-HERUPUMHSA-N Ala-Trp-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O TVUFMYKTYXTRPY-HERUPUMHSA-N 0.000 description 2
- QDGMZAOSMNGBLP-MRFFXTKBSA-N Ala-Trp-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)N QDGMZAOSMNGBLP-MRFFXTKBSA-N 0.000 description 2
- YCTIYBUTCKNOTI-UWJYBYFXSA-N Ala-Tyr-Asp Chemical compound 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 YCTIYBUTCKNOTI-UWJYBYFXSA-N 0.000 description 2
- DCGLNNVKIZXQOJ-FXQIFTODSA-N Arg-Asn-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N DCGLNNVKIZXQOJ-FXQIFTODSA-N 0.000 description 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
- RWCLSUOSKWTXLA-FXQIFTODSA-N Arg-Asp-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O RWCLSUOSKWTXLA-FXQIFTODSA-N 0.000 description 2
- 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 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
- 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 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
- CVXXSWQORBZAAA-SRVKXCTJSA-N Arg-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N CVXXSWQORBZAAA-SRVKXCTJSA-N 0.000 description 2
- CLICCYPMVFGUOF-IHRRRGAJSA-N Arg-Lys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O CLICCYPMVFGUOF-IHRRRGAJSA-N 0.000 description 2
- PAXHINASXXXILC-SRVKXCTJSA-N Asn-Asp-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N)O PAXHINASXXXILC-SRVKXCTJSA-N 0.000 description 2
- VJTWLBMESLDOMK-WDSKDSINSA-N Asn-Gln-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O VJTWLBMESLDOMK-WDSKDSINSA-N 0.000 description 2
- 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 2
- SNAKIVFVLVUCKB-UHFFFAOYSA-N Asn-Glu-Ala-Lys Natural products NCCCCC(C(O)=O)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(N)CC(N)=O SNAKIVFVLVUCKB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- COWITDLVHMZSIW-CIUDSAMLSA-N Asn-Lys-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O COWITDLVHMZSIW-CIUDSAMLSA-N 0.000 description 2
- SZNGQSBRHFMZLT-IHRRRGAJSA-N Asn-Pro-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SZNGQSBRHFMZLT-IHRRRGAJSA-N 0.000 description 2
- MKJBPDLENBUHQU-CIUDSAMLSA-N Asn-Ser-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O MKJBPDLENBUHQU-CIUDSAMLSA-N 0.000 description 2
- JPPLRQVZMZFOSX-UWJYBYFXSA-N Asn-Tyr-Ala Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=C(O)C=C1 JPPLRQVZMZFOSX-UWJYBYFXSA-N 0.000 description 2
- DATSKXOXPUAOLK-KKUMJFAQSA-N Asn-Tyr-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O DATSKXOXPUAOLK-KKUMJFAQSA-N 0.000 description 2
- ZAESWDKAMDVHLL-RCOVLWMOSA-N Asn-Val-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O ZAESWDKAMDVHLL-RCOVLWMOSA-N 0.000 description 2
- BLQBMRNMBAYREH-UWJYBYFXSA-N Asp-Ala-Tyr Chemical compound N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O BLQBMRNMBAYREH-UWJYBYFXSA-N 0.000 description 2
- 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 2
- PSLSTUMPZILTAH-BYULHYEWSA-N Asp-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O PSLSTUMPZILTAH-BYULHYEWSA-N 0.000 description 2
- HOBNTSHITVVNBN-ZPFDUUQYSA-N Asp-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N HOBNTSHITVVNBN-ZPFDUUQYSA-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
- 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 2
- RXBGWGRSWXOBGK-KKUMJFAQSA-N Asp-Lys-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RXBGWGRSWXOBGK-KKUMJFAQSA-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
- HJZLUGQGJWXJCJ-CIUDSAMLSA-N Asp-Pro-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJZLUGQGJWXJCJ-CIUDSAMLSA-N 0.000 description 2
- AHWRSSLYSGLBGD-CIUDSAMLSA-N Asp-Pro-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AHWRSSLYSGLBGD-CIUDSAMLSA-N 0.000 description 2
- MNQMTYSEKZHIDF-GCJQMDKQSA-N Asp-Thr-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O MNQMTYSEKZHIDF-GCJQMDKQSA-N 0.000 description 2
- KNDCWFXCFKSEBM-AVGNSLFASA-N Asp-Tyr-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O KNDCWFXCFKSEBM-AVGNSLFASA-N 0.000 description 2
- SQIARYGNVQWOSB-BZSNNMDCSA-N Asp-Tyr-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SQIARYGNVQWOSB-BZSNNMDCSA-N 0.000 description 2
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 2
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 2
- ALNKNYKSZPSLBD-ZDLURKLDSA-N Cys-Thr-Gly Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O ALNKNYKSZPSLBD-ZDLURKLDSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 102100031675 DnaJ homolog subfamily C member 5 Human genes 0.000 description 2
- 241000713730 Equine infectious anemia virus Species 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 102100031562 Excitatory amino acid transporter 2 Human genes 0.000 description 2
- XZWYTXMRWQJBGX-VXBMVYAYSA-N FLAG peptide Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 XZWYTXMRWQJBGX-VXBMVYAYSA-N 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 241000714165 Feline leukemia virus Species 0.000 description 2
- 101710099785 Ferritin, heavy subunit Proteins 0.000 description 2
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 2
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 2
- KCJJFESQRXGTGC-BQBZGAKWSA-N Gln-Glu-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O KCJJFESQRXGTGC-BQBZGAKWSA-N 0.000 description 2
- ORYMMTRPKVTGSJ-XVKPBYJWSA-N Gln-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O ORYMMTRPKVTGSJ-XVKPBYJWSA-N 0.000 description 2
- YPMDZWPZFOZYFG-GUBZILKMSA-N Gln-Leu-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YPMDZWPZFOZYFG-GUBZILKMSA-N 0.000 description 2
- IHSGESFHTMFHRB-GUBZILKMSA-N Gln-Lys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(N)=O IHSGESFHTMFHRB-GUBZILKMSA-N 0.000 description 2
- 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 2
- DCWNCMRZIZSZBL-KKUMJFAQSA-N Gln-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)N)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O DCWNCMRZIZSZBL-KKUMJFAQSA-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
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 2
- ITYRYNUZHPNCIK-GUBZILKMSA-N Glu-Ala-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O ITYRYNUZHPNCIK-GUBZILKMSA-N 0.000 description 2
- 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 2
- IESFZVCAVACGPH-PEFMBERDSA-N Glu-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O IESFZVCAVACGPH-PEFMBERDSA-N 0.000 description 2
- 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 2
- AUTNXSQEVVHSJK-YVNDNENWSA-N Glu-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O AUTNXSQEVVHSJK-YVNDNENWSA-N 0.000 description 2
- MTAOBYXRYJZRGQ-WDSKDSINSA-N Glu-Gly-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MTAOBYXRYJZRGQ-WDSKDSINSA-N 0.000 description 2
- HILMIYALTUQTRC-XVKPBYJWSA-N Glu-Gly-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HILMIYALTUQTRC-XVKPBYJWSA-N 0.000 description 2
- WTMZXOPHTIVFCP-QEWYBTABSA-N Glu-Ile-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 WTMZXOPHTIVFCP-QEWYBTABSA-N 0.000 description 2
- 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 2
- HRBYTAIBKPNZKQ-AVGNSLFASA-N Glu-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O HRBYTAIBKPNZKQ-AVGNSLFASA-N 0.000 description 2
- MFNUFCFRAZPJFW-JYJNAYRXSA-N Glu-Lys-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFNUFCFRAZPJFW-JYJNAYRXSA-N 0.000 description 2
- JDUKCSSHWNIQQZ-IHRRRGAJSA-N Glu-Phe-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O JDUKCSSHWNIQQZ-IHRRRGAJSA-N 0.000 description 2
- DXVOKNVIKORTHQ-GUBZILKMSA-N Glu-Pro-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O DXVOKNVIKORTHQ-GUBZILKMSA-N 0.000 description 2
- MWTGQXBHVRTCOR-GLLZPBPUSA-N Glu-Thr-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MWTGQXBHVRTCOR-GLLZPBPUSA-N 0.000 description 2
- HGJREIGJLUQBTJ-SZMVWBNQSA-N Glu-Trp-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(O)=O HGJREIGJLUQBTJ-SZMVWBNQSA-N 0.000 description 2
- YQPFCZVKMUVZIN-AUTRQRHGSA-N Glu-Val-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O YQPFCZVKMUVZIN-AUTRQRHGSA-N 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- UGVQELHRNUDMAA-BYPYZUCNSA-N Gly-Ala-Gly Chemical compound [NH3+]CC(=O)N[C@@H](C)C(=O)NCC([O-])=O UGVQELHRNUDMAA-BYPYZUCNSA-N 0.000 description 2
- 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 2
- 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 2
- BHPQOIPBLYJNAW-NGZCFLSTSA-N Gly-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN BHPQOIPBLYJNAW-NGZCFLSTSA-N 0.000 description 2
- SCWYHUQOOFRVHP-MBLNEYKQSA-N Gly-Ile-Thr Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SCWYHUQOOFRVHP-MBLNEYKQSA-N 0.000 description 2
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 2
- VBOBNHSVQKKTOT-YUMQZZPRSA-N Gly-Lys-Ala Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O VBOBNHSVQKKTOT-YUMQZZPRSA-N 0.000 description 2
- LOEANKRDMMVOGZ-YUMQZZPRSA-N Gly-Lys-Asp Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(O)=O)C(O)=O LOEANKRDMMVOGZ-YUMQZZPRSA-N 0.000 description 2
- VDCRBJACQKOSMS-JSGCOSHPSA-N Gly-Phe-Val Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O VDCRBJACQKOSMS-JSGCOSHPSA-N 0.000 description 2
- POJJAZJHBGXEGM-YUMQZZPRSA-N Gly-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)CN POJJAZJHBGXEGM-YUMQZZPRSA-N 0.000 description 2
- ZZWUYQXMIFTIIY-WEDXCCLWSA-N Gly-Thr-Leu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O ZZWUYQXMIFTIIY-WEDXCCLWSA-N 0.000 description 2
- XHVONGZZVUUORG-WEDXCCLWSA-N Gly-Thr-Lys Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN XHVONGZZVUUORG-WEDXCCLWSA-N 0.000 description 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
- 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
- BAYQNCWLXIDLHX-ONGXEEELSA-N Gly-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN BAYQNCWLXIDLHX-ONGXEEELSA-N 0.000 description 2
- 241000713858 Harvey murine sarcoma virus Species 0.000 description 2
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 2
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 2
- 101000866287 Homo sapiens Excitatory amino acid transporter 2 Proteins 0.000 description 2
- NKVZTQVGUNLLQW-JBDRJPRFSA-N Ile-Ala-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)O)N NKVZTQVGUNLLQW-JBDRJPRFSA-N 0.000 description 2
- YOTNPRLPIPHQSB-XUXIUFHCSA-N Ile-Arg-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOTNPRLPIPHQSB-XUXIUFHCSA-N 0.000 description 2
- SCHZQZPYHBWYEQ-PEFMBERDSA-N Ile-Asn-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N SCHZQZPYHBWYEQ-PEFMBERDSA-N 0.000 description 2
- DFJJAVZIHDFOGQ-MNXVOIDGSA-N Ile-Glu-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N DFJJAVZIHDFOGQ-MNXVOIDGSA-N 0.000 description 2
- SLQVFYWBGNNOTK-BYULHYEWSA-N Ile-Gly-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)N)C(=O)O)N SLQVFYWBGNNOTK-BYULHYEWSA-N 0.000 description 2
- 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 2
- PHRWFSFCNJPWRO-PPCPHDFISA-N Ile-Leu-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N PHRWFSFCNJPWRO-PPCPHDFISA-N 0.000 description 2
- RENBRDSDKPSRIH-HJWJTTGWSA-N Ile-Phe-Met Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)O RENBRDSDKPSRIH-HJWJTTGWSA-N 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 108010061833 Integrases Proteins 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- 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 2
- VCSBGUACOYUIGD-CIUDSAMLSA-N Leu-Asn-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VCSBGUACOYUIGD-CIUDSAMLSA-N 0.000 description 2
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 2
- 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
- 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
- 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
- KUIDCYNIEJBZBU-AJNGGQMLSA-N Leu-Ile-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O KUIDCYNIEJBZBU-AJNGGQMLSA-N 0.000 description 2
- IAJFFZORSWOZPQ-SRVKXCTJSA-N Leu-Leu-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IAJFFZORSWOZPQ-SRVKXCTJSA-N 0.000 description 2
- REPBGZHJKYWFMJ-KKUMJFAQSA-N Leu-Lys-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N REPBGZHJKYWFMJ-KKUMJFAQSA-N 0.000 description 2
- QNTJIDXQHWUBKC-BZSNNMDCSA-N Leu-Lys-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QNTJIDXQHWUBKC-BZSNNMDCSA-N 0.000 description 2
- KIZIOFNVSOSKJI-CIUDSAMLSA-N Leu-Ser-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N KIZIOFNVSOSKJI-CIUDSAMLSA-N 0.000 description 2
- SBANPBVRHYIMRR-GARJFASQSA-N Leu-Ser-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N SBANPBVRHYIMRR-GARJFASQSA-N 0.000 description 2
- 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 2
- ISSAURVGLGAPDK-KKUMJFAQSA-N Leu-Tyr-Asp 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(O)=O)C(O)=O ISSAURVGLGAPDK-KKUMJFAQSA-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
- 208000009829 Lewy Body Disease Diseases 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 101001022947 Lithobates catesbeianus Ferritin, lower subunit Proteins 0.000 description 2
- VHXMZJGOKIMETG-CQDKDKBSSA-N Lys-Ala-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCCCN)N VHXMZJGOKIMETG-CQDKDKBSSA-N 0.000 description 2
- HIIZIQUUHIXUJY-GUBZILKMSA-N Lys-Asp-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HIIZIQUUHIXUJY-GUBZILKMSA-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
- 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 2
- KJIXWRWPOCKYLD-IHRRRGAJSA-N Lys-Lys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N KJIXWRWPOCKYLD-IHRRRGAJSA-N 0.000 description 2
- YTJFXEDRUOQGSP-DCAQKATOSA-N Lys-Pro-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O YTJFXEDRUOQGSP-DCAQKATOSA-N 0.000 description 2
- WQDKIVRHTQYJSN-DCAQKATOSA-N Lys-Ser-Arg Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N WQDKIVRHTQYJSN-DCAQKATOSA-N 0.000 description 2
- QLFAPXUXEBAWEK-NHCYSSNCSA-N Lys-Val-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QLFAPXUXEBAWEK-NHCYSSNCSA-N 0.000 description 2
- FVKRQMQQFGBXHV-QXEWZRGKSA-N Met-Asp-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O FVKRQMQQFGBXHV-QXEWZRGKSA-N 0.000 description 2
- FBLBCGLSRXBANI-KKUMJFAQSA-N Met-Phe-Glu Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N FBLBCGLSRXBANI-KKUMJFAQSA-N 0.000 description 2
- BJPQKNHZHUCQNQ-SRVKXCTJSA-N Met-Pro-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCSC)N BJPQKNHZHUCQNQ-SRVKXCTJSA-N 0.000 description 2
- OVTOTTGZBWXLFU-QXEWZRGKSA-N Met-Val-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O OVTOTTGZBWXLFU-QXEWZRGKSA-N 0.000 description 2
- 241000713862 Moloney murine sarcoma virus Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 108010079364 N-glycylalanine Proteins 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- XMPUYNHKEPFERE-IHRRRGAJSA-N Phe-Asp-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 XMPUYNHKEPFERE-IHRRRGAJSA-N 0.000 description 2
- CUMXHKAOHNWRFQ-BZSNNMDCSA-N Phe-Asp-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 CUMXHKAOHNWRFQ-BZSNNMDCSA-N 0.000 description 2
- DNAXXTQSTKOHFO-QEJZJMRPSA-N Phe-Lys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 DNAXXTQSTKOHFO-QEJZJMRPSA-N 0.000 description 2
- UXQFHEKRGHYJRA-STQMWFEESA-N Phe-Met-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O UXQFHEKRGHYJRA-STQMWFEESA-N 0.000 description 2
- FUAIIFPQELBNJF-ULQDDVLXSA-N Phe-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N FUAIIFPQELBNJF-ULQDDVLXSA-N 0.000 description 2
- FGWUALWGCZJQDJ-URLPEUOOSA-N Phe-Thr-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FGWUALWGCZJQDJ-URLPEUOOSA-N 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- UVKNEILZSJMKSR-FXQIFTODSA-N Pro-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1 UVKNEILZSJMKSR-FXQIFTODSA-N 0.000 description 2
- JARJPEMLQAWNBR-GUBZILKMSA-N Pro-Asp-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JARJPEMLQAWNBR-GUBZILKMSA-N 0.000 description 2
- 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 2
- KIPIKSXPPLABPN-CIUDSAMLSA-N Pro-Glu-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1 KIPIKSXPPLABPN-CIUDSAMLSA-N 0.000 description 2
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 2
- VPEVBAUSTBWQHN-NHCYSSNCSA-N Pro-Glu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O VPEVBAUSTBWQHN-NHCYSSNCSA-N 0.000 description 2
- QCMYJBKTMIWZAP-AVGNSLFASA-N Pro-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 QCMYJBKTMIWZAP-AVGNSLFASA-N 0.000 description 2
- POQFNPILEQEODH-FXQIFTODSA-N Pro-Ser-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O POQFNPILEQEODH-FXQIFTODSA-N 0.000 description 2
- 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 2
- 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 2
- 241000700159 Rattus Species 0.000 description 2
- GXXTUIUYTWGPMV-FXQIFTODSA-N Ser-Arg-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O GXXTUIUYTWGPMV-FXQIFTODSA-N 0.000 description 2
- 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 2
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 2
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 2
- ZXLUWXWISXIFIX-ACZMJKKPSA-N Ser-Asn-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZXLUWXWISXIFIX-ACZMJKKPSA-N 0.000 description 2
- VQBCMLMPEWPUTB-ACZMJKKPSA-N Ser-Glu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O VQBCMLMPEWPUTB-ACZMJKKPSA-N 0.000 description 2
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 2
- SFTZTYBXIXLRGQ-JBDRJPRFSA-N Ser-Ile-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O SFTZTYBXIXLRGQ-JBDRJPRFSA-N 0.000 description 2
- 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 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
- FPCGZYMRFFIYIH-CIUDSAMLSA-N Ser-Lys-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O FPCGZYMRFFIYIH-CIUDSAMLSA-N 0.000 description 2
- 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 2
- BSXKBOUZDAZXHE-CIUDSAMLSA-N Ser-Pro-Glu Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O BSXKBOUZDAZXHE-CIUDSAMLSA-N 0.000 description 2
- JGUWRQWULDWNCM-FXQIFTODSA-N Ser-Val-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O JGUWRQWULDWNCM-FXQIFTODSA-N 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 108010052160 Site-specific recombinase Proteins 0.000 description 2
- LVHHEVGYAZGXDE-KDXUFGMBSA-N Thr-Ala-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(=O)O)N)O LVHHEVGYAZGXDE-KDXUFGMBSA-N 0.000 description 2
- NAXBBCLCEOTAIG-RHYQMDGZSA-N Thr-Arg-Lys Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O NAXBBCLCEOTAIG-RHYQMDGZSA-N 0.000 description 2
- LMMDEZPNUTZJAY-GCJQMDKQSA-N Thr-Asp-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O LMMDEZPNUTZJAY-GCJQMDKQSA-N 0.000 description 2
- KZSYAEWQMJEGRZ-RHYQMDGZSA-N Thr-Leu-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O KZSYAEWQMJEGRZ-RHYQMDGZSA-N 0.000 description 2
- SCSVNSNWUTYSFO-WDCWCFNPSA-N Thr-Lys-Glu Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O SCSVNSNWUTYSFO-WDCWCFNPSA-N 0.000 description 2
- XKWABWFMQXMUMT-HJGDQZAQSA-N Thr-Pro-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XKWABWFMQXMUMT-HJGDQZAQSA-N 0.000 description 2
- IQPWNQRRAJHOKV-KATARQTJSA-N Thr-Ser-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN IQPWNQRRAJHOKV-KATARQTJSA-N 0.000 description 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
- YOPQYBJJNSIQGZ-JNPHEJMOSA-N Thr-Tyr-Tyr Chemical compound C([C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 YOPQYBJJNSIQGZ-JNPHEJMOSA-N 0.000 description 2
- 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 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
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- SVGAWGVHFIYAEE-JSGCOSHPSA-N Trp-Gly-Gln Chemical compound C1=CC=C2C(C[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)=CNC2=C1 SVGAWGVHFIYAEE-JSGCOSHPSA-N 0.000 description 2
- GQHAIUPYZPTADF-FDARSICLSA-N Trp-Ile-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 GQHAIUPYZPTADF-FDARSICLSA-N 0.000 description 2
- PKZIWSHDJYIPRH-JBACZVJFSA-N Trp-Tyr-Gln Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O PKZIWSHDJYIPRH-JBACZVJFSA-N 0.000 description 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
- JFDGVHXRCKEBAU-KKUMJFAQSA-N Tyr-Asp-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N)O JFDGVHXRCKEBAU-KKUMJFAQSA-N 0.000 description 2
- STTVVMWQKDOKAM-YESZJQIVSA-N Tyr-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O STTVVMWQKDOKAM-YESZJQIVSA-N 0.000 description 2
- 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 2
- 102000044159 Ubiquitin Human genes 0.000 description 2
- 108090000848 Ubiquitin Proteins 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- IZFVRRYRMQFVGX-NRPADANISA-N Val-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N IZFVRRYRMQFVGX-NRPADANISA-N 0.000 description 2
- YFOCMOVJBQDBCE-NRPADANISA-N Val-Ala-Glu Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N YFOCMOVJBQDBCE-NRPADANISA-N 0.000 description 2
- 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 2
- SZTTYWIUCGSURQ-AUTRQRHGSA-N Val-Glu-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SZTTYWIUCGSURQ-AUTRQRHGSA-N 0.000 description 2
- PTFPUAXGIKTVNN-ONGXEEELSA-N Val-His-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)NCC(=O)O)N PTFPUAXGIKTVNN-ONGXEEELSA-N 0.000 description 2
- HPANGHISDXDUQY-ULQDDVLXSA-N Val-Lys-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N HPANGHISDXDUQY-ULQDDVLXSA-N 0.000 description 2
- ZXYPHBKIZLAQTL-QXEWZRGKSA-N Val-Pro-Asp Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)O)N ZXYPHBKIZLAQTL-QXEWZRGKSA-N 0.000 description 2
- AJNUKMZFHXUBMK-GUBZILKMSA-N Val-Ser-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N AJNUKMZFHXUBMK-GUBZILKMSA-N 0.000 description 2
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- HTONZBWRYUKUKC-RCWTZXSCSA-N Val-Thr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HTONZBWRYUKUKC-RCWTZXSCSA-N 0.000 description 2
- OWFGFHQMSBTKLX-UFYCRDLUSA-N Val-Tyr-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N OWFGFHQMSBTKLX-UFYCRDLUSA-N 0.000 description 2
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 2
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 108010081404 acein-2 Proteins 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 108010045350 alanyl-tyrosyl-alanine Proteins 0.000 description 2
- 108010041407 alanylaspartic acid Proteins 0.000 description 2
- 108010087924 alanylproline Proteins 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 2
- 108010059459 arginyl-threonyl-phenylalanine Proteins 0.000 description 2
- 210000004507 artificial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 108010044804 gamma-glutamyl-seryl-glycine Proteins 0.000 description 2
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 2
- 108010050475 glycyl-leucyl-tyrosine Proteins 0.000 description 2
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 2
- 108010010147 glycylglutamine Proteins 0.000 description 2
- 108010015792 glycyllysine Proteins 0.000 description 2
- 108010077515 glycylproline Proteins 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 108010040030 histidinoalanine Proteins 0.000 description 2
- 108010028295 histidylhistidine Proteins 0.000 description 2
- 108010025306 histidylleucine Proteins 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 108010078274 isoleucylvaline Proteins 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 2
- 108010012058 leucyltyrosine Proteins 0.000 description 2
- 229960004502 levodopa Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 108010043322 lysyl-tryptophyl-alpha-lysine Proteins 0.000 description 2
- 108010038320 lysylphenylalanine Proteins 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000002241 neurite Anatomy 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 108010018625 phenylalanylarginine Proteins 0.000 description 2
- 108010012581 phenylalanylglutamate Proteins 0.000 description 2
- 108010004914 prolylarginine Proteins 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000013608 rAAV vector Substances 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000003523 substantia nigra Anatomy 0.000 description 2
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 108010035534 tyrosyl-leucyl-alanine Proteins 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 108010000998 wheylin-2 peptide Proteins 0.000 description 2
- NGXDNMNOQDVTRL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-(4-azido-2-nitroanilino)hexanoate Chemical compound [O-][N+](=O)C1=CC(N=[N+]=[N-])=CC=C1NCCCCCC(=O)ON1C(=O)CCC1=O NGXDNMNOQDVTRL-UHFFFAOYSA-N 0.000 description 1
- QYEAAMBIUQLHFQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 QYEAAMBIUQLHFQ-UHFFFAOYSA-N 0.000 description 1
- OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-N 0.000 description 1
- IESDGNYHXIOKRW-YXMSTPNBSA-N (2s)-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s,3r)-2-amino-3-hydroxybutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IESDGNYHXIOKRW-YXMSTPNBSA-N 0.000 description 1
- BQMDWLHBHLILMV-HVTWWXFQSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(O)=O BQMDWLHBHLILMV-HVTWWXFQSA-N 0.000 description 1
- DIBLBAURNYJYBF-XLXZRNDBSA-N (2s)-2-[[(2s)-2-[[2-[[(2s)-6-amino-2-[[(2s)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 DIBLBAURNYJYBF-XLXZRNDBSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- ZBQCCTCQUCOXBO-UHFFFAOYSA-N 4-(4-aminophenyl)-2,2,6,6-tetramethylcyclohex-3-en-1-amine Chemical compound CC1(C)C(N)C(C)(C)CC(C=2C=CC(N)=CC=2)=C1 ZBQCCTCQUCOXBO-UHFFFAOYSA-N 0.000 description 1
- OGHAROSJZRTIOK-KQYNXXCUSA-O 7-methylguanosine Chemical compound C1=2N=C(N)NC(=O)C=2[N+](C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OGHAROSJZRTIOK-KQYNXXCUSA-O 0.000 description 1
- 101800000263 Acidic protein Proteins 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
- 229920001817 Agar Polymers 0.000 description 1
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 1
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 1
- UGLPMYSCWHTZQU-AUTRQRHGSA-N Ala-Ala-Tyr Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 UGLPMYSCWHTZQU-AUTRQRHGSA-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
- 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
- WDIYWDJLXOCGRW-ACZMJKKPSA-N Ala-Asp-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WDIYWDJLXOCGRW-ACZMJKKPSA-N 0.000 description 1
- LSLIRHLIUDVNBN-CIUDSAMLSA-N Ala-Asp-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN LSLIRHLIUDVNBN-CIUDSAMLSA-N 0.000 description 1
- ZODMADSIQZZBSQ-FXQIFTODSA-N Ala-Gln-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZODMADSIQZZBSQ-FXQIFTODSA-N 0.000 description 1
- YIGLXQRFQVWFEY-NRPADANISA-N Ala-Gln-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O YIGLXQRFQVWFEY-NRPADANISA-N 0.000 description 1
- KXEVYGKATAMXJJ-ACZMJKKPSA-N Ala-Glu-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O KXEVYGKATAMXJJ-ACZMJKKPSA-N 0.000 description 1
- WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-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
- BEMGNWZECGIJOI-WDSKDSINSA-N Ala-Gly-Glu Chemical compound [H]N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O BEMGNWZECGIJOI-WDSKDSINSA-N 0.000 description 1
- MQIGTEQXYCRLGK-BQBZGAKWSA-N Ala-Gly-Pro Chemical compound C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O MQIGTEQXYCRLGK-BQBZGAKWSA-N 0.000 description 1
- 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 1
- JDIQCVUDDFENPU-ZKWXMUAHSA-N Ala-His-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CNC=N1 JDIQCVUDDFENPU-ZKWXMUAHSA-N 0.000 description 1
- LTSBJNNXPBBNDT-HGNGGELXSA-N Ala-His-Gln Chemical compound N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(=O)O LTSBJNNXPBBNDT-HGNGGELXSA-N 0.000 description 1
- OKEWAFFWMHBGPT-XPUUQOCRSA-N Ala-His-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CN=CN1 OKEWAFFWMHBGPT-XPUUQOCRSA-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
- DVJSJDDYCYSMFR-ZKWXMUAHSA-N Ala-Ile-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O DVJSJDDYCYSMFR-ZKWXMUAHSA-N 0.000 description 1
- RGQCNKIDEQJEBT-CQDKDKBSSA-N Ala-Leu-Tyr Chemical compound 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 RGQCNKIDEQJEBT-CQDKDKBSSA-N 0.000 description 1
- XHNLCGXYBXNRIS-BJDJZHNGSA-N Ala-Lys-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XHNLCGXYBXNRIS-BJDJZHNGSA-N 0.000 description 1
- PMQXMXAASGFUDX-SRVKXCTJSA-N Ala-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCCN PMQXMXAASGFUDX-SRVKXCTJSA-N 0.000 description 1
- VCSABYLVNWQYQE-SRVKXCTJSA-N Ala-Lys-Lys Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CCCCN)C(O)=O VCSABYLVNWQYQE-SRVKXCTJSA-N 0.000 description 1
- DRARURMRLANNLS-GUBZILKMSA-N Ala-Met-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(O)=O DRARURMRLANNLS-GUBZILKMSA-N 0.000 description 1
- DHBKYZYFEXXUAK-ONGXEEELSA-N Ala-Phe-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 DHBKYZYFEXXUAK-ONGXEEELSA-N 0.000 description 1
- HYIDEIQUCBKIPL-CQDKDKBSSA-N Ala-Phe-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N HYIDEIQUCBKIPL-CQDKDKBSSA-N 0.000 description 1
- JAQNUEWEJWBVAY-WBAXXEDZSA-N Ala-Phe-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 JAQNUEWEJWBVAY-WBAXXEDZSA-N 0.000 description 1
- MAZZQZWCCYJQGZ-GUBZILKMSA-N Ala-Pro-Arg Chemical compound [H]N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MAZZQZWCCYJQGZ-GUBZILKMSA-N 0.000 description 1
- IORKCNUBHNIMKY-CIUDSAMLSA-N Ala-Pro-Glu Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O IORKCNUBHNIMKY-CIUDSAMLSA-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
- YYAVDNKUWLAFCV-ACZMJKKPSA-N Ala-Ser-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O YYAVDNKUWLAFCV-ACZMJKKPSA-N 0.000 description 1
- 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 1
- NZGRHTKZFSVPAN-BIIVOSGPSA-N Ala-Ser-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N NZGRHTKZFSVPAN-BIIVOSGPSA-N 0.000 description 1
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 1
- WQKAQKZRDIZYNV-VZFHVOOUSA-N Ala-Ser-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WQKAQKZRDIZYNV-VZFHVOOUSA-N 0.000 description 1
- SYIFFFHSXBNPMC-UWJYBYFXSA-N Ala-Ser-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N SYIFFFHSXBNPMC-UWJYBYFXSA-N 0.000 description 1
- 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
- OEVCHROQUIVQFZ-YTLHQDLWSA-N Ala-Thr-Ala Chemical compound C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](C)C(O)=O OEVCHROQUIVQFZ-YTLHQDLWSA-N 0.000 description 1
- 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 1
- VNFSAYFQLXPHPY-CIQUZCHMSA-N Ala-Thr-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNFSAYFQLXPHPY-CIQUZCHMSA-N 0.000 description 1
- IOFVWPYSRSCWHI-JXUBOQSCSA-N Ala-Thr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)N IOFVWPYSRSCWHI-JXUBOQSCSA-N 0.000 description 1
- SAHQGRZIQVEJPF-JXUBOQSCSA-N Ala-Thr-Lys Chemical compound C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN SAHQGRZIQVEJPF-JXUBOQSCSA-N 0.000 description 1
- XMIAMUXIMWREBJ-HERUPUMHSA-N Ala-Trp-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(=O)N)C(=O)O)N XMIAMUXIMWREBJ-HERUPUMHSA-N 0.000 description 1
- PHQXWZGXKAFWAZ-ZLIFDBKOSA-N Ala-Trp-Lys Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CCCCN)C(O)=O)=CNC2=C1 PHQXWZGXKAFWAZ-ZLIFDBKOSA-N 0.000 description 1
- AENHOIXXHKNIQL-AUTRQRHGSA-N Ala-Tyr-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]([NH3+])C)CC1=CC=C(O)C=C1 AENHOIXXHKNIQL-AUTRQRHGSA-N 0.000 description 1
- BHFOJPDOQPWJRN-XDTLVQLUSA-N Ala-Tyr-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(N)=O)C(O)=O BHFOJPDOQPWJRN-XDTLVQLUSA-N 0.000 description 1
- VYMJAWXRWHJIMS-LKTVYLICSA-N Ala-Tyr-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N VYMJAWXRWHJIMS-LKTVYLICSA-N 0.000 description 1
- XAXMJQUMRJAFCH-CQDKDKBSSA-N Ala-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 XAXMJQUMRJAFCH-CQDKDKBSSA-N 0.000 description 1
- JNJHNBXBGNJESC-KKXDTOCCSA-N Ala-Tyr-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JNJHNBXBGNJESC-KKXDTOCCSA-N 0.000 description 1
- MUGAESARFRGOTQ-IGNZVWTISA-N Ala-Tyr-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N MUGAESARFRGOTQ-IGNZVWTISA-N 0.000 description 1
- 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 1
- LYILPUNCKACNGF-NAKRPEOUSA-N Ala-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)N LYILPUNCKACNGF-NAKRPEOUSA-N 0.000 description 1
- ZDILXFDENZVOTL-BPNCWPANSA-N Ala-Val-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDILXFDENZVOTL-BPNCWPANSA-N 0.000 description 1
- 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
- 102000001049 Amyloid Human genes 0.000 description 1
- 108010094108 Amyloid Proteins 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 101100403802 Arabidopsis thaliana NAC032 gene Proteins 0.000 description 1
- 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 1
- OTOXOKCIIQLMFH-KZVJFYERSA-N Arg-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N OTOXOKCIIQLMFH-KZVJFYERSA-N 0.000 description 1
- XPSGESXVBSQZPL-SRVKXCTJSA-N Arg-Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XPSGESXVBSQZPL-SRVKXCTJSA-N 0.000 description 1
- 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 1
- HJVGMOYJDDXLMI-AVGNSLFASA-N Arg-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CCCNC(N)=N HJVGMOYJDDXLMI-AVGNSLFASA-N 0.000 description 1
- 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
- MAISCYVJLBBRNU-DCAQKATOSA-N Arg-Asn-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N MAISCYVJLBBRNU-DCAQKATOSA-N 0.000 description 1
- PQWTZSNVWSOFFK-FXQIFTODSA-N Arg-Asp-Asn Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)CN=C(N)N PQWTZSNVWSOFFK-FXQIFTODSA-N 0.000 description 1
- JSHVMZANPXCDTL-GMOBBJLQSA-N Arg-Asp-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JSHVMZANPXCDTL-GMOBBJLQSA-N 0.000 description 1
- VXXHDZKEQNGXNU-QXEWZRGKSA-N Arg-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N VXXHDZKEQNGXNU-QXEWZRGKSA-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
- JCAISGGAOQXEHJ-ZPFDUUQYSA-N Arg-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N JCAISGGAOQXEHJ-ZPFDUUQYSA-N 0.000 description 1
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 1
- MZRBYBIQTIKERR-GUBZILKMSA-N Arg-Glu-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MZRBYBIQTIKERR-GUBZILKMSA-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
- JQFJNGVSGOUQDH-XIRDDKMYSA-N Arg-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCN=C(N)N)N)C(O)=O)=CNC2=C1 JQFJNGVSGOUQDH-XIRDDKMYSA-N 0.000 description 1
- WVNFNPGXYADPPO-BQBZGAKWSA-N Arg-Gly-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O WVNFNPGXYADPPO-BQBZGAKWSA-N 0.000 description 1
- IRRMIGDCPOPZJW-ULQDDVLXSA-N Arg-His-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O IRRMIGDCPOPZJW-ULQDDVLXSA-N 0.000 description 1
- OKKMBOSPBDASEP-CYDGBPFRSA-N Arg-Ile-Met Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(O)=O OKKMBOSPBDASEP-CYDGBPFRSA-N 0.000 description 1
- GXXWTNKNFFKTJB-NAKRPEOUSA-N Arg-Ile-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O GXXWTNKNFFKTJB-NAKRPEOUSA-N 0.000 description 1
- HJDNZFIYILEIKR-OSUNSFLBSA-N Arg-Ile-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HJDNZFIYILEIKR-OSUNSFLBSA-N 0.000 description 1
- JEXPNDORFYHJTM-IHRRRGAJSA-N Arg-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCCN=C(N)N JEXPNDORFYHJTM-IHRRRGAJSA-N 0.000 description 1
- 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 1
- COXMUHNBYCVVRG-DCAQKATOSA-N Arg-Leu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O COXMUHNBYCVVRG-DCAQKATOSA-N 0.000 description 1
- PZBSKYJGKNNYNK-ULQDDVLXSA-N Arg-Leu-Tyr Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O PZBSKYJGKNNYNK-ULQDDVLXSA-N 0.000 description 1
- FSNVAJOPUDVQAR-AVGNSLFASA-N Arg-Lys-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FSNVAJOPUDVQAR-AVGNSLFASA-N 0.000 description 1
- SSZGOKWBHLOCHK-DCAQKATOSA-N Arg-Lys-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N SSZGOKWBHLOCHK-DCAQKATOSA-N 0.000 description 1
- RIIVUOJDDQXHRV-SRVKXCTJSA-N Arg-Lys-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O RIIVUOJDDQXHRV-SRVKXCTJSA-N 0.000 description 1
- BTJVOUQWFXABOI-IHRRRGAJSA-N Arg-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCNC(N)=N BTJVOUQWFXABOI-IHRRRGAJSA-N 0.000 description 1
- XUGATJVGQUGQKY-ULQDDVLXSA-N Arg-Lys-Phe Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XUGATJVGQUGQKY-ULQDDVLXSA-N 0.000 description 1
- NYDIVDKTULRINZ-AVGNSLFASA-N Arg-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NYDIVDKTULRINZ-AVGNSLFASA-N 0.000 description 1
- INXWADWANGLMPJ-JYJNAYRXSA-N Arg-Phe-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CC1=CC=CC=C1 INXWADWANGLMPJ-JYJNAYRXSA-N 0.000 description 1
- VEAIMHJZTIDCIH-KKUMJFAQSA-N Arg-Phe-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VEAIMHJZTIDCIH-KKUMJFAQSA-N 0.000 description 1
- KZXPVYVSHUJCEO-ULQDDVLXSA-N Arg-Phe-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=CC=C1 KZXPVYVSHUJCEO-ULQDDVLXSA-N 0.000 description 1
- AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 description 1
- PRLPSDIHSRITSF-UNQGMJICSA-N Arg-Phe-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PRLPSDIHSRITSF-UNQGMJICSA-N 0.000 description 1
- SLQQPJBDBVPVQV-JYJNAYRXSA-N Arg-Phe-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O SLQQPJBDBVPVQV-JYJNAYRXSA-N 0.000 description 1
- 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 1
- AMIQZQAAYGYKOP-FXQIFTODSA-N Arg-Ser-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O AMIQZQAAYGYKOP-FXQIFTODSA-N 0.000 description 1
- JPAWCMXVNZPJLO-IHRRRGAJSA-N Arg-Ser-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JPAWCMXVNZPJLO-IHRRRGAJSA-N 0.000 description 1
- ASQKVGRCKOFKIU-KZVJFYERSA-N Arg-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ASQKVGRCKOFKIU-KZVJFYERSA-N 0.000 description 1
- MOGMYRUNTKYZFB-UNQGMJICSA-N Arg-Thr-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MOGMYRUNTKYZFB-UNQGMJICSA-N 0.000 description 1
- UVTGNSWSRSCPLP-UHFFFAOYSA-N Arg-Tyr Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccc(O)cc1)C(=O)O UVTGNSWSRSCPLP-UHFFFAOYSA-N 0.000 description 1
- NVPHRWNWTKYIST-BPNCWPANSA-N Arg-Tyr-Ala Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=C(O)C=C1 NVPHRWNWTKYIST-BPNCWPANSA-N 0.000 description 1
- 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
- XRLOBFSLPCHYLQ-ULQDDVLXSA-N Arg-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](CCCN=C(N)N)N)O XRLOBFSLPCHYLQ-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
- WTUZDHWWGUQEKN-SRVKXCTJSA-N Arg-Val-Met Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O WTUZDHWWGUQEKN-SRVKXCTJSA-N 0.000 description 1
- 102000003823 Aromatic-L-amino-acid decarboxylases Human genes 0.000 description 1
- 108090000121 Aromatic-L-amino-acid decarboxylases Proteins 0.000 description 1
- SLKLLQWZQHXYSV-CIUDSAMLSA-N Asn-Ala-Lys Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O SLKLLQWZQHXYSV-CIUDSAMLSA-N 0.000 description 1
- XWGJDUSDTRPQRK-ZLUOBGJFSA-N Asn-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O XWGJDUSDTRPQRK-ZLUOBGJFSA-N 0.000 description 1
- IARGXWMWRFOQPG-GCJQMDKQSA-N Asn-Ala-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IARGXWMWRFOQPG-GCJQMDKQSA-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
- ZZXMOQIUIJJOKZ-ZLUOBGJFSA-N Asn-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(N)=O ZZXMOQIUIJJOKZ-ZLUOBGJFSA-N 0.000 description 1
- XXAOXVBAWLMTDR-ZLUOBGJFSA-N Asn-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)N XXAOXVBAWLMTDR-ZLUOBGJFSA-N 0.000 description 1
- QPTAGIPWARILES-AVGNSLFASA-N Asn-Gln-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QPTAGIPWARILES-AVGNSLFASA-N 0.000 description 1
- HCAUEJAQCXVQQM-ACZMJKKPSA-N Asn-Glu-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HCAUEJAQCXVQQM-ACZMJKKPSA-N 0.000 description 1
- MSBDSTRUMZFSEU-PEFMBERDSA-N Asn-Glu-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MSBDSTRUMZFSEU-PEFMBERDSA-N 0.000 description 1
- OLVIPTLKNSAYRJ-YUMQZZPRSA-N Asn-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N OLVIPTLKNSAYRJ-YUMQZZPRSA-N 0.000 description 1
- RAKKBBHMTJSXOY-XVYDVKMFSA-N Asn-His-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O RAKKBBHMTJSXOY-XVYDVKMFSA-N 0.000 description 1
- ZKDGORKGHPCZOV-DCAQKATOSA-N Asn-His-Arg Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N ZKDGORKGHPCZOV-DCAQKATOSA-N 0.000 description 1
- XLHLPYFMXGOASD-CIUDSAMLSA-N Asn-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N XLHLPYFMXGOASD-CIUDSAMLSA-N 0.000 description 1
- ACKNRKFVYUVWAC-ZPFDUUQYSA-N Asn-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ACKNRKFVYUVWAC-ZPFDUUQYSA-N 0.000 description 1
- SEKBHZJLARBNPB-GHCJXIJMSA-N Asn-Ile-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O SEKBHZJLARBNPB-GHCJXIJMSA-N 0.000 description 1
- PNHQRQTVBRDIEF-CIUDSAMLSA-N Asn-Leu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)N)N PNHQRQTVBRDIEF-CIUDSAMLSA-N 0.000 description 1
- 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
- NYGILGUOUOXGMJ-YUMQZZPRSA-N Asn-Lys-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O NYGILGUOUOXGMJ-YUMQZZPRSA-N 0.000 description 1
- GIQCDTKOIPUDSG-GARJFASQSA-N Asn-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)N)N)C(=O)O GIQCDTKOIPUDSG-GARJFASQSA-N 0.000 description 1
- RBOBTTLFPRSXKZ-BZSNNMDCSA-N Asn-Phe-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RBOBTTLFPRSXKZ-BZSNNMDCSA-N 0.000 description 1
- 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 1
- 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 1
- GMUOCGCDOYYWPD-FXQIFTODSA-N Asn-Pro-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O GMUOCGCDOYYWPD-FXQIFTODSA-N 0.000 description 1
- SUIJFTJDTJKSRK-IHRRRGAJSA-N Asn-Pro-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 SUIJFTJDTJKSRK-IHRRRGAJSA-N 0.000 description 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
- HPBNLFLSSQDFQW-WHFBIAKZSA-N Asn-Ser-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O HPBNLFLSSQDFQW-WHFBIAKZSA-N 0.000 description 1
- NCXTYSVDWLAQGZ-ZKWXMUAHSA-N Asn-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O NCXTYSVDWLAQGZ-ZKWXMUAHSA-N 0.000 description 1
- JBDLMLZNDRLDIX-HJGDQZAQSA-N Asn-Thr-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O JBDLMLZNDRLDIX-HJGDQZAQSA-N 0.000 description 1
- KZYSHAMXEBPJBD-JRQIVUDYSA-N Asn-Thr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KZYSHAMXEBPJBD-JRQIVUDYSA-N 0.000 description 1
- LGCVSPFCFXWUEY-IHPCNDPISA-N Asn-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N LGCVSPFCFXWUEY-IHPCNDPISA-N 0.000 description 1
- XLDMSQYOYXINSZ-QXEWZRGKSA-N Asn-Val-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N XLDMSQYOYXINSZ-QXEWZRGKSA-N 0.000 description 1
- KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 1
- PBVLJOIPOGUQQP-CIUDSAMLSA-N Asp-Ala-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O PBVLJOIPOGUQQP-CIUDSAMLSA-N 0.000 description 1
- VPPXTHJNTYDNFJ-CIUDSAMLSA-N Asp-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N VPPXTHJNTYDNFJ-CIUDSAMLSA-N 0.000 description 1
- NECWUSYTYSIFNC-DLOVCJGASA-N Asp-Ala-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 NECWUSYTYSIFNC-DLOVCJGASA-N 0.000 description 1
- OERMIMJQPQUIPK-FXQIFTODSA-N Asp-Arg-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O OERMIMJQPQUIPK-FXQIFTODSA-N 0.000 description 1
- QHAJMRDEWNAIBQ-FXQIFTODSA-N Asp-Arg-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O QHAJMRDEWNAIBQ-FXQIFTODSA-N 0.000 description 1
- IXIWEFWRKIUMQX-DCAQKATOSA-N Asp-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O IXIWEFWRKIUMQX-DCAQKATOSA-N 0.000 description 1
- MRQQMVZUHXUPEV-IHRRRGAJSA-N Asp-Arg-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O MRQQMVZUHXUPEV-IHRRRGAJSA-N 0.000 description 1
- JDHOJQJMWBKHDB-CIUDSAMLSA-N Asp-Asn-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N JDHOJQJMWBKHDB-CIUDSAMLSA-N 0.000 description 1
- TVVYVAUGRHNTGT-UGYAYLCHSA-N Asp-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)CC(O)=O TVVYVAUGRHNTGT-UGYAYLCHSA-N 0.000 description 1
- ZRAOLTNMSCSCLN-ZLUOBGJFSA-N Asp-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)C(=O)O ZRAOLTNMSCSCLN-ZLUOBGJFSA-N 0.000 description 1
- 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 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
- IJHUZMGJRGNXIW-CIUDSAMLSA-N Asp-Glu-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IJHUZMGJRGNXIW-CIUDSAMLSA-N 0.000 description 1
- XAJRHVUUVUPFQL-ACZMJKKPSA-N Asp-Glu-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XAJRHVUUVUPFQL-ACZMJKKPSA-N 0.000 description 1
- 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
- PDECQIHABNQRHN-GUBZILKMSA-N Asp-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O PDECQIHABNQRHN-GUBZILKMSA-N 0.000 description 1
- YDJVIBMKAMQPPP-LAEOZQHASA-N Asp-Glu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O YDJVIBMKAMQPPP-LAEOZQHASA-N 0.000 description 1
- SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 1
- WSGVTKZFVJSJOG-RCOVLWMOSA-N Asp-Gly-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O WSGVTKZFVJSJOG-RCOVLWMOSA-N 0.000 description 1
- SWTQDYFZVOJVLL-KKUMJFAQSA-N Asp-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)O)N)O SWTQDYFZVOJVLL-KKUMJFAQSA-N 0.000 description 1
- KTTCQQNRRLCIBC-GHCJXIJMSA-N Asp-Ile-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O KTTCQQNRRLCIBC-GHCJXIJMSA-N 0.000 description 1
- 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 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
- RTXQQDVBACBSCW-CFMVVWHZSA-N Asp-Ile-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RTXQQDVBACBSCW-CFMVVWHZSA-N 0.000 description 1
- XLILXFRAKOYEJX-GUBZILKMSA-N Asp-Leu-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O XLILXFRAKOYEJX-GUBZILKMSA-N 0.000 description 1
- 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 1
- LBOVBQONZJRWPV-YUMQZZPRSA-N Asp-Lys-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O LBOVBQONZJRWPV-YUMQZZPRSA-N 0.000 description 1
- AKKUDRZKFZWPBH-SRVKXCTJSA-N Asp-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N AKKUDRZKFZWPBH-SRVKXCTJSA-N 0.000 description 1
- YWLDTBBUHZJQHW-KKUMJFAQSA-N Asp-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N YWLDTBBUHZJQHW-KKUMJFAQSA-N 0.000 description 1
- ZXRQJQCXPSMNMR-XIRDDKMYSA-N Asp-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N ZXRQJQCXPSMNMR-XIRDDKMYSA-N 0.000 description 1
- HXVILZUZXFLVEN-DCAQKATOSA-N Asp-Met-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O HXVILZUZXFLVEN-DCAQKATOSA-N 0.000 description 1
- GYWQGGUCMDCUJE-DLOVCJGASA-N Asp-Phe-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O GYWQGGUCMDCUJE-DLOVCJGASA-N 0.000 description 1
- LTCKTLYKRMCFOC-KKUMJFAQSA-N Asp-Phe-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O LTCKTLYKRMCFOC-KKUMJFAQSA-N 0.000 description 1
- UCHSVZYJKJLPHF-BZSNNMDCSA-N Asp-Phe-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O UCHSVZYJKJLPHF-BZSNNMDCSA-N 0.000 description 1
- USNJAPJZSGTTPX-XVSYOHENSA-N Asp-Phe-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O USNJAPJZSGTTPX-XVSYOHENSA-N 0.000 description 1
- UKGGPJNBONZZCM-WDSKDSINSA-N Asp-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O UKGGPJNBONZZCM-WDSKDSINSA-N 0.000 description 1
- KPSHWSWFPUDEGF-FXQIFTODSA-N Asp-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(O)=O KPSHWSWFPUDEGF-FXQIFTODSA-N 0.000 description 1
- HICVMZCGVFKTPM-BQBZGAKWSA-N Asp-Pro-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HICVMZCGVFKTPM-BQBZGAKWSA-N 0.000 description 1
- UAXIKORUDGGIGA-DCAQKATOSA-N Asp-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CCCCN)C(=O)O UAXIKORUDGGIGA-DCAQKATOSA-N 0.000 description 1
- 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
- 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 1
- KGHLGJAXYSVNJP-WHFBIAKZSA-N Asp-Ser-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O KGHLGJAXYSVNJP-WHFBIAKZSA-N 0.000 description 1
- 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 1
- YUELDQUPTAYEGM-XIRDDKMYSA-N Asp-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)O)N YUELDQUPTAYEGM-XIRDDKMYSA-N 0.000 description 1
- GHAHOJDCBRXAKC-IHPCNDPISA-N Asp-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N GHAHOJDCBRXAKC-IHPCNDPISA-N 0.000 description 1
- USENATHVGFXRNO-SRVKXCTJSA-N Asp-Tyr-Asp Chemical compound OC(=O)C[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 USENATHVGFXRNO-SRVKXCTJSA-N 0.000 description 1
- PLOKOIJSGCISHE-BYULHYEWSA-N Asp-Val-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PLOKOIJSGCISHE-BYULHYEWSA-N 0.000 description 1
- QPDUWAUSSWGJSB-NGZCFLSTSA-N Asp-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N QPDUWAUSSWGJSB-NGZCFLSTSA-N 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000713756 Caprine arthritis encephalitis virus Species 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 241001161843 Chandra Species 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000004405 Collectins Human genes 0.000 description 1
- 108090000909 Collectins Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 102100039683 Cyclin-G-associated kinase Human genes 0.000 description 1
- FMDCYTBSPZMPQE-JBDRJPRFSA-N Cys-Ala-Ile Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FMDCYTBSPZMPQE-JBDRJPRFSA-N 0.000 description 1
- SZQCDCKIGWQAQN-FXQIFTODSA-N Cys-Arg-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O SZQCDCKIGWQAQN-FXQIFTODSA-N 0.000 description 1
- BPHKULHWEIUDOB-FXQIFTODSA-N Cys-Gln-Gln Chemical compound SC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BPHKULHWEIUDOB-FXQIFTODSA-N 0.000 description 1
- 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
- HAYVLBZZBDCKRA-SRVKXCTJSA-N Cys-His-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CS)N HAYVLBZZBDCKRA-SRVKXCTJSA-N 0.000 description 1
- 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 1
- DIUBVGXMXONJCF-KKUMJFAQSA-N Cys-His-Tyr Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O DIUBVGXMXONJCF-KKUMJFAQSA-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
- 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 1
- YWEHYKGJWHPGPY-XGEHTFHBSA-N Cys-Thr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N)O YWEHYKGJWHPGPY-XGEHTFHBSA-N 0.000 description 1
- 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 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
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108010090461 DFG peptide Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100020977 DnaJ homolog subfamily A member 1 Human genes 0.000 description 1
- 102100029716 DnaJ homolog subfamily A member 3, mitochondrial Human genes 0.000 description 1
- 102100029715 DnaJ homolog subfamily A member 4 Human genes 0.000 description 1
- 102100029721 DnaJ homolog subfamily B member 1 Human genes 0.000 description 1
- 102100037927 DnaJ homolog subfamily B member 11 Human genes 0.000 description 1
- 102100037888 DnaJ homolog subfamily B member 12 Human genes 0.000 description 1
- 102100023318 DnaJ homolog subfamily B member 13 Human genes 0.000 description 1
- 102100023316 DnaJ homolog subfamily B member 14 Human genes 0.000 description 1
- 102100029714 DnaJ homolog subfamily B member 2 Human genes 0.000 description 1
- 102100029708 DnaJ homolog subfamily B member 3 Human genes 0.000 description 1
- 102100029707 DnaJ homolog subfamily B member 4 Human genes 0.000 description 1
- 102100029701 DnaJ homolog subfamily B member 5 Human genes 0.000 description 1
- 102100035425 DnaJ homolog subfamily B member 6 Human genes 0.000 description 1
- 102100035426 DnaJ homolog subfamily B member 7 Human genes 0.000 description 1
- 102100035424 DnaJ homolog subfamily B member 8 Human genes 0.000 description 1
- 102100035419 DnaJ homolog subfamily B member 9 Human genes 0.000 description 1
- 102100035420 DnaJ homolog subfamily C member 1 Human genes 0.000 description 1
- 102100023317 DnaJ homolog subfamily C member 10 Human genes 0.000 description 1
- 102100023283 DnaJ homolog subfamily C member 11 Human genes 0.000 description 1
- 102100034108 DnaJ homolog subfamily C member 12 Human genes 0.000 description 1
- 102100034109 DnaJ homolog subfamily C member 13 Human genes 0.000 description 1
- 102100034115 DnaJ homolog subfamily C member 15 Human genes 0.000 description 1
- 102100034110 DnaJ homolog subfamily C member 16 Human genes 0.000 description 1
- 102100022267 DnaJ homolog subfamily C member 17 Human genes 0.000 description 1
- 102100022268 DnaJ homolog subfamily C member 18 Human genes 0.000 description 1
- 102100031695 DnaJ homolog subfamily C member 2 Human genes 0.000 description 1
- 102100022265 DnaJ homolog subfamily C member 21 Human genes 0.000 description 1
- 102100022266 DnaJ homolog subfamily C member 22 Human genes 0.000 description 1
- 102100022262 DnaJ homolog subfamily C member 24 Human genes 0.000 description 1
- 102100026984 DnaJ homolog subfamily C member 25 Human genes 0.000 description 1
- 102100024105 DnaJ homolog subfamily C member 27 Human genes 0.000 description 1
- 102100024101 DnaJ homolog subfamily C member 28 Human genes 0.000 description 1
- 102100031681 DnaJ homolog subfamily C member 3 Human genes 0.000 description 1
- 102100024096 DnaJ homolog subfamily C member 30, mitochondrial Human genes 0.000 description 1
- 102100031682 DnaJ homolog subfamily C member 4 Human genes 0.000 description 1
- 102100024961 DnaJ homolog subfamily C member 5B Human genes 0.000 description 1
- 102100022840 DnaJ homolog subfamily C member 7 Human genes 0.000 description 1
- 102100022839 DnaJ homolog subfamily C member 8 Human genes 0.000 description 1
- 102100022845 DnaJ homolog subfamily C member 9 Human genes 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000710188 Encephalomyocarditis virus Species 0.000 description 1
- 102100039328 Endoplasmin Human genes 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 241001524679 Escherichia virus M13 Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 102100039950 Eukaryotic initiation factor 4A-I Human genes 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 108010046276 FLP recombinase Proteins 0.000 description 1
- 241000714188 Friend murine leukemia virus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 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
- RZSLYUUFFVHFRQ-FXQIFTODSA-N Gln-Ala-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O RZSLYUUFFVHFRQ-FXQIFTODSA-N 0.000 description 1
- MLZRSFQRBDNJON-GUBZILKMSA-N Gln-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N MLZRSFQRBDNJON-GUBZILKMSA-N 0.000 description 1
- OYTPNWYZORARHL-XHNCKOQMSA-N Gln-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N OYTPNWYZORARHL-XHNCKOQMSA-N 0.000 description 1
- SHERTACNJPYHAR-ACZMJKKPSA-N Gln-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O SHERTACNJPYHAR-ACZMJKKPSA-N 0.000 description 1
- KZKBJEUWNMQTLV-XDTLVQLUSA-N Gln-Ala-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KZKBJEUWNMQTLV-XDTLVQLUSA-N 0.000 description 1
- WOACHWLUOFZLGJ-GUBZILKMSA-N Gln-Arg-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O WOACHWLUOFZLGJ-GUBZILKMSA-N 0.000 description 1
- RGRMOYQUIJVQQD-SRVKXCTJSA-N Gln-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)N)N RGRMOYQUIJVQQD-SRVKXCTJSA-N 0.000 description 1
- LJEPDHWNQXPXMM-NHCYSSNCSA-N Gln-Arg-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O LJEPDHWNQXPXMM-NHCYSSNCSA-N 0.000 description 1
- INFBPLSHYFALDE-ACZMJKKPSA-N Gln-Asn-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O INFBPLSHYFALDE-ACZMJKKPSA-N 0.000 description 1
- OETQLUYCMBARHJ-CIUDSAMLSA-N Gln-Asn-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OETQLUYCMBARHJ-CIUDSAMLSA-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
- CYTSBCIIEHUPDU-ACZMJKKPSA-N Gln-Asp-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O CYTSBCIIEHUPDU-ACZMJKKPSA-N 0.000 description 1
- KZEUVLLVULIPNX-GUBZILKMSA-N Gln-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N KZEUVLLVULIPNX-GUBZILKMSA-N 0.000 description 1
- MADFVRSKEIEZHZ-DCAQKATOSA-N Gln-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N MADFVRSKEIEZHZ-DCAQKATOSA-N 0.000 description 1
- BLOXULLYFRGYKZ-GUBZILKMSA-N Gln-Glu-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BLOXULLYFRGYKZ-GUBZILKMSA-N 0.000 description 1
- NSNUZSPSADIMJQ-WDSKDSINSA-N Gln-Gly-Asp Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O NSNUZSPSADIMJQ-WDSKDSINSA-N 0.000 description 1
- CLPQUWHBWXFJOX-BQBZGAKWSA-N Gln-Gly-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O CLPQUWHBWXFJOX-BQBZGAKWSA-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
- DWDBJWAXPXXYLP-SRVKXCTJSA-N Gln-His-Arg Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N DWDBJWAXPXXYLP-SRVKXCTJSA-N 0.000 description 1
- JXBZEDIQFFCHPZ-PEFMBERDSA-N Gln-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](CCC(=O)N)N JXBZEDIQFFCHPZ-PEFMBERDSA-N 0.000 description 1
- FTIJVMLAGRAYMJ-MNXVOIDGSA-N Gln-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(N)=O FTIJVMLAGRAYMJ-MNXVOIDGSA-N 0.000 description 1
- ITZWDGBYBPUZRG-KBIXCLLPSA-N Gln-Ile-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O ITZWDGBYBPUZRG-KBIXCLLPSA-N 0.000 description 1
- ARPVSMCNIDAQBO-YUMQZZPRSA-N Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ARPVSMCNIDAQBO-YUMQZZPRSA-N 0.000 description 1
- LGIKBBLQVSWUGK-DCAQKATOSA-N Gln-Leu-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGIKBBLQVSWUGK-DCAQKATOSA-N 0.000 description 1
- KHNJVFYHIKLUPD-SRVKXCTJSA-N Gln-Leu-Met Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CCC(=O)N)N KHNJVFYHIKLUPD-SRVKXCTJSA-N 0.000 description 1
- XZLLTYBONVKGLO-SDDRHHMPSA-N Gln-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XZLLTYBONVKGLO-SDDRHHMPSA-N 0.000 description 1
- XZUUUKNKNWVPHQ-JYJNAYRXSA-N Gln-Phe-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O XZUUUKNKNWVPHQ-JYJNAYRXSA-N 0.000 description 1
- UESYBOXFJWJVSB-AVGNSLFASA-N Gln-Phe-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O UESYBOXFJWJVSB-AVGNSLFASA-N 0.000 description 1
- XUMFMAVDHQDATI-DCAQKATOSA-N Gln-Pro-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XUMFMAVDHQDATI-DCAQKATOSA-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
- WLRYGVYQFXRJDA-DCAQKATOSA-N Gln-Pro-Pro Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 WLRYGVYQFXRJDA-DCAQKATOSA-N 0.000 description 1
- OSCLNNWLKKIQJM-WDSKDSINSA-N Gln-Ser-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O OSCLNNWLKKIQJM-WDSKDSINSA-N 0.000 description 1
- BYKZWDGMJLNFJY-XKBZYTNZSA-N Gln-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)O BYKZWDGMJLNFJY-XKBZYTNZSA-N 0.000 description 1
- DYVMTEWCGAVKSE-HJGDQZAQSA-N Gln-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](CCC(=O)N)N)O DYVMTEWCGAVKSE-HJGDQZAQSA-N 0.000 description 1
- DUGYCMAIAKAQPB-GLLZPBPUSA-N Gln-Thr-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O DUGYCMAIAKAQPB-GLLZPBPUSA-N 0.000 description 1
- GTBXHETZPUURJE-KKUMJFAQSA-N Gln-Tyr-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GTBXHETZPUURJE-KKUMJFAQSA-N 0.000 description 1
- SGVGIVDZLSHSEN-RYUDHWBXSA-N Gln-Tyr-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O SGVGIVDZLSHSEN-RYUDHWBXSA-N 0.000 description 1
- ZFBBMCKQSNJZSN-AUTRQRHGSA-N Gln-Val-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZFBBMCKQSNJZSN-AUTRQRHGSA-N 0.000 description 1
- QZQYITIKPAUDGN-GVXVVHGQSA-N Gln-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)N)N QZQYITIKPAUDGN-GVXVVHGQSA-N 0.000 description 1
- CSMHMEATMDCQNY-DZKIICNBSA-N Gln-Val-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CSMHMEATMDCQNY-DZKIICNBSA-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
- OGMQXTXGLDNBSS-FXQIFTODSA-N Glu-Ala-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O OGMQXTXGLDNBSS-FXQIFTODSA-N 0.000 description 1
- 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 1
- RLZBLVSJDFHDBL-KBIXCLLPSA-N Glu-Ala-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RLZBLVSJDFHDBL-KBIXCLLPSA-N 0.000 description 1
- MXOODARRORARSU-ACZMJKKPSA-N Glu-Ala-Ser Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)O)N MXOODARRORARSU-ACZMJKKPSA-N 0.000 description 1
- 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 1
- 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 1
- GLWXKFRTOHKGIT-ACZMJKKPSA-N Glu-Asn-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O GLWXKFRTOHKGIT-ACZMJKKPSA-N 0.000 description 1
- RJONUNZIMUXUOI-GUBZILKMSA-N Glu-Asn-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N RJONUNZIMUXUOI-GUBZILKMSA-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
- JVSBYEDSSRZQGV-GUBZILKMSA-N Glu-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O JVSBYEDSSRZQGV-GUBZILKMSA-N 0.000 description 1
- HJIFPJUEOGZWRI-GUBZILKMSA-N Glu-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N HJIFPJUEOGZWRI-GUBZILKMSA-N 0.000 description 1
- OXEMJGCAJFFREE-FXQIFTODSA-N Glu-Gln-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O OXEMJGCAJFFREE-FXQIFTODSA-N 0.000 description 1
- CJWANNXUTOATSJ-DCAQKATOSA-N Glu-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)O)N CJWANNXUTOATSJ-DCAQKATOSA-N 0.000 description 1
- LVCHEMOPBORRLB-DCAQKATOSA-N Glu-Gln-Lys Chemical compound NCCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCC(O)=O)C(O)=O LVCHEMOPBORRLB-DCAQKATOSA-N 0.000 description 1
- VFZIDQZAEBORGY-GLLZPBPUSA-N Glu-Gln-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VFZIDQZAEBORGY-GLLZPBPUSA-N 0.000 description 1
- HUFCEIHAFNVSNR-IHRRRGAJSA-N Glu-Gln-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HUFCEIHAFNVSNR-IHRRRGAJSA-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
- NKLRYVLERDYDBI-FXQIFTODSA-N Glu-Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKLRYVLERDYDBI-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
- BUZMZDDKFCSKOT-CIUDSAMLSA-N Glu-Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BUZMZDDKFCSKOT-CIUDSAMLSA-N 0.000 description 1
- APHGWLWMOXGZRL-DCAQKATOSA-N Glu-Glu-His Chemical compound N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O APHGWLWMOXGZRL-DCAQKATOSA-N 0.000 description 1
- IQACOVZVOMVILH-FXQIFTODSA-N Glu-Glu-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O IQACOVZVOMVILH-FXQIFTODSA-N 0.000 description 1
- OGNJZUXUTPQVBR-BQBZGAKWSA-N Glu-Gly-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O OGNJZUXUTPQVBR-BQBZGAKWSA-N 0.000 description 1
- 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 1
- CXRWMMRLEMVSEH-PEFMBERDSA-N Glu-Ile-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O CXRWMMRLEMVSEH-PEFMBERDSA-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
- XTZDZAXYPDISRR-MNXVOIDGSA-N Glu-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N XTZDZAXYPDISRR-MNXVOIDGSA-N 0.000 description 1
- ZHNHJYYFCGUZNQ-KBIXCLLPSA-N Glu-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(O)=O ZHNHJYYFCGUZNQ-KBIXCLLPSA-N 0.000 description 1
- KRRFFAHEAOCBCQ-SIUGBPQLSA-N Glu-Ile-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KRRFFAHEAOCBCQ-SIUGBPQLSA-N 0.000 description 1
- INGJLBQKTRJLFO-UKJIMTQDSA-N Glu-Ile-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(O)=O INGJLBQKTRJLFO-UKJIMTQDSA-N 0.000 description 1
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 1
- GJBUAAAIZSRCDC-GVXVVHGQSA-N Glu-Leu-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O GJBUAAAIZSRCDC-GVXVVHGQSA-N 0.000 description 1
- SJJHXJDSNQJMMW-SRVKXCTJSA-N Glu-Lys-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O SJJHXJDSNQJMMW-SRVKXCTJSA-N 0.000 description 1
- CUPSDFQZTVVTSK-GUBZILKMSA-N Glu-Lys-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O CUPSDFQZTVVTSK-GUBZILKMSA-N 0.000 description 1
- UJMNFCAHLYKWOZ-DCAQKATOSA-N Glu-Lys-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O UJMNFCAHLYKWOZ-DCAQKATOSA-N 0.000 description 1
- 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
- AQNYKMCFCCZEEL-JYJNAYRXSA-N Glu-Lys-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AQNYKMCFCCZEEL-JYJNAYRXSA-N 0.000 description 1
- PMSMKNYRZCKVMC-DRZSPHRISA-N Glu-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)N PMSMKNYRZCKVMC-DRZSPHRISA-N 0.000 description 1
- 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 1
- ZIYGTCDTJJCDDP-JYJNAYRXSA-N Glu-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZIYGTCDTJJCDDP-JYJNAYRXSA-N 0.000 description 1
- 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 1
- ALMBZBOCGSVSAI-ACZMJKKPSA-N Glu-Ser-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ALMBZBOCGSVSAI-ACZMJKKPSA-N 0.000 description 1
- 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 1
- QOXDAWODGSIDDI-GUBZILKMSA-N Glu-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N QOXDAWODGSIDDI-GUBZILKMSA-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
- MFYLRRCYBBJYPI-JYJNAYRXSA-N Glu-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O MFYLRRCYBBJYPI-JYJNAYRXSA-N 0.000 description 1
- LSYFGBRDBIQYAQ-FHWLQOOXSA-N Glu-Tyr-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LSYFGBRDBIQYAQ-FHWLQOOXSA-N 0.000 description 1
- ZALGPUWUVHOGAE-GVXVVHGQSA-N Glu-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZALGPUWUVHOGAE-GVXVVHGQSA-N 0.000 description 1
- NTNUEBVGKMVANB-NHCYSSNCSA-N Glu-Val-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O NTNUEBVGKMVANB-NHCYSSNCSA-N 0.000 description 1
- FVGOGEGGQLNZGH-DZKIICNBSA-N Glu-Val-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FVGOGEGGQLNZGH-DZKIICNBSA-N 0.000 description 1
- WGYHAAXZWPEBDQ-IFFSRLJSSA-N Glu-Val-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGYHAAXZWPEBDQ-IFFSRLJSSA-N 0.000 description 1
- 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
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- RLFSBAPJTYKSLG-WHFBIAKZSA-N Gly-Ala-Asp Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O RLFSBAPJTYKSLG-WHFBIAKZSA-N 0.000 description 1
- MFVQGXGQRIXBPK-WDSKDSINSA-N Gly-Ala-Glu Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFVQGXGQRIXBPK-WDSKDSINSA-N 0.000 description 1
- 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 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
- CLODWIOAKCSBAN-BQBZGAKWSA-N Gly-Arg-Asp Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(O)=O)C(O)=O CLODWIOAKCSBAN-BQBZGAKWSA-N 0.000 description 1
- 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 1
- KRRMJKMGWWXWDW-STQMWFEESA-N Gly-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KRRMJKMGWWXWDW-STQMWFEESA-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
- 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
- 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 1
- MHHUEAIBJZWDBH-YUMQZZPRSA-N Gly-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CN MHHUEAIBJZWDBH-YUMQZZPRSA-N 0.000 description 1
- LCNXZQROPKFGQK-WHFBIAKZSA-N Gly-Asp-Ser Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O LCNXZQROPKFGQK-WHFBIAKZSA-N 0.000 description 1
- QGZSAHIZRQHCEQ-QWRGUYRKSA-N Gly-Asp-Tyr Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QGZSAHIZRQHCEQ-QWRGUYRKSA-N 0.000 description 1
- TZOVVRJYUDETQG-RCOVLWMOSA-N Gly-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CN TZOVVRJYUDETQG-RCOVLWMOSA-N 0.000 description 1
- GZBZACMXFIPIDX-WHFBIAKZSA-N Gly-Cys-Asp Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)CN)C(=O)O GZBZACMXFIPIDX-WHFBIAKZSA-N 0.000 description 1
- UEGIPZAXNBYCCP-NKWVEPMBSA-N Gly-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)CN)C(=O)O UEGIPZAXNBYCCP-NKWVEPMBSA-N 0.000 description 1
- QCTLGOYODITHPQ-WHFBIAKZSA-N Gly-Cys-Ser Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O QCTLGOYODITHPQ-WHFBIAKZSA-N 0.000 description 1
- CQZDZKRHFWJXDF-WDSKDSINSA-N Gly-Gln-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CN CQZDZKRHFWJXDF-WDSKDSINSA-N 0.000 description 1
- DTRUBYPMMVPQPD-YUMQZZPRSA-N Gly-Gln-Arg Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DTRUBYPMMVPQPD-YUMQZZPRSA-N 0.000 description 1
- BYYNJRSNDARRBX-YFKPBYRVSA-N Gly-Gln-Gly Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O BYYNJRSNDARRBX-YFKPBYRVSA-N 0.000 description 1
- PABFFPWEJMEVEC-JGVFFNPUSA-N Gly-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)CN)C(=O)O PABFFPWEJMEVEC-JGVFFNPUSA-N 0.000 description 1
- MOJKRXIRAZPZLW-WDSKDSINSA-N Gly-Glu-Ala Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O MOJKRXIRAZPZLW-WDSKDSINSA-N 0.000 description 1
- HFXJIZNEXNIZIJ-BQBZGAKWSA-N Gly-Glu-Gln Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HFXJIZNEXNIZIJ-BQBZGAKWSA-N 0.000 description 1
- XTQFHTHIAKKCTM-YFKPBYRVSA-N Gly-Glu-Gly Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O XTQFHTHIAKKCTM-YFKPBYRVSA-N 0.000 description 1
- ZQIMMEYPEXIYBB-IUCAKERBSA-N Gly-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN ZQIMMEYPEXIYBB-IUCAKERBSA-N 0.000 description 1
- 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 1
- FQKKPCWTZZEDIC-XPUUQOCRSA-N Gly-His-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 FQKKPCWTZZEDIC-XPUUQOCRSA-N 0.000 description 1
- UESJMAMHDLEHGM-NHCYSSNCSA-N Gly-Ile-Leu Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O UESJMAMHDLEHGM-NHCYSSNCSA-N 0.000 description 1
- DKEXFJVMVGETOO-LURJTMIESA-N Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CN DKEXFJVMVGETOO-LURJTMIESA-N 0.000 description 1
- YTSVAIMKVLZUDU-YUMQZZPRSA-N Gly-Leu-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YTSVAIMKVLZUDU-YUMQZZPRSA-N 0.000 description 1
- TWTPDFFBLQEBOE-IUCAKERBSA-N Gly-Leu-Gln Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O TWTPDFFBLQEBOE-IUCAKERBSA-N 0.000 description 1
- 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 1
- WDEHMRNSGHVNOH-VHSXEESVSA-N Gly-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)CN)C(=O)O WDEHMRNSGHVNOH-VHSXEESVSA-N 0.000 description 1
- NTBOEZICHOSJEE-YUMQZZPRSA-N Gly-Lys-Ser Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O NTBOEZICHOSJEE-YUMQZZPRSA-N 0.000 description 1
- 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 1
- NSVOVKWEKGEOQB-LURJTMIESA-N Gly-Pro-Gly Chemical compound NCC(=O)N1CCC[C@H]1C(=O)NCC(O)=O NSVOVKWEKGEOQB-LURJTMIESA-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
- IXHQLZIWBCQBLQ-STQMWFEESA-N Gly-Pro-Phe Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IXHQLZIWBCQBLQ-STQMWFEESA-N 0.000 description 1
- YOBGUCWZPXJHTN-BQBZGAKWSA-N Gly-Ser-Arg Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YOBGUCWZPXJHTN-BQBZGAKWSA-N 0.000 description 1
- IALQAMYQJBZNSK-WHFBIAKZSA-N Gly-Ser-Asn Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O IALQAMYQJBZNSK-WHFBIAKZSA-N 0.000 description 1
- FGPLUIQCSKGLTI-WDSKDSINSA-N Gly-Ser-Glu Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O FGPLUIQCSKGLTI-WDSKDSINSA-N 0.000 description 1
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 1
- ZLCLYFGMKFCDCN-XPUUQOCRSA-N Gly-Ser-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(O)=O ZLCLYFGMKFCDCN-XPUUQOCRSA-N 0.000 description 1
- JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 1
- FFALDIDGPLUDKV-ZDLURKLDSA-N Gly-Thr-Ser Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O FFALDIDGPLUDKV-ZDLURKLDSA-N 0.000 description 1
- PYFHPYDQHCEVIT-KBPBESRZSA-N Gly-Trp-Gln Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(O)=O PYFHPYDQHCEVIT-KBPBESRZSA-N 0.000 description 1
- GNNJKUYDWFIBTK-QWRGUYRKSA-N Gly-Tyr-Asp Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O GNNJKUYDWFIBTK-QWRGUYRKSA-N 0.000 description 1
- GJHWILMUOANXTG-WPRPVWTQSA-N Gly-Val-Arg Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GJHWILMUOANXTG-WPRPVWTQSA-N 0.000 description 1
- 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 1
- SYOJVRNQCXYEOV-XVKPBYJWSA-N Gly-Val-Glu Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SYOJVRNQCXYEOV-XVKPBYJWSA-N 0.000 description 1
- FULZDMOZUZKGQU-ONGXEEELSA-N Gly-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN FULZDMOZUZKGQU-ONGXEEELSA-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
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 208000032008 Glycogen storage disease due to glycogen debranching enzyme deficiency Diseases 0.000 description 1
- 206010053250 Glycogen storage disease type III Diseases 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 description 1
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 description 1
- 101150031823 HSP70 gene Proteins 0.000 description 1
- 101710089250 Heat shock 70 kDa protein 5 Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 206010063629 Hippocampal sclerosis Diseases 0.000 description 1
- 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 1
- 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 1
- SVHKVHBPTOMLTO-DCAQKATOSA-N His-Arg-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O SVHKVHBPTOMLTO-DCAQKATOSA-N 0.000 description 1
- WMKXFMUJRCEGRP-SRVKXCTJSA-N His-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N WMKXFMUJRCEGRP-SRVKXCTJSA-N 0.000 description 1
- STOOMQFEJUVAKR-KKUMJFAQSA-N His-His-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)C1=CNC=N1 STOOMQFEJUVAKR-KKUMJFAQSA-N 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- AKAPKBNIVNPIPO-KKUMJFAQSA-N His-His-Lys Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CC=1NC=NC=1)C1=CN=CN1 AKAPKBNIVNPIPO-KKUMJFAQSA-N 0.000 description 1
- JBSLJUPMTYLLFH-MELADBBJSA-N His-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CN=CN3)N)C(=O)O JBSLJUPMTYLLFH-MELADBBJSA-N 0.000 description 1
- 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 1
- SKOKHBGDXGTDDP-MELADBBJSA-N His-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N SKOKHBGDXGTDDP-MELADBBJSA-N 0.000 description 1
- KHUFDBQXGLEIHC-BZSNNMDCSA-N His-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CN=CN1 KHUFDBQXGLEIHC-BZSNNMDCSA-N 0.000 description 1
- PYNPBMCLAKTHJL-SRVKXCTJSA-N His-Pro-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O PYNPBMCLAKTHJL-SRVKXCTJSA-N 0.000 description 1
- LNDVNHOSZQPJGI-AVGNSLFASA-N His-Pro-Pro Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CN=CN1 LNDVNHOSZQPJGI-AVGNSLFASA-N 0.000 description 1
- ZHHLTWUOWXHVQJ-YUMQZZPRSA-N His-Ser-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N ZHHLTWUOWXHVQJ-YUMQZZPRSA-N 0.000 description 1
- ILUVWFTXAUYOBW-CUJWVEQBSA-N His-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CN=CN1)N)O ILUVWFTXAUYOBW-CUJWVEQBSA-N 0.000 description 1
- DLTCGJZBNFOWFL-LKTVYLICSA-N His-Tyr-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC2=CN=CN2)N DLTCGJZBNFOWFL-LKTVYLICSA-N 0.000 description 1
- QLBXWYXMLHAREM-PYJNHQTQSA-N His-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC1=CN=CN1)N QLBXWYXMLHAREM-PYJNHQTQSA-N 0.000 description 1
- FFYYUUWROYYKFY-IHRRRGAJSA-N His-Val-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O FFYYUUWROYYKFY-IHRRRGAJSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000886209 Homo sapiens Cyclin-G-associated kinase Proteins 0.000 description 1
- 101000931227 Homo sapiens DnaJ homolog subfamily A member 1 Proteins 0.000 description 1
- 101000931210 Homo sapiens DnaJ homolog subfamily A member 2 Proteins 0.000 description 1
- 101000866012 Homo sapiens DnaJ homolog subfamily A member 3, mitochondrial Proteins 0.000 description 1
- 101000866014 Homo sapiens DnaJ homolog subfamily A member 4 Proteins 0.000 description 1
- 101000866018 Homo sapiens DnaJ homolog subfamily B member 1 Proteins 0.000 description 1
- 101000805858 Homo sapiens DnaJ homolog subfamily B member 11 Proteins 0.000 description 1
- 101000805849 Homo sapiens DnaJ homolog subfamily B member 12 Proteins 0.000 description 1
- 101000908037 Homo sapiens DnaJ homolog subfamily B member 13 Proteins 0.000 description 1
- 101000908034 Homo sapiens DnaJ homolog subfamily B member 14 Proteins 0.000 description 1
- 101000866020 Homo sapiens DnaJ homolog subfamily B member 2 Proteins 0.000 description 1
- 101000866004 Homo sapiens DnaJ homolog subfamily B member 3 Proteins 0.000 description 1
- 101000866008 Homo sapiens DnaJ homolog subfamily B member 4 Proteins 0.000 description 1
- 101000866011 Homo sapiens DnaJ homolog subfamily B member 5 Proteins 0.000 description 1
- 101000804112 Homo sapiens DnaJ homolog subfamily B member 6 Proteins 0.000 description 1
- 101000804114 Homo sapiens DnaJ homolog subfamily B member 7 Proteins 0.000 description 1
- 101000804109 Homo sapiens DnaJ homolog subfamily B member 8 Proteins 0.000 description 1
- 101000804119 Homo sapiens DnaJ homolog subfamily B member 9 Proteins 0.000 description 1
- 101000804122 Homo sapiens DnaJ homolog subfamily C member 1 Proteins 0.000 description 1
- 101000908042 Homo sapiens DnaJ homolog subfamily C member 10 Proteins 0.000 description 1
- 101000908069 Homo sapiens DnaJ homolog subfamily C member 11 Proteins 0.000 description 1
- 101000870234 Homo sapiens DnaJ homolog subfamily C member 12 Proteins 0.000 description 1
- 101000870239 Homo sapiens DnaJ homolog subfamily C member 13 Proteins 0.000 description 1
- 101000870172 Homo sapiens DnaJ homolog subfamily C member 15 Proteins 0.000 description 1
- 101000870184 Homo sapiens DnaJ homolog subfamily C member 16 Proteins 0.000 description 1
- 101000902079 Homo sapiens DnaJ homolog subfamily C member 17 Proteins 0.000 description 1
- 101000902076 Homo sapiens DnaJ homolog subfamily C member 18 Proteins 0.000 description 1
- 101000845887 Homo sapiens DnaJ homolog subfamily C member 2 Proteins 0.000 description 1
- 101000902110 Homo sapiens DnaJ homolog subfamily C member 21 Proteins 0.000 description 1
- 101000902105 Homo sapiens DnaJ homolog subfamily C member 22 Proteins 0.000 description 1
- 101000902093 Homo sapiens DnaJ homolog subfamily C member 24 Proteins 0.000 description 1
- 101001054519 Homo sapiens DnaJ homolog subfamily C member 25 Proteins 0.000 description 1
- 101001054007 Homo sapiens DnaJ homolog subfamily C member 27 Proteins 0.000 description 1
- 101001053999 Homo sapiens DnaJ homolog subfamily C member 28 Proteins 0.000 description 1
- 101000845898 Homo sapiens DnaJ homolog subfamily C member 3 Proteins 0.000 description 1
- 101001054001 Homo sapiens DnaJ homolog subfamily C member 30, mitochondrial Proteins 0.000 description 1
- 101000845897 Homo sapiens DnaJ homolog subfamily C member 4 Proteins 0.000 description 1
- 101000845893 Homo sapiens DnaJ homolog subfamily C member 5 Proteins 0.000 description 1
- 101000909016 Homo sapiens DnaJ homolog subfamily C member 5B Proteins 0.000 description 1
- 101000903053 Homo sapiens DnaJ homolog subfamily C member 7 Proteins 0.000 description 1
- 101000903063 Homo sapiens DnaJ homolog subfamily C member 8 Proteins 0.000 description 1
- 101000903036 Homo sapiens DnaJ homolog subfamily C member 9 Proteins 0.000 description 1
- 101000959666 Homo sapiens Eukaryotic initiation factor 4A-I Proteins 0.000 description 1
- 101001080292 Homo sapiens Iron-sulfur cluster co-chaperone protein HscB Proteins 0.000 description 1
- 101000669640 Homo sapiens Mitochondrial import inner membrane translocase subunit TIM14 Proteins 0.000 description 1
- 101000904783 Homo sapiens Putative tyrosine-protein phosphatase auxilin Proteins 0.000 description 1
- 101000631620 Homo sapiens Translocation protein SEC63 homolog Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 101001042049 Human herpesvirus 1 (strain 17) Transcriptional regulator ICP22 Proteins 0.000 description 1
- 101000999690 Human herpesvirus 2 (strain HG52) E3 ubiquitin ligase ICP22 Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000714192 Human spumaretrovirus Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 101150027427 ICP4 gene Proteins 0.000 description 1
- LQSBBHNVAVNZSX-GHCJXIJMSA-N Ile-Ala-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)N)C(=O)O)N LQSBBHNVAVNZSX-GHCJXIJMSA-N 0.000 description 1
- RWIKBYVJQAJYDP-BJDJZHNGSA-N Ile-Ala-Lys Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN RWIKBYVJQAJYDP-BJDJZHNGSA-N 0.000 description 1
- WZPIKDWQVRTATP-SYWGBEHUSA-N Ile-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)CC)C(O)=O)=CNC2=C1 WZPIKDWQVRTATP-SYWGBEHUSA-N 0.000 description 1
- HERITAGIPLEJMT-GVARAGBVSA-N Ile-Ala-Tyr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HERITAGIPLEJMT-GVARAGBVSA-N 0.000 description 1
- SACHLUOUHCVIKI-GMOBBJLQSA-N Ile-Arg-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N SACHLUOUHCVIKI-GMOBBJLQSA-N 0.000 description 1
- 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 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
- QSPLUJGYOPZINY-ZPFDUUQYSA-N Ile-Asp-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N QSPLUJGYOPZINY-ZPFDUUQYSA-N 0.000 description 1
- NPROWIBAWYMPAZ-GUDRVLHUSA-N Ile-Asp-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N NPROWIBAWYMPAZ-GUDRVLHUSA-N 0.000 description 1
- WZDCVAWMBUNDDY-KBIXCLLPSA-N Ile-Glu-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)O)N WZDCVAWMBUNDDY-KBIXCLLPSA-N 0.000 description 1
- AREBLHSMLMRICD-PYJNHQTQSA-N Ile-His-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N AREBLHSMLMRICD-PYJNHQTQSA-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
- KLBVGHCGHUNHEA-BJDJZHNGSA-N Ile-Leu-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)O)N KLBVGHCGHUNHEA-BJDJZHNGSA-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
- TVYWVSJGSHQWMT-AJNGGQMLSA-N Ile-Leu-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N TVYWVSJGSHQWMT-AJNGGQMLSA-N 0.000 description 1
- GVKKVHNRTUFCCE-BJDJZHNGSA-N Ile-Leu-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)O)N GVKKVHNRTUFCCE-BJDJZHNGSA-N 0.000 description 1
- DSDPLOODKXISDT-XUXIUFHCSA-N Ile-Leu-Val Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O DSDPLOODKXISDT-XUXIUFHCSA-N 0.000 description 1
- UIEZQYNXCYHMQS-BJDJZHNGSA-N Ile-Lys-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)O)N UIEZQYNXCYHMQS-BJDJZHNGSA-N 0.000 description 1
- PARSHQDZROHERM-NHCYSSNCSA-N Ile-Lys-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)O)N PARSHQDZROHERM-NHCYSSNCSA-N 0.000 description 1
- XHBYEMIUENPZLY-GMOBBJLQSA-N Ile-Pro-Asn Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O XHBYEMIUENPZLY-GMOBBJLQSA-N 0.000 description 1
- BATWGBRIZANGPN-ZPFDUUQYSA-N Ile-Pro-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)N)C(=O)O)N BATWGBRIZANGPN-ZPFDUUQYSA-N 0.000 description 1
- JHNJNTMTZHEDLJ-NAKRPEOUSA-N Ile-Ser-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O JHNJNTMTZHEDLJ-NAKRPEOUSA-N 0.000 description 1
- XMYURPUVJSKTMC-KBIXCLLPSA-N Ile-Ser-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N XMYURPUVJSKTMC-KBIXCLLPSA-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
- YCKPUHHMCFSUMD-IUKAMOBKSA-N Ile-Thr-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N YCKPUHHMCFSUMD-IUKAMOBKSA-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
- WCNWGAUZWWSYDG-SVSWQMSJSA-N Ile-Thr-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)O)N WCNWGAUZWWSYDG-SVSWQMSJSA-N 0.000 description 1
- OMDWJWGZGMCQND-CFMVVWHZSA-N Ile-Tyr-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N OMDWJWGZGMCQND-CFMVVWHZSA-N 0.000 description 1
- PRTZQMBYUZFSFA-XEGUGMAKSA-N Ile-Tyr-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)NCC(=O)O)N PRTZQMBYUZFSFA-XEGUGMAKSA-N 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 102100027530 Iron-sulfur cluster co-chaperone protein HscB Human genes 0.000 description 1
- 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 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 239000004158 L-cystine Substances 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
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 1
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 101000839464 Leishmania braziliensis Heat shock 70 kDa protein Proteins 0.000 description 1
- LJHGALIOHLRRQN-DCAQKATOSA-N Leu-Ala-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N LJHGALIOHLRRQN-DCAQKATOSA-N 0.000 description 1
- 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 1
- WSGXUIQTEZDVHJ-GARJFASQSA-N Leu-Ala-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(O)=O WSGXUIQTEZDVHJ-GARJFASQSA-N 0.000 description 1
- YOZCKMXHBYKOMQ-IHRRRGAJSA-N Leu-Arg-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOZCKMXHBYKOMQ-IHRRRGAJSA-N 0.000 description 1
- XYUBOFCTGPZFSA-WDSOQIARSA-N Leu-Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 XYUBOFCTGPZFSA-WDSOQIARSA-N 0.000 description 1
- OGCQGUIWMSBHRZ-CIUDSAMLSA-N Leu-Asn-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OGCQGUIWMSBHRZ-CIUDSAMLSA-N 0.000 description 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
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 1
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 1
- VQPPIMUZCZCOIL-GUBZILKMSA-N Leu-Gln-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O VQPPIMUZCZCOIL-GUBZILKMSA-N 0.000 description 1
- 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 1
- KAFOIVJDVSZUMD-DCAQKATOSA-N Leu-Gln-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-DCAQKATOSA-N 0.000 description 1
- AXZGZMGRBDQTEY-SRVKXCTJSA-N Leu-Gln-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O AXZGZMGRBDQTEY-SRVKXCTJSA-N 0.000 description 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
- YSKSXVKQLLBVEX-SZMVWBNQSA-N Leu-Gln-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 YSKSXVKQLLBVEX-SZMVWBNQSA-N 0.000 description 1
- 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 1
- HPBCTWSUJOGJSH-MNXVOIDGSA-N Leu-Glu-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HPBCTWSUJOGJSH-MNXVOIDGSA-N 0.000 description 1
- 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
- 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 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
- VBZOAGIPCULURB-QWRGUYRKSA-N Leu-Gly-His Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N VBZOAGIPCULURB-QWRGUYRKSA-N 0.000 description 1
- KVOFSTUWVSQMDK-KKUMJFAQSA-N Leu-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CN=CN1 KVOFSTUWVSQMDK-KKUMJFAQSA-N 0.000 description 1
- OYQUOLRTJHWVSQ-SRVKXCTJSA-N Leu-His-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O OYQUOLRTJHWVSQ-SRVKXCTJSA-N 0.000 description 1
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 1
- FAELBUXXFQLUAX-AJNGGQMLSA-N Leu-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C FAELBUXXFQLUAX-AJNGGQMLSA-N 0.000 description 1
- LXKNSJLSGPNHSK-KKUMJFAQSA-N Leu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N LXKNSJLSGPNHSK-KKUMJFAQSA-N 0.000 description 1
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 1
- RZXLZBIUTDQHJQ-SRVKXCTJSA-N Leu-Lys-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O RZXLZBIUTDQHJQ-SRVKXCTJSA-N 0.000 description 1
- ZGUMORRUBUCXEH-AVGNSLFASA-N Leu-Lys-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZGUMORRUBUCXEH-AVGNSLFASA-N 0.000 description 1
- BGZCJDGBBUUBHA-KKUMJFAQSA-N Leu-Lys-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O BGZCJDGBBUUBHA-KKUMJFAQSA-N 0.000 description 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
- AUNMOHYWTAPQLA-XUXIUFHCSA-N Leu-Met-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AUNMOHYWTAPQLA-XUXIUFHCSA-N 0.000 description 1
- LQUIENKUVKPNIC-ULQDDVLXSA-N Leu-Met-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LQUIENKUVKPNIC-ULQDDVLXSA-N 0.000 description 1
- BIZNDKMFQHDOIE-KKUMJFAQSA-N Leu-Phe-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=CC=C1 BIZNDKMFQHDOIE-KKUMJFAQSA-N 0.000 description 1
- KTOIECMYZZGVSI-BZSNNMDCSA-N Leu-Phe-His Chemical compound C([C@H](NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=CC=C1 KTOIECMYZZGVSI-BZSNNMDCSA-N 0.000 description 1
- WMIOEVKKYIMVKI-DCAQKATOSA-N Leu-Pro-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WMIOEVKKYIMVKI-DCAQKATOSA-N 0.000 description 1
- 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 1
- UCXQIIIFOOGYEM-ULQDDVLXSA-N Leu-Pro-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UCXQIIIFOOGYEM-ULQDDVLXSA-N 0.000 description 1
- JIHDFWWRYHSAQB-GUBZILKMSA-N Leu-Ser-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JIHDFWWRYHSAQB-GUBZILKMSA-N 0.000 description 1
- LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 description 1
- LCNASHSOFMRYFO-WDCWCFNPSA-N Leu-Thr-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(N)=O LCNASHSOFMRYFO-WDCWCFNPSA-N 0.000 description 1
- LJBVRCDPWOJOEK-PPCPHDFISA-N Leu-Thr-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LJBVRCDPWOJOEK-PPCPHDFISA-N 0.000 description 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
- VJGQRELPQWNURN-JYJNAYRXSA-N Leu-Tyr-Glu 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](CCC(O)=O)C(O)=O VJGQRELPQWNURN-JYJNAYRXSA-N 0.000 description 1
- OZTZJMUZVAVJGY-BZSNNMDCSA-N Leu-Tyr-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N OZTZJMUZVAVJGY-BZSNNMDCSA-N 0.000 description 1
- JGKHAFUAPZCCDU-BZSNNMDCSA-N Leu-Tyr-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=CC=C(O)C=C1 JGKHAFUAPZCCDU-BZSNNMDCSA-N 0.000 description 1
- XZNJZXJZBMBGGS-NHCYSSNCSA-N Leu-Val-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O XZNJZXJZBMBGGS-NHCYSSNCSA-N 0.000 description 1
- LMDVGHQPPPLYAR-IHRRRGAJSA-N Leu-Val-His Chemical compound N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O LMDVGHQPPPLYAR-IHRRRGAJSA-N 0.000 description 1
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 1
- PNPYKQFJGRFYJE-GUBZILKMSA-N Lys-Ala-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNPYKQFJGRFYJE-GUBZILKMSA-N 0.000 description 1
- UWKNTTJNVSYXPC-CIUDSAMLSA-N Lys-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN UWKNTTJNVSYXPC-CIUDSAMLSA-N 0.000 description 1
- WXJKFRMKJORORD-DCAQKATOSA-N Lys-Arg-Ala Chemical compound NC(=N)NCCC[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CCCCN WXJKFRMKJORORD-DCAQKATOSA-N 0.000 description 1
- NQCJGQHHYZNUDK-DCAQKATOSA-N Lys-Arg-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CCCN=C(N)N NQCJGQHHYZNUDK-DCAQKATOSA-N 0.000 description 1
- DGAAQRAUOFHBFJ-CIUDSAMLSA-N Lys-Asn-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O DGAAQRAUOFHBFJ-CIUDSAMLSA-N 0.000 description 1
- YKIRNDPUWONXQN-GUBZILKMSA-N Lys-Asn-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YKIRNDPUWONXQN-GUBZILKMSA-N 0.000 description 1
- ZQCVMVCVPFYXHZ-SRVKXCTJSA-N Lys-Asn-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCCN ZQCVMVCVPFYXHZ-SRVKXCTJSA-N 0.000 description 1
- HKCCVDWHHTVVPN-CIUDSAMLSA-N Lys-Asp-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O HKCCVDWHHTVVPN-CIUDSAMLSA-N 0.000 description 1
- OVIVOCSURJYCTM-GUBZILKMSA-N Lys-Asp-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O OVIVOCSURJYCTM-GUBZILKMSA-N 0.000 description 1
- QIJVAFLRMVBHMU-KKUMJFAQSA-N Lys-Asp-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QIJVAFLRMVBHMU-KKUMJFAQSA-N 0.000 description 1
- KWUKZRFFKPLUPE-HJGDQZAQSA-N Lys-Asp-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KWUKZRFFKPLUPE-HJGDQZAQSA-N 0.000 description 1
- NTBFKPBULZGXQL-KKUMJFAQSA-N Lys-Asp-Tyr Chemical compound NCCCC[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 NTBFKPBULZGXQL-KKUMJFAQSA-N 0.000 description 1
- MWVUEPNEPWMFBD-SRVKXCTJSA-N Lys-Cys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCCCN MWVUEPNEPWMFBD-SRVKXCTJSA-N 0.000 description 1
- GGNOBVSOZPHLCE-GUBZILKMSA-N Lys-Gln-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O GGNOBVSOZPHLCE-GUBZILKMSA-N 0.000 description 1
- IRRZDAIFYHNIIN-JYJNAYRXSA-N Lys-Gln-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IRRZDAIFYHNIIN-JYJNAYRXSA-N 0.000 description 1
- GJJQCBVRWDGLMQ-GUBZILKMSA-N Lys-Glu-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O GJJQCBVRWDGLMQ-GUBZILKMSA-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
- LPAJOCKCPRZEAG-MNXVOIDGSA-N Lys-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCCCN LPAJOCKCPRZEAG-MNXVOIDGSA-N 0.000 description 1
- 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
- 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
- WGLAORUKDGRINI-WDCWCFNPSA-N Lys-Glu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGLAORUKDGRINI-WDCWCFNPSA-N 0.000 description 1
- ODUQLUADRKMHOZ-JYJNAYRXSA-N Lys-Glu-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N)O ODUQLUADRKMHOZ-JYJNAYRXSA-N 0.000 description 1
- GQZMPWBZQALKJO-UWVGGRQHSA-N Lys-Gly-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O GQZMPWBZQALKJO-UWVGGRQHSA-N 0.000 description 1
- XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 1
- ISHNZELVUVPCHY-ZETCQYMHSA-N Lys-Gly-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O ISHNZELVUVPCHY-ZETCQYMHSA-N 0.000 description 1
- FGMHXLULNHTPID-KKUMJFAQSA-N Lys-His-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CN=CN1 FGMHXLULNHTPID-KKUMJFAQSA-N 0.000 description 1
- KYNNSEJZFVCDIV-ZPFDUUQYSA-N Lys-Ile-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O KYNNSEJZFVCDIV-ZPFDUUQYSA-N 0.000 description 1
- ONPDTSFZAIWMDI-AVGNSLFASA-N Lys-Leu-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O ONPDTSFZAIWMDI-AVGNSLFASA-N 0.000 description 1
- WVJNGSFKBKOKRV-AJNGGQMLSA-N Lys-Leu-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WVJNGSFKBKOKRV-AJNGGQMLSA-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
- WRODMZBHNNPRLN-SRVKXCTJSA-N Lys-Leu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O WRODMZBHNNPRLN-SRVKXCTJSA-N 0.000 description 1
- 108010003266 Lys-Leu-Tyr-Asp Proteins 0.000 description 1
- LJADEBULDNKJNK-IHRRRGAJSA-N Lys-Leu-Val Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LJADEBULDNKJNK-IHRRRGAJSA-N 0.000 description 1
- PYFNONMJYNJENN-AVGNSLFASA-N Lys-Lys-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N PYFNONMJYNJENN-AVGNSLFASA-N 0.000 description 1
- WBSCNDJQPKSPII-KKUMJFAQSA-N Lys-Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O WBSCNDJQPKSPII-KKUMJFAQSA-N 0.000 description 1
- ATNKHRAIZCMCCN-BZSNNMDCSA-N Lys-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N ATNKHRAIZCMCCN-BZSNNMDCSA-N 0.000 description 1
- BXPHMHQHYHILBB-BZSNNMDCSA-N Lys-Lys-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BXPHMHQHYHILBB-BZSNNMDCSA-N 0.000 description 1
- URGPVYGVWLIRGT-DCAQKATOSA-N Lys-Met-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O URGPVYGVWLIRGT-DCAQKATOSA-N 0.000 description 1
- PIXVFCBYEGPZPA-JYJNAYRXSA-N Lys-Phe-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N PIXVFCBYEGPZPA-JYJNAYRXSA-N 0.000 description 1
- ZJSZPXISKMDJKQ-JYJNAYRXSA-N Lys-Phe-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=CC=C1 ZJSZPXISKMDJKQ-JYJNAYRXSA-N 0.000 description 1
- BPDXWKVZNCKUGG-BZSNNMDCSA-N Lys-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](CCCCN)N BPDXWKVZNCKUGG-BZSNNMDCSA-N 0.000 description 1
- LMGNWHDWJDIOPK-DKIMLUQUSA-N Lys-Phe-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LMGNWHDWJDIOPK-DKIMLUQUSA-N 0.000 description 1
- LUAJJLPHUXPQLH-KKUMJFAQSA-N Lys-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCCN)N LUAJJLPHUXPQLH-KKUMJFAQSA-N 0.000 description 1
- XFANQCRHTMOEAP-WDSOQIARSA-N Lys-Pro-Trp Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O XFANQCRHTMOEAP-WDSOQIARSA-N 0.000 description 1
- YSPZCHGIWAQVKQ-AVGNSLFASA-N Lys-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCN YSPZCHGIWAQVKQ-AVGNSLFASA-N 0.000 description 1
- HKXSZKJMDBHOTG-CIUDSAMLSA-N Lys-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCCCN HKXSZKJMDBHOTG-CIUDSAMLSA-N 0.000 description 1
- MGKFCQFVPKOWOL-CIUDSAMLSA-N Lys-Ser-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N MGKFCQFVPKOWOL-CIUDSAMLSA-N 0.000 description 1
- DNWBUCHHMRQWCZ-GUBZILKMSA-N Lys-Ser-Gln Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O DNWBUCHHMRQWCZ-GUBZILKMSA-N 0.000 description 1
- WZVSHTFTCYOFPL-GARJFASQSA-N Lys-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCCN)N)C(=O)O WZVSHTFTCYOFPL-GARJFASQSA-N 0.000 description 1
- DIBZLYZXTSVGLN-CIUDSAMLSA-N Lys-Ser-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O DIBZLYZXTSVGLN-CIUDSAMLSA-N 0.000 description 1
- YRNRVKTYDSLKMD-KKUMJFAQSA-N Lys-Ser-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YRNRVKTYDSLKMD-KKUMJFAQSA-N 0.000 description 1
- PLOUVAYOMTYJRG-JXUBOQSCSA-N Lys-Thr-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O PLOUVAYOMTYJRG-JXUBOQSCSA-N 0.000 description 1
- IEVXCWPVBYCJRZ-IXOXFDKPSA-N Lys-Thr-His Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IEVXCWPVBYCJRZ-IXOXFDKPSA-N 0.000 description 1
- DLCAXBGXGOVUCD-PPCPHDFISA-N Lys-Thr-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DLCAXBGXGOVUCD-PPCPHDFISA-N 0.000 description 1
- RPWTZTBIFGENIA-VOAKCMCISA-N Lys-Thr-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O RPWTZTBIFGENIA-VOAKCMCISA-N 0.000 description 1
- CAVRAQIDHUPECU-UVOCVTCTSA-N Lys-Thr-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAVRAQIDHUPECU-UVOCVTCTSA-N 0.000 description 1
- KDBDVESGGJYVEH-PMVMPFDFSA-N Lys-Trp-Phe Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)CCCCN)C(O)=O)C1=CC=CC=C1 KDBDVESGGJYVEH-PMVMPFDFSA-N 0.000 description 1
- NROQVSYLPRLJIP-PMVMPFDFSA-N Lys-Trp-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NROQVSYLPRLJIP-PMVMPFDFSA-N 0.000 description 1
- RMKJOQSYLQQRFN-KKUMJFAQSA-N Lys-Tyr-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O RMKJOQSYLQQRFN-KKUMJFAQSA-N 0.000 description 1
- XATKLFSXFINPSB-JYJNAYRXSA-N Lys-Tyr-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O XATKLFSXFINPSB-JYJNAYRXSA-N 0.000 description 1
- RQILLQOQXLZTCK-KBPBESRZSA-N Lys-Tyr-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O RQILLQOQXLZTCK-KBPBESRZSA-N 0.000 description 1
- PSVAVKGDUAKZKU-BZSNNMDCSA-N Lys-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](CCCCN)N)O PSVAVKGDUAKZKU-BZSNNMDCSA-N 0.000 description 1
- VWPJQIHBBOJWDN-DCAQKATOSA-N Lys-Val-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O VWPJQIHBBOJWDN-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
- XBAJINCXDBTJRH-WDSOQIARSA-N Lys-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](CCCCN)N XBAJINCXDBTJRH-WDSOQIARSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- OLWAOWXIADGIJG-AVGNSLFASA-N Met-Arg-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(O)=O OLWAOWXIADGIJG-AVGNSLFASA-N 0.000 description 1
- DNDVVILEHVMWIS-LPEHRKFASA-N Met-Asp-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N DNDVVILEHVMWIS-LPEHRKFASA-N 0.000 description 1
- PTYVBBNIAQWUFV-DCAQKATOSA-N Met-Cys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCSC)N PTYVBBNIAQWUFV-DCAQKATOSA-N 0.000 description 1
- GVIVXNFKJQFTCE-YUMQZZPRSA-N Met-Gly-Gln Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O GVIVXNFKJQFTCE-YUMQZZPRSA-N 0.000 description 1
- HZVXPUHLTZRQEL-UWVGGRQHSA-N Met-Leu-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O HZVXPUHLTZRQEL-UWVGGRQHSA-N 0.000 description 1
- KMSMNUFBNCHMII-IHRRRGAJSA-N Met-Leu-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN KMSMNUFBNCHMII-IHRRRGAJSA-N 0.000 description 1
- YLBUMXYVQCHBPR-ULQDDVLXSA-N Met-Leu-Tyr Chemical compound CSCC[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 YLBUMXYVQCHBPR-ULQDDVLXSA-N 0.000 description 1
- YYEIFXZOBZVDPH-DCAQKATOSA-N Met-Lys-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O YYEIFXZOBZVDPH-DCAQKATOSA-N 0.000 description 1
- AOFZWWDTTJLHOU-ULQDDVLXSA-N Met-Lys-Tyr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AOFZWWDTTJLHOU-ULQDDVLXSA-N 0.000 description 1
- PHURAEXVWLDIGT-LPEHRKFASA-N Met-Ser-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N PHURAEXVWLDIGT-LPEHRKFASA-N 0.000 description 1
- SPSSJSICDYYTQN-HJGDQZAQSA-N Met-Thr-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(N)=O SPSSJSICDYYTQN-HJGDQZAQSA-N 0.000 description 1
- XLTSAUGGDYRFLS-UMPQAUOISA-N Met-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](CCSC)N)O XLTSAUGGDYRFLS-UMPQAUOISA-N 0.000 description 1
- UZBQXELAFPCGRV-SZMVWBNQSA-N Met-Trp-Arg Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UZBQXELAFPCGRV-SZMVWBNQSA-N 0.000 description 1
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 1
- 102000006890 Methyl-CpG-Binding Protein 2 Human genes 0.000 description 1
- 108010072388 Methyl-CpG-Binding Protein 2 Proteins 0.000 description 1
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 1
- 101710115937 Microtubule-associated protein tau Proteins 0.000 description 1
- 102100039325 Mitochondrial import inner membrane translocase subunit TIM14 Human genes 0.000 description 1
- 101000834887 Mus musculus Alpha-synuclein Proteins 0.000 description 1
- 101100117262 Mus musculus Dnajc5 gene Proteins 0.000 description 1
- 101100444898 Mus musculus Egr1 gene Proteins 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 108010066154 Nuclear Export Signals Proteins 0.000 description 1
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108010088535 Pep-1 peptide Proteins 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 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 1
- 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 1
- MPGJIHFJCXTVEX-KKUMJFAQSA-N Phe-Arg-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O MPGJIHFJCXTVEX-KKUMJFAQSA-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
- ZENDEDYRYVHBEG-SRVKXCTJSA-N Phe-Asp-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 ZENDEDYRYVHBEG-SRVKXCTJSA-N 0.000 description 1
- UMKYAYXCMYYNHI-AVGNSLFASA-N Phe-Gln-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N UMKYAYXCMYYNHI-AVGNSLFASA-N 0.000 description 1
- RJYBHZVWJPUSLB-QEWYBTABSA-N Phe-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=CC=C1)N RJYBHZVWJPUSLB-QEWYBTABSA-N 0.000 description 1
- NAXPHWZXEXNDIW-JTQLQIEISA-N Phe-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 NAXPHWZXEXNDIW-JTQLQIEISA-N 0.000 description 1
- FXPZZKBHNOMLGA-HJWJTTGWSA-N Phe-Ile-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N FXPZZKBHNOMLGA-HJWJTTGWSA-N 0.000 description 1
- MIICYIIBVYQNKE-QEWYBTABSA-N Phe-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](CC1=CC=CC=C1)N MIICYIIBVYQNKE-QEWYBTABSA-N 0.000 description 1
- KRYSMKKRRRWOCZ-QEWYBTABSA-N Phe-Ile-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KRYSMKKRRRWOCZ-QEWYBTABSA-N 0.000 description 1
- DVOCGBNHAUHKHJ-DKIMLUQUSA-N Phe-Ile-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O DVOCGBNHAUHKHJ-DKIMLUQUSA-N 0.000 description 1
- TXKWKTWYTIAZSV-KKUMJFAQSA-N Phe-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N TXKWKTWYTIAZSV-KKUMJFAQSA-N 0.000 description 1
- MSHZERMPZKCODG-ACRUOGEOSA-N Phe-Leu-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 MSHZERMPZKCODG-ACRUOGEOSA-N 0.000 description 1
- YCCUXNNKXDGMAM-KKUMJFAQSA-N Phe-Leu-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YCCUXNNKXDGMAM-KKUMJFAQSA-N 0.000 description 1
- MJAYDXWQQUOURZ-JYJNAYRXSA-N Phe-Lys-Gln Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O MJAYDXWQQUOURZ-JYJNAYRXSA-N 0.000 description 1
- DOXQMJCSSYZSNM-BZSNNMDCSA-N Phe-Lys-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O DOXQMJCSSYZSNM-BZSNNMDCSA-N 0.000 description 1
- PEFJUUYFEGBXFA-BZSNNMDCSA-N Phe-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 PEFJUUYFEGBXFA-BZSNNMDCSA-N 0.000 description 1
- IEOHQGFKHXUALJ-JYJNAYRXSA-N Phe-Met-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IEOHQGFKHXUALJ-JYJNAYRXSA-N 0.000 description 1
- JDMKQHSHKJHAHR-UHFFFAOYSA-N Phe-Phe-Leu-Tyr Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)CC1=CC=CC=C1 JDMKQHSHKJHAHR-UHFFFAOYSA-N 0.000 description 1
- RVEVENLSADZUMS-IHRRRGAJSA-N Phe-Pro-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O RVEVENLSADZUMS-IHRRRGAJSA-N 0.000 description 1
- AFNJAQVMTIQTCB-DLOVCJGASA-N Phe-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=CC=C1 AFNJAQVMTIQTCB-DLOVCJGASA-N 0.000 description 1
- BONHGTUEEPIMPM-AVGNSLFASA-N Phe-Ser-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O BONHGTUEEPIMPM-AVGNSLFASA-N 0.000 description 1
- VFDRDMOMHBJGKD-UFYCRDLUSA-N Phe-Tyr-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N VFDRDMOMHBJGKD-UFYCRDLUSA-N 0.000 description 1
- GAMLAXHLYGLQBJ-UFYCRDLUSA-N Phe-Val-Tyr Chemical compound N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)CC1=CC=C(C=C1)O)C(C)C)CC1=CC=CC=C1 GAMLAXHLYGLQBJ-UFYCRDLUSA-N 0.000 description 1
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 1
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 description 1
- 101710103494 Platelet-derived growth factor subunit B Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- VCYJKOLZYPYGJV-AVGNSLFASA-N Pro-Arg-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VCYJKOLZYPYGJV-AVGNSLFASA-N 0.000 description 1
- CYQQWUPHIZVCNY-GUBZILKMSA-N Pro-Arg-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CYQQWUPHIZVCNY-GUBZILKMSA-N 0.000 description 1
- UTAUEDINXUMHLG-FXQIFTODSA-N Pro-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1 UTAUEDINXUMHLG-FXQIFTODSA-N 0.000 description 1
- 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 1
- VJLJGKQAOQJXJG-CIUDSAMLSA-N Pro-Asp-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VJLJGKQAOQJXJG-CIUDSAMLSA-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
- VOZIBWWZSBIXQN-SRVKXCTJSA-N Pro-Glu-Lys Chemical compound NCCCC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1)C(O)=O VOZIBWWZSBIXQN-SRVKXCTJSA-N 0.000 description 1
- 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
- HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-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
- 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 1
- AFXCXDQNRXTSBD-FJXKBIBVSA-N Pro-Gly-Thr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O AFXCXDQNRXTSBD-FJXKBIBVSA-N 0.000 description 1
- KWMUAKQOVYCQJQ-ZPFDUUQYSA-N Pro-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@@H]1CCCN1 KWMUAKQOVYCQJQ-ZPFDUUQYSA-N 0.000 description 1
- LXLFEIHKWGHJJB-XUXIUFHCSA-N Pro-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 LXLFEIHKWGHJJB-XUXIUFHCSA-N 0.000 description 1
- GURGCNUWVSDYTP-SRVKXCTJSA-N Pro-Leu-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GURGCNUWVSDYTP-SRVKXCTJSA-N 0.000 description 1
- XYSXOCIWCPFOCG-IHRRRGAJSA-N Pro-Leu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XYSXOCIWCPFOCG-IHRRRGAJSA-N 0.000 description 1
- MRYUJHGPZQNOAD-IHRRRGAJSA-N Pro-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 MRYUJHGPZQNOAD-IHRRRGAJSA-N 0.000 description 1
- HATVCTYBNCNMAA-AVGNSLFASA-N Pro-Leu-Met Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O HATVCTYBNCNMAA-AVGNSLFASA-N 0.000 description 1
- RMODQFBNDDENCP-IHRRRGAJSA-N Pro-Lys-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O RMODQFBNDDENCP-IHRRRGAJSA-N 0.000 description 1
- 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
- PCWLNNZTBJTZRN-AVGNSLFASA-N Pro-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 PCWLNNZTBJTZRN-AVGNSLFASA-N 0.000 description 1
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- 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 1
- BGWKULMLUIUPKY-BQBZGAKWSA-N Pro-Ser-Gly Chemical compound OC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 BGWKULMLUIUPKY-BQBZGAKWSA-N 0.000 description 1
- 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 1
- BXHRXLMCYSZSIY-STECZYCISA-N Pro-Tyr-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1)C(O)=O BXHRXLMCYSZSIY-STECZYCISA-N 0.000 description 1
- FIDNSJUXESUDOV-JYJNAYRXSA-N Pro-Tyr-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O FIDNSJUXESUDOV-JYJNAYRXSA-N 0.000 description 1
- 102100023922 Putative tyrosine-protein phosphatase auxilin Human genes 0.000 description 1
- 108010079005 RDV peptide Proteins 0.000 description 1
- 108020005161 RNA Caps Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 235000011449 Rosa Nutrition 0.000 description 1
- 101150020107 SCN8A gene Proteins 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 102100034272 Sacsin Human genes 0.000 description 1
- 101710102928 Sacsin Proteins 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 229920002684 Sepharose Polymers 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
- 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
- JPIDMRXXNMIVKY-VZFHVOOUSA-N Ser-Ala-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JPIDMRXXNMIVKY-VZFHVOOUSA-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
- 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 1
- 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 1
- HZWAHWQZPSXNCB-BPUTZDHNSA-N Ser-Arg-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HZWAHWQZPSXNCB-BPUTZDHNSA-N 0.000 description 1
- 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 1
- VGNYHOBZJKWRGI-CIUDSAMLSA-N Ser-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO VGNYHOBZJKWRGI-CIUDSAMLSA-N 0.000 description 1
- BYIROAKULFFTEK-CIUDSAMLSA-N Ser-Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO BYIROAKULFFTEK-CIUDSAMLSA-N 0.000 description 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
- HEQPKICPPDOSIN-SRVKXCTJSA-N Ser-Asp-Tyr Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HEQPKICPPDOSIN-SRVKXCTJSA-N 0.000 description 1
- 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 1
- BLPYXIXXCFVIIF-FXQIFTODSA-N Ser-Cys-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N)CN=C(N)N BLPYXIXXCFVIIF-FXQIFTODSA-N 0.000 description 1
- KNCJWSPMTFFJII-ZLUOBGJFSA-N Ser-Cys-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(O)=O KNCJWSPMTFFJII-ZLUOBGJFSA-N 0.000 description 1
- MOVJSUIKUNCVMG-ZLUOBGJFSA-N Ser-Cys-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O)N)O MOVJSUIKUNCVMG-ZLUOBGJFSA-N 0.000 description 1
- RNMRYWZYFHHOEV-CIUDSAMLSA-N Ser-Gln-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RNMRYWZYFHHOEV-CIUDSAMLSA-N 0.000 description 1
- VMVNCJDKFOQOHM-GUBZILKMSA-N Ser-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N VMVNCJDKFOQOHM-GUBZILKMSA-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
- FMDHKPRACUXATF-ACZMJKKPSA-N Ser-Gln-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O FMDHKPRACUXATF-ACZMJKKPSA-N 0.000 description 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
- PVDTYLHUWAEYGY-CIUDSAMLSA-N Ser-Glu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PVDTYLHUWAEYGY-CIUDSAMLSA-N 0.000 description 1
- 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 1
- HJEBZBMOTCQYDN-ACZMJKKPSA-N Ser-Glu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HJEBZBMOTCQYDN-ACZMJKKPSA-N 0.000 description 1
- BRGQQXQKPUCUJQ-KBIXCLLPSA-N Ser-Glu-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BRGQQXQKPUCUJQ-KBIXCLLPSA-N 0.000 description 1
- UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-N 0.000 description 1
- MUARUIBTKQJKFY-WHFBIAKZSA-N Ser-Gly-Asp Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MUARUIBTKQJKFY-WHFBIAKZSA-N 0.000 description 1
- IOVHBRCQOGWAQH-ZKWXMUAHSA-N Ser-Gly-Ile Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IOVHBRCQOGWAQH-ZKWXMUAHSA-N 0.000 description 1
- KDGARKCAKHBEDB-NKWVEPMBSA-N Ser-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CO)N)C(=O)O KDGARKCAKHBEDB-NKWVEPMBSA-N 0.000 description 1
- HMRAQFJFTOLDKW-GUBZILKMSA-N Ser-His-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O HMRAQFJFTOLDKW-GUBZILKMSA-N 0.000 description 1
- RIAKPZVSNBBNRE-BJDJZHNGSA-N Ser-Ile-Leu Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O RIAKPZVSNBBNRE-BJDJZHNGSA-N 0.000 description 1
- 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 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
- UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 description 1
- XXNYYSXNXCJYKX-DCAQKATOSA-N Ser-Leu-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O XXNYYSXNXCJYKX-DCAQKATOSA-N 0.000 description 1
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 1
- JWOBLHJRDADHLN-KKUMJFAQSA-N Ser-Leu-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JWOBLHJRDADHLN-KKUMJFAQSA-N 0.000 description 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
- XUDRHBPSPAPDJP-SRVKXCTJSA-N Ser-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO XUDRHBPSPAPDJP-SRVKXCTJSA-N 0.000 description 1
- LPSKHZWBQONOQJ-XIRDDKMYSA-N Ser-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N LPSKHZWBQONOQJ-XIRDDKMYSA-N 0.000 description 1
- QJKPECIAWNNKIT-KKUMJFAQSA-N Ser-Lys-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QJKPECIAWNNKIT-KKUMJFAQSA-N 0.000 description 1
- UGGWCAFQPKANMW-FXQIFTODSA-N Ser-Met-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O UGGWCAFQPKANMW-FXQIFTODSA-N 0.000 description 1
- XNXRTQZTFVMJIJ-DCAQKATOSA-N Ser-Met-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O XNXRTQZTFVMJIJ-DCAQKATOSA-N 0.000 description 1
- UGTZYIPOBYXWRW-SRVKXCTJSA-N Ser-Phe-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O UGTZYIPOBYXWRW-SRVKXCTJSA-N 0.000 description 1
- WOJYIMBIKTWKJO-KKUMJFAQSA-N Ser-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](CO)N WOJYIMBIKTWKJO-KKUMJFAQSA-N 0.000 description 1
- RHAPJNVNWDBFQI-BQBZGAKWSA-N Ser-Pro-Gly Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O RHAPJNVNWDBFQI-BQBZGAKWSA-N 0.000 description 1
- 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 1
- HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 1
- KQNDIKOYWZTZIX-FXQIFTODSA-N Ser-Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQNDIKOYWZTZIX-FXQIFTODSA-N 0.000 description 1
- 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
- PYTKULIABVRXSC-BWBBJGPYSA-N Ser-Ser-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PYTKULIABVRXSC-BWBBJGPYSA-N 0.000 description 1
- 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 1
- XJDMUQCLVSCRSJ-VZFHVOOUSA-N Ser-Thr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O XJDMUQCLVSCRSJ-VZFHVOOUSA-N 0.000 description 1
- KKKVOZNCLALMPV-XKBZYTNZSA-N Ser-Thr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KKKVOZNCLALMPV-XKBZYTNZSA-N 0.000 description 1
- 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 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
- VEVYMLNYMULSMS-AVGNSLFASA-N Ser-Tyr-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VEVYMLNYMULSMS-AVGNSLFASA-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
- OSFZCEQJLWCIBG-BZSNNMDCSA-N Ser-Tyr-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OSFZCEQJLWCIBG-BZSNNMDCSA-N 0.000 description 1
- BEBVVQPDSHHWQL-NRPADANISA-N Ser-Val-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O BEBVVQPDSHHWQL-NRPADANISA-N 0.000 description 1
- LGIMRDKGABDMBN-DCAQKATOSA-N Ser-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N LGIMRDKGABDMBN-DCAQKATOSA-N 0.000 description 1
- ODRUTDLAONAVDV-IHRRRGAJSA-N Ser-Val-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ODRUTDLAONAVDV-IHRRRGAJSA-N 0.000 description 1
- HSWXBJCBYSWBPT-GUBZILKMSA-N Ser-Val-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)C(O)=O HSWXBJCBYSWBPT-GUBZILKMSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108091081024 Start codon Proteins 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
- 108050009621 Synapsin Proteins 0.000 description 1
- 102000001435 Synapsin Human genes 0.000 description 1
- NJEMRSFGDNECGF-GCJQMDKQSA-N Thr-Ala-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O NJEMRSFGDNECGF-GCJQMDKQSA-N 0.000 description 1
- FQPQPTHMHZKGFM-XQXXSGGOSA-N Thr-Ala-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O FQPQPTHMHZKGFM-XQXXSGGOSA-N 0.000 description 1
- KEGBFULVYKYJRD-LFSVMHDDSA-N Thr-Ala-Phe Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KEGBFULVYKYJRD-LFSVMHDDSA-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
- DGDCHPCRMWEOJR-FQPOAREZSA-N Thr-Ala-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 DGDCHPCRMWEOJR-FQPOAREZSA-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
- CAGTXGDOIFXLPC-KZVJFYERSA-N Thr-Arg-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CCCN=C(N)N CAGTXGDOIFXLPC-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
- LHUBVKCLOVALIA-HJGDQZAQSA-N Thr-Arg-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O LHUBVKCLOVALIA-HJGDQZAQSA-N 0.000 description 1
- 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 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
- 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 1
- KRPKYGOFYUNIGM-XVSYOHENSA-N Thr-Asp-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N)O KRPKYGOFYUNIGM-XVSYOHENSA-N 0.000 description 1
- 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 1
- ASJDFGOPDCVXTG-KATARQTJSA-N Thr-Cys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O ASJDFGOPDCVXTG-KATARQTJSA-N 0.000 description 1
- KWQBJOUOSNJDRR-XAVMHZPKSA-N Thr-Cys-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N)O KWQBJOUOSNJDRR-XAVMHZPKSA-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
- OYTNZCBFDXGQGE-XQXXSGGOSA-N Thr-Gln-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C)C(=O)O)N)O OYTNZCBFDXGQGE-XQXXSGGOSA-N 0.000 description 1
- VUVCRYXYUUPGSB-GLLZPBPUSA-N Thr-Gln-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N)O VUVCRYXYUUPGSB-GLLZPBPUSA-N 0.000 description 1
- DIPIPFHFLPTCLK-LOKLDPHHSA-N Thr-Gln-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O DIPIPFHFLPTCLK-LOKLDPHHSA-N 0.000 description 1
- VULNJDORNLBPNG-SWRJLBSHSA-N Thr-Glu-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O VULNJDORNLBPNG-SWRJLBSHSA-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
- JQAWYCUUFIMTHE-WLTAIBSBSA-N Thr-Gly-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JQAWYCUUFIMTHE-WLTAIBSBSA-N 0.000 description 1
- 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
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 1
- 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 1
- MEJHFIOYJHTWMK-VOAKCMCISA-N Thr-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)[C@@H](C)O MEJHFIOYJHTWMK-VOAKCMCISA-N 0.000 description 1
- MECLEFZMPPOEAC-VOAKCMCISA-N Thr-Leu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MECLEFZMPPOEAC-VOAKCMCISA-N 0.000 description 1
- NCXVJIQMWSGRHY-KXNHARMFSA-N Thr-Leu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O NCXVJIQMWSGRHY-KXNHARMFSA-N 0.000 description 1
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 1
- KRDSCBLRHORMRK-JXUBOQSCSA-N Thr-Lys-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O KRDSCBLRHORMRK-JXUBOQSCSA-N 0.000 description 1
- ZXIHABSKUITPTN-IXOXFDKPSA-N Thr-Lys-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O ZXIHABSKUITPTN-IXOXFDKPSA-N 0.000 description 1
- XSEPSRUDSPHMPX-KATARQTJSA-N Thr-Lys-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O XSEPSRUDSPHMPX-KATARQTJSA-N 0.000 description 1
- QFCQNHITJPRQTB-IEGACIPQSA-N Thr-Lys-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O QFCQNHITJPRQTB-IEGACIPQSA-N 0.000 description 1
- DXPURPNJDFCKKO-RHYQMDGZSA-N Thr-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O DXPURPNJDFCKKO-RHYQMDGZSA-N 0.000 description 1
- 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 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
- LKJCABTUFGTPPY-HJGDQZAQSA-N Thr-Pro-Gln Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O LKJCABTUFGTPPY-HJGDQZAQSA-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
- CSNBWOJOEOPYIJ-UVOCVTCTSA-N Thr-Thr-Lys Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O CSNBWOJOEOPYIJ-UVOCVTCTSA-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
- JAWUQFCGNVEDRN-MEYUZBJRSA-N Thr-Tyr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O JAWUQFCGNVEDRN-MEYUZBJRSA-N 0.000 description 1
- OGOYMQWIWHGTGH-KZVJFYERSA-N Thr-Val-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O OGOYMQWIWHGTGH-KZVJFYERSA-N 0.000 description 1
- FYBFTPLPAXZBOY-KKHAAJSZSA-N Thr-Val-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O FYBFTPLPAXZBOY-KKHAAJSZSA-N 0.000 description 1
- BKVICMPZWRNWOC-RHYQMDGZSA-N Thr-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O BKVICMPZWRNWOC-RHYQMDGZSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 102100029006 Translocation protein SEC63 homolog Human genes 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- LCPVBXOHXMBLFW-JSGCOSHPSA-N Trp-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)=CNC2=C1 LCPVBXOHXMBLFW-JSGCOSHPSA-N 0.000 description 1
- RSUXQZNWAOTBQF-XIRDDKMYSA-N Trp-Arg-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N RSUXQZNWAOTBQF-XIRDDKMYSA-N 0.000 description 1
- HYLNRGXEQACDKG-NYVOZVTQSA-N Trp-Asn-Trp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HYLNRGXEQACDKG-NYVOZVTQSA-N 0.000 description 1
- DVAAUUVLDFKTAQ-VHWLVUOQSA-N Trp-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N DVAAUUVLDFKTAQ-VHWLVUOQSA-N 0.000 description 1
- DQDXHYIEITXNJY-BPUTZDHNSA-N Trp-Gln-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N DQDXHYIEITXNJY-BPUTZDHNSA-N 0.000 description 1
- CZWIHKFGHICAJX-BPUTZDHNSA-N Trp-Glu-Glu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 CZWIHKFGHICAJX-BPUTZDHNSA-N 0.000 description 1
- FNOQJVHFVLVMOS-AAEUAGOBSA-N Trp-Gly-Asn Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)N)C(=O)O)N FNOQJVHFVLVMOS-AAEUAGOBSA-N 0.000 description 1
- CXPJPTFWKXNDKV-NUTKFTJISA-N Trp-Leu-Ala Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 CXPJPTFWKXNDKV-NUTKFTJISA-N 0.000 description 1
- UJRIVCPPPMYCNA-HOCLYGCPSA-N Trp-Leu-Gly Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N UJRIVCPPPMYCNA-HOCLYGCPSA-N 0.000 description 1
- NWQCKAPDGQMZQN-IHPCNDPISA-N Trp-Lys-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O NWQCKAPDGQMZQN-IHPCNDPISA-N 0.000 description 1
- UUIYFDAWNBSWPG-IHPCNDPISA-N Trp-Lys-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N UUIYFDAWNBSWPG-IHPCNDPISA-N 0.000 description 1
- GFUOTIPYXKAPAH-BVSLBCMMSA-N Trp-Pro-Phe Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O GFUOTIPYXKAPAH-BVSLBCMMSA-N 0.000 description 1
- IYHRKILQAQWODS-VJBMBRPKSA-N Trp-Trp-Glu 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)O)C(=O)O)N IYHRKILQAQWODS-VJBMBRPKSA-N 0.000 description 1
- 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 1
- WTXQBCCKXIKKHB-JYJNAYRXSA-N Tyr-Arg-Arg 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](CCCNC(N)=N)C(O)=O WTXQBCCKXIKKHB-JYJNAYRXSA-N 0.000 description 1
- 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 1
- IIJWXEUNETVJPV-IHRRRGAJSA-N Tyr-Arg-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N)O IIJWXEUNETVJPV-IHRRRGAJSA-N 0.000 description 1
- SCCKSNREWHMKOJ-SRVKXCTJSA-N Tyr-Asn-Ser Chemical compound N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O SCCKSNREWHMKOJ-SRVKXCTJSA-N 0.000 description 1
- BARBHMSSVWPKPZ-IHRRRGAJSA-N Tyr-Asp-Arg 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](CCCNC(N)=N)C(O)=O BARBHMSSVWPKPZ-IHRRRGAJSA-N 0.000 description 1
- BEIGSKUPTIFYRZ-SRVKXCTJSA-N Tyr-Asp-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O BEIGSKUPTIFYRZ-SRVKXCTJSA-N 0.000 description 1
- YGKVNUAKYPGORG-AVGNSLFASA-N Tyr-Asp-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YGKVNUAKYPGORG-AVGNSLFASA-N 0.000 description 1
- NLMXVDDEQFKQQU-CFMVVWHZSA-N Tyr-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)CC1=CC=C(O)C=C1 NLMXVDDEQFKQQU-CFMVVWHZSA-N 0.000 description 1
- MNMYOSZWCKYEDI-JRQIVUDYSA-N Tyr-Asp-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MNMYOSZWCKYEDI-JRQIVUDYSA-N 0.000 description 1
- SMLCYZYQFRTLCO-UWJYBYFXSA-N Tyr-Cys-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O SMLCYZYQFRTLCO-UWJYBYFXSA-N 0.000 description 1
- QUILOGWWLXMSAT-IHRRRGAJSA-N Tyr-Gln-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O QUILOGWWLXMSAT-IHRRRGAJSA-N 0.000 description 1
- 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
- XQYHLZNPOTXRMQ-KKUMJFAQSA-N Tyr-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XQYHLZNPOTXRMQ-KKUMJFAQSA-N 0.000 description 1
- KOVXHANYYYMBRF-IRIUXVKKSA-N Tyr-Glu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O KOVXHANYYYMBRF-IRIUXVKKSA-N 0.000 description 1
- CDHQEOXPWBDFPL-QWRGUYRKSA-N Tyr-Gly-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 CDHQEOXPWBDFPL-QWRGUYRKSA-N 0.000 description 1
- GIOBXJSONRQHKQ-RYUDHWBXSA-N Tyr-Gly-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O GIOBXJSONRQHKQ-RYUDHWBXSA-N 0.000 description 1
- JKUZFODWJGEQAP-KBPBESRZSA-N Tyr-Gly-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N)O JKUZFODWJGEQAP-KBPBESRZSA-N 0.000 description 1
- AZGZDDNKFFUDEH-QWRGUYRKSA-N Tyr-Gly-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AZGZDDNKFFUDEH-QWRGUYRKSA-N 0.000 description 1
- WVGKPKDWYQXWLU-BZSNNMDCSA-N Tyr-His-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCCN)C(=O)O)N)O WVGKPKDWYQXWLU-BZSNNMDCSA-N 0.000 description 1
- USYGMBIIUDLYHJ-GVARAGBVSA-N Tyr-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 USYGMBIIUDLYHJ-GVARAGBVSA-N 0.000 description 1
- KIJLSRYAUGGZIN-CFMVVWHZSA-N Tyr-Ile-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O KIJLSRYAUGGZIN-CFMVVWHZSA-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
- PRONOHBTMLNXCZ-BZSNNMDCSA-N Tyr-Leu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PRONOHBTMLNXCZ-BZSNNMDCSA-N 0.000 description 1
- OFHKXNKJXURPSY-ULQDDVLXSA-N Tyr-Met-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O OFHKXNKJXURPSY-ULQDDVLXSA-N 0.000 description 1
- AVFGBGGRZOKSFS-KJEVXHAQSA-N Tyr-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O AVFGBGGRZOKSFS-KJEVXHAQSA-N 0.000 description 1
- RIVVDNTUSRVTQT-IRIUXVKKSA-N Tyr-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O RIVVDNTUSRVTQT-IRIUXVKKSA-N 0.000 description 1
- LVILBTSHPTWDGE-PMVMPFDFSA-N Tyr-Trp-Lys Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(O)=O)C1=CC=C(O)C=C1 LVILBTSHPTWDGE-PMVMPFDFSA-N 0.000 description 1
- OJCISMMNNUNNJA-BZSNNMDCSA-N Tyr-Tyr-Asp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(O)=O)C(O)=O)C1=CC=C(O)C=C1 OJCISMMNNUNNJA-BZSNNMDCSA-N 0.000 description 1
- DJSYPCWZPNHQQE-FHWLQOOXSA-N Tyr-Tyr-Gln Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C1=CC=C(O)C=C1 DJSYPCWZPNHQQE-FHWLQOOXSA-N 0.000 description 1
- 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 1
- KKHRWGYHBZORMQ-NHCYSSNCSA-N Val-Arg-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKHRWGYHBZORMQ-NHCYSSNCSA-N 0.000 description 1
- UDNYEPLJTRDMEJ-RCOVLWMOSA-N Val-Asn-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N UDNYEPLJTRDMEJ-RCOVLWMOSA-N 0.000 description 1
- NMPXRFYMZDIBRF-ZOBUZTSGSA-N Val-Asn-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N NMPXRFYMZDIBRF-ZOBUZTSGSA-N 0.000 description 1
- 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 1
- OVLIFGQSBSNGHY-KKHAAJSZSA-N Val-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N)O OVLIFGQSBSNGHY-KKHAAJSZSA-N 0.000 description 1
- COSLEEOIYRPTHD-YDHLFZDLSA-N Val-Asp-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 COSLEEOIYRPTHD-YDHLFZDLSA-N 0.000 description 1
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 1
- SRWWRLKBEJZFPW-IHRRRGAJSA-N Val-Cys-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N SRWWRLKBEJZFPW-IHRRRGAJSA-N 0.000 description 1
- XTAUQCGQFJQGEJ-NHCYSSNCSA-N Val-Gln-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N XTAUQCGQFJQGEJ-NHCYSSNCSA-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
- PWRITNSESKQTPW-NRPADANISA-N Val-Gln-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N PWRITNSESKQTPW-NRPADANISA-N 0.000 description 1
- RKIGNDAHUOOIMJ-BQFCYCMXSA-N Val-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 RKIGNDAHUOOIMJ-BQFCYCMXSA-N 0.000 description 1
- WFENBJPLZMPVAX-XVKPBYJWSA-N Val-Gly-Glu Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O WFENBJPLZMPVAX-XVKPBYJWSA-N 0.000 description 1
- SDSCOOZQQGUQFC-GVXVVHGQSA-N Val-His-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N SDSCOOZQQGUQFC-GVXVVHGQSA-N 0.000 description 1
- LKUDRJSNRWVGMS-QSFUFRPTSA-N Val-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(C)C)N LKUDRJSNRWVGMS-QSFUFRPTSA-N 0.000 description 1
- APQIVBCUIUDSMB-OSUNSFLBSA-N Val-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C(C)C)N APQIVBCUIUDSMB-OSUNSFLBSA-N 0.000 description 1
- AGXGCFSECFQMKB-NHCYSSNCSA-N Val-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N AGXGCFSECFQMKB-NHCYSSNCSA-N 0.000 description 1
- XTDDIVQWDXMRJL-IHRRRGAJSA-N Val-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N XTDDIVQWDXMRJL-IHRRRGAJSA-N 0.000 description 1
- 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 1
- WDIWOIRFNMLNKO-ULQDDVLXSA-N Val-Leu-Tyr Chemical compound CC(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 WDIWOIRFNMLNKO-ULQDDVLXSA-N 0.000 description 1
- RWOGENDAOGMHLX-DCAQKATOSA-N Val-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N RWOGENDAOGMHLX-DCAQKATOSA-N 0.000 description 1
- GVJUTBOZZBTBIG-AVGNSLFASA-N Val-Lys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N GVJUTBOZZBTBIG-AVGNSLFASA-N 0.000 description 1
- YMTOEGGOCHVGEH-IHRRRGAJSA-N Val-Lys-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O YMTOEGGOCHVGEH-IHRRRGAJSA-N 0.000 description 1
- CXWJFWAZIVWBOS-XQQFMLRXSA-N Val-Lys-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N CXWJFWAZIVWBOS-XQQFMLRXSA-N 0.000 description 1
- JAKHAONCJJZVHT-DCAQKATOSA-N Val-Lys-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N JAKHAONCJJZVHT-DCAQKATOSA-N 0.000 description 1
- UOUIMEGEPSBZIV-ULQDDVLXSA-N Val-Lys-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UOUIMEGEPSBZIV-ULQDDVLXSA-N 0.000 description 1
- SBJCTAZFSZXWSR-AVGNSLFASA-N Val-Met-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N SBJCTAZFSZXWSR-AVGNSLFASA-N 0.000 description 1
- QPPZEDOTPZOSEC-RCWTZXSCSA-N Val-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](C(C)C)N)O QPPZEDOTPZOSEC-RCWTZXSCSA-N 0.000 description 1
- MJFSRZZJQWZHFQ-SRVKXCTJSA-N Val-Met-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)O)N MJFSRZZJQWZHFQ-SRVKXCTJSA-N 0.000 description 1
- CKTMJBPRVQWPHU-JSGCOSHPSA-N Val-Phe-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)O)N CKTMJBPRVQWPHU-JSGCOSHPSA-N 0.000 description 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
- KSFXWENSJABBFI-ZKWXMUAHSA-N Val-Ser-Asn Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KSFXWENSJABBFI-ZKWXMUAHSA-N 0.000 description 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
- TVGWMCTYUFBXAP-QTKMDUPCSA-N Val-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N)O TVGWMCTYUFBXAP-QTKMDUPCSA-N 0.000 description 1
- DVLWZWNAQUBZBC-ZNSHCXBVSA-N Val-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N)O DVLWZWNAQUBZBC-ZNSHCXBVSA-N 0.000 description 1
- JAIZPWVHPQRYOU-ZJDVBMNYSA-N Val-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O JAIZPWVHPQRYOU-ZJDVBMNYSA-N 0.000 description 1
- DFQZDQPLWBSFEJ-LSJOCFKGSA-N Val-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)O)N DFQZDQPLWBSFEJ-LSJOCFKGSA-N 0.000 description 1
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 102100023038 WD and tetratricopeptide repeats protein 1 Human genes 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 1
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 1
- 108010060035 arginylproline Proteins 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 208000021018 autosomal dominant inheritance Diseases 0.000 description 1
- 208000021024 autosomal recessive inheritance Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- XMQFTWRPUQYINF-UHFFFAOYSA-N bensulfuron-methyl Chemical compound COC(=O)C1=CC=CC=C1CS(=O)(=O)NC(=O)NC1=NC(OC)=CC(OC)=N1 XMQFTWRPUQYINF-UHFFFAOYSA-N 0.000 description 1
- 235000012216 bentonite Nutrition 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
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000004915 chaperone-mediated autophagy Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 108010059354 cysteine string protein Proteins 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- SHWINQXIGSEZAP-UHFFFAOYSA-N dimethyl heptanedioate Chemical compound COC(=O)CCCCCC(=O)OC SHWINQXIGSEZAP-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 101150052825 dnaK gene Proteins 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 108010022937 endoplasmin Proteins 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 1
- 108010046775 glutamyl-isoleucyl-leucyl-aspartyl-valine Proteins 0.000 description 1
- 108010073628 glutamyl-valyl-phenylalanine Proteins 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- LXJXRIRHZLFYRP-UHFFFAOYSA-N glyceraldehyde 3-phosphate Chemical compound O=CC(O)COP(O)(O)=O LXJXRIRHZLFYRP-UHFFFAOYSA-N 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 201000004543 glycogen storage disease III Diseases 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 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 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 108010036413 histidylglycine Proteins 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 108010031424 isoleucyl-prolyl-proline Proteins 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 235000007260 kalia Nutrition 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 108010077158 leucinyl-arginyl-tryptophan Proteins 0.000 description 1
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 1
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 1
- 108010072591 lysyl-leucyl-alanyl-arginine Proteins 0.000 description 1
- 101710130522 mRNA export factor Proteins 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
- 108010068488 methionylphenylalanine Proteins 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000002071 myeloproliferative effect Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 244000309711 non-enveloped viruses Species 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 108010025488 pinealon Proteins 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010015796 prolylisoleucine Proteins 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000000272 proprioceptive effect Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 210000000449 purkinje cell Anatomy 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 108010048818 seryl-histidine Proteins 0.000 description 1
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 108010005652 splenotritin Proteins 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000004960 subcellular localization Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 102000003137 synaptotagmin Human genes 0.000 description 1
- 108060008004 synaptotagmin Proteins 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 108010084932 tryptophyl-proline Proteins 0.000 description 1
- 108010044292 tryptophyltyrosine Proteins 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 108010072644 valyl-alanyl-prolyl-glycine Proteins 0.000 description 1
- 108010052774 valyl-lysyl-glycyl-phenylalanyl-tyrosine Proteins 0.000 description 1
- 108010015385 valyl-prolyl-proline Proteins 0.000 description 1
- 108010009962 valyltyrosine Proteins 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
-
- 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
公开了一类新型融合蛋白来募集细胞的先天分子伴侣机制,特别是Hsp70介导的系统,以特异性地减少α‑突触核蛋白介导的蛋白质聚集和相关的蛋白质构象病。
Description
相关申请的交叉引用
本申请根据35 U.S.C.§119(e)要求于2020年6月5日提交的美国临时专利申请63/035,297的优先权。上述申请的全部内容在此通过引用以其整体并入。
序列表
本申请通过引用以其整体并入名称为“269548-493385_ST25.txt”(68KB)的序列表,所述序列表于2021年6月4日下午1:09创建,并且随同以电子方式提交。
技术领域
描述并请求保护包含一个或多个J结构域、α-突触核蛋白结合结构域、接头、靶向试剂、表位、细胞穿透剂及其组合的新的融合蛋白。另外,本公开内容描述了这些新型融合蛋白的用途,并且同样描述并请求保护其对先天性分子伴侣机制,例如Hsp70介导的系统的募集,以特异性减少α-突触核蛋白介导的蛋白质聚集和相关的蛋白病。
背景技术
细胞内表达的所有蛋白质都需要正确折叠成其预期结构,以便正常发挥功能。越来越多的疾病和病症显示出与蛋白质的不适当折叠和/或蛋白质和脂蛋白以及传染性蛋白质物质的不适当沉积和聚集相关。也被称为构象疾病或蛋白质构象病的由错误折叠引起的疾病的实例包括阿尔茨海默氏病(AD)、肌萎缩侧索硬化(ALS)和额颞叶痴呆(FTLD)。突变蛋白在细胞中聚集,导致典型的细胞毒性细胞包涵体。
各种各样的神经退行性疾病在病理学上被表征为由淀粉样原纤维构成的细胞内或细胞外蛋白质聚集物的积累(Forman等人,(2004)Nat Med.10:1055-1063)。例如,阿尔茨海默氏病(AD)的病理学通过分别由β-淀粉样蛋白和微管相关蛋白tau构成的老年斑块和神经原纤维缠结来定义。
帕金森氏病(PD)是仅次于阿尔茨海默氏病(AD)的第二大常见神经退行性病症。超过1%的60岁以上的人患有该疾病,仅在美国就具有超过100万患者。PD患者经历运动迟缓、僵直、震颤、平衡困难和约40% PD患者中不同的痴呆表现,其中一些人在疾病的后期发展AD样痴呆。PD的主要病理特征是黑质中的多巴胺能神经元的丧失和异常蛋白质聚集物的存在,所述蛋白质聚集物在神经元细胞质中形成丝状包涵体,在PD脑中被称为路易体(LB)或路易神经突(神经纤维)(LN)(Galvin等人,(2001)Arch Neurol 58,186-190;Lang和Lozano,(1998)N Engl J Med 339,1044-1053;Lang和Lozano,(1998)N Engl J Med 339,1130-1143)。大多数PD是散发性的。家族形式PD的占所有病例的约10%,并且可以是常染色体隐性遗传或常染色体显性遗传,提示了该病症的复杂病因学(Lang和Lozano综述的)(Lang和Lozano,(1998)N Engl J Med 339,1044-1053;Lang和Lozano,(1998)N Engl JMed 339,1130-1143)。另外,环境因素也在PD的发展中起重要作用(由Di Monte,2003综述的)(Di Monte等人,(2003)Lancet Neurol 2,531-538)。
PD与几个基因座的遗传连锁的发现提供了鉴定促成该疾病的发病机制的遗传因素的希望。对源于意大利南部的一个家族中的患有罕见的、显性遗传的PD变体的患者的研究将该病症与染色体4q21-23上的基因座(park 1)相联系,先前鉴定的被称为α-突触核蛋白(SNCA)的基因定位于所述基因座中(Jakes等人,(1994)FEBS Lett 345,27-32;Shibazaki等人,(1995)Cytogenet Cell Genet 71,54-55;Polymeropoulos等人,(1996)Science 274,1197-1199)。关于α-突触核蛋白参与家族性PD的直接证据通过鉴定基因中的错义突变来提供,所述错义突变导致在这个意大利裔美国家族和其后三个不相关的希腊家族中的氨基酸53处的A-T取代(Polymeropoulos等人,(1997)Science 276,2045-2047)。随后,在一个德国家族中鉴定了在α-突触核蛋白基因的位置30处将丙氨酸变为脯氨酸的第二种突变(Kruger等人,(1998)Nat Genet 18,106-108)。LB的免疫组织化学检查显示了LB含有许多不同的蛋白质。最一致地被描述的蛋白质是神经丝、泛素和alpha-突触核蛋白(α-突触核蛋白)(Takeda等人,(1998)Am J Pathol 152,367-372;Gai等人,Brain 118(Pt 6),1447-1459)。错误折叠的α-突触核蛋白的大型近核聚集物占优势地存在于PD脑的路易体以及营养不良性路易神经突(LN)中(Dickson,(2012)Cold Spring Harb Perspect Med 2;Stefanis,(2012)Cold Spring Harb Perspect Med 2,a009399;Lashuel等人,(2013)NatRev Neurosci 14,38-48),提示了α-突触核蛋白的错误折叠作为与聚集的α-突触核蛋白累积相关的神经退行性疾病的发病机制的罪魁祸首(Baba等人,(1998)Am J Pathol 152,879-884;Kalia等人,(2013)Ann Neurol 73,155-169)。
α-突触核蛋白基因编码~19kDa的140个氨基酸的蛋白质。虽然α-突触核蛋白的功能尚未完全明确,但存在提示α-突触核蛋白在神经递质释放中具有作用的证据(Liu等人,(2004)EMBO J 23,4506-4516;Chandra等人,(2005)Cell 123,383-396;Fortin等人,(2005)J Neurosci 25,10913-10921)。α-突触核蛋白在哺乳动物脑各处高度表达,但在与膜和囊泡结构相关的突触前神经末梢中富集。小鼠具有α-突触核蛋白的功能同源物。小鼠α-突触核蛋白基因的纯合子敲除是可存活、可育和几乎正常的(Abeliovich等人,(2000)Neuron 25,239-252)。α-突触核蛋白-/-小鼠显示出伴随配对刺激的增加的DA释放、纹状体DA的减少以及DA依赖性运动对苯丙胺的应答减弱,提示了α-突触核蛋白是DA神经传递的调节剂。具有α-突触核蛋白过表达的小鼠是表面上正常的,尽管在具有人α-突触核蛋白高表达的小鼠品系中存在DA神经末梢的明显退化,但并未观察到DA神经元的丧失(Masliah和Rockenstein,(2000)J Neural Transm Suppl 59,175-183)。A53Tα-突触核蛋白突变体的过表达诱导了大量神经变性(Lee等人,(2002)Proc Natl Acad Sci U S A 99,8968-8973;Giasson等人,(2002)Neuron 34,521-533;Dawson等人,(2002)Neuron 35,219-222)。由腺相关病毒(AAV)介导的过表达腺相关野生型和突变型α-突触核蛋白的大鼠中的DA神经元的进行性丧失提示了,PD模型可被用于测试PD治疗(Kirik等人,(2002)Neuron 35,219-222)。
目前,不存在用于PD的预防或治愈,而是仅存在对症治疗,如药物治疗和手术治疗。多巴胺能黑质神经元的退化导致向纹状体的多巴胺能投射的丧失,其代表PD中的神经化学途径的主要缺陷。因此,用于PD的一种治疗是多巴胺(DA)的替换,其中患者服用药物左旋多巴。左旋多巴通过芳香族L-氨基酸脱羧酶(AADC)转换成多巴胺。然而,由于众多副作用,这种益处是暂时的(由Nutt 2003综述)(Nutt,(2003)Exp Neurol 184,9-13)。另外,随着疾病进展,可用的AADC更少,使得患者可能经历增加的失能时间(off-time),例如僵硬、僵直和痉挛。因此,存在开发用于这种破坏性疾病的新治疗的大量需要。
热休克70kDa蛋白(在本文中被称为“Hsp70”)构成各种各样物种的细胞中普遍存在的一类伴侣蛋白(Tavaria等人,(1996)Cell Stress Chaperones 1,23-28)。Hsp70需要被称为共伴侣蛋白的辅助蛋白质,例如J结构域蛋白和核苷酸交换因子(NEF)(Hartl等人,(2009)Nat Struct Mol Biol 16,574-581),以便发挥功能。在用于折叠蛋白质的Hsp70分子伴侣机制的目前模型中,Hsp70在ATP和ADP结合状态之间循环,并且J结构域蛋白与需要折叠或重新折叠的另一种蛋白质(被称为“客户蛋白质”)结合,与Hsp70的ATP结合形式(Hsp70-ATP)相互作用(Young(2010)Biochem Cell Biol 88,291-300;Mayer,(2010)MolCell 39,321-331)。J结构域蛋白-客户复合物与Hsp70-ATP的结合刺激ATP水解,这导致Hsp70蛋白中的构象变化,关闭螺旋盖,并从而稳定客户蛋白质与Hsp70-ADP之间的相互作用,以及引发J结构域蛋白的释放,所述J结构域蛋白然后自由地结合另一个客户蛋白质。
因此,根据该模型,J结构域蛋白通过充当桥梁,以及促进将各种各样的客户蛋白质捕获和提交到Hsp70机制内以促进折叠或重新折叠成正确的构象,在Hsp70机制内发挥关键作用(Kampinga&Craig(2010)Nat Rev Mol Cell Biol 11,579-592)。J结构域家族在范围为从原核生物(DnaJ蛋白)到真核生物(Hsp40蛋白家族)的物种中是广泛保守的。J结构域(约60-80aa)由四个螺旋构成:I、II、III和IV。螺旋II和III经由含有“HPD基序”的柔性环连接,所述HPD基序在J结构域中是高度保守的,并且被认为对于活性至关重要(Tsai&Douglas,(1996)J Biol Chem 271,9347-9354)。已发现HPD序列内的突变消除了J结构域的功能。
鉴于上文提供的诸如PD等蛋白质构象病的背景,似乎明确的是,减少错误折叠蛋白质的水平可以充当治疗、预防或以其它方式改善这些破坏性病症的症状的手段,并且对细胞修复蛋白质错误折叠的先天能力的募集将是合乎逻辑的选择。
发明内容
发明人已开发了一类新型融合蛋白来募集细胞的先天分子伴侣机制,特别是Hsp70介导的系统,以特异性减少α-突触核蛋白介导的蛋白质错误折叠。与发明人使用包含与Hsp70相互作用的共分子伴侣Hsp40蛋白(也被称为J蛋白)的片段的融合蛋白来增强蛋白质分泌和表达的先前研究不同,本研究采用含有J结构域的融合蛋白用于减少由α-突触核蛋白蛋白质引起的蛋白质错误折叠和细胞毒性的目的。在这个背景下,本发明人已意外地发现了,功能所需的J结构域元件与在增强蛋白质表达和分泌中使用J结构域相当不同,证实了关于本融合蛋白的作用模式的不同机制。本文所述的融合蛋白包含J结构域和对α-突触核蛋白具有亲和力的结构域。融合蛋白内α-突触核蛋白结合结构域的存在导致α-突触核蛋白蛋白质的错误折叠的特异性减少。
E1.因此,在第一个方面,本文公开的是分离的融合蛋白,其包含J蛋白的J结构域和α-突触核蛋白结合结构域。
E2.E1的融合蛋白,其中所述J蛋白的J结构域是真核起源的。
E3.E1-E2中任何一项的融合蛋白,其中所述J蛋白的J结构域是人起源的。
E4.E1-E3中任何一项的融合蛋白,其中所述J蛋白的J结构域是胞质定位的。
E5.E1-E4中任何一项的融合蛋白,其中所述J蛋白的J结构域选自SEQ ID No:1-50。
E6.E1-E5中任何一项的融合蛋白,其中所述J结构域包含选自SEQ ID NO:1、5、6、10、16、24、25、31和49的序列。
E7.E1-E6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:5的序列。
E8.E1-E6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:10的序列。
E9.E1-E6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:16的序列。
E10.E1-E6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:25的序列。
E11.E1-E6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:31的序列。
E12.E1-E11中任何一项的融合蛋白,其中当使用ELISA测定进行测量时,所述α-突触核蛋白结合结构域对于α-突触核蛋白具有1μM或更小,例如300nM或更小、100nM或更小、30nM或更小、10nM或更小的KD。
E13.E1-E12中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含选自SEQ ID NO:51-65的序列。
E14.E1-E13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:51的序列。
E15.E1-E13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:52的序列。
E16.E1-E13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:63的序列。
E17.E1-E13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:64的序列。
E18.E1-E17中任何一项的融合蛋白,其包含多个α-突触核蛋白结合结构域。
E19.E1-E18中任何一项的融合蛋白,其由两个α-突触核蛋白结合结构域组成。
E20.E1-E19中任何一项的融合蛋白,其由三个α-突触核蛋白结合结构域组成。
E21.E1-E20中任何一项的融合蛋白,其包含以下构建体之一:
a.DNAJ-X-S,
b.DNAJ-X-S-X-S,
c.DNAJ-X-S-X-S-X-S,
d.S-X-DNAJ,
e.S-X-S-X-DNAJ,
f.S-X-S-X-S-X-DNAJ,
g.S-X-DNAJ-X-S,
h.S-X-DNAJ-X-S-X-S,
i.S-X-S-X-DNAJ-X-S-X-S-X-S,
j.S-X-S-X-S-X-DNAJ-X-S,
k.S-X-S-X-S-X-DNAJ-X-S-X-S,
l.S-X-S-X-S-X-DNAJ-X-S-X-S-X-S,
m.DnaJ-X-DnaJ-X-S-X-S,
n.S-X-DnaJ-X-DnaJ,和
o.S-X-S-X-DnaJ-X-DnaJ,
其中,
S是α-突触核蛋白结合结构域,
DNAJ是J蛋白的J结构域,和
X是任选的接头。
E22.E1-E21中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:5的J结构域序列和SEQ ID NO:51的α-突触核蛋白结合结构域序列。
E23.E1-E22中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:5的J结构域序列和SEQ ID NO:51的α-突触核蛋白结合结构域序列的两个拷贝。
E24.E1-E23中任何一项的融合蛋白,其中所述融合蛋白包含选自SEQ ID NO:88、90-96、98-100的序列。
E25.E1-E24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:88的序列。
E26.E1-E24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:90的序列。
E27.E1-E24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:99的序列。
E28.E1-E24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:100的序列。
E29.E1-E28中任何一项的融合蛋白,其进一步包含靶向试剂。
E30.E1-E29中任何一项的融合蛋白,其进一步包含表位。
E31.E30的融合蛋白,其中所述表位是选自SEQ ID NO:77-83的多肽。
E32.E1-E31中任何一项的融合蛋白,其进一步包含细胞穿透剂。
E33.E32的融合蛋白,其中所述细胞穿透剂包含选自SEQ ID NO:84-87的肽序列。
E34.E1-E33中任何一项的融合蛋白,其进一步包含信号序列。
E35.E34的融合蛋白,其中所述信号序列包含选自SEQ ID NO:102-104的肽序列。
E36.E1-E35中任何一项的融合蛋白,其能够减少细胞中的α-突触核蛋白蛋白质的错误折叠。
E37.E1-E36中任何一项的融合蛋白,其能够减少细胞中的磷酸化的α-突触核蛋白蛋白质。
E38.E1-E37中任何一项的融合蛋白,其能够减少α-突触核蛋白蛋白质的分泌。
E39.E1-E38中任何一项的融合蛋白,其能够减少α-突触核蛋白介导的细胞毒性。
E40.一种核酸序列,其编码E1-E39中任何一项的融合蛋白。
E41.E40的核酸序列,其中所述核酸是DNA。
E42.E41中任何一项的核酸序列,其中所述核酸是RNA。
E43.E40-E42中任何一项的核酸序列,其中所述核酸包含至少一种修饰的核酸。
E44.E40-E43中任何一项的核酸序列,其进一步包含启动子区、5'UTR、3'UTR如多聚(A)信号。
E45.E44的核酸序列,其中所述启动子区包含选自CMV增强子序列、CMV启动子、CBA启动子、UBC启动子、GUSB启动子、NSE启动子、突触素(Synapsin)启动子、MeCP2启动子和GFAP启动子的序列。
E46.一种载体,其包含E40-E45中任何一项的核酸序列。
E47.E46的载体,其中所述载体选自腺相关病毒(AAV)、腺病毒、慢病毒、逆转录病毒、疱疹病毒、痘病毒(牛痘或粘液瘤)、副粘病毒(麻疹、RSV或新城疫病毒)、杆状病毒、呼肠孤病毒、甲病毒和黄病毒。
E48.一种病毒颗粒,其包含衣壳和E46或E47的载体。
E49.E48的病毒颗粒,其中所述衣壳选自AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV11、AAV12、假型AAV、恒河猴衍生的AAV、AAVrh8、AAVrh10和AAV-DJanAAV衣壳突变体、AAV杂合血清型、嗜器官性AAV、嗜心性AAV和嗜心性AAVM41突变体。
E50.E48或E49的病毒颗粒,其中所述衣壳选自AAV2、AAV5、AAV8、AAV9和AAVrh10。
E51.E48-E50中任何一项的病毒颗粒,其中所述衣壳是AAV2。
E52.E48-E50中任何一项的病毒颗粒,其中所述衣壳是AAV5。
E53.E48-E50中任何一项的病毒颗粒,其中所述衣壳是AAV8。
E54.E48-E50中任何一项的病毒颗粒,其中所述衣壳是AAV9。
E55.E48-E50中任何一项的病毒颗粒,其中所述衣壳是AAV rh10。
E56.一种药物组合物,其包含选自以下的药剂和药学上可接受的载剂或赋形剂:E1-E39中任何一项的融合蛋白、表达E1-E39的融合蛋白的细胞、E40-E45中任何一项的核酸、E46-E47中任何一项的载体、E48-E55中任何一项的病毒颗粒。
E57.减少细胞中的α-突触核蛋白蛋白质毒性的方法,其包括使所述细胞与有效量的选自以下的一种或多种药剂接触:E1-E39中任何一项的融合蛋白、表达E1-E39的融合蛋白的细胞、E40-E45中任何一项的核酸、E46-E47中任何一项的载体、E48-E55中任何一项的病毒颗粒和E56的药物组合物。
E58.E57的方法,其中所述细胞在受试者中。
E59.E57-E58中任何一项的方法,其中所述受试者是人。
E60.E57-E59中任何一项的方法,其中所述细胞是中枢神经系统的细胞。
E61.E57-E60中任何一项的方法,其中所述受试者被鉴定为患有α-突触核蛋白疾病。
E62.E61的方法,其中所述α-突触核蛋白疾病选自PD、路易体痴呆、多系统萎缩以及与聚集的α-突触核蛋白蛋白质的异常累积相关的疾病(突触核蛋白病)。
E63.E61或E62的方法,其中所述α-突触核蛋白疾病是PD。
E64.E57-E63中任何一项的方法,其中当与对照细胞相比时,存在所述细胞中的错误折叠的α-突触核蛋白蛋白质的量减少。
E65.在需要其的受试者中治疗α-突触核蛋白疾病、预防α-突触核蛋白疾病或延迟α-突触核蛋白疾病的进展的方法,所述方法包括施用有效量的选自以下的一种或多种药剂:E1-E39中任何一项的融合蛋白、表达E1-E39的融合蛋白的细胞、E40-E45中任何一项的核酸、E46-E47中任何一项的载体、E48-E55中任何一项的病毒颗粒和E56的药物组合物。
E66.E65的方法,其中所述α-突触核蛋白疾病选自PD、路易体痴呆、多系统萎缩以及与聚集的α-突触核蛋白蛋白质的异常累积相关的疾病(突触核蛋白病)。
E67.E65的方法,其中所述α-突触核蛋白疾病是PD。
E68.以下中的一种或多种在受试者中预防α-突触核蛋白疾病或延迟α-突触核蛋白疾病的进展中的用途:E1-E39中任何一项的融合蛋白、表达E1-E39的融合蛋白的细胞、E40-E45中任何一项的核酸、E46-E47中任何一项的载体、E48-E55中任何一项的病毒颗粒和E56的药物组合物。
E69.以下中的一种或多种在制备用于治疗或预防受试者中的α-突触核蛋白疾病的药物中的用途:E1-E39中任何一项的融合蛋白、表达E1-E39的融合蛋白的细胞、E40-E45中任何一项的核酸、E46-E47中任何一项的载体、E48-E55中任何一项的病毒颗粒和E56的药物组合物。
E70.E68或E69的用途,其中所述α-突触核蛋白疾病是PD。
附图说明
图1A显示了代表性的人J结构域序列的Clustal Omega序列比对。高度保守的HPD结构域显示于突出显示的框中。
图1B显示了代表性的人J结构域序列的Clustal Omega序列比对。
图2显示了包含J结构域和α-突触核蛋白结合结构域的一些代表性融合蛋白构建体以及对照构建体。
图3显示了表达包含J结构域和α-突触核蛋白结合结构域的融合蛋白的效应。图3A:野生型(WT)α-突触核蛋白(Syn(WT):条1-3)或突变型α-突触核蛋白(Syn(A53T):条4-6)在HEK293细胞中单独表达,或者与加上Flag表位标签的融合蛋白(J-SynBP1:条2和5)或对照融合蛋白构建体(J(MT)-SynBP1:条3和6)一起表达,所述加上Flag表位标签的融合蛋白包含J结构域DnaJB1和α-突触核蛋白结合结构域,所述对照融合蛋白构建体包含突变的J结构域(含有P33Q取代)和α-突触核蛋白结合肽。两天后,细胞在Tris缓冲液(补充有蛋白酶抑制剂混合物的10mM Tris,pH 7.4、140mM NaCl、1mM EDTA)中进行匀浆化。突变型α-突触核蛋白水平的聚集用夹心ELISA进行定量,其中聚集的α-突触核蛋白被包被的Syn-O4抗体捕获,随后为用HRP缀合的抗α-突触核蛋白抗体(BioLegend:A15115A)的检测。图3B裂解物制备自HEK293细胞,所述HEK293细胞用野生型Syn(WT)(泳道1-3)或突变型Syn(A53T)(泳道4-6)单独瞬时转染或与融合蛋白构建体共表达。在短暂的超声处理后,使细胞裂解物经受用抗α-突触核蛋白抗体(Ab-2:上图)、Flag抗体(中图)或抗微管蛋白抗体(下图)的SDS-PAGE/免疫印迹。
图4显示了在共表达包含J结构域和α-突触核蛋白结合结构域的融合蛋白的细胞中,分泌到培养基内的α-突触核蛋白的量的减少。用野生型(条2)或突变型(A53T;条4)α-突触核蛋白单独转染细胞导致突触核蛋白的分泌,如通过ELISA可检测到的。与包含正常(条3)或突变的J结构域(含有P33Q取代;条5)的融合蛋白构建体共表达导致可检测水平的分泌的α-突触核蛋白的消除。
图5显示了各种细胞过程的抑制剂在表达融合蛋白构建体的细胞中的总α-突触核蛋白水平方面的效应。细胞用野生型(泳道2)或突变型(泳道3-8)α-突触核蛋白进行转染,并且还用JB1-SynBP1融合蛋白(泳道4-8)进行转染。细胞还用晚期自噬的抑制剂巴佛洛霉素A1(泳道5和6中分别为10nM和100nM)或蛋白酶体抑制剂MG132(泳道7和8中分别为0.1μM和1μM)进行处理。用抗突触核蛋白抗体探测细胞裂解物。
图6显示了各种细胞过程的抑制剂在表达融合蛋白构建体的细胞中的聚集的α-突触核蛋白水平方面的效应。细胞用野生型或突变型α-突触核蛋白进行转染,并且还用JB1-SynBP1融合蛋白进行转染。细胞还用晚期自噬的抑制剂巴佛洛霉素A1(10nM和100nM)或蛋白酶体抑制剂MG132(0.1μM和1μM)进行处理。通过使用抗聚集的突触核蛋白抗体的ELISA确定细胞裂解物中聚集的突触核蛋白。
图7显示了在U87-MG神经胶质瘤细胞中,通过JB1-SynBP1构建体改善α-突触核蛋白(A53T)介导的细胞毒性。单独地或与JB1-SynBP1构建体一起用慢病毒感染U87MG细胞来表达野生型(“SynWT”)或突变型(“SynA53T”)α-突触核蛋白。在感染后7天,从U87-MG细胞中收集培养基。培养基中的乳酸脱氢酶(LDH)活性通过LDH-CytoxTM测定试剂盒(BioLegend)进行测量,并且表示为相对于单独表达SynWT的细胞中LDH水平的值。
定义
如在说明书和权利要求中使用的,单数形式“一个(a)”、“一种(an)”和“该(the)”包括复数指涉,除非上下文另有明确说明。例如,术语“一个细胞(a cell)”包括多个细胞,包括其混合物。
术语“多肽”、“肽”和“蛋白质”在本文中可互换使用,以指任何长度的氨基酸聚合物。聚合物可以是线性或分支的,它可以包含修饰的氨基酸,并且它可以被非氨基酸中断。该术语还包括已例如通过二硫键形成、糖基化、脂化、乙酰化、磷酸化或任何其它操纵(例如与标记组分缀合)进行修饰的氨基酸聚合物。
如本文使用的,术语“氨基酸”是指天然和/或非天然或合成氨基酸,包括但不限于D或L旋光异构体以及氨基酸类似物和拟肽。使用标准的单字母或三字母代码来指示氨基酸。
“宿主细胞”包括单体细胞或细胞培养物,其可以是或已是主题载体的接受者。宿主细胞包括单个宿主细胞的后代。由于自然、意外或有意的突变,后代可能不一定与原始亲本细胞完全一致(在形态学或总DNA互补体的基因组方面)。宿主细胞包括用本发明的载体体内转染的细胞。
当被用于描述本文公开的各种多肽时,“分离的”意指已被鉴定并且与其自然环境的组分分开和/或从其自然环境的组分中回收的多肽。其自然环境的污染物组分是通常将会干扰多肽的诊断或治疗用途的材料,并且可能包括酶、激素和其它蛋白质或非蛋白质溶质。如对于本领域技术人员显而易见的,非天然存在的多核苷酸、肽、多肽、蛋白质、抗体或其片段不需要“分离”以将其与其天然存在的对应物区分开。另外,“浓缩的”、“分开的”或“稀释的”多核苷酸、肽、多肽、蛋白质、抗体或其片段与其天然存在的对应物是可区别的,因为每体积的分子浓度或数目一般大于其天然存在的对应物。一般而言,通过重组手段制备并在宿主细胞中表达的多肽被视为“分离的”。
“分离的”多核苷酸或编码多肽的核酸或其它编码多肽的核酸是被鉴定且与至少一种污染物核酸分子分开的核酸分子,其通常在编码多肽的核酸的天然来源中与所述污染物核酸分子结合。分离的编码多肽的核酸分子处于不同于其在自然界中发现的形式或环境。因此,分离的编码多肽的核酸分子不同于如天然细胞中存在的特定的编码多肽的核酸分子。然而,分离的编码多肽的核酸分子包括在通常表达该多肽的细胞中包含的编码多肽的核酸分子,在所述细胞中,例如,所述核酸分子在不同于天然细胞的染色体或染色体外定位中。
术语“多核苷酸”、“核酸”、“核苷酸”和“寡核苷酸”可互换使用。它们是指任何长度的核苷酸的聚合形式,所述核苷酸为脱氧核糖核苷酸或核糖核苷酸,或其类似物。多核苷酸可以具有任何三维结构,并且可以执行已知或未知的任何功能。下述是多核苷酸的非限制性实例:基因或基因片段的编码区或非编码区、由连锁分析限定的一个或多个基因座、外显子、内含子、信使RNA(mRNA)、转运RNA、核糖体RNA、核酶、cDNA、重组多核苷酸、分支多核苷酸、质粒、载体、任何序列的分离DNA、任何序列的分离RNA、核酸探针和引物。多核苷酸可以包含修饰的核苷酸,例如甲基化核苷酸和核苷酸类似物。如果存在的话,对核苷酸结构的修饰可以在聚合物组装之前或之后进行赋予。核苷酸序列可能被非核苷酸组分中断。在聚合后,多核苷酸可以例如通过用标记组分缀合来进行进一步修饰。
如本文定义的,术语“α-突触核蛋白病症”或“突触核蛋白病”是指与细胞内α-突触核蛋白聚集物,特别是α-突触核蛋白突变蛋白的聚集物的形成相关的病症。α-突触核蛋白病症的实例包括但不限于帕金森症(包括PD)、路易体痴呆、多系统萎缩以及与聚集的α-突触核蛋白蛋白质的异常累积相关的疾病(突触核蛋白病)。
“载体”是将插入的核酸分子转移到宿主细胞内和/或在宿主细胞之间转移的核酸分子,其优选地在适当的宿主中自主复制。该术语包括主要发挥功能用于将DNA或RNA插入细胞内的载体,主要发挥功能用于复制DNA或RNA的复制载体,以及发挥功能用于转录和/或翻译DNA或RNA的表达载体。还包括的是提供多于一种以上功能的载体。“表达载体”是在被引入适当的宿主细胞内时可以被转录并翻译成一种或多种多肽的多核苷酸。“表达系统”通常意味着包含表达载体的合适的宿主细胞,所述表达载体可以发挥功能以产生所需的表达产物。
术语“可操作地连接的”是指所描述组分的并置,其中所述组分处于允许它们以其预期方式发挥功能的关系中。“可操作地连接”到编码序列的控制序列以这样的方式进行连接,使得编码序列的表达在与控制序列相容的条件下实现。“可操作连接的”序列可以包括与目的基因邻接的表达控制序列以及反式或在一定距离处起作用以控制目的基因的表达控制序列两者。术语“表达控制序列”是指这样的多核苷酸序列,其为影响其所连接的编码序列的表达和加工所必需的。表达控制序列包括适当的转录起始、终止、启动子和增强子序列;有效的RNA加工信号,例如剪接和多聚腺苷酸化信号;稳定细胞质mRNA的序列;增强翻译效率的序列(例如Kozak共有序列);增强蛋白质稳定性的序列;以及在需要时,增强蛋白质分泌的序列。此类控制序列的性质取决于宿主生物而不同;在原核生物中,此类控制序列一般包括启动子、核糖体结合位点和转录终止序列;在真核生物中,一般地,此类控制序列包括启动子和转录终止序列。术语“控制序列”预期包括其存在对于表达和加工至关重要的组分,并且还可以包括其存在是有利的另外组分,例如前导序列和融合配偶体序列。除非另有说明,否则本文中将编码本发明的融合蛋白的核酸分子插入表达载体内的描述或陈述意指,当含有所插入的核酸分子的表达载体被引入相容的宿主细胞或生物的相容细胞内时,所插入的核酸也已在载体内可操作地连接至功能性启动子以及所编码的融合蛋白表达所需的其它转录和翻译控制元件。
当应用于多核苷酸时,“重组”意指多核苷酸是体外克隆、限制和/或连接步骤以及其它程序的各种组合的产物,所述其它程序导致可潜在地在宿主细胞中表达的构建体。
术语“基因”和“基因片段”在本文中可互换使用。它们是指含有至少一个开放阅读框的多核苷酸,其能够在进行转录和翻译后编码特定的蛋白质。基因或基因片段可以是基因组或cDNA,只要该多核苷酸含有至少一个开放阅读框,其可以覆盖整个编码区或其区段。“融合基因”是由连接在一起的至少两种异源多核苷酸构成的基因。
术语“疾病”和“病症”可互换使用,以指示根据本领域可接受的医学标准和实践来鉴定的病理状态。
如本文使用的,术语“有效量”是指疗法的量,其足以减少或改善疾病或者其一种或多种症状的严重程度和/或持续时间;预防有害状态或病理状态的进展;引起病理状态的消退;预防与病理状态相关的一种或多种症状的复发、发展、发作或进展;检测病症;或者增强或改善疗法的一种或多种预防效应或治疗效应(例如另一种预防剂或治疗剂的施用)。
如本文使用的,术语“J结构域”是指保留加速Hsp70及其同源物的固有ATP酶催化活性的能力的片段。已确定了各种J蛋白的J结构域(参见例如Kampinga等人(2010)Nat.Rev.,11:579-592;Hennessy等人(2005)Protein Science,14:1697-1709,其各自通过引用以其整体并入),并且通过许多标志进行表征:其特征在于四个α-螺旋(I、II、III、IV),并且通常在螺旋II和III之间具有高度保守的具有组氨酸、脯氨酸和天冬氨酸的三肽序列基序(被称为“HPD基序”)。通常,J蛋白的J结构域的长度在50至70个氨基酸之间,并且J结构域与Hsp70-ATP伴侣蛋白的相互作用(结合)位点据信是从螺旋II内延伸的区域,并且HPD基序是刺激Hsp70 ATP酶活性所必需的。如本文使用的,术语“J结构域”意在包括保留加速Hsp70固有ATP酶活性的能力的天然J结构域序列及其功能变体,所述能力可以使用本领域众所周知的方法进行测量(参见例如Horne等人(2010)J.Biol.Chem.,285,21679-21688,其通过引用以其整体并入本文)。表1中提供了人J结构域的非限制性列表。
具体实施方式
本发明人已发现了使细胞与包含J蛋白的J结构域和α-突触核蛋白结合结构域的融合蛋白构建体进行一定接触具有出乎意料的减少突变型α-突触核蛋白蛋白质的聚集的效应。突变型α-突触核蛋白的聚集据信导致许多破坏性疾病,包括但不限于帕金森症、路易体痴呆、多系统萎缩、与聚集的α-突触核蛋白蛋白质的异常累积相关的疾病(突触核蛋白病)。相应地,本文提供了例如在需要其的受试者中治疗α-突触核蛋白病症的有用组合物和方法。
为了克服与基于分子伴侣的疗法相关的问题,我们调查了是否有可能设计具有高度特异性的人工伴侣蛋白。我们设计了一系列融合蛋白构建体,其包含用于Hsp70结合/激活的效应结构域(J结构域序列)和赋予对α-突触核蛋白蛋白质的特异性的结构域。所得到的融合蛋白发挥作用来加速Hsp70及其同源物的固有ATP酶催化活性,导致蛋白质折叠增加、聚集减少和/或清除加速。
I.融合蛋白构建体
a.可用于本发明中的J结构域
已确定了各种J蛋白的J结构域。参见例如Kampinga等人,Nat.Rev.,11:579-592(2010);Hennessy等人,Protein Science,14:1697-1709(2005)。可用于制备本发明的融合蛋白的J结构域具有主要加速HSP70ATP酶活性的J结构域的关键限定特征。相应地,可用于本发明中的分离的J结构域包含多肽结构域,其特征在于四个α-螺旋(I、II、III、IV),并且通常在螺旋II和III之间具有高度保守的组氨酸、脯氨酸和天冬氨酸的三肽序列(被称为“HPD基序”)。通常,J蛋白的J结构域的长度在50至70个氨基酸之间,并且J结构域与Hsp70-ATP伴侣蛋白的相互作用(结合)位点据信是从螺旋II内延伸的区域,并且HPD基序对于原生活性是基础的。代表性的J结构域包括但不限于DnaJB1、DnaJB2、DnaJB6、DnaJC6的J结构域,SV40的大T抗原的J结构域和哺乳动物半胱氨酸链蛋白(cysteine string protein)(CSP-α)的J结构域。表1中提供了可以用于本发明的融合蛋白中的这些和其它J结构域的氨基酸序列。保守的HPD基序以粗体突出显示。
表1.代表性的人J结构域序列
在一个实施方案中,融合蛋白包含选自以下的J结构域序列:选自SEQ ID NO:1-50的多肽序列。本发明人已证实了包含保守的“HPD”基序的J结构域具有活性(数据未显示)。因此,在另一个实施方案中,融合蛋白包含含有保守的“HPD”基序的J结构域序列。例如,在特定实施方案中,融合蛋白包含选自以下的J结构域序列:选自SEQ ID NO:1-15和17-50的多肽序列。在另一个实施方案中,融合蛋白包含选自以下的J结构域序列:选自SEQ ID NO:1、5、6、10、16、24、25、31和49的多肽序列。
b.α-突触核蛋白结合结构域
融合蛋白还包含至少一个α-突触核蛋白结合结构域。α-突触核蛋白结合结构域可以是单链多肽或者与J结构域连接以形成融合蛋白的多聚体多肽。
理想的是,α-突触核蛋白结合结构域拥有足够的亲和力,使得能够结合α-突触核蛋白蛋白质(当在细胞内以病理水平存在时)。因此,在一个实施方案中,融合蛋白包含α-突触核蛋白结合结构域,当在96孔微量滴定板上通过ELISA进行测试时,所述α-突触核蛋白结合结构域对于α-突触核蛋白具有例如2μM或更小、1μM或更小、500nM或更小、300nM或更小、100nM或更小、30nM或更小的KD。在另一个实施方案中,融合蛋白包含α-突触核蛋白结合结构域,当在96孔微量滴定板上通过ELISA进行测试时,所述α-突触核蛋白结合结构域对于聚集形式的α-突触核蛋白具有例如2μM或更小、1μM或更小、500nM或更小、300nM或更小、100nM或更小、30nM或更小的KD。在仍然另一个实施方案中,α-突触核蛋白结合结构域对于聚集形式的α-突触核蛋白具有选择性;例如,当与对于可溶形式的α-突触核蛋白的亲和力相比时,α-突触核蛋白结合结构域对于聚集形式的α-突触核蛋白具有至少两倍高,例如至少3倍高、至少4倍高、至少5倍高、至少10倍高、至少30倍高、至少100倍高的亲和力。
α-突触核蛋白结合结构域先前已被鉴定和表征(参见例如美国专利号7,605,133、WO 2019/161386、Abe等人,(2007)BMC Bioinformatics,8:451,所述参考文献各自通过引用并入本文)。因此,在另一个实施方案中,融合蛋白包含选自SEQ ID NO:51-64的α-突触核蛋白结合(参见例如表2)。在一个特定实施方案中,融合蛋白包含SEQ ID NO:51的α-突触核蛋白结合结构域。在另一个实施方案中,融合蛋白包含SEQ ID NO:63的α-突触核蛋白结合结构域。
在仍然另一个实施方案中,融合蛋白包含J结构域和α-突触核蛋白结合结构域,其中所述α-突触核蛋白结合结构域并不包含SEQ ID NO:65的序列。在仍然另一个实施方案中,融合蛋白包含J结构域和α-突触核蛋白结合结构域,其中所述融合蛋白并不包含SEQ IDNO:65的序列。在特定实施方案中,融合蛋白包含J结构域和α-突触核蛋白结合结构域,其中所述融合蛋白并不包含SEQ ID NO:65的序列,并且所述J结构域选自SEQ ID NO:1、5、6、10、16、24、25、31和49,并且所述α-突触核蛋白结合结构域附着到J结构域的C末端,伴随或不伴随任选的接头。
在另一个方面,融合蛋白包含J结构域和靶结合蛋白SEQ ID NO:65。包含QBP1(SEQID NO:65)的融合蛋白构建体先前已显示了减少A53Tα-突触核蛋白中机械稳定和超机械稳定构象异构体的形成(Hervás等人,(2012)PLoS Biol.10(5):e1001335)。因此,在特定实施方案中,融合蛋白包含SEQ ID NO:65的α-突触核蛋白结合结构域。在特定实施方案中,融合蛋白构建体包含选自SEQ ID NO:1、5、6、10、16、24、25、31和49的J结构域序列,以及SEQ IDNO:65的α-突触核蛋白结合结构域。在一个实施方案中,融合蛋白构建体包含SEQ ID NO:5的J结构域序列和SEQ ID NO:65的α-突触核蛋白结合结构域。
在另一个实施方案中,融合蛋白还考虑了使用与J结构域化学缀合的α-突触核蛋白结合结构域。α-突触核蛋白结合结构域可以直接缀合至J结构域。可替代地,它可以通过接头与J结构域缀合。例如,存在大量化学交联剂,其为本领域技术人员已知的,并且可用于使α-突触核蛋白结合结构域与J结构域交联,或者使靶向结构域与包含α-突触核蛋白结合结构域和J结构域的融合蛋白交联。例如,交联剂是异双官能交联剂,其可以被用于以逐步的方式连接分子。异双官能交联剂提供了设计用于缀合蛋白质的更特异性偶联方法的能力,从而减少了诸如同蛋白聚合物等不想要的副反应的发生。各种各样的异双官能交联剂在本领域中已知的,包括琥珀酰亚胺基4-(N-马来酰亚胺甲基)环己烷-1-羧酸酯(SMCC)、间马来酰亚胺苯甲酰基-N-羟基琥珀酰亚胺酯(MBS);N-琥珀酰亚胺基(4-碘乙酰基)氨基苯甲酸酯(SIAB)、琥珀酰亚胺基4-(对马来酰亚胺苯基)丁酸酯(SMPB)、1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC);4-琥珀酰亚胺基氧羰基-a-甲基-a-(2-吡啶二硫代)-甲苯(SMPT)、N-琥珀酰亚胺基3-(2-吡啶二硫代)丙酸酯(SPDP)、琥珀酰亚胺基6-[3-(2-吡啶二硫代)丙酸酯]己酸酯(LC-SPDP)。具有N-羟基琥珀酰亚胺部分的那些交联剂可以作为N-羟基磺基琥珀酰亚胺类似物获得,其一般具有更大的水溶性。另外,在连接链内具有二硫桥的那些交联剂可以替代地作为烷基衍生物合成,以便减少体内的接头切割量。除异双官能交联剂之外,还存在许多其它交联剂,包括同双官能交联剂和光反应性交联剂。辛二酸二琥珀酰亚胺酯(DSS)、二马来酰亚胺基己烷(BMH)和庚二亚氨酸二甲酯2HCl(Forbes-Cori病)是有用的同双官能交联剂的实例,以及双-[B-(4-叠氮基水杨基氨基)乙基]二硫化物(BASED)和N-琥珀酰亚胺基-6(4'-叠氮基-2'-硝基苯基氨基)己酸酯(SANPAH)是用于本公开内容中的有用的光反应性交联剂的实例。关于蛋白质偶联技术的新近综述,参见通过引用并入本文的Means等人,(1990)Bioconj.Chem.1:2-12。
表2:α-突触核蛋白结合结构域的实例
c.任选的接头
本文所述的融合蛋白可以任选地含有一个或多个接头。接头可以是肽的或非肽的。接头的目的尤其是在蛋白质内的功能结构域之间(例如在J结构域和α-突触核蛋白结合结构域之间、在α-突触核蛋白结合结构域的串联排列之间、在J结构域和α-突触核蛋白结合结构域与任选的靶向试剂之间或者在J结构域和α-突触核蛋白结合结构域与任选的检测结构域或表位之间)提供足够的距离,用于各结构域的最佳功能。显然,接头优选地不干扰根据本发明的融合蛋白的J结构域、靶蛋白结合结构域分别的功能。如果接头存在于本发明的融合蛋白中,则选择其来减弱由靶蛋白(α-突触核蛋白蛋白质)引起的细胞毒性,并且如果直接附着达到所期望的效果,则可以省略接头。存在于本发明的融合蛋白中的接头可以包含一个或多个氨基酸,其由存在于表达载体的克隆位点内或周围的核酸区段上的核苷酸序列编码,所述表达载体内框内插入了编码如本文所述的蛋白质结构域或整个融合蛋白的核酸区段。在一个实施方案中,肽接头的长度在1个氨基酸至20个氨基酸之间。在另一个实施方案中,肽接头的长度在2个氨基酸至15个氨基酸之间。在仍然另一个实施方案中,肽接头的长度在2个氨基酸至10个氨基酸之间。
选择一种或多种多肽接头来产生根据本发明的融合蛋白在本领域从业人员的知识和技术内。参见例如Arai等人,Protein Eng.,14(8):529-532(2001);Crasto等人,Protein Eng.,13(5):309-314(2000);George等人,Protein Eng.,15(11):871-879(2003);Robinson等人,Proc.Natl.Acad.Sci.USA,95:5929-5934(1998),所述参考文献各自通过引用以其整体并入本文。可以用于制备根据本发明的融合蛋白的具有两个或更多个氨基酸的接头的实例包括但不限于下表3中提供的那些。
表3:接头序列
SEQ ID NO: | 长度 | 序列 |
66 | 2 | SR |
67 | 4 | GTGS |
68 | 5 | GLESR |
69 | 4 | GGSG |
70 | 5 | GGGGS |
71 | 5 | DIAAA |
72 | 5 | EAAAK |
73 | 15 | GGGGSGGGGSGGGGS |
74 | 11 | AEAAAKEAAAK |
75 | 15 | SGGGSGGGGSGGGGS |
76 | 25 | DIGGGGSGGGGSGGGGSGGGGSAAA |
d.靶向试剂
本文公开的融合蛋白可以进一步包含靶向部分。如本文使用的,术语“靶向部分”和“靶向试剂”可互换使用,并且是指与融合蛋白相关的物质,其增强融合蛋白在细胞或受试者体内的结合、转运、累积、停留时间、生物利用度或者修饰融合蛋白的生物活性或疗效。靶向部分可以在组织、细胞和/或亚细胞水平上具有功能性。例如,在将融合蛋白施用到受试者内之后,靶向部分可以指导融合蛋白定位到特定细胞、组织或器官,或者细胞内分布。在一个实施方案中,靶向部分定位于融合蛋白的N末端处。在另一个实施方案中,靶向部分定位于融合蛋白的C末端处。在仍然另一个实施方案中,靶向部分在内部定位。在另一个实施方案中,靶向部分经由化学缀合附着至融合蛋白。在进一步的实施方案中,靶向部分可以是用于亚细胞定位的氨基酸序列,例如核定位信号或核输出信号。靶向部分可以包括但不限于有机或无机分子、肽、肽模拟物、蛋白质、抗体或其片段、生长因子、酶、凝集素、抗原或免疫原、病毒或其组分、病毒载体、受体、受体配体、毒素、多核苷酸、寡核苷酸或适体、核苷酸、碳水化合物、糖、脂质、糖脂、核蛋白、糖蛋白、脂蛋白、类固醇、激素、生长因子、化学引诱剂、细胞因子、趋化因子、药物或小分子等等。
在本发明的一个示例性实施方案中,靶向部分增强平台或其相关配体和/或活性剂在靶细胞或组织中的结合、转运、累积、停留时间、生物利用度或者修饰平台或其相关配体和/或活性剂的生物活性或疗效,所述靶细胞或组织例如神经元细胞、中枢神经系统和/或周围神经系统。因此,靶向部分可以对于与中枢神经系统相关的细胞受体具有特异性,或者以其它方式与经由血脑屏障(BBB)向CNS的递送增强相关。因而,如上所述,配体可以既是配体又是靶向部分。
在一些实施方案中,靶向部分可以是细胞穿透肽,例如,如通过引用以其整体并入的美国专利号10,111,965中所述。在另一个实施方案中,靶向部分可以是抗体或者其抗原结合片段或单链衍生物,例如,如通过引用以其整体并入本文的美国序列号16/131,591中所述。靶向部分可以通过与核心直接或间接结合而偶联到用于靶向细胞递送的平台。例如,在其中核心包含纳米颗粒的实施方案中,靶向部分与纳米颗粒的缀合可以利用用于将PEG栓系到纳米颗粒的类似官能团。因此,靶向部分可以通过靶向部分的官能化而与纳米颗粒直接结合。可替代地,如上文讨论的,靶向部分可以通过靶向部分与官能化PEG的缀合而与纳米颗粒间接结合。靶向部分可以通过共价、非共价或静电相互作用附着到核心。在一个实施方案中,靶向部分是肽。在一个特定实施方案中,靶向部分是共价附着到融合蛋白的N末端的肽。
e.表位
在某些实施方案中,本发明的融合蛋白含有任选的表位或标签,其可以赋予融合蛋白另外的特性。如本文使用的,术语“表位”和“标签”可互换使用,以指通常长度为300个氨基酸或更少的氨基酸序列,其通常附着到融合蛋白的N末端或C末端端部。在一个实施方案中,本发明的融合蛋白进一步包含用于促进纯化的表位。下表4中提供的可用于纯化的此类表位的实例包括人IgG1 Fc序列(SEQ ID NO:77)、FLAG表位(DYKDDDDK,SEQ ID NO:78)、His6表位(SEQ ID NO:79)、c-myc(SEQ ID NO:80)、HA(SEQ ID NO:81)、V5表位(SEQ ID NO:82)或谷胱甘肽-s-转移酶(SEQ ID NO:83)。在另一个实施方案中,本发明的融合蛋白进一步包含表位,其在被施用到受试者(例如人)内时被用于增加融合蛋白的半衰期。可用于增加半衰期的此类表位的实例包括人Fc序列。因此,在一个特定实施方案中,除J结构域和α-突触核蛋白结合结构域之外,融合蛋白还包含人Fc表位。表位位于融合蛋白的C末端处。
表4:表位的代表性实例
f.细胞穿透肽
在另外其它实施方案中,本文所述的融合蛋白可以进一步包含细胞穿透肽。已知细胞穿透肽将缀合的货物携带到细胞内,所述缀合的货物无论是小分子、肽、蛋白质还是核酸。本发明的融合蛋白中的细胞穿透肽的非限制性实例包括但不限于:聚阳离子肽,例如HIV TAT肽49-57、聚精氨酸和穿透肽(penetratin)pAntan(43-58);两亲性肽,例如pep-1;疏水肽,例如C405Y;等等。参见下表5。
表5:细胞穿透肽的实例
SEQ ID NO: | 长度 | 序列 |
84 | 9 | RKKRRQRRR |
85 | 15 | RQIKWFQNRRMKWKK |
86 | 21 | KETWWETWWTEWSQPKKKRKV |
87 | 17 | CSIPPEVKFNKPFVYLI |
因此,在一个实施方案中,融合蛋白包含细胞穿透肽和融合蛋白,其中所述细胞穿透肽选自SEQ ID NO:84-87,并且所述融合蛋白选自SEQ ID NO:88、90-96、98-100。在另一个实施方案中,融合蛋白包含SEQ ID NO:84的细胞穿透肽,并且融合蛋白选自SEQ ID NO:88、90-96、98-100。在另一个实施方案中,融合蛋白包含SEQ ID NO:85的细胞穿透肽,并且融合蛋白选自SEQ ID NO:88、90-96、98-100。在仍然另一个实施方案中,融合蛋白包含SEQID NO:86的细胞穿透肽,并且融合蛋白选自SEQ ID NO:88、90-96、98-100。在又另一个实施方案中,融合蛋白包含SEQ ID NO:87的细胞穿透肽,并且融合蛋白选自SEQ ID NO:88、90-96、98-100。可以将表达具有细胞穿透肽的融合蛋白构建体的细胞施用于受试者,例如人受试者(例如患有α-突触核蛋白病症或处于患有α-突触核蛋白病症的风险中的患者)。融合蛋白分泌自所述细胞,其帮助减少含α-突触核蛋白蛋白质的聚集和/或相关的细胞毒性。
g.J结构域和α-突触核蛋白结合结构域的排列
本文所述的融合蛋白可以多种方式进行排列。在一个实施方案中,α-突触核蛋白结合结构域附着到J结构域的C末端侧。在另一个实施方案中,α-突触核蛋白结合结构域附着到J结构域的N末端侧。在任一配置中,α-突触核蛋白结合结构域和J结构域可以任选地经由如上所述的接头分开。
在一些实施方案中,J结构域可以附着到多个α-突触核蛋白结合结构域,例如两个α-突触核蛋白结合结构域、三个α-突触核蛋白结合结构域、四个α-突触核蛋白结合结构域或更多个。α-突触核蛋白结合结构域可以附着到J结构域的N末端侧。可替代地,α-突触核蛋白结合结构域可以附着到J结构域的C末端侧。在仍然另一个实施方案中,α-突触核蛋白结合结构域可以附着到J结构域的N末端和C末端侧上。多个α-突触核蛋白结合结构域中的每一个可以是相同的α-突触核蛋白结合结构域。在另一个实施方案中,融合蛋白中的多个α-突触核蛋白结合结构域中的每一个可以是不同的α-突触核蛋白结合结构域(即不同的序列)。
在一些实施方案中,融合蛋白可以包含选自下组的结构:
a.DNAJ-X-S,
b.DNAJ-X-S-X-S,
c.DNAJ-X-S-X-S-X-S,
d.S-X-DNAJ,
e.S-X-S-X-DNAJ,
f.S-X-S-X-S-X-DNAJ,
g.S-X-DNAJ-X-S,
h.S-X-DNAJ-X-S-X-S,
i.S-X-S-X-DNAJ-X-S-X-S-X-S,
j.S-X-S-X-S-X-DNAJ-X-S,
k.S-X-S-X-S-X-DNAJ-X-S-X-S,
l.S-X-S-X-S-X-DNAJ-X-S-X-S-X-S,
m.DnaJ-X-DnaJ-X-S-X-S,
n.S-X-DnaJ-X-DnaJ,和
o.S-X-S-X-DnaJ-X-DnaJ,
其中,
S是α-突触核蛋白结合结构域,
DNAJ是J蛋白的J结构域,和
X是任选的接头。
在一个实施方案中,融合蛋白包含选自SEQ ID NO:1-15和17-50的J结构域。在另一个实施方案中,融合蛋白包含选自SEQ ID NO:1、5、6、10、16、24、25、31和49的J结构域。在一个特定实施方案中,融合蛋白包含SEQ ID NO:5的J结构域。
在另一个实施方案中,α-突触核蛋白结合结构域选自SEQ ID NO:51-64。在一个特定实施方案中,α-突触核蛋白结合结构域是SEQ ID NO:49。在另一个实施方案中,α-突触核蛋白结合结构域是SEQ ID NO:63。在仍然另一个实施方案中,α-突触核蛋白结合结构域是SEQ ID NO:64。
在仍然另一个实施方案中,融合蛋白包含SEQ ID NO:5的J结构域和SEQ ID NO:51的α-突触核蛋白结合结构域。在另一个实施方案中,融合蛋白包含SEQ ID NO:5的J结构域和SEQ ID NO:51的α-突触核蛋白结合结构域的至少两个拷贝。
包含J结构域和α-突触核蛋白结合结构域的融合蛋白构建体以及对照构建体的非限制性实例在图2中示意性地进行描绘,并且还在下表6中显示。在一个实施方案中,特异性融合蛋白构建体选自SEQ ID NO:88、90-96、98-100。
表6:融合蛋白构建体和对照构建体
II.编码融合蛋白构建体的核酸
根据本发明的另一个方面,提供了分离的核酸,其包含选自以下的多核苷酸序列:(a)编码任何前述实施方案的融合蛋白的多核苷酸,或(b)(a)的多核苷酸的互补体。本发明提供了编码包含J结构域和α-突触核蛋白结合结构域的融合蛋白的分离的核酸,以及与编码融合蛋白的此类核酸分子互补的序列,包括其同源变体。在另一个方面,本发明包括产生以下的方法:编码本文公开的融合蛋白的核酸,以及与编码融合蛋白的核酸分子互补的序列,包括其同源变体。根据本发明的这个方面的核酸可以是前信使RNA(前体mRNA)、信使RNA(mRNA)、RNA、基因组DNA(gDNA)、PCR扩增的DNA、互补DNA(cDNA)、合成DNA或重组DNA。
在又另一个方面,公开的是生产融合蛋白的方法,其包括(a)合成和/或组装编码融合蛋白的核苷酸,(b)将编码基因掺入适合于宿主细胞的表达载体内,(c)用表达载体转化适当的宿主细胞,并且(d)在引起或允许融合蛋白在转化的宿主细胞中表达的条件下培养宿主细胞,从而产生具有生物活性的融合蛋白,其通过本领域已知的标准蛋白质纯化方法作为分离的融合蛋白进行回收。分子生物学中的标准重组技术被用于制备本发明的多核苷酸和表达载体。
按照本发明,编码本文公开的融合蛋白的核酸序列(或其互补体)被用于生成指导融合蛋白在适当的宿主细胞中的表达的重组DNA分子。几种克隆策略适合于执行本发明,其中许多种被用于生成包含编码本发明的融合蛋白的基因或其互补体的构建体。在一些实施方案中,克隆策略被用于产生编码本发明的融合蛋白或其互补体的基因。
在某些实施方案中,编码一种或多种融合蛋白的核酸是RNA分子,并且可以是前信使RNA(前体mRNA)、信使RNA(mRNA)、RNA、基因组DNA(gDNA)、PCR扩增的DNA、互补DNA(cDNA)、合成DNA或重组DNA。在各个实施方案中,核酸是引入细胞内以便瞬时表达所需多肽的mRNA。如本文使用的,“瞬时”是指非整合的转基因表达数小时、数天或数周的时间段,其中所述表达的时间段小于多核苷酸在被整合到基因组内或包含在细胞中的稳定的质粒复制子内时的表达时间段。
在特定实施方案中,编码多肽的mRNA是体外转录的mRNA。如本文使用的,“体外转录的RNA”是指RNA,优选已体外合成的mRNA。一般地,体外转录的RNA由体外转录载体生成的。体外转录载体包含被用于生成体外转录的RNA的模板。在特定实施方案中,mRNA可以进一步包含5'帽或修饰的5'帽和/或多聚(A)序列。如本文使用的,5'帽(也被称为RNA帽、RNA7-甲基鸟苷帽或RNA m7G帽)是在转录起始后不久已被加至真核信使RNA的“前端”或5'端的修饰的鸟嘌呤核苷酸。5'帽包含末端基团,其连接到第一个转录的核苷酸,并且被核糖体识别并被保护免受RNA酶。可以修饰加帽部分以调节mRNA的功能性,例如其稳定性或翻译效率。在特定实施方案中,mRNA包含介于约50至约5000个腺嘌呤的多聚(A)序列。在一个实施方案中,mRNA包含介于约100至约1000个碱基、介于约200至约500个碱基或介于约300至约400个碱基的多聚(A)序列。在一个实施方案中,mRNA包含约65个碱基、约100个碱基、约200个碱基、约300个碱基、约400个碱基、约500个碱基、约600个碱基、约700个碱基、约800个碱基、约900个碱基或者约1000个或更多个碱基的多聚(A)序列。多聚(A)序列可以化学地或酶促地进行修饰,以调节mRNA功能性,例如定位、稳定性或翻译效率。如本文使用的,术语“多核苷酸变体”和“变体”等等是指展示出与参考多核苷酸序列的基本序列同一性的多核苷酸或者在下文定义的严格条件下与参考序列杂交的多核苷酸。这些术语包括这样的多核苷酸,其中与参考多核苷酸相比,一个或多个核苷酸已被添加或缺失或替换为不同的核苷酸。在这方面,本领域众所周知的是,可以对参考多核苷酸进行某些改变,包括突变、添加、缺失和取代,由此,改变的多核苷酸保留参考多核苷酸的生物学功能或活性。
在某些实施方案中,核酸序列包含编码核酸盒内的目的基因(例如包含J结构域和聚谷氨酰胺结合结构域的融合蛋白)的核苷酸序列。如本文使用的,术语“核酸盒”或“表达盒”是指载体内的遗传序列,其可以表达RNA,且随后表达多肽。在一个实施方案中,核酸盒含有一个或多个目的基因,例如一个或多个目的多核苷酸。在另一个实施方案中,核酸盒含有一种或多种表达控制序列,例如启动子、增强子、多聚(A)序列和一个或多个目的基因(例如一个或多个目的多核苷酸)。载体可以包含1、2、3、4、5、6、7、8、9或10个或更多个核酸盒。核酸盒在载体内按位置且序贯地进行定向,使得盒中的核酸可以转录成RNA,并且在必要时,翻译成蛋白质或多肽,在转化细胞中经历活性所需的适当的翻译后修饰,并且通过靶向适当的细胞内区室或分泌到细胞外区室内而易位到适当的区室用于生物活性。优选地,盒具有适于准备好插入载体内的其3'和5'端,例如,它在每一端处具有限制性核酸内切酶位点。盒可以作为单一单元被取出和插入质粒或病毒载体内。
适用于特定实施方案中的说明性遍在表达控制序列包括但不限于巨细胞病毒(CMV)立即早期启动子,病毒猿猴病毒40(SV40)(例如早期或晚期),莫洛尼鼠白血病病毒(MoMLV)LTR启动子,劳氏肉瘤病毒(RSV)LTR,单纯疱疹病毒(HSV)(胸苷激酶)启动子,来自牛痘病毒的H5、P7.5和Pl l启动子,延伸因子1-α(EFla)启动子,早期生长应答1(EGR1),铁蛋白H(FerH),铁蛋白L(FerL),3-磷酸甘油醛脱氢酶(GAPDH),真核翻译起始因子4A1(EIF4A1),热休克70kDa蛋白5(HSPA5),热休克蛋白90kDaβ成员1(HSP90B1),热休克蛋白70kDa(HSP70),β-驱动蛋白(b-KIN),人ROSA 26基因座(Irions等人,NatureBiotechnology 25,1477-1482(2007)),泛素C启动子(UBC),磷酸甘油酸激酶-1(PGK)启动子,巨细胞病毒增强子/鸡β-肌动蛋白(CAG)启动子(Okabe等人(1997)FEBS let.407:313-9),b-肌动蛋白启动子和骨髓增生性肉瘤病毒增强子(负控制区缺失),dl587rev引物结合位点取代的(MND)U3启动子(Haas等人,Journal of Virology.2003;77(l7):9439-9450)。在一个实施方案中,至少一种元件可以与本文所述的多核苷酸一起使用,以增强转基因靶特异性和表达(参见例如Powell等人(2015)Discovery Medicine 19(102):49-57,其内容通过引用以其整体并入本文),例如启动子。在大多数组织中促进表达的启动子包括但不限于人延伸因子la-亚基(EFla)、立即早期巨细胞病毒(CMV)、鸡β-肌动蛋白(CBA)及其衍生物CAG、β葡糖醛酸酶(GUSB)或泛素C(UBC)。组织特异性表达元件可以被用于限制对某些细胞类型的表达,例如但不限于神经系统启动子,其可以被用于限制对神经元、星形胶质细胞或少突胶质细胞的表达。用于神经元的组织特异性表达元件的非限制性实例包括神经元特异性烯醇化酶(NSE)、血小板衍生生长因子(PDGF)、血小板衍生生长因子B链(PDGF-β)、突触蛋白(Syn)、甲基-CpG结合蛋白2(MeCP2)、CaMKII、mGluR2、NFL、NFH、ηβ2、PPE、Enk和EAAT2启动子。用于星形胶质细胞的组织特异性表达元件的非限制性实例包括胶质纤维酸性蛋白(GFAP)和EAAT2启动子。用于少突胶质细胞的组织特异性表达元件的非限制性实例包括髓鞘碱性蛋白(MBP)启动子。Yu等人(2011,Molecular Pain,7:63,通过引用以其整体并入)使用慢病毒载体评估在大鼠DRG细胞和原代DRG细胞中处于CAG、EFIa、PGK和UBC启动子下的eGFP表达,并且发现了UBC显示比其它3种启动子更弱的表达,并且存在对于所有启动子可见的仅10-12%的神经胶质细胞表达。Soderblom等人(E.Neuro 2015,通过引用以其整体并入)在运动皮层中注射后,在具有CMV和UBC启动子的AAV8以及具有CMV启动子的AAV2中的eGFP表达。含有UBC或EFIa启动子的质粒的鼻内施用显示了比具有CMV启动子的表达更大的持续气道表达(参见例如Gill等人,(2001)Gene Therapy,第8卷,1539-1546;通过引用以其整体并入)。Husain等人(2009,Gene Therapy,通过引用以其整体并入)评估了具有hGUSB启动子、HSV-1LAT启动子和NSE启动子的HβH构建体,并且发现了在小鼠脑中HβH构建体显示比NSE更弱的表达。Passini和Wolfe(J.Virol.2001,12382-12392,通过引用以其整体并入)评估了HβH载体在新生小鼠中脑室内注射之后的长期效应,并且发现了存在至少1年的持续表达。通过Xu等人(2001,Gene Therapy,8,1323-1332;通过引用以其整体并入)发现了,在使用NF-L和NF-H启动子时,与CMV-lacZ、CMV-luc、EF、GFAP、hENK、nAChR、PPE、PPE+wpre、NSE(0.3kb)、NSE(1.8kb)和NSE(1.8kb+wpre)相比,在所有脑区域中的表达低。Xu等人发现了启动子活性按降序为NSE(1.8kb)、EF、NSE(0.3kb)、GFAP、CMV、hENK、PPE、NFL和NFH。NFL是650个核苷酸的启动子,而NFH是920个核苷酸的启动子,这两者均不存在于肝中,但NFH在感觉本体感受神经元、脑和脊髓中是丰富的,而NFH存在于心脏中。Scn8a是470个核苷酸的启动子,其在DRG、脊髓和脑各处表达,其中在海马神经元和小脑浦肯野细胞、皮质、丘脑和下丘脑中可见特别高的表达(参见例如Drews等人2007和Raymond等人2004;通过引用以其整体并入)。
III.包含编码融合蛋白的核酸的载体
还提供了包含根据本发明的核酸的载体。此类载体优选包含另外的核酸序列,例如编码磷酸酶的核酸序列转录/翻译所必需的元件(例如启动子和/或终止子序列)。所述载体还可以包含编码选择标记物(例如抗生素)的核酸序列,以选择或维持用所述载体转化的宿主细胞。术语“载体”在本文中被用于指能够转移或转运另一种核酸分子的核酸分子。转移的核酸一般与载体核酸分子连接,例如插入到其内。载体可以包括指导细胞中的自主复制的序列,或可以包括足以允许整合到宿主细胞DNA内的序列。在特定实施方案中,非病毒载体被用于将本文考虑的一种或多种多核苷酸递送至受影响的细胞(例如神经元细胞)。在一个实施方案中,载体是编码融合蛋白的体外合成或合成制备的mRNA,所述融合蛋白包含J结构域和α-突触核蛋白结合结构域。非病毒载体的说明性实例包括但不限于mRNA、质粒(例如DNA质粒或RNA质粒)、转座子、粘粒和细菌人工染色体。
载体的说明性实例包括但不限于质粒、自主复制序列和转座元件,例如piggyBac、睡美人、Mosl、Tcl/水手(mariner)、Tol2、mini-Tol2、Tc3、MuA、Himar I、青蛙王子(FrogPrince)及其衍生物。载体的另外的说明性实例包括但不限于质粒,噬菌粒,粘粒,诸如酵母人工染色体(YAC)、细菌人工染色体(BAC)或Pl衍生的人工染色体(PAC)等人工染色体,诸如λ噬菌体或M13噬菌体等细菌噬菌体,和动物病毒。可用作载体的病毒的说明性实例包括但不限于逆转录病毒(包括慢病毒)、腺病毒、腺相关病毒、疱疹病毒(例如单纯疱疹病毒)、痘病毒、杆状病毒、乳头状瘤病毒和乳多空病毒(例如SV40)。表达载体的说明性实例包括但不限于用于在哺乳动物细胞中表达的pClneo载体(Promega);用于哺乳动物细胞中慢病毒介导的基因转移和表达的pLenti4/V 5-DESTTM、pLenti6/V 5-DESTTM和pLenti6.2/V 5-GW/lacZ(Invitrogen)。在特定实施方案中,本文公开的多肽的编码序列可以连接到此类表达载体内,用于在哺乳动物细胞中表达多肽。
在特定实施方案中,载体是游离型载体或染色体外维持的载体。如本文使用的,术语“游离型”是指能够在不整合到宿主的染色体DNA内的情况下复制且不从分裂的宿主细胞中逐渐丢失的载体,其也意味着所述载体在染色体外或游离型地复制。
载体可以包含用于各种各样的位点特异性重组酶中任一种的一个或多个重组位点。应理解,位点特异性重组酶的靶位点是除载体整合所需的任何位点之外的,所述载体例如逆转录病毒载体或慢病毒载体。如本文使用的,术语“重组序列”、“重组位点”或“位点特异性重组位点”是指重组酶识别且与之结合的特定核酸序列。
例如,关于Cre重组酶的一个重组位点是loxP,其是包含侧接8个碱基对的核心序列的两个13个碱基对的反向重复(充当重组酶结合位点)的34个碱基对的序列(参见Sauer,B.,Current Opinion in Biotechnology 5:521-527(1994)的图1)。FLP重组酶的合适的识别位点包括但不限于:FRT(McLeod等人,1996),FI、F2、F3(Schlake和Bode,1994),FyFs(Schlake和Bode,1994),FRT(LE)(Senecoff等人,1988),FRT(RE)(Senecoff等人,1988)。
识别序列的其它实例是attB、attP、attL和attR序列,其被重组酶l整合酶(例如phi-c3l)识别。pC3l SSR仅介导异型位点attB(长度为34bp)和attP(长度为39bp)之间的重组(Groth等人,2000)。为噬菌体整合酶分别在细菌和噬菌体基因组上的附着位点命名的attB和attP两者都含有很可能被同二聚体结合的不完全的反向重复(Groth等人,2000)。产物位点attL和attR对进一步的tpQA 1介导的重组是有效惰性的(Belteki等人,2003),使得反应不可逆。对于催化插入,已发现将携带attB的DNA插入基因组attP位点内比将attP位点插入基因组attB位点内更容易(Thyagarajan等人,2001;Belteki等人,2003)。因此,典型的策略通过同源重组将携带attP的“对接位点”定位到所限定的基因座内,其然后与携带attB的进入序列配对用于插入。
如本文使用的,“内部核糖体进入位点”或“IRES”是指这样的元件,其促进直接内部核糖体进入顺反子(蛋白质编码区)的起始密码子,例如ATG,从而导致基因的帽不依赖性翻译。参见例如,Jackson等人,1990.Trends Biochem Sci 15(12):477-83)以及Jackson和Kaminski.1995.RNA 1(10):985-1000。在特定实施方案中,载体包括编码一种或多种多肽的一种或多种目的多核苷酸。在特定实施方案中,为了实现多种多肽各自的有效翻译,所述多核苷酸序列可以被一个或多个IRES序列或编码自切割多肽的多核苷酸序列分开。在一个实施方案中,在本文考虑的多核苷酸中使用的IRES是EMCV IRES。
如本文使用的,术语“Kozak序列”是指一种短核苷酸序列,其极大地促进了mRNA与核糖体的小亚基的初始结合并增加了翻译。(Kozak,1986.Cell.44(2):283-92和Kozak,1987.Nucleic Acids Res.15(20):8125-48)。在特定实施方案中,载体包含具有共有Kozak序列并且编码包含J结构域和α-突触核蛋白结合结构域的融合蛋白的多核苷酸。指导异源核酸转录本的有效终止和多聚腺苷酸化的元件增加了异源基因表达。转录终止信号一般在多聚腺苷酸化信号的下游发现。在特定实施方案中,载体包含编码待表达多肽的多核苷酸3'的多聚腺苷酸化序列。
适用于本文考虑的特定实施方案中的病毒载体系统的说明性实例包括但不限于腺相关病毒(AAV)、逆转录病毒、单纯疱疹病毒、腺病毒和牛痘病毒载体。
在各个实施方案中,通过用包含一种或多种多核苷酸的重组腺相关病毒(rAAV)转导细胞,将编码包含J结构域和聚谷氨酰胺结合结构域的融合蛋白的一种或多种多核苷酸引入细胞,例如神经元细胞内。AAV是小型(~26nm)复制缺陷型的、主要是游离型的无包膜病毒。AAV可以感染分裂细胞和非分裂细胞两者,并且可以将其基因组掺入宿主细胞的基因组内。重组AAV(rAAV)通常最低限度由转基因及其调控序列以及5'和3'AAV反向末端重复(ITR)构成。ITR序列的长度为约145bp。在特定实施方案中,rAAV包含从以下中分离的ITR和衣壳序列:AAV1、AAV2(例如在通过引用以其整体并入本文的US6962815B2中进行描述)、AAV3、AAV4、AAV5(例如在通过引用以其整体并入本文的US7479554B2中进行描述)、AAV6、AAV7、AAV8(例如在通过引用以其整体并入本文的US7282199B2中进行描述)、AAV9(例如在通过引用以其整体并入本文的US9737618B2中进行描述)、AAV rh10(例如在通过引用以其整体并入本文的US9790472B2中进行描述)或AAV10。在一个实施方案中,本发明的载体被封装在选自AAV2、AAV5、AAV8、AAV9和AAV rh10的衣壳内。在一个实施方案中,载体被封装在AAV2中。在一个实施方案中,载体被封装在AAV5中。在一个实施方案中,载体被封装在AAV8中。在一个实施方案中,载体被封装在AAV9中。在仍然另一个实施方案中,载体被封装在AAVrh10中。
在一些实施方案中,使用嵌合rAAV,ITR序列分离自一种AAV血清型,而衣壳序列分离自不同的AAV血清型。例如,具有衍生自AAV2的ITR序列和衍生自AAV6的衣壳序列的rAAV被称为AAV2/AAV6。在特定实施方案中,rAAV载体可以包含来自AAV2的ITR,以及来自AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9或AAV10中任何一种的衣壳蛋白。在优选实施方案中,rAAV包含衍生自AAV2的ITR序列和衍生自AAV6的衣壳序列。在优选实施方案中,rAAV包含衍生自AAV2的ITR序列和衍生自AAV2的衣壳序列。
在一些实施方案中,改造和选择方法可以被应用于AAV衣壳,以使其更有可能转导目的细胞。
rAAV载体的构建、生产及其纯化已公开于例如美国专利号9,169,494;9,169,492;9,012,224;8,889,641;8,809,058;和8,784,799中,所述专利的每一个均通过引用以其整体并入本文。
IV.递送
在特定实施方案中,编码包含J结构域和α-突触核蛋白结合结构域的融合蛋白的一种或多种多核苷酸通过非病毒载体或病毒载体被引入细胞内。在特定实施方案中考虑的多核苷酸的非病毒递送的示例性方法包括但不限于:电穿孔、声致穿孔、脂质转染、显微注射、生物弹道、病毒体、脂质体、免疫脂质体、纳米颗粒、聚阳离子或脂质核酸缀合物、裸露DNA、人工病毒粒子、DEAE-葡聚糖介导的转移、基因枪和热休克。
在特定实施方案中考虑的适用于特定实施方案中的多核苷酸递送系统的说明性实例包括但不限于由Amaxa Biosystems、Maxcyte,Inc.、BTX Molecular DeliverySystems和Copernicus Therapeutics Inc提供的那些。脂质转染试剂是商业销售的(例如TransfectamTM和LipofectinTM)。适合于多核苷酸的有效受体识别脂质转染的阳离子脂质和中性脂质已在文献中进行描述。参见例如Liu等人,(2003)Gene Therapy.10:180-187;和Balazs等人,(20W)Journal of Drug Delivery.2011:1-12。在特定实施方案中也考虑了抗体靶向的、细菌衍生的、基于无生命纳米细胞的递送。
在特定实施方案中考虑的包含多核苷酸的病毒载体可以通过施用于个别患者来进行体内递送,通常通过全身施用(例如静脉内、腹膜内、肌内、皮下或颅内输注),通过鞘内注射、脑室内注射或局部应用,如下所述。可替代地,载体可以被递送至离体细胞,例如从个别患者外植的细胞(例如动员的外周血、淋巴细胞、骨髓抽吸物、组织活组织检查等)或通用供体造血干细胞,随后为将细胞重新植入患者内。
在一个实施方案中,将包含编码本文公开的融合蛋白的多核苷酸的病毒载体被直接施用于生物用于体内细胞转导。
适当地进行包装和配制的病毒载体可以经由鞘内递送而被递送到中枢神经系统(CNS)内。例如,腺相关病毒载体可以使用美国序列号15/771,481中描述的方法进行递送,所述专利通过引用以其整体并入本文。
可替代地,可以施用裸露DNA。施用是通过通常被用于将分子引入与血液或组织细胞的最终接触的任何途径,包括但不限于注射、输注、局部应用和电穿孔。施用此类核酸的合适方法对本领域技术人员是可用且众所周知的,并且尽管可以使用多于一种途径来施用特定组合物,但特定途径经常可以提供比另一种途径更直接和更有效的反应。
在各个实施方案中,通过用包含一种或多种多核苷酸的逆转录病毒(例如慢病毒)转导细胞,将编码本文公开的融合蛋白的一种或多种多核苷酸引入细胞内,例如神经元细胞或神经元干细胞内。如本文使用的,术语“逆转录病毒”是指这样的RNA病毒,其将其基因组RNA逆转录成线性双链DNA拷贝,并且随后将其基因组DNA共价整合到宿主基因组内。适用于特定实施方案中的说明性逆转录病毒包括但不限于:莫洛尼鼠白血病病毒(M-MuLV)、莫洛尼鼠肉瘤病毒(MoMSV)、哈维鼠肉瘤病毒(HaMuSV)、鼠乳腺肿瘤病毒(MuMTV)、长臂猿白血病病毒(GaLV)、猫白血病病毒(FLV)、泡沫病毒、Friend鼠白血病病毒、鼠干细胞病毒(MSCV)和劳氏肉瘤病毒(RSV))和慢病毒。如本文使用的,术语“慢病毒”是指一组(或属)复杂逆转录病毒。示例性慢病毒包括但不限于:HIV(人免疫缺陷病毒;包括HIV 1型和HIV 2);维斯纳梅迪病毒(visna-maedi virus)(VMV)病毒;山羊关节炎脑炎病毒(CAEV);马传染性贫血病毒(EIAV);猫免疫缺陷病毒(FIV);牛免疫缺陷病毒(BIV);和猿猴免疫缺陷病毒(SIV)。在一个实施方案中,基于HIV的载体主链(即HIV顺式作用序列元件)是优选的。
作为修饰LTR的结果,慢病毒载体优选含有几种安全性增强。“自我失活”(SIN)载体是指复制缺陷型载体,例如,其中被称为U3区的右(3')LTR增强子-启动子区已(例如通过缺失或取代)进行修饰,以防止病毒转录超出第一轮病毒复制。通过用异源启动子替换5'LTR的U3区来在病毒颗粒的生产过程中驱动病毒基因组的转录,提供了另外的安全性增强。可以使用的异源启动子的实例包括例如病毒性猿猴病毒40(SV40)(例如早期或晚期)、巨细胞病毒(CMV)(例如立即早期)、莫洛尼鼠白血病病毒(MoMLV)、劳氏肉瘤病毒(RSV)和单纯疱疹病毒(HSV)(胸苷激酶)启动子。在某些实施方案中,根据已知方法产生慢病毒载体。参见例如Kutner等人,BMC Biotechnol.2009;9:10.Doi:10.1186/1472-6750-9-10;Kutner等人,Nat.Protoc.2009;4(4):495-505.Doi:l0.l038/nprot.2009.22。
根据本文考虑的某些特定实施方案,大部分或所有病毒载体主链序列衍生自慢病毒,例如HIV-1。然而,应理解,可以使用或组合许多不同来源的逆转录病毒和/或慢病毒序列,并且可以容许某些慢病毒序列中的众多取代和改变,而不损害转移载体执行本文所述功能的能力。此外,各种慢病毒载体是本领域已知的,参见Naldini等人,(l996a、l996b和1998);Zufferey等人,(1997);Dull等人,1998,美国专利号6,013,516;和5,994,136,其中许多可适于生产本文考虑的病毒载体或转移质粒。
在各个实施方案中,通过用包含一种或多种多核苷酸的腺病毒转导细胞,将编码本文公开的融合蛋白的一种或多种多核苷酸引入靶细胞内。基于腺病毒的载体能够在许多细胞类型中具有非常高的转导效率,并且不需要细胞分裂。使用此类载体,已获得了高滴度和高表达水平。这种载体可以在相对简单的系统中以大数量进行生产。大多数腺病毒载体被改造,以使得转基因替换Ad Ela、E1b和/或E3基因;随后,复制缺陷型载体在反式供应缺失的基因功能的人293细胞中进行繁殖。Ad载体可以在体内转导多重类型的组织,包括非分裂的分化细胞,例如在肝、肾和肌肉中发现的那些细胞。常规Ad载体具有大的携带容量。
复制缺陷型的目前的腺病毒载体的生成和繁殖可以利用被定名为293的独特的辅助细胞系,其通过Ad5 DNA片段转化自人胚肾细胞,并且组成地表达El蛋白(Graham等人,1977)。由于E3区域在腺病毒基因组中是可有可无的(Jones&Shenk,1978),因此目前的腺病毒载体在293细胞的帮助下在E1、D3或这两个区域中携带外来DNA(Graham&Prevec,1991)。腺病毒载体已被用于真核基因表达(Levrero等人,1991;Gomez-Foix等人,1992)和疫苗开发(Grunhaus&Horwitz,1992;Graham&Prevec,1992)中。将重组腺病毒施用于不同组织的研究包括气管滴注(Rosenfeld等人,1991;Rosenfeld等人,1992)、肌肉注射(Ragot等人,1993)、外周静脉内注射(Herz&Gerard,1993)和进入脑内的立体定向接种(Le Gal LaSalle等人,1993)。在临床试验中使用Ad载体的实例涉及通过肌内注射用于抗肿瘤免疫的多核苷酸疗法(Sterman等人,Hum.Gene Ther.7:1083-9(1998))。
在各个实施方案中,通过用包含一种或多种多核苷酸的单纯疱疹病毒(例如HSV-1、HSV-2)转导细胞,将编码本发明的融合蛋白的一种或多种多核苷酸引入受试者的靶细胞内。
成熟的HSV病毒粒子由具有病毒基因组的有包膜的二十面体衣壳组成,所述病毒基因组由152kb的线性双链DNA分子组成。在一个实施方案中,基于HSV的病毒载体缺乏一种或多种必需或非必需的HSV基因。在一个实施方案中,基于HSV的病毒载体是复制缺陷型的。大多数复制缺陷型HSV载体含有缺失,以去除一种或多种立即早期、早期或晚期HSV基因,以防止复制。例如,HSV载体可能缺乏选自以下的立即早期基因:ICP4、ICP22、ICP27、ICP47及其组合。HSV载体的优点在于其进入可以导致长期DNA表达的潜伏阶段的能力,以及可以容纳至高25kb的外源DNA插入的其大型病毒DNA基因组。基于HSV的载体在例如美国专利号5,837,532、5,846,782和5,804,413以及国际专利申请WO 91/02788、WO 96/04394、WO 98/15637和WO 99/06583中进行描述,所述内容的每一个均通过引用以其整体并入本文。
V.表达融合蛋白的细胞
在又另一个方面,本发明提供了表达本文所述的融合蛋白的细胞。可以用编码如本文上文所述的融合蛋白的载体来转染细胞。在一个实施方案中,细胞是原核细胞。在另一个实施方案中,细胞是真核细胞。在仍然另一个实施方案中,细胞是哺乳动物细胞。在特定实施方案中,细胞是人细胞。在另一个实施方案中,细胞是衍生自患者的人细胞,所述患者患有α-突触核蛋白介导的病症或处于患有其的风险中,所述病症包括但不限于ALS、FTD和阿尔茨海默氏病。细胞可以是神经元细胞或肌细胞。
表达融合蛋白的细胞可以用于生产融合蛋白。在该实施方案中,细胞用过表达融合蛋白的载体进行转染。融合蛋白可以任选地含有表位,例如人Fc结构域或FLAG表位,如本文上文所述的,其将会促进纯化(分别使用蛋白A或抗FLAG抗体柱)。表位可以经由接头或蛋白酶底物序列连接到融合蛋白的剩余部分,使得在纯化期间或之后,表位可以从融合蛋白中去除。
表达融合蛋白的细胞也可以用于治疗背景下。在一个实施方案中,从需要治疗的患者(例如患有α-突触核蛋白介导的病症或处于患有其的风险中的患者)中收集细胞。在一个实施方案中,细胞是神经元细胞。然后用表达融合蛋白的载体转染收集的细胞。然后可以加工被转染的细胞以富集或选择被转染的细胞。被转染的细胞也可以进行处理,以分化成不同类型的细胞,例如神经元细胞。在加工后,可以将被转染的细胞施用于患者。在一个实施方案中,通过经由鞘内注射、颅内注射或脑室内注射以直接注射到中枢神经系统内来施用细胞。
在替代的实施方案中,可以使用表达融合蛋白的分泌形式的细胞。例如,融合蛋白构建体可以被设计为在N末端端部上具有信号序列。代表性信号序列显示于下表7中。
表7:代表性信号序列
SEQ ID NO: | 长度 | 序列 |
102 | 17 | MGVKVLFALICIAVAEA |
103 | 19 | MAPVQLLGLLVLFLPAMRC |
104 | 19 | MAVLGLLFCLVTFPSCVLS |
因此,在一个实施方案中,融合蛋白包含信号序列和融合蛋白,其中所述信号序列选自SEQ ID NO:102-104,并且所述融合蛋白选自SEQ ID NO:88、90-96、98-100。在另一个实施方案中,融合蛋白包含SEQ ID NO:102的信号序列,并且融合蛋白选自SEQ ID NO:88、90-96、98-100。在另一个实施方案中,融合蛋白包含SEQ ID NO:103的信号序列,并且融合蛋白选自SEQ ID NO:88、90-96、98-100。在另一个实施方案中,融合蛋白包含SEQ ID NO:104的信号序列,并且融合蛋白选自SEQ ID NO:88、90-96、98-100。可以将表达具有信号序列的融合蛋白构建体的细胞施用于受试者,例如人受试者(例如患有α-突触核蛋白病症或处于患有其的风险中的患者)。融合蛋白分泌自所述细胞,其帮助减少α-突触核蛋白蛋白质的聚集和/或相关的细胞毒性。
如本文上文所述,在某些实施方案中,融合蛋白可以进一步包含细胞穿透肽。表达包含信号序列和细胞穿透肽的融合蛋白的细胞将会能够分泌缺乏信号序列的融合蛋白。然后,也包含细胞穿透肽的分泌的融合蛋白将会能够进入附近的细胞,并且具有减少这些细胞中由α-突触核蛋白蛋白质介导的聚集和/或细胞毒性的潜力。
VI.使用方法
在另一个方面,本发明提供了用于在病症和/或α-突触核蛋白病症、由α-突触核蛋白聚集介导的病症或状况中实现有益效应的方法。α-突触核蛋白病症选自肌萎缩侧索硬化(ALS)、额颞叶痴呆(FTD)、帕金森症、亨廷顿氏病、阿尔茨海默氏病、海马硬化和路易体痴呆。
在一些实施方案中,本发明提供了用于治疗患有α-突触核蛋白疾病、病症或状况的受试者(例如人)的方法,其包括以下步骤:向受试者施用治疗或预防有效量的融合蛋白、编码此类融合蛋白的核酸或编码本文所述的融合蛋白的病毒载体,其中所述施用导致与α-突触核蛋白疾病、病症或状况相关的一种或多种生物化学或生理参数或临床终点的改善。
在其它实施方案中,本发明提供了减少细胞中的α-突触核蛋白聚集的方法。细胞可以是培养的细胞或分离的细胞。细胞也可以来自受试者,例如人受试者。在一个实施方案中,细胞在人受试者的中枢神经系统中。在另一个实施方案中,人受试者患有α-突触核蛋白病症疾病或处于患有其的风险中,所述疾病包括但不限于肌萎缩侧索硬化(ALS)、额颞叶痴呆(FTD)和阿尔茨海默氏病。在一个特定实施方案中,α-突触核蛋白病症是肌萎缩侧索硬化。
可以以多种方式来检测α-突触核蛋白的聚集。在一个实例中,聚集的α-突触核蛋白蛋白质可以在用特异性识别α-突触核蛋白构象的抗体的ELISA中进行检测。α-突触核蛋白蛋白质聚集的减少也可以直接在细胞中进行检测,例如使用伴随检测α-突触核蛋白蛋白质的标记试剂的免疫荧光显微镜检查(参见例如Ding等人,(2015)Oncotarget,6:24178-24191;Chou等人,(2015)Hum.Mol.Genet.24:5154-5173和实施例1)。在某些实施方案中,当与对照相比时,α-突触核蛋白多肽水平的更大减少指示了更高的效力。
因此,在一个实施方案中,该方法包括使细胞与一定量的融合蛋白或者编码融合蛋白的核酸、载体或病毒颗粒接触,当与未处理的细胞或对照细胞相比时,所述量使α-突触核蛋白蛋白质的聚集有效减少至少10%,例如至少15%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少75%、至少80%、至少90%、至少95%、至少98%、至少99%。
如下文实施例中1所示,已发现了包含J结构域和α-突触核蛋白结合结构域的融合蛋白的表达减少含有α-突触核蛋白的报告基因构建体的总体水平。因此,在另一个实施方案中,该方法包括使细胞与一定量的融合蛋白,表达融合蛋白的细胞,编码融合蛋白的核酸、载体或病毒颗粒接触,当与未处理的细胞或对照细胞相比时,所述量使α-突触核蛋白蛋白质的水平有效减少至少10%,例如至少15%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少75%、至少80%、至少90%、至少95%、至少98%、至少99%。
VII.药物组合物
本文考虑的组合物可以包括包含J结构域和α-突触核蛋白结合结构域的一种或多种融合蛋白、编码此类融合蛋白的多核苷酸、包含其的载体、遗传修饰的细胞等,如本文考虑的。组合物包括但不限于药物组合物。“药物组合物”是指在药学上可接受或生理学上可接受的溶液中配制的组合物,用于单独地或者与一种或多种其它治疗方式组合地施用于细胞或动物。还应理解,需要时,组合物也可以与其它药剂组合进行施用,所述其它药剂例如细胞因子、生长因子、激素、小分子、化学治疗剂、前药、药物、抗体或其它各种药物活性剂。对于还可以包括在组合物中的其它组分实际上没有限制,条件是该另外的药剂并不不利地影响组合物递送预期疗法的能力。短语“药学上可接受的”在本文中用于指这样的化合物、材料、组合物、载体和/或剂型,其在合理医学判断的范围内,适用于与人体和动物的组织接触,而无过度毒性、刺激、过敏反应或其它问题或并发症,与合理的收益/风险比相称。如本文使用的,“药学上可接受的载剂”、“稀释剂”或“赋形剂”包括但不限于已被美国食品和药物管理局(United States Food and Drug Administration)批准为可接受用于人或驯养动物的任何佐剂、载剂、赋形剂、助流剂、甜味剂、稀释剂、防腐剂、染料/着色剂、增味剂、表面活性剂、润湿剂、分散剂、助悬剂、稳定剂、等渗剂、溶剂、表面活性剂或乳化剂。示例性的药学上可接受的载剂包括但不限于:糖,例如乳糖、葡萄糖和蔗糖;淀粉,例如玉米淀粉和马铃薯淀粉;纤维素及其衍生物,例如羧甲基纤维素钠、乙基纤维素、乙酸纤维素;黄蓍胶;麦芽;明胶;滑石;可可脂、蜡、动物脂肪和植物脂肪、石蜡、硅酮、膨润土、硅酸、氧化锌;油,例如花生油、棉籽油、红花油、芝麻油、橄榄油、玉米油和大豆油;二醇,例如丙二醇;多元醇,例如甘油、山梨糖醇、甘露糖醇和聚乙二醇;酯,例如油酸乙酯和月桂酸乙酯;琼脂;缓冲剂,例如氢氧化镁和氢氧化铝;海藻酸;无热原水;等渗盐水;林格氏溶液;乙醇;磷酸盐缓冲溶液;以及药物制剂中采用的任何其它相容物质。
VIII.剂量
本文所述的组合物(例如包括融合蛋白构建体、核酸或基因治疗病毒颗粒的组合物)的剂量可以取决于多种因素而变化,所述因素例如化合物的药效学特性;施用模式;接受者的年龄、健康和重量;症状的性质和程度;治疗的频率和同期治疗(如果存在的话)的类型;以及化合物在待治疗动物中的清除率。本文所述的组合物最初可以以合适的剂量进行施用,所述剂量可以取决于临床应答根据需要进行调整。在一些方面,组合物的剂量是预防有效量或治疗有效量。
IX.试剂盒
考虑了包括以下的试剂盒:(a)本文所述的包括融合蛋白构建体、编码此类融合蛋白的核酸或包含此类核酸的病毒颗粒的药物组合物,其减少细胞或受试者中的α-突触核蛋白蛋白质的聚集,和(b)具有执行本文描述的任何方法的说明书的包装插页。在一些方面,试剂盒包括(a)本文所述的包含本文描述的组合物的药物组合物,其减少细胞或受试者中的α-突触核蛋白蛋白质的聚集,(b)另外的治疗剂,以及(c)具有执行本文描述的任何方法的说明书的包装插页。
实施例
为了测试是否可以特别地改造J结构域以促进聚集蛋白的正确折叠,我们设计并测试了被设计为靶向α-突触核蛋白蛋白质的许多融合蛋白构建体。
实施例1:融合蛋白设计
A.方法
一般技术和材料
除非另有说明,否则本发明的实践采用免疫学、生物化学、化学、分子生物学、微生物学、细胞生物学、基因组学和重组DNA的常规技术,其在本领域的技术内。参见Sambrook,J.等人,“Molecular Cloning:A Laboratory Manual,”第3版,Cold Spring HarborLaboratory Press,2001;“Current protocols in molecular biology”,F.M.Ausubel等人,编辑,1987;系列“Methods in Enzymology,”Academic Press,San Diego,Calif.;“PCR2:a practical approach”,M.J.MacPherson,B.D.Hames和G.R.Taylor编辑,OxfordUniversity Press,1995;“Antibodies,a laboratory manual”Harlow,E.和Lane,D.编辑,Cold Spring Harbor Laboratory,1988;“Goodman&Gilman’s The PharmacologicalBasis of Therapeutics,”第11版,McGraw-Hill,2005;以及Freshney,R.I.,“Culture ofAnimal Cells:A Manual of Basic Technique,”第4版,John Wiley&Sons,Somerset,N J,2000,所述参考文献的内容通过引用以其整体并入本文。HEK-293细胞(人胚肾细胞)购自美国典型培养物保藏中心(American Type Culture Collection)(Manassas,VA)。抗FLAG抗体购自Thermo Fisher Scientific。兔抗GFP抗体购自GenScripts(Piscataway,NJ)。为了易于纯化和表征,除SEQ ID NO:88-101中提供的序列之外,该实施例1中使用的一些融合蛋白构建体还含有在蛋白质的C末端或N末端处的SEQ ID NO:78的FLAG表位,加上短的接头序列。
蛋白质在HEK293细胞中的表达与检测
用Lipofectamine 3000转染试剂(Thermo Fisher Scientific),将编码各种蛋白质构建体的表达载体质粒转染到HEK293细胞内。使用免疫印迹测定,对细胞裂解物分析表达的蛋白质。在分析之前,将培养基的样品离心,以去除碎片。细胞在含有2mM PMSF和蛋白酶混合物(Complete Protease Inhibitor Cocktail;Sigma)的裂解缓冲液(10mM Tris-HCl,pH 8.0、150mM NaCl、10mM EDTA、2% SDS)中进行裂解。在短暂的超声处理后,使用免疫印迹测定,对样品分析表达的蛋白质。对于免疫印迹分析,使样品在SDS样品缓冲液中煮沸并且在聚丙烯酰胺电泳上运行。其后,将分离的蛋白质条带转移到PVDF膜上。
使用化学发光信号检测表达的蛋白质。简言之,使印迹与能够结合特定表位的一抗(例如抗α-突触核蛋白抗体)反应。在冲洗掉未反应的一抗后,允许酶联的二抗(例如HRP连接的抗IgG抗体)与结合到印迹的一抗分子反应。在冲洗后,加入化学发光试剂,并且在X光片上捕获印迹中所得的化学发光信号。
BFA/MG132温育
用Lipofectamine 3000转染试剂(Thermo Fisher Scientific),将编码各种蛋白质构建体的表达载体质粒转染到HEK293细胞内。在转染后一天,将培养基更换为含有巴佛洛霉素a1(BFA)或MG132的新鲜培养基,并且使细胞再温育48小时。细胞在补充有蛋白酶抑制剂混合物(Complete Protease Inhibitor Cocktail;Sigma)和2mM PMSF的裂解缓冲液(20mM Tris,pH 7.4、150mM NaCl、1mM EDTA、0.1% NP-40)中进行裂解。在短暂的超声处理后,在ELISA或免疫印迹测定中分析细胞裂解物。
ELISA(酶联免疫吸附测定)
用α-突触核蛋白聚集物特异性抗体Syn-O4(BioLegend)监测表达的α-突触核蛋白的聚集状态。Syn-O4是构象特异性的单克隆抗体,其特异性识别α-突触核蛋白聚集物,而不是蛋白质的可溶性单体形式58。微量滴定板孔在4℃下用Syn-O4包被过夜,并且在包被后,将孔用PBS洗涤3次,用含有1% BSA的PBS封闭1小时,并且再次用PBS洗涤。
在表达后,将培养的细胞在含有2mM PMSF和蛋白酶混合物的裂解缓冲液(20mMTris-HCl,pH 7.4、150mM NaCl、1mM EDTA、0.1%NP-40)中裂解,随后为短暂的超声处理。在通过离心去除碎片后,将细胞裂解物加入孔中并在4℃下温育过夜。然后将孔用PBS洗涤3次,与HRP连接的抗α-突触核蛋白抗体一起在含有1% BSA的PBS中温育1小时,并且再次用PBS洗涤3次。最后,用在0.1M乙酸钠(pH 6.0)的缓冲液中的0.01mg/ml 3',3',5',5'-四甲基联苯胺(TMB)和0.01%H2O2测定过氧化物酶活性。在加入等体积的1M HCl后,在450nm处确定光密度。报告构建体
我们首先调查了靶向α-突触核蛋白的融合蛋白是否改善其在培养细胞中的聚集。为此,我们生成了表达野生型α-突触核蛋白以及已知与家族性帕金森氏病相关的突变体形式(含有A53T取代)的两种构建体(参见下表8)。将HEK293细胞进行培养,并且用编码野生型(SEQ ID NO:105)或突变型(SEQ ID NO:106)α-突触核蛋白的质粒进行转染。
表8:突触核蛋白构建体
融合蛋白构建体
为了确定J结构域是否可以被用于减少α-突触核蛋白聚集,首先通过野生型或突变型突触核蛋白与融合蛋白的共表达进行初始实验,所述融合蛋白包含衍生自Hsp40 J结构域蛋白(来自人DnaJB1)的J结构域序列,其与突触核蛋白结合肽SynBP1缀合(参见下表9中的构建体1)。如图3A中所示,野生型或突变型(A53T)α-突触核蛋白在HEK293细胞中的表达导致聚集的α-突触核蛋白的出现,如通过关于细胞裂解物的ELISA检测的(参见条1和4)。构建体1的共表达导致可检测的聚集α-突触核蛋白的量的急剧减少(条2和5)。然而,在J结构域内高度保守的HPD基序内含有P33Q突变的构建体1的突变型变体的共表达导致更高的总体聚集(参见条3和6),提示了减少聚集的机制是通过HSP70系统。使用抗α-突触核蛋白抗体执行细胞裂解物的蛋白质印迹分析,以确定融合蛋白是否影响α-突触核蛋白的总体水平。如图3B中所示,所有细胞均具有相对相似的α-突触核蛋白水平,提示了聚集的α-突触核蛋白的减少不仅仅是由于α-突触核蛋白的降解。
表9.融合蛋白构建体和对照
已知分泌α-突触核蛋白。因此,我们调查了融合蛋白构建体是否有效减少分泌的α-突触核蛋白的量。从单独表达野生型(条2和3)或突变型(条4和5)α-突触核蛋白或者还表达构建体1(JB1-SynBP1;条3和5)的细胞中收集培养基,并且通过ELISA分析测试分泌的α-突触核蛋白的水平。如图4中所示,当在没有融合蛋白构建体的情况下进行表达时,野生型和突变型(A53T)α-突触核蛋白形式两者均进行分泌(分别为条2和4)。然而,共表达构建体1的细胞没有可检测的分泌到培养基内的α-突触核蛋白,如通过ELISA测量的(分别关于野生型和突变型α-突触核蛋白的条3和5)。
我们接下来调查了融合蛋白在减少聚集方面的机制。HEK293细胞用单独的或者伴随构建体1(JB1-SynBP1)以及伴随BFA(巴佛洛霉素A1,自噬晚期的抑制剂)或MG132(蛋白酶体抑制剂)的野生型或突变型(A53T)α-突触核蛋白进行转染。图5和图6显示了结果,其也总结于下表10中(值针对单独的野生型对照进行归一化)。如可以看出的,构建体1在还表达突变型(A53T)α-突触核蛋白的细胞中的表达导致总α-突触核蛋白适度减少(从134.9%到99%),但聚集的α-突触核蛋白更明显地减少(从111.5%到53.9%)。用10nM或100nM的BFA处理这些细胞导致总α-突触核蛋白和聚集的α-突触核蛋白恢复到与单独表达突变型α-突触核蛋白(即没有也用融合蛋白构建体1进行转染)的细胞相匹配的水平。巴佛洛霉素A1是晚期自噬的有力抑制剂,提示了融合蛋白构建体经由分子伴侣介导的自噬发挥其效应。
相比之下,用蛋白酶体抑制剂MG132处理细胞对α-突触核蛋白的总水平或聚集水平几乎没有影响。
表10.抑制剂在融合蛋白介导的α-突触核蛋白聚集减少方面的效应
对另外的构建体测试了减少突变型(A53T)突触核蛋白聚集的能力。下表11显示了包含不同突触核蛋白结合结构域的许多其它构建体能够减少α-突触核蛋白聚集。有趣的是,先前显示与聚谷氨酰胺重复结合的构建体10,一种包含QBP1的融合蛋白构建体,也显示了有力地减少α-突触核蛋白聚集的能力。
表11.含有各种α-突触核蛋白结合结构域的融合蛋白构建体在减少聚集方面的效应
为了进一步优化J结构域和α-突触核蛋白结合结构域的排列,测试了另外的构建体。下表12显示了采用替代的J结构域(构建体6,使用衍生自DnaJB6的J结构域;构建体7,使用衍生自DnaJB13的J结构域)或者在J结构域和α-突触核蛋白结合结构域之间的不同接头的构建体的能力。
表12.含有各种α-突触核蛋白结合结构域的融合蛋白构建体在减少聚集方面的效应
接下来,进行实验以确定各种融合蛋白构建体的表达是否对磷酸化的α-突触核蛋白的水平具有作用。下表13显示了各种融合蛋白构建体的表达对在Ser129处磷酸化的突变型(A53T)α-突触核蛋白的水平具有显著作用。
表13.共表达各种融合蛋白构建体对磷酸化的α-突触核蛋白(Ser129)水平的作用。
最后,进行了实验,以确定各种融合蛋白构建体的表达是否能够通过突变型(A53T)α-突触核蛋白的表达来改善细胞毒性。尽管野生型(WT)或突变型(A53T)α-突触核蛋白的表达并不在HEK293细胞中诱导显著的细胞毒性(数据未显示),但在U-87MG细胞中观察到由α-突触核蛋白引起的细胞毒性效应,如在感染后7天从U87-MG细胞收集的培养基中的LDH活性增加所证明的,如通过LDH-CytotoxTM测定试剂盒(BioLegend,San Diego,CA,USA)测量的(图7)。与JB1-SynBP1(构建体1)的共表达强烈抑制了α-突触核蛋白的细胞毒性效应。我们将这些结果解释为意指融合蛋白构建体能够减少α-突触核蛋白介导的细胞毒性。
实施例2:编码融合蛋白构建体的AAV载体
示例性基因治疗载体由携带密码子优化的cDNA的AAV9载体构建,所述cDNA编码表6的融合蛋白构建体,特别是构建体1、3、4和5,处于含有巨细胞病毒(CMV)早期增强子元件和鸡β-肌动蛋白启动子的CAG启动子的控制下。编码JB1-SynBP1的cDNA定位于Kozak序列的下游,并且通过牛生长激素多聚腺苷酸化(BGHpA)信号进行多聚腺苷酸化。整个盒的侧翼为两个AAV-9非编码末端反向序列。
使用类似于上述的杆状病毒表达系统来制备重组AAV载体(Urabe等人,2002、Unzu等人,2011(Kotin,2011中综述的))。简言之,三种重组杆状病毒被用于感染SF9昆虫细胞,其中一种编码用于复制和包装的REP,一种编码关于AAV9衣壳的CAP-5,以及一种具有表达盒。使用AVB Sepharose高速亲和介质(GE Healthcare Life Sciences,Piscataway,NJ)执行纯化。使用QPCR伴随用于转基因的引物-探针组合来滴定载体,并且将滴度表示为每ml的基因组拷贝(GC/ml)。载体的滴度为大约8x 1013至2x 1014GC/ml。
实施例3:在PD的小鼠模型中的功效测试
上文制备的载体在PD的小鼠模型中进行测试。有用的模型包括Fares等人,(2006)Proc.Natl.Acad.Sci.USA,113:E912-E921中描述的小鼠模型,所述模型通过在SNCA-/-背景下的人α-突触核蛋白表达来生成,这导致原代神经元中过度磷酸化(在S129处)和泛素阳性的LB样包涵体,其在大小增大并掺入了可溶性蛋白质。
为了测试本申请中描述的测试化合物或已知化合物在动物模型中的效应,将含有编码融合蛋白的载体的不同AAV病毒颗粒和相应的对照施用于转基因动物。在一个实施方案中,病毒颗粒通过尾静脉注射进行施用。在另一个实施方案中,病毒颗粒通过肌内注射进行施用。在仍然另一个实施方案中,颗粒通过颅内注射进行施用,例如如Stanek等人,(2014)Hum.Gene.Ther.25:461-474中所述的。
在施用后,监测疾病进展并且将其与对照注射小鼠进行比较。在一个实施方案中,在动物中评估PD样包涵体的发展。也可以使用复制PD样病理学的几种其它动物模型。
其它方面
本说明书中提到的所有出版物、专利和专利申请都通过引用以其整体并入本文,其程度如同每个个别出版物、专利或专利申请被具体地且个别地指明通过引用以其整体并入。当发现本申请中的术语在通过引用并入本文的文件中被不同地定义时,本文提供的定义将充当该术语的定义。
虽然本发明已与其具体方面结合进行描述,但应理解,本发明能够进行进一步修改,并且本申请预期涵盖本发明的任何变化、用途或改编,一般而言遵循本发明的原则且包括与本公开内容的此类偏离,所述偏离在本发明所属领域内的已知或习惯的实践内,并且可以被应用于上文阐述的基本特征,并且遵循所请求保护的范围。
序列表
<110> SOLA BioSciences LLC
<120> 用于治疗突触核蛋白病的组合物和方法
<130> 269548-493385
<150> US 63/035,297
<151> 2020-06-05
<160> 106
<170> PatentIn version 3.5
<210> 1
<211> 63
<212> PRT
<213> 人工的
<220>
<223> DNAJA1
<400> 1
Thr Tyr Tyr Asp Val Leu Gly Val Lys Pro Asn Ala Thr Gln Glu Glu
1 5 10 15
Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Tyr His Pro Asp Lys
20 25 30
Asn Pro Asn Glu Gly Glu Lys Phe Lys Gln Ile Ser Gln Ala Tyr Glu
35 40 45
Val Leu Ser Asp Ala Lys Lys Arg Glu Leu Tyr Asp Lys Gly Gly
50 55 60
<210> 2
<211> 63
<212> PRT
<213> 人工的
<220>
<223> DNAJA2
<400> 2
Lys Leu Tyr Asp Ile Leu Gly Val Pro Pro Gly Ala Ser Glu Asn Glu
1 5 10 15
Leu Lys Lys Ala Tyr Arg Lys Leu Ala Lys Glu Tyr His Pro Asp Lys
20 25 30
Asn Pro Asn Ala Gly Asp Lys Phe Lys Glu Ile Ser Phe Ala Tyr Glu
35 40 45
Val Leu Ser Asn Pro Glu Lys Arg Glu Leu Tyr Asp Arg Tyr Gly
50 55 60
<210> 3
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJA3
<400> 3
Asp Tyr Tyr Gln Ile Leu Gly Val Pro Arg Asn Ala Ser Gln Lys Glu
1 5 10 15
Ile Lys Lys Ala Tyr Tyr Gln Leu Ala Lys Lys Tyr His Pro Asp Thr
20 25 30
Asn Lys Asp Asp Pro Lys Ala Lys Glu Lys Phe Ser Gln Leu Ala Glu
35 40 45
Ala Tyr Glu Val Leu Ser Asp Glu Val Lys Arg Lys Gln Tyr Asp Ala
50 55 60
Tyr Gly
65
<210> 4
<211> 67
<212> PRT
<213> 人工的
<220>
<223> DNAJA4
<400> 4
Glu Thr Gln Tyr Tyr Asp Ile Leu Gly Val Lys Pro Ser Ala Ser Pro
1 5 10 15
Glu Glu Ile Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Tyr His Pro
20 25 30
Asp Lys Asn Pro Asp Glu Gly Glu Lys Phe Lys Leu Ile Ser Gln Ala
35 40 45
Tyr Glu Val Leu Ser Asp Pro Lys Lys Arg Asp Val Tyr Asp Gln Gly
50 55 60
Gly Glu Gln
65
<210> 5
<211> 69
<212> PRT
<213> 人工的
<220>
<223> DNAJB1
<400> 5
Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser Asp
1 5 10 15
Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His Pro
20 25 30
Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile Ala
35 40 45
Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe Asp
50 55 60
Arg Tyr Gly Glu Glu
65
<210> 6
<211> 70
<212> PRT
<213> 人工的
<220>
<223> DNAJB2
<400> 6
Ala Ser Tyr Tyr Glu Ile Leu Asp Val Pro Arg Ser Ala Ser Ala Asp
1 5 10 15
Asp Ile Lys Lys Ala Tyr Arg Arg Lys Ala Leu Gln Trp His Pro Asp
20 25 30
Lys Asn Pro Asp Asn Lys Glu Phe Ala Glu Lys Lys Phe Lys Glu Val
35 40 45
Ala Glu Ala Tyr Glu Val Leu Ser Asp Lys His Lys Arg Glu Ile Tyr
50 55 60
Asp Arg Tyr Gly Arg Glu
65 70
<210> 7
<211> 69
<212> PRT
<213> 人工的
<220>
<223> DNAJB3
<400> 7
Met Val Asp Tyr Tyr Glu Val Leu Asp Val Pro Arg Gln Ala Ser Ser
1 5 10 15
Glu Ala Ile Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Trp His Pro
20 25 30
Asp Lys Asn Pro Glu Asn Lys Glu Glu Ala Glu Arg Arg Phe Lys Gln
35 40 45
Val Ala Glu Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Asp Ile
50 55 60
Tyr Asp Arg Tyr Gly
65
<210> 8
<211> 69
<212> PRT
<213> 人工的
<220>
<223> DNAJB4
<400> 8
Gly Lys Asp Tyr Tyr Cys Ile Leu Gly Ile Glu Lys Gly Ala Ser Asp
1 5 10 15
Glu Asp Ile Lys Lys Ala Tyr Arg Lys Gln Ala Leu Lys Phe His Pro
20 25 30
Asp Lys Asn Lys Ser Pro Gln Ala Glu Glu Lys Phe Lys Glu Val Ala
35 40 45
Glu Ala Tyr Glu Val Leu Ser Asp Pro Lys Lys Arg Glu Ile Tyr Asp
50 55 60
Gln Phe Gly Glu Glu
65
<210> 9
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJB5
<400> 9
Asp Tyr Tyr Lys Ile Leu Gly Ile Pro Ser Gly Ala Asn Glu Asp Glu
1 5 10 15
Ile Lys Lys Ala Tyr Arg Lys Met Ala Leu Lys Tyr His Pro Asp Lys
20 25 30
Asn Lys Glu Pro Asn Ala Glu Glu Lys Phe Lys Glu Ile Ala Glu Ala
35 40 45
Tyr Asp Val Leu Ser Asp Pro Lys Lys Arg Gly Leu Tyr Asp Gln Tyr
50 55 60
Gly
65
<210> 10
<211> 68
<212> PRT
<213> 人工的
<220>
<223> DNAJB6
<400> 10
Val Asp Tyr Tyr Glu Val Leu Gly Val Gln Arg His Ala Ser Pro Glu
1 5 10 15
Asp Ile Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Trp His Pro Asp
20 25 30
Lys Asn Pro Glu Asn Lys Glu Glu Ala Glu Arg Lys Phe Lys Gln Val
35 40 45
Ala Glu Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Asp Ile Tyr
50 55 60
Asp Lys Tyr Gly
65
<210> 11
<211> 67
<212> PRT
<213> 人工的
<220>
<223> DNAJB7
<400> 11
Asp Tyr Tyr Glu Val Leu Gly Leu Gln Arg Tyr Ala Ser Pro Glu Asp
1 5 10 15
Ile Lys Lys Ala Tyr His Lys Val Ala Leu Lys Trp His Pro Asp Lys
20 25 30
Asn Pro Glu Asn Lys Glu Glu Ala Glu Arg Lys Phe Lys Glu Val Ala
35 40 45
Glu Ala Tyr Glu Val Leu Ser Asn Asp Glu Lys Arg Asp Ile Tyr Asp
50 55 60
Lys Tyr Gly
65
<210> 12
<211> 67
<212> PRT
<213> 人工的
<220>
<223> DNAJB8
<400> 12
Asn Tyr Tyr Glu Val Leu Gly Val Gln Ala Ser Ala Ser Pro Glu Asp
1 5 10 15
Ile Lys Lys Ala Tyr Arg Lys Leu Ala Leu Arg Trp His Pro Asp Lys
20 25 30
Asn Pro Asp Asn Lys Glu Glu Ala Glu Lys Lys Phe Lys Leu Val Ser
35 40 45
Glu Ala Tyr Glu Val Leu Ser Asp Ser Lys Lys Arg Ser Leu Tyr Asp
50 55 60
Arg Ala Gly
65
<210> 13
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJB9
<400> 13
Ser Tyr Tyr Asp Ile Leu Gly Val Pro Lys Ser Ala Ser Glu Arg Gln
1 5 10 15
Ile Lys Lys Ala Phe His Lys Leu Ala Met Lys Tyr His Pro Asp Lys
20 25 30
Asn Lys Ser Pro Asp Ala Glu Ala Lys Phe Arg Glu Ile Ala Glu Ala
35 40 45
Tyr Glu Thr Leu Ser Asp Ala Asn Arg Arg Lys Glu Tyr Asp Thr Leu
50 55 60
Gly
65
<210> 14
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJB11
<400> 14
Asp Phe Tyr Lys Ile Leu Gly Val Pro Arg Ser Ala Ser Ile Lys Asp
1 5 10 15
Ile Lys Lys Ala Tyr Arg Lys Leu Ala Leu Gln Leu His Pro Asp Arg
20 25 30
Asn Pro Asp Asp Pro Gln Ala Gln Glu Lys Phe Gln Asp Leu Gly Ala
35 40 45
Ala Tyr Glu Val Leu Ser Asp Ser Glu Lys Arg Lys Gln Tyr Asp Thr
50 55 60
Tyr Gly
65
<210> 15
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJB12
<400> 15
Tyr Glu Ile Leu Gly Val Ser Arg Gly Ala Ser Asp Glu Asp Leu Lys
1 5 10 15
Lys Ala Tyr Arg Arg Leu Ala Leu Lys Phe His Pro Asp Lys Asn His
20 25 30
Ala Pro Gly Ala Thr Glu Ala Phe Lys Ala Ile Gly Thr Ala Tyr Ala
35 40 45
Val Leu Ser Asn Pro Glu Lys Arg Lys Gln Tyr Asp Gln Phe Gly Asp
50 55 60
Asp
65
<210> 16
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJB13
<400> 16
Asp Tyr Tyr Ser Val Leu Gly Ile Thr Arg Asn Ser Glu Asp Ala Gln
1 5 10 15
Ile Lys Gln Ala Tyr Arg Arg Leu Ala Leu Lys His His Pro Leu Lys
20 25 30
Ser Asn Glu Pro Ser Ser Ala Glu Ile Phe Arg Gln Ile Ala Glu Ala
35 40 45
Tyr Asp Val Leu Ser Asp Pro Met Lys Arg Gly Ile Tyr Asp Lys Phe
50 55 60
Gly
65
<210> 17
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJB14
<400> 17
Asn Tyr Tyr Glu Val Leu Gly Val Thr Lys Asp Ala Gly Asp Glu Asp
1 5 10 15
Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Phe His Pro Asp Lys
20 25 30
Asn His Ala Pro Gly Ala Thr Asp Ala Phe Lys Lys Ile Gly Asn Ala
35 40 45
Tyr Ala Val Leu Ser Asn Pro Glu Lys Arg Lys Gln Tyr Asp Leu Thr
50 55 60
Gly
65
<210> 18
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC1
<400> 18
Asn Phe Tyr Gln Phe Leu Gly Val Gln Gln Asp Ala Ser Ser Ala Asp
1 5 10 15
Ile Arg Lys Ala Tyr Arg Lys Leu Ser Leu Thr Leu His Pro Asp Lys
20 25 30
Asn Lys Asp Glu Asn Ala Glu Thr Gln Phe Arg Gln Leu Val Ala Ile
35 40 45
Tyr Glu Val Leu Lys Asp Asp Glu Arg Arg Gln Arg Tyr Asp Asp Ile
50 55 60
Leu
65
<210> 19
<211> 74
<212> PRT
<213> 人工的
<220>
<223> DNAJC2
<400> 19
Asp His Tyr Ala Val Leu Gly Leu Gly His Val Arg Tyr Lys Ala Thr
1 5 10 15
Gln Arg Gln Ile Lys Ala Ala His Lys Ala Met Val Leu Lys His His
20 25 30
Pro Asp Lys Arg Lys Ala Ala Gly Glu Pro Ile Lys Glu Gly Asp Asn
35 40 45
Asp Tyr Phe Thr Cys Ile Thr Lys Ala Tyr Glu Met Leu Ser Asp Pro
50 55 60
Val Lys Arg Arg Ala Phe Asn Ser Val Asp
65 70
<210> 20
<211> 69
<212> PRT
<213> 人工的
<220>
<223> DNAJC3
<400> 20
Asp Tyr Tyr Lys Ile Leu Gly Val Lys Arg Asn Ala Lys Lys Gln Glu
1 5 10 15
Ile Ile Lys Ala Tyr Arg Lys Leu Ala Leu Gln Trp His Pro Asp Asn
20 25 30
Phe Gln Asn Glu Glu Glu Lys Lys Lys Ala Glu Lys Lys Phe Ile Asp
35 40 45
Ile Ala Ala Ala Lys Glu Val Leu Ser Asp Pro Glu Met Arg Lys Lys
50 55 60
Phe Asp Asp Gly Glu
65
<210> 21
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJC4
<400> 21
Thr Tyr Tyr Glu Leu Leu Gly Val His Pro Gly Ala Ser Thr Glu Glu
1 5 10 15
Val Lys Arg Ala Phe Phe Ser Lys Ser Lys Glu Leu His Pro Asp Arg
20 25 30
Asp Pro Gly Asn Pro Ser Leu His Ser Arg Phe Val Glu Leu Ser Glu
35 40 45
Ala Tyr Arg Val Leu Ser Arg Glu Gln Ser Arg Arg Ser Tyr Asp Asp
50 55 60
Gln Leu
65
<210> 22
<211> 70
<212> PRT
<213> 人工的
<220>
<223> DNAJC5
<400> 22
Gly Glu Ser Leu Tyr His Val Leu Gly Leu Asp Lys Asn Ala Thr Ser
1 5 10 15
Asp Asp Ile Lys Lys Ser Tyr Arg Lys Leu Ala Leu Lys Tyr His Pro
20 25 30
Asp Lys Asn Pro Asp Asn Pro Glu Ala Ala Asp Lys Phe Lys Glu Ile
35 40 45
Asn Asn Ala His Ala Ile Leu Thr Asp Ala Thr Lys Arg Asn Ile Tyr
50 55 60
Asp Lys Tyr Gly Ser Leu
65 70
<210> 23
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJC5B
<400> 23
Ala Leu Tyr Glu Ile Leu Gly Leu His Lys Gly Ala Ser Asn Glu Glu
1 5 10 15
Ile Lys Lys Thr Tyr Arg Lys Leu Ala Leu Lys His His Pro Asp Lys
20 25 30
Asn Pro Asp Asp Pro Ala Ala Thr Glu Lys Phe Lys Glu Ile Asn Asn
35 40 45
Ala His Ala Ile Leu Thr Asp Ile Ser Lys Arg Ser Ile Tyr Asp Lys
50 55 60
Tyr Gly
65
<210> 24
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC6
<400> 24
Thr Lys Trp Lys Pro Val Gly Met Ala Asp Leu Val Thr Pro Glu Gln
1 5 10 15
Val Lys Lys Val Tyr Arg Lys Ala Val Leu Val Val His Pro Asp Lys
20 25 30
Ala Thr Gly Gln Pro Tyr Glu Gln Tyr Ala Lys Met Ile Phe Met Glu
35 40 45
Leu Asn Asp Ala Trp Ser Glu Phe Glu Asn Gln Gly Gln Lys Pro Leu
50 55 60
Tyr
65
<210> 25
<211> 71
<212> PRT
<213> 人工的
<220>
<223> DNAJC7
<400> 25
Asp Tyr Tyr Lys Ile Leu Gly Val Asp Lys Asn Ala Ser Glu Asp Glu
1 5 10 15
Ile Lys Lys Ala Tyr Arg Lys Arg Ala Leu Met His His Pro Asp Arg
20 25 30
His Ser Gly Ala Ser Ala Glu Val Gln Lys Glu Glu Glu Lys Lys Phe
35 40 45
Lys Glu Val Gly Glu Ala Phe Thr Ile Leu Ser Asp Pro Lys Lys Lys
50 55 60
Thr Arg Tyr Asp Ser Gly Gln
65 70
<210> 26
<211> 68
<212> PRT
<213> 人工的
<220>
<223> DNAJC8
<400> 26
Asn Pro Phe Glu Val Leu Gln Ile Asp Pro Glu Val Thr Asp Glu Glu
1 5 10 15
Ile Lys Lys Arg Phe Arg Gln Leu Ser Ile Leu Val His Pro Asp Lys
20 25 30
Asn Gln Asp Asp Ala Asp Arg Ala Gln Lys Ala Phe Glu Ala Val Asp
35 40 45
Lys Ala Tyr Lys Leu Leu Leu Asp Gln Glu Gln Lys Lys Arg Ala Leu
50 55 60
Asp Val Ile Gln
65
<210> 27
<211> 68
<212> PRT
<213> 人工的
<220>
<223> DNAJC9
<400> 27
Asp Leu Tyr Arg Val Leu Gly Val Arg Arg Glu Ala Ser Asp Gly Glu
1 5 10 15
Val Arg Arg Gly Tyr His Lys Val Ser Leu Gln Val His Pro Asp Arg
20 25 30
Val Gly Glu Gly Asp Lys Glu Asp Ala Thr Arg Arg Phe Gln Ile Leu
35 40 45
Gly Lys Val Tyr Ser Val Leu Ser Asp Arg Glu Gln Arg Ala Val Tyr
50 55 60
Asp Glu Gln Gly
65
<210> 28
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJC10
<400> 28
Asp Phe Tyr Ser Leu Leu Gly Val Ser Lys Thr Ala Ser Ser Arg Glu
1 5 10 15
Ile Arg Gln Ala Phe Lys Lys Leu Ala Leu Lys Leu His Pro Asp Lys
20 25 30
Asn Pro Asn Asn Pro Asn Ala His Gly Asp Phe Leu Lys Ile Asn Arg
35 40 45
Ala Tyr Glu Val Leu Lys Asp Glu Asp Leu Arg Lys Lys Tyr Asp Lys
50 55 60
Tyr Gly
65
<210> 29
<211> 69
<212> PRT
<213> 人工的
<220>
<223> DNAJC11
<400> 29
Asp Tyr Tyr Ser Leu Leu Asn Val Arg Arg Glu Ala Ser Ser Glu Glu
1 5 10 15
Leu Lys Ala Ala Tyr Arg Arg Leu Cys Met Leu Tyr His Pro Asp Lys
20 25 30
His Arg Asp Pro Glu Leu Lys Ser Gln Ala Glu Arg Leu Phe Asn Leu
35 40 45
Val His Gln Ala Tyr Glu Val Leu Ser Asp Pro Gln Thr Arg Ala Ile
50 55 60
Tyr Asp Ile Tyr Gly
65
<210> 30
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJC12
<400> 30
Asp Tyr Tyr Thr Leu Leu Gly Cys Asp Glu Leu Ser Ser Val Glu Gln
1 5 10 15
Ile Leu Ala Glu Phe Lys Val Arg Ala Leu Glu Cys His Pro Asp Lys
20 25 30
His Pro Glu Asn Pro Lys Ala Val Glu Thr Phe Gln Lys Leu Gln Lys
35 40 45
Ala Lys Glu Ile Leu Thr Asn Glu Glu Ser Arg Ala Arg Tyr Asp His
50 55 60
Trp Arg
65
<210> 31
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJC13
<400> 31
Asp Ala Tyr Glu Val Leu Asn Leu Pro Gln Gly Gln Gly Pro His Asp
1 5 10 15
Glu Ser Lys Ile Arg Lys Ala Tyr Phe Arg Leu Ala Gln Lys Tyr His
20 25 30
Pro Asp Lys Asn Pro Glu Gly Arg Asp Met Phe Glu Lys Val Asn Lys
35 40 45
Ala Tyr Glu Phe Leu Cys Thr Lys Ser Ala Lys Ile Val Asp Gly Pro
50 55 60
Asp Pro
65
<210> 32
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC14
<400> 32
Asn Pro Phe His Val Leu Gly Val Glu Ala Thr Ala Ser Asp Val Glu
1 5 10 15
Leu Lys Lys Ala Tyr Arg Gln Leu Ala Val Met Val His Pro Asp Lys
20 25 30
Asn His His Pro Arg Ala Glu Glu Ala Phe Lys Val Leu Arg Ala Ala
35 40 45
Trp Asp Ile Val Ser Asn Ala Glu Lys Arg Lys Glu Tyr Glu Met Lys
50 55 60
Arg
65
<210> 33
<211> 55
<212> PRT
<213> 人工的
<220>
<223> DNAJC15
<400> 33
Glu Ala Gly Leu Ile Leu Gly Val Ser Pro Ser Ala Gly Lys Ala Lys
1 5 10 15
Ile Arg Thr Ala His Arg Arg Val Met Ile Leu Asn His Pro Asp Lys
20 25 30
Gly Gly Ser Pro Tyr Val Ala Ala Lys Ile Asn Glu Ala Lys Asp Leu
35 40 45
Leu Glu Thr Thr Thr Lys His
50 55
<210> 34
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC16
<400> 34
Asp Pro Tyr Arg Val Leu Gly Val Ser Arg Thr Ala Ser Gln Ala Asp
1 5 10 15
Ile Lys Lys Ala Tyr Lys Lys Leu Ala Arg Glu Trp His Pro Asp Lys
20 25 30
Asn Lys Asp Pro Gly Ala Glu Asp Lys Phe Ile Gln Ile Ser Lys Ala
35 40 45
Tyr Glu Ile Leu Ser Asn Glu Glu Lys Arg Ser Asn Tyr Asp Gln Tyr
50 55 60
Gly
65
<210> 35
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJC17
<400> 35
Asp Leu Tyr Ala Leu Leu Gly Ile Glu Glu Lys Ala Ala Asp Lys Glu
1 5 10 15
Val Lys Lys Ala Tyr Arg Gln Lys Ala Leu Ser Cys His Pro Asp Lys
20 25 30
Asn Pro Asp Asn Pro Arg Ala Ala Glu Leu Phe His Gln Leu Ser Gln
35 40 45
Ala Leu Glu Val Leu Thr Asp Ala Ala Ala Arg Ala Ala Tyr Asp Lys
50 55 60
Val Arg
65
<210> 36
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC18
<400> 36
Asn Tyr Tyr Glu Ile Leu Gly Val Ser Arg Asp Ala Ser Asp Glu Glu
1 5 10 15
Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Phe His Pro Asp Lys
20 25 30
Asn Cys Ala Pro Gly Ala Thr Asp Ala Phe Lys Ala Ile Gly Asn Ala
35 40 45
Phe Ala Val Leu Ser Asn Pro Asp Lys Arg Leu Arg Tyr Asp Glu Tyr
50 55 60
Gly
65
<210> 37
<211> 55
<212> PRT
<213> 人工的
<220>
<223> DNAJC19
<400> 37
Glu Ala Ala Leu Ile Leu Gly Val Ser Pro Thr Ala Asn Lys Gly Lys
1 5 10 15
Ile Arg Asp Ala His Arg Arg Ile Met Leu Leu Asn His Pro Asp Lys
20 25 30
Gly Gly Ser Pro Tyr Ile Ala Ala Lys Ile Asn Glu Ala Lys Asp Leu
35 40 45
Leu Glu Gly Gln Ala Lys Lys
50 55
<210> 38
<211> 72
<212> PRT
<213> 人工的
<220>
<223> DNAJC20
<400> 38
Asp Tyr Phe Ser Leu Met Asp Cys Asn Arg Ser Phe Arg Val Asp Thr
1 5 10 15
Ala Lys Leu Gln His Arg Tyr Gln Gln Leu Gln Arg Leu Val His Pro
20 25 30
Asp Phe Phe Ser Gln Arg Ser Gln Thr Glu Lys Asp Phe Ser Glu Lys
35 40 45
His Ser Thr Leu Val Asn Asp Ala Tyr Lys Thr Leu Leu Ala Pro Leu
50 55 60
Ser Arg Gly Leu Tyr Leu Leu Lys
65 70
<210> 39
<211> 67
<212> PRT
<213> 人工的
<220>
<223> DNAJC21
<400> 39
Cys His Tyr Glu Ala Leu Gly Val Arg Arg Asp Ala Ser Glu Glu Glu
1 5 10 15
Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Trp His Pro Asp Lys
20 25 30
Asn Leu Asp Asn Ala Ala Glu Ala Ala Glu Gln Phe Lys Leu Ile Gln
35 40 45
Ala Ala Tyr Asp Val Leu Ser Asp Pro Gln Glu Arg Ala Trp Tyr Asp
50 55 60
Asn His Arg
65
<210> 40
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC22
<400> 40
Leu Ala Tyr Gln Val Leu Gly Leu Ser Glu Gly Ala Thr Asn Glu Glu
1 5 10 15
Ile His Arg Ser Tyr Gln Glu Leu Val Lys Val Trp His Pro Asp His
20 25 30
Asn Leu Asp Gln Thr Glu Glu Ala Gln Arg His Phe Leu Glu Ile Gln
35 40 45
Ala Ala Tyr Glu Val Leu Ser Gln Pro Arg Lys Pro Trp Gly Ser Arg
50 55 60
Arg
65
<210> 41
<211> 62
<212> PRT
<213> 人工的
<220>
<223> DNAJC23
<400> 41
Asn Pro Tyr Glu Val Leu Asn Leu Asp Pro Gly Ala Thr Val Ala Glu
1 5 10 15
Ile Lys Lys Gln Tyr Arg Leu Leu Ser Leu Lys Tyr His Pro Asp Lys
20 25 30
Gly Gly Asp Glu Val Met Phe Met Arg Ile Ala Lys Ala Tyr Ala Ala
35 40 45
Leu Thr Asp Glu Glu Ser Arg Lys Asn Trp Glu Glu Phe Gly
50 55 60
<210> 42
<211> 72
<212> PRT
<213> 人工的
<220>
<223> DNAJC24
<400> 42
Asp Trp Tyr Ser Ile Leu Gly Ala Asp Pro Ser Ala Asn Ile Ser Asp
1 5 10 15
Leu Lys Gln Lys Tyr Gln Lys Leu Ile Leu Met Tyr His Pro Asp Lys
20 25 30
Gln Ser Thr Asp Val Pro Ala Gly Thr Val Glu Glu Cys Val Gln Lys
35 40 45
Phe Ile Glu Ile Asp Gln Ala Trp Lys Ile Leu Gly Asn Glu Glu Thr
50 55 60
Lys Arg Glu Tyr Asp Leu Gln Arg
65 70
<210> 43
<211> 76
<212> PRT
<213> 人工的
<220>
<223> DNAJC25
<400> 43
Asp Cys Tyr Glu Val Leu Gly Val Ser Arg Ser Ala Gly Lys Ala Glu
1 5 10 15
Ile Ala Arg Ala Tyr Arg Gln Leu Ala Arg Arg Tyr His Pro Asp Arg
20 25 30
Tyr Arg Pro Gln Pro Gly Asp Glu Gly Pro Gly Arg Thr Pro Gln Ser
35 40 45
Ala Glu Glu Ala Phe Leu Leu Val Ala Thr Ala Tyr Glu Thr Leu Lys
50 55 60
Asp Glu Glu Thr Arg Lys Asp Tyr Asp Tyr Met Leu
65 70 75
<210> 44
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC26
<400> 44
Ser Arg Trp Thr Pro Val Gly Met Ala Asp Leu Val Ala Pro Glu Gln
1 5 10 15
Val Lys Lys His Tyr Arg Arg Ala Val Leu Ala Val His Pro Asp Lys
20 25 30
Ala Ala Gly Gln Pro Tyr Glu Gln His Ala Lys Met Ile Phe Met Glu
35 40 45
Leu Asn Asp Ala Trp Ser Glu Phe Glu Asn Gln Gly Ser Arg Pro Leu
50 55 60
Phe
65
<210> 45
<211> 57
<212> PRT
<213> 人工的
<220>
<223> DNAJC27
<400> 45
Asp Ser Trp Asp Met Leu Gly Val Lys Pro Gly Ala Ser Arg Asp Glu
1 5 10 15
Val Asn Lys Ala Tyr Arg Lys Leu Ala Val Leu Leu His Pro Asp Lys
20 25 30
Cys Val Ala Pro Gly Ser Glu Asp Ala Phe Lys Ala Val Val Asn Ala
35 40 45
Arg Thr Ala Leu Leu Lys Asn Ile Lys
50 55
<210> 46
<211> 65
<212> PRT
<213> 人工的
<220>
<223> DNAJC28
<400> 46
Glu Tyr Tyr Arg Leu Leu Asn Val Glu Glu Gly Cys Ser Ala Asp Glu
1 5 10 15
Val Arg Glu Ser Phe His Lys Leu Ala Lys Gln Tyr His Pro Asp Ser
20 25 30
Gly Ser Asn Thr Ala Asp Ser Ala Thr Phe Ile Arg Ile Glu Lys Ala
35 40 45
Tyr Arg Lys Val Leu Ser His Val Ile Glu Gln Thr Asn Ala Ser Gln
50 55 60
Ser
65
<210> 47
<211> 88
<212> PRT
<213> 人工的
<220>
<223> DNAJC29
<400> 47
Ile Leu Lys Glu Val Thr Ser Val Val Glu Gln Ala Trp Lys Leu Pro
1 5 10 15
Glu Ser Glu Arg Lys Lys Ile Ile Arg Arg Leu Tyr Leu Lys Trp His
20 25 30
Pro Asp Lys Asn Pro Glu Asn His Asp Ile Ala Asn Glu Val Phe Lys
35 40 45
His Leu Gln Asn Glu Ile Asn Arg Leu Glu Lys Gln Ala Phe Leu Asp
50 55 60
Gln Asn Ala Asp Arg Ala Ser Arg Arg Thr Phe Ser Thr Ser Ala Ser
65 70 75 80
Arg Phe Gln Ser Asp Lys Tyr Ser
85
<210> 48
<211> 66
<212> PRT
<213> 人工的
<220>
<223> DNAJC30
<400> 48
Ala Leu Tyr Asp Leu Leu Gly Val Pro Ser Thr Ala Thr Gln Ala Gln
1 5 10 15
Ile Lys Ala Ala Tyr Tyr Arg Gln Cys Phe Leu Tyr His Pro Asp Arg
20 25 30
Asn Ser Gly Ser Ala Glu Ala Ala Glu Arg Phe Thr Arg Ile Ser Gln
35 40 45
Ala Tyr Val Val Leu Gly Ser Ala Thr Leu Arg Arg Lys Tyr Asp Arg
50 55 60
Gly Leu
65
<210> 49
<211> 64
<212> PRT
<213> 人工的
<220>
<223> SV40 J结构域
<400> 49
Gln Leu Met Asp Leu Leu Gly Leu Glu Arg Ser Ala Trp Gly Asn Ile
1 5 10 15
Pro Leu Met Arg Lys Ala Tyr Leu Lys Lys Cys Lys Glu Phe His Pro
20 25 30
Asp Lys Gly Gly Asp Glu Glu Lys Met Lys Lys Met Asn Thr Leu Tyr
35 40 45
Lys Lys Met Glu Asp Gly Val Lys Tyr Ala His Gln Pro Asp Phe Gly
50 55 60
<210> 50
<211> 70
<212> PRT
<213> 人工的
<220>
<223> 细菌J-结构域
<400> 50
Lys Gln Asp Tyr Tyr Glu Ile Leu Gly Val Ser Lys Thr Ala Glu Glu
1 5 10 15
Arg Glu Ile Arg Lys Ala Tyr Lys Arg Leu Ala Met Lys Tyr His Pro
20 25 30
Asp Arg Asn Gln Gly Asp Lys Glu Ala Glu Ala Lys Phe Lys Glu Ile
35 40 45
Lys Glu Ala Tyr Glu Val Leu Thr Asp Ser Gln Lys Arg Ala Ala Tyr
50 55 60
Asp Gln Tyr Gly His Ala
65 70
<210> 51
<211> 10
<212> PRT
<213> 人工的
<220>
<223> SynBP1
<400> 51
Lys Asp Gly Ile Val Asn Gly Val Lys Ala
1 5 10
<210> 52
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP2
<400> 52
Trp Arg Gln Thr Arg Lys Asp
1 5
<210> 53
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP3
<400> 53
His Tyr Ala Lys Asn Pro Ile
1 5
<210> 54
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP4
<400> 54
Ala Thr Ile Asn Lys Ser Leu
1 5
<210> 55
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP5
<400> 55
Arg Arg Arg Gly Met Ala Ile
1 5
<210> 56
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP6
<400> 56
Thr Lys His Gly Pro Arg Lys
1 5
<210> 57
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP7
<400> 57
Ser Leu Lys Arg Leu Pro Lys
1 5
<210> 58
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP8
<400> 58
Arg Leu Arg Gly Arg Asn Gln
1 5
<210> 59
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP9
<400> 59
Trp Pro Phe His His His Arg
1 5
<210> 60
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP10
<400> 60
His Leu Tyr His His Lys Thr
1 5
<210> 61
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP11
<400> 61
Thr His Ile His His Pro Ser
1 5
<210> 62
<211> 7
<212> PRT
<213> 人工的
<220>
<223> SynBP12
<400> 62
Met Met Met Met Met Arg Leu
1 5
<210> 63
<211> 248
<212> PRT
<213> 人工的
<220>
<223> NAC32 (胞内抗体)
<400> 63
Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn
20 25 30
Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu
35 40 45
Trp Leu Gly Arg Thr Phe Tyr Arg Ser Lys Trp Tyr Asn Asp Tyr Ala
50 55 60
Ala Ser Val Lys Ser Arg Ile Thr Ile Asp Pro Asp Thr Ser Lys Asn
65 70 75 80
Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Thr Arg Gln Asn Leu Ala Gly Pro Phe Asp Ser Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ile Leu Gly Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val
130 135 140
Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
145 150 155 160
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn Tyr Leu Ala
165 170 175
Trp Tyr Gln Gln Lys Ala Gly Gln Ala Pro Arg Leu Leu Ile Ser Gly
180 185 190
Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly
195 200 205
Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp
210 215 220
Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Thr Ala Phe Gly
225 230 235 240
Pro Gly Thr Lys Val Asp Ile Lys
245
<210> 64
<211> 247
<212> PRT
<213> 人工的
<220>
<223> Syn_scFv
<400> 64
Leu Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly
1 5 10 15
Gln Arg Val Ala Ile Ser Cys Thr Gly Thr Ser Ser Asp Ile Gly Thr
20 25 30
Gly Tyr Asp Val Asn Trp Tyr Gln His Leu Pro Gly Thr Ala Pro Arg
35 40 45
Leu Leu Ile Tyr Gly Asn Thr Tyr Arg Pro Ser Gly Val Pro Asp Arg
50 55 60
Phe Ser Ala Ser Thr Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val
65 70 75 80
Ile Thr Asp Leu Gln Ala Glu Asp Glu Gly Asp Tyr Tyr Cys Gln Ser
85 90 95
Phe Asp Asn Ser Leu Arg Gly Ser Val Phe Gly Gly Gly Thr Lys Val
100 105 110
Thr Val Leu Gly Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys
115 120 125
Ala Ser Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Lys Pro
130 135 140
Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe Ile Leu Ser
145 150 155 160
Asp Tyr Tyr Met Thr Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Leu Ala Val Ile Asp Ile Thr Ser Ser Tyr Thr Asn Tyr Ala Asp
180 185 190
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser
195 200 205
Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ala Arg Leu Glu Ser Gly Phe Phe Asp Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser
245
<210> 65
<211> 11
<212> PRT
<213> 人工的
<220>
<223> QBP1
<400> 65
Ser Asn Trp Lys Trp Trp Pro Gly Ile Phe Asp
1 5 10
<210> 66
<400> 66
000
<210> 67
<211> 4
<212> PRT
<213> 人工的
<220>
<223> GTGS
<400> 67
Gly Thr Gly Ser
1
<210> 68
<211> 5
<212> PRT
<213> 人工的
<220>
<223> GLESR
<400> 68
Gly Leu Glu Ser Arg
1 5
<210> 69
<211> 4
<212> PRT
<213> 人工的
<220>
<223> GGSG
<400> 69
Gly Gly Ser Gly
1
<210> 70
<211> 5
<212> PRT
<213> 人工的
<220>
<223> GGGGS
<400> 70
Gly Gly Gly Gly Ser
1 5
<210> 71
<211> 5
<212> PRT
<213> 人工的
<220>
<223> DIAAA
<400> 71
Asp Ile Ala Ala Ala
1 5
<210> 72
<211> 5
<212> PRT
<213> 人工的
<220>
<223> EAAAK
<400> 72
Glu Ala Ala Ala Lys
1 5
<210> 73
<211> 15
<212> PRT
<213> 人工的
<220>
<223> GGGGSGGGGSGGGGS
<400> 73
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 74
<211> 11
<212> PRT
<213> 人工的
<220>
<223> AEAAAKEAAAK
<400> 74
Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys
1 5 10
<210> 75
<211> 15
<212> PRT
<213> 人工的
<220>
<223> SGGGSGGGGSGGGGS
<400> 75
Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 76
<211> 25
<212> PRT
<213> 人工的
<220>
<223> DIGGGGSGGGGSGGGGSGGGGSAAA
<400> 76
Asp Ile Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
1 5 10 15
Ser Gly Gly Gly Gly Ser Ala Ala Ala
20 25
<210> 77
<211> 232
<212> PRT
<213> 人工的
<220>
<223> 人IgG1 Fc结构域
<400> 77
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
20 25 30
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
35 40 45
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
50 55 60
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
65 70 75 80
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
85 90 95
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
100 105 110
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
115 120 125
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
130 135 140
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
145 150 155 160
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
165 170 175
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
180 185 190
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
195 200 205
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
210 215 220
Ser Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 78
<211> 8
<212> PRT
<213> 人工的
<220>
<223> FLAG表位
<400> 78
Asp Tyr Lys Asp Asp Asp Asp Lys
1 5
<210> 79
<211> 6
<212> PRT
<213> 人工的
<220>
<223> His6
<400> 79
His His His His His His
1 5
<210> 80
<211> 10
<212> PRT
<213> 人工的
<220>
<223> c-myc
<400> 80
Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu
1 5 10
<210> 81
<211> 9
<212> PRT
<213> 人工的
<220>
<223> HA
<400> 81
Tyr Pro Tyr Asp Val Pro Asp Tyr Ala
1 5
<210> 82
<211> 14
<212> PRT
<213> 人工的
<220>
<223> V5表位
<400> 82
Gly Lys Pro Ile Pro Asn Pro Leu Leu Gly Leu Asp Ser Thr
1 5 10
<210> 83
<211> 220
<212> PRT
<213> 人工的
<220>
<223> 谷胱甘肽-S-转移酶
<400> 83
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp
210 215 220
<210> 84
<211> 9
<212> PRT
<213> 人工的
<220>
<223> RKKRRQRRR
<400> 84
Arg Lys Lys Arg Arg Gln Arg Arg Arg
1 5
<210> 85
<211> 15
<212> PRT
<213> 人工的
<220>
<223> RQIKWFQNRRMKWKK
<400> 85
Arg Gln Ile Lys Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys
1 5 10 15
<210> 86
<211> 21
<212> PRT
<213> 人工的
<220>
<223> KETWWETWWTEWSQPKKKRKV
<400> 86
Lys Glu Thr Trp Trp Glu Thr Trp Trp Thr Glu Trp Ser Gln Pro Lys
1 5 10 15
Lys Lys Arg Lys Val
20
<210> 87
<211> 17
<212> PRT
<213> 人工的
<220>
<223> CSIPPEVKFNKPFVYLI
<400> 87
Cys Ser Ile Pro Pro Glu Val Lys Phe Asn Lys Pro Phe Val Tyr Leu
1 5 10 15
Ile
<210> 88
<211> 110
<212> PRT
<213> 人工的
<220>
<223> JB1-SynBP1
<400> 88
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Asp Ile Gly Gly Gly
65 70 75 80
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
85 90 95
Ser Ala Ala Ala Lys Asp Gly Ile Val Asn Gly Val Lys Ala
100 105 110
<210> 89
<211> 110
<212> PRT
<213> 人工的
<220>
<223> J(P33Q)-SynBP1
<400> 89
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Gln Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Asp Ile Gly Gly Gly
65 70 75 80
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
85 90 95
Ser Ala Ala Ala Lys Asp Gly Ile Val Asn Gly Val Lys Ala
100 105 110
<210> 90
<211> 120
<212> PRT
<213> 人工的
<220>
<223> JB1-2XSynBP1
<400> 90
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Asp Ile Gly Gly Gly
65 70 75 80
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
85 90 95
Ser Ala Ala Ala Lys Asp Gly Ile Val Asn Gly Val Lys Ala Lys Asp
100 105 110
Gly Ile Val Asn Gly Val Lys Ala
115 120
<210> 91
<211> 123
<212> PRT
<213> 人工的
<220>
<223> SynBP1-JB1-SynBP1
<400> 91
Met Lys Asp Gly Ile Val Asn Gly Val Lys Ala Glu Phe Met Gly Lys
1 5 10 15
Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser Asp Glu Glu
20 25 30
Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His Pro Asp Lys
35 40 45
Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile Ala Glu Ala
50 55 60
Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe Asp Arg Tyr
65 70 75 80
Gly Glu Glu Gly Leu Lys Gly Ser Asp Ile Gly Gly Gly Gly Ser Gly
85 90 95
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala
100 105 110
Ala Lys Asp Gly Ile Val Asn Gly Val Lys Ala
115 120
<210> 92
<211> 90
<212> PRT
<213> 人工的
<220>
<223> SynBP2-JB1
<400> 92
Met Trp Arg Gln Thr Arg Lys Asp Glu Phe Met Gly Lys Asp Tyr Tyr
1 5 10 15
Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser Asp Glu Glu Ile Lys Arg
20 25 30
Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His Pro Asp Lys Asn Lys Glu
35 40 45
Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile Ala Glu Ala Tyr Asp Val
50 55 60
Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe Asp Arg Tyr Gly Glu Glu
65 70 75 80
Gly Leu Lys Gly Ser Asp Ile Ala Ala Ala
85 90
<210> 93
<211> 111
<212> PRT
<213> 人工的
<220>
<223> JB6-SynBP1
<400> 93
Met Val Asp Tyr Tyr Glu Val Leu Gly Val Gln Arg His Ala Ser Pro
1 5 10 15
Glu Asp Ile Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Trp His Pro
20 25 30
Asp Lys Asn Pro Glu Asn Lys Glu Glu Ala Glu Arg Lys Phe Lys Gln
35 40 45
Val Ala Glu Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Asp Ile
50 55 60
Tyr Asp Lys Tyr Gly Lys Glu Gly Leu Asn Gly Gly Asp Ile Gly Gly
65 70 75 80
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
85 90 95
Gly Ser Ala Ala Ala Lys Asp Gly Ile Val Asn Gly Val Lys Ala
100 105 110
<210> 94
<211> 110
<212> PRT
<213> 人工的
<220>
<223> JB13-SynBP1
<400> 94
Met Gly Gln Asp Tyr Tyr Ser Val Leu Gly Ile Thr Arg Asn Ser Glu
1 5 10 15
Asp Ala Gln Ile Lys Gln Ala Tyr Arg Arg Leu Ala Leu Lys His His
20 25 30
Pro Leu Lys Ser Asn Glu Pro Ser Ser Ala Glu Ile Phe Arg Gln Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Met Lys Arg Gly Ile Tyr
50 55 60
Asp Lys Phe Gly Glu Glu Gly Leu Lys Gly Gly Asp Ile Gly Gly Gly
65 70 75 80
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
85 90 95
Ser Ala Ala Ala Lys Asp Gly Ile Val Asn Gly Val Lys Ala
100 105 110
<210> 95
<211> 348
<212> PRT
<213> 人工的
<220>
<223> JB1-NAC32
<400> 95
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Asp Ile Gly Gly Gly
65 70 75 80
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
85 90 95
Ser Ala Ala Ala Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val
100 105 110
Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser
115 120 125
Val Ser Ser Asn Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser
130 135 140
Arg Gly Leu Glu Trp Leu Gly Arg Thr Phe Tyr Arg Ser Lys Trp Tyr
145 150 155 160
Asn Asp Tyr Ala Ala Ser Val Lys Ser Arg Ile Thr Ile Asp Pro Asp
165 170 175
Thr Ser Lys Asn Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu
180 185 190
Asp Thr Ala Val Tyr Tyr Cys Thr Arg Gln Asn Leu Ala Gly Pro Phe
195 200 205
Asp Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ile Leu
210 215 220
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
225 230 235 240
Ser Glu Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro
245 250 255
Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser
260 265 270
Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Ala Gly Gln Ala Pro Arg Leu
275 280 285
Leu Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe
290 295 300
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu
305 310 315 320
Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser
325 330 335
Thr Ala Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
340 345
<210> 96
<211> 347
<212> PRT
<213> 人工的
<220>
<223> JB1-Syn_scFv
<400> 96
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Asp Ile Gly Gly Gly
65 70 75 80
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
85 90 95
Ser Ala Ala Ala Leu Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser
100 105 110
Gly Ala Pro Gly Gln Arg Val Ala Ile Ser Cys Thr Gly Thr Ser Ser
115 120 125
Asp Ile Gly Thr Gly Tyr Asp Val Asn Trp Tyr Gln His Leu Pro Gly
130 135 140
Thr Ala Pro Arg Leu Leu Ile Tyr Gly Asn Thr Tyr Arg Pro Ser Gly
145 150 155 160
Val Pro Asp Arg Phe Ser Ala Ser Thr Gly Ser Lys Ser Gly Thr Ser
165 170 175
Ala Ser Leu Val Ile Thr Asp Leu Gln Ala Glu Asp Glu Gly Asp Tyr
180 185 190
Tyr Cys Gln Ser Phe Asp Asn Ser Leu Arg Gly Ser Val Phe Gly Gly
195 200 205
Gly Thr Lys Val Thr Val Leu Gly Glu Gly Lys Ser Ser Gly Ser Gly
210 215 220
Ser Glu Ser Lys Ala Ser Glu Val Gln Leu Val Gln Ser Gly Gly Gly
225 230 235 240
Val Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly
245 250 255
Phe Ile Leu Ser Asp Tyr Tyr Met Thr Trp Ile Arg Gln Ala Pro Gly
260 265 270
Lys Gly Leu Glu Trp Leu Ala Val Ile Asp Ile Thr Ser Ser Tyr Thr
275 280 285
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
290 295 300
Ala Lys Asn Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
305 310 315 320
Thr Ala Val Tyr Tyr Cys Ala Arg Leu Glu Ser Gly Phe Phe Asp Tyr
325 330 335
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
340 345
<210> 97
<211> 111
<212> PRT
<213> 人工的
<220>
<223> JB1-QBP1
<400> 97
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Asp Ile Gly Gly Gly
65 70 75 80
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
85 90 95
Ser Ala Ala Ala Ser Asn Trp Lys Trp Trp Pro Gly Ile Phe Asp
100 105 110
<210> 98
<211> 90
<212> PRT
<213> 人工的
<220>
<223> JB1GGGS_SynBP1
<400> 98
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Lys Asp Gly Ile Val Asn Gly Val Lys Ala
85 90
<210> 99
<211> 90
<212> PRT
<213> 人工的
<220>
<223> JB1EAAAK-SynBP1
<400> 99
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Glu Ala Ala Ala Lys
65 70 75 80
Lys Asp Gly Ile Val Asn Gly Val Lys Ala
85 90
<210> 100
<211> 85
<212> PRT
<213> 人工的
<220>
<223> JB1SynBP1
<400> 100
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Lys Asp Gly Ile Val
65 70 75 80
Asn Gly Val Lys Ala
85
<210> 101
<211> 91
<212> PRT
<213> 人工的
<220>
<223> JB1GGGGS-QBP1
<400> 101
Met Gly Lys Asp Tyr Tyr Gln Thr Leu Gly Leu Ala Arg Gly Ala Ser
1 5 10 15
Asp Glu Glu Ile Lys Arg Ala Tyr Arg Arg Gln Ala Leu Arg Tyr His
20 25 30
Pro Asp Lys Asn Lys Glu Pro Gly Ala Glu Glu Lys Phe Lys Glu Ile
35 40 45
Ala Glu Ala Tyr Asp Val Leu Ser Asp Pro Arg Lys Arg Glu Ile Phe
50 55 60
Asp Arg Tyr Gly Glu Glu Gly Leu Lys Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Ser Asn Trp Lys Trp Trp Pro Gly Ile Phe Asp
85 90
<210> 102
<211> 17
<212> PRT
<213> 人工的
<220>
<223> MGVKVLFALICIAVAEA
<400> 102
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala
<210> 103
<211> 19
<212> PRT
<213> 人工的
<220>
<223> MAPVQLLGLLVLFLPAMRC
<400> 103
Met Ala Pro Val Gln Leu Leu Gly Leu Leu Val Leu Phe Leu Pro Ala
1 5 10 15
Met Arg Cys
<210> 104
<211> 19
<212> PRT
<213> 人工的
<220>
<223> MAVLGLLFCLVTFPSCVLS
<400> 104
Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser
<210> 105
<211> 140
<212> PRT
<213> 人工的
<220>
<223> α-突触核蛋白
<400> 105
Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val
1 5 10 15
Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys
20 25 30
Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val
35 40 45
Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr
50 55 60
Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys
65 70 75 80
Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys
85 90 95
Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile
100 105 110
Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro
115 120 125
Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala
130 135 140
<210> 106
<211> 140
<212> PRT
<213> 人工的
<220>
<223> α-突触核蛋白(A53T)
<400> 106
Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val
1 5 10 15
Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys
20 25 30
Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val
35 40 45
Val His Gly Val Thr Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr
50 55 60
Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys
65 70 75 80
Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys
85 90 95
Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile
100 105 110
Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro
115 120 125
Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala
130 135 140
Claims (70)
1.因此,在第一个方面,本文公开的是分离的融合蛋白,其包含J蛋白的J结构域和α-突触核蛋白结合结构域。
2.权利要求1的融合蛋白,其中所述J蛋白的J结构域是真核起源的。
3.权利要求1或权利要求2中任何一项的融合蛋白,其中所述J蛋白的J结构域是人起源的。
4.权利要求1-3中任何一项的融合蛋白,其中所述J蛋白的J结构域是胞质定位的。
5.权利要求1-4中任何一项的融合蛋白,其中所述J蛋白的J结构域选自SEQ ID No:1-50。
6.权利要求1-5中任何一项的融合蛋白,其中所述J结构域包含选自SEQ ID NO:1、5、6、10、16、24、25、31和49的序列。
7.权利要求1-6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:5的序列。
8.权利要求1-6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:10的序列。
9.权利要求1-6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:16的序列。
10.权利要求1-6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:25的序列。
11.权利要求1-6中任何一项的融合蛋白,其中所述J结构域包含SEQ ID NO:31的序列。
12.权利要求1-11中任何一项的融合蛋白,其中当使用ELISA测定进行测量时,所述α-突触核蛋白结合结构域对于α-突触核蛋白具有1μM或更小,例如300nM或更小、100nM或更小、30nM或更小、10nM或更小的KD。
13.权利要求1-12中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含选自SEQ ID NO:51-64的序列。
14.权利要求1-13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:51的序列。
15.权利要求1-13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:52的序列。
16.权利要求1-13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:63的序列。
17.权利要求1-13中任何一项的融合蛋白,其中所述α-突触核蛋白结合结构域包含SEQID NO:64的序列。
18.权利要求1-17中任何一项的融合蛋白,其包含多个α-突触核蛋白结合结构域。
19.权利要求1-18中任何一项的融合蛋白,其由两个α-突触核蛋白结合结构域组成。
20.权利要求1-19中任何一项的融合蛋白,其由三个α-突触核蛋白结合结构域组成。
21.权利要求1-20中任何一项的融合蛋白,其包含以下构建体之一:
i.DNAJ-X-S,
ii.DNAJ-X-S-X-S,
iii.DNAJ-X-S-X-S-X-S,
iv.S-X-DNAJ,
v.S-X-S-X-DNAJ,
vi.S-X-S-X-S-X-DNAJ,
vii.S-X-DNAJ-X-S,
viii.S-X-DNAJ-X-S-X-S,
ix.S-X-S-X-DNAJ-X-S-X-S-X-S,
x.S-X-S-X-S-X-DNAJ-X-S,
xi.S-X-S-X-S-X-DNAJ-X-S-X-S,
xii.S-X-S-X-S-X-DNAJ-X-S-X-S-X-S,
xiii.DnaJ-X-DnaJ-X-S-X-S,
xiv.S-X-DnaJ-X-DnaJ,和
xv.S-X-S-X-DnaJ-X-DnaJ,
其中,
S是α-突触核蛋白结合结构域,
DNAJ是J蛋白的J结构域,和
X是任选的接头。
22.权利要求1-21中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:5的J结构域序列和SEQ ID NO:51的α-突触核蛋白结合结构域序列。
23.权利要求1-22中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:5的J结构域序列和SEQ ID NO:51的α-突触核蛋白结合结构域序列的两个拷贝。
24.权利要求1-23中任何一项的融合蛋白,其中所述融合蛋白包含选自SEQ ID NO:88、90-96、98-100的序列。
25.权利要求1-24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:88的序列。
26.权利要求1-24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:90的序列。
27.权利要求1-24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:99的序列。
28.权利要求1-24中任何一项的融合蛋白,其中所述融合蛋白包含SEQ ID NO:100的序列。
29.权利要求1-28中任何一项的融合蛋白,其进一步包含靶向试剂。
30.权利要求1-29中任何一项的融合蛋白,其进一步包含表位。
31.权利要求30的融合蛋白,其中所述表位是选自SEQ ID NO:77-83的多肽。
32.权利要求1-31中任何一项的融合蛋白,其进一步包含细胞穿透剂。
33.权利要求32的融合蛋白,其中所述细胞穿透剂包含选自SEQ IDNO:84-87的肽序列。
34.权利要求1-33中任何一项的融合蛋白,其进一步包含信号序列。
35.权利要求34的融合蛋白,其中所述信号序列包含选自SEQ IDNO:102-104的肽序列。
36.权利要求1-35中任何一项的融合蛋白,其能够减少细胞中的α-突触核蛋白蛋白质的错误折叠。
37.权利要求1-36中任何一项的融合蛋白,其能够减少细胞中的磷酸化的α-突触核蛋白蛋白质。
38.权利要求1-37中任何一项的融合蛋白,其能够减少α-突触核蛋白蛋白质的分泌。
39.权利要求1-38中任何一项的融合蛋白,其能够减少α-突触核蛋白介导的细胞毒性。
40.一种核酸序列,其编码权利要求1-39中任何一项的融合蛋白。
41.权利要求40的核酸序列,其中所述核酸是DNA。
42.权利要求41中任何一项的核酸序列,其中所述核酸是RNA。
43.权利要求40-42中任何一项的核酸序列,其中所述核酸包含至少一种修饰的核酸。
44.权利要求40-43中任何一项的核酸序列,其进一步包含启动子区、5'UTR、3'UTR如多聚(A)信号。
45.权利要求44的核酸序列,其中所述启动子区包含选自CMV增强子序列、CMV启动子、CBA启动子、UBC启动子、GUSB启动子、NSE启动子、突触素启动子、MeCP2启动子和GFAP启动子的序列。
46.一种载体,其包含权利要求40-45中任何一项的核酸序列。
47.权利要求46的载体,其中所述载体选自腺相关病毒(AAV)、腺病毒、慢病毒、逆转录病毒、疱疹病毒、痘病毒(牛痘或粘液瘤)、副粘病毒(麻疹、RSV或新城疫病毒)、杆状病毒、呼肠孤病毒、甲病毒和黄病毒。
48.一种病毒颗粒,其包含衣壳和权利要求46或权利要求47的载体。
49.权利要求48的病毒颗粒,其中所述衣壳选自AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV11、AAV12、假型AAV、恒河猴衍生的AAV、AAVrh8、AAVrh10和AAV-DJan AAV衣壳突变体、AAV杂合血清型、嗜器官性AAV、嗜心性AAV和嗜心性AAVM41突变体。
50.权利要求48或权利要求49的病毒颗粒,其中所述衣壳选自AAV2、AAV5、AAV8、AAV9和AAVrh10。
51.权利要求48-50中任何一项的病毒颗粒,其中所述衣壳是AAV2。
52.权利要求48-50中任何一项的病毒颗粒,其中所述衣壳是AAV5。
53.权利要求48-50中任何一项的病毒颗粒,其中所述衣壳是AAV8。
54.权利要求48-50中任何一项的病毒颗粒,其中所述衣壳是AAV9。
55.权利要求48-50中任何一项的病毒颗粒,其中所述衣壳是AAV rh10。
56.一种药物组合物,其包含选自以下的药剂和药学上可接受的载剂或赋形剂:权利要求1-39中任何一项的融合蛋白、表达权利要求1-39中任一项的融合蛋白的细胞、权利要求40-45中任何一项的核酸、权利要求46-47中任何一项的载体、权利要求48-55中任何一项的病毒颗粒。
57.减少细胞中的α-突触核蛋白蛋白质毒性的方法,其包括使所述细胞与有效量的选自以下的一种或多种药剂接触:权利要求1-39中任何一项的融合蛋白、表达权利要求1-39中任一项的融合蛋白的细胞、权利要求40-45中任何一项的核酸、权利要求46-47中任何一项的载体、权利要求48-55中任何一项的病毒颗粒和权利要求56的药物组合物。
58.权利要求57的方法,其中所述细胞在受试者中。
59.权利要求57-58中任何一项的方法,其中所述受试者是人。
60.权利要求57-59中任何一项的方法,其中所述细胞是中枢神经系统的细胞。
61.权利要求57-60中任何一项的方法,其中所述受试者被鉴定为患有α-突触核蛋白疾病。
62.权利要求61的方法,其中所述α-突触核蛋白疾病选自PD、路易体痴呆、多系统萎缩以及与聚集的α-突触核蛋白蛋白质的异常累积相关的疾病(突触核蛋白病)。
63.权利要求61或权利要求62的方法,其中所述α-突触核蛋白疾病是PD。
64.权利要求57-63中任何一项的方法,其中当与对照细胞相比时,存在所述细胞中的错误折叠的α-突触核蛋白蛋白质的量减少。
65.在需要其的受试者中治疗α-突触核蛋白疾病、预防α-突触核蛋白疾病或延迟α-突触核蛋白疾病的进展的方法,所述方法包括施用有效量的选自以下的一种或多种药剂:权利要求1-39中任何一项的融合蛋白、表达权利要求1-39中任一项的融合蛋白的细胞、权利要求40-45中任何一项的核酸、权利要求46-47中任何一项的载体、权利要求48-55中任何一项的病毒颗粒和权利要求56的药物组合物。
66.权利要求65的方法,其中所述α-突触核蛋白疾病选自PD、路易体痴呆、多系统萎缩以及与聚集的α-突触核蛋白蛋白质的异常累积相关的疾病(突触核蛋白病)。
67.权利要求65的方法,其中所述α-突触核蛋白疾病是PD。
68.以下中的一种或多种在受试者中预防α-突触核蛋白疾病或延迟α-突触核蛋白疾病的进展中的用途:权利要求1-39中任何一项的融合蛋白、表达权利要求1-39中任一项的融合蛋白的细胞、权利要求40-45中任何一项的核酸、权利要求46-47中任何一项的载体、权利要求48-55中任何一项的病毒颗粒和权利要求56的药物组合物。
69.以下中的一种或多种在制备用于治疗或预防受试者中的α-突触核蛋白疾病的药物中的用途:权利要求1-39中任何一项的融合蛋白、表达权利要求1-39中任一项的融合蛋白的细胞、权利要求40-45中任何一项的核酸、权利要求46-47中任何一项的载体、权利要求48-55中任何一项的病毒颗粒和权利要求56的药物组合物。
70.权利要求68或权利要求69的用途,其中所述α-突触核蛋白疾病是PD。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063035297P | 2020-06-05 | 2020-06-05 | |
US63/035297 | 2020-06-05 | ||
PCT/US2021/035958 WO2021248038A1 (en) | 2020-06-05 | 2021-06-04 | Compositions and methods for the treatment of synucleinopathies |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116096737A true CN116096737A (zh) | 2023-05-09 |
Family
ID=76708439
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202180058141.7A Pending CN116096737A (zh) | 2020-06-05 | 2021-06-04 | 用于治疗突触核蛋白病的组合物和方法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20230234997A1 (zh) |
EP (1) | EP4161953A1 (zh) |
JP (1) | JP2023529371A (zh) |
CN (1) | CN116096737A (zh) |
CA (1) | CA3183251A1 (zh) |
WO (1) | WO2021248038A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117402251A (zh) * | 2023-12-15 | 2024-01-16 | 中国医学科学院基础医学研究所 | 一种抗小g蛋白rbj的抗体及其应用 |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8918616D0 (en) | 1989-08-15 | 1989-09-27 | Univ Glasgow | Herpes simplex virus type 1 mutant |
US5804413A (en) | 1992-07-31 | 1998-09-08 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Herpes simplex virus strains for gene transfer |
GB9415319D0 (en) | 1994-07-29 | 1994-09-21 | Medical Res Council | HSV viral vector |
US5846782A (en) | 1995-11-28 | 1998-12-08 | Genvec, Inc. | Targeting adenovirus with use of constrained peptide motifs |
US6093570A (en) | 1995-06-07 | 2000-07-25 | The University Of North Carolina At Chapel Hill | Helper virus-free AAV production |
US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
EP1002119A1 (en) | 1997-07-31 | 2000-05-24 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Targeted hsv vectors |
US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
AU762220B2 (en) | 1998-05-28 | 2003-06-19 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | AAV5 vector and uses thereof |
AU2001269723B9 (en) | 2000-06-01 | 2006-11-16 | University Of North Carolina At Chapel Hill | Duplexed parvovirus vectors |
JP2004502781A (ja) | 2000-07-07 | 2004-01-29 | パナシア ファーマシューティカルズ インコーポレーテッド | 神経組織の損傷を予防するため、およびα−シヌクレイン疾患を処置するための方法 |
WO2002053703A2 (en) | 2001-01-05 | 2002-07-11 | Children's Hospital, Inc. | Aav2 vectors and methods |
BRPI0214119B8 (pt) | 2001-11-13 | 2021-05-25 | Univ Pennsylvania | vírus adenoassociado recombinante, método de geração do referido vírus e composição compreendendo o referido vírus |
PT1453547T (pt) | 2001-12-17 | 2016-12-28 | Univ Pennsylvania | Sequências do vírus adeno-associado (aav) do serotipo 8, vetores contendo as mesmas, e utilizações destas |
PT3211085T (pt) | 2003-09-30 | 2021-06-17 | Univ Pennsylvania | Clados de vírus adeno-associados (aav), sequências, vetores que as contêm, e suas utilizações |
EP1828390B1 (en) | 2004-12-15 | 2012-06-13 | The University Of North Carolina At Chapel Hill | Chimeric vectors |
EP2396343B1 (en) | 2009-02-11 | 2017-05-17 | The University of North Carolina At Chapel Hill | Modified virus vectors and methods of making and using the same |
WO2011088081A1 (en) | 2010-01-12 | 2011-07-21 | The University Of North Carolina At Chapel Hill | Restrictive inverted terminal repeats for viral vectors |
WO2011097456A2 (en) | 2010-02-05 | 2011-08-11 | The University Of North Carolina At Chapel Hill | Compositions and methods for enhanced parvovirus transduction |
WO2014053879A1 (en) | 2012-10-04 | 2014-04-10 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
EP2929045B1 (en) * | 2012-12-05 | 2020-12-02 | SOLA Biosciences LLC | Protein expression enhancing polypeptides |
TW201815818A (zh) * | 2016-09-26 | 2018-05-01 | 美商碩拿生物科學有限責任公司 | 細胞相關之分泌增強融合蛋白 |
WO2019161386A1 (en) | 2018-02-19 | 2019-08-22 | New York University | Alpha-synuclein single domain antibodies |
-
2021
- 2021-06-04 CA CA3183251A patent/CA3183251A1/en active Pending
- 2021-06-04 EP EP21736438.9A patent/EP4161953A1/en active Pending
- 2021-06-04 JP JP2022574541A patent/JP2023529371A/ja active Pending
- 2021-06-04 WO PCT/US2021/035958 patent/WO2021248038A1/en active Application Filing
- 2021-06-04 CN CN202180058141.7A patent/CN116096737A/zh active Pending
- 2021-06-04 US US18/007,978 patent/US20230234997A1/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117402251A (zh) * | 2023-12-15 | 2024-01-16 | 中国医学科学院基础医学研究所 | 一种抗小g蛋白rbj的抗体及其应用 |
CN117402251B (zh) * | 2023-12-15 | 2024-02-23 | 中国医学科学院基础医学研究所 | 一种抗小g蛋白rbj的抗体及其应用 |
Also Published As
Publication number | Publication date |
---|---|
JP2023529371A (ja) | 2023-07-10 |
US20230234997A1 (en) | 2023-07-27 |
WO2021248038A1 (en) | 2021-12-09 |
EP4161953A1 (en) | 2023-04-12 |
CA3183251A1 (en) | 2021-12-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR20220070075A (ko) | 아데노-관련 바이러스 변이체 캡시드 및 그 용도 | |
TW202315946A (zh) | 組織選擇性轉基因表現 | |
JP2023524414A (ja) | Tdp-43プロテイノパチーの処置のための組成物および方法 | |
JP2018518946A (ja) | アンジェルマン症候群の遺伝子治療法のための組み換えube3a遺伝子 | |
CN110869031A (zh) | 用于天使人综合征的基因治疗方法的修饰的ube3a基因 | |
US20230226223A1 (en) | Compositions and Methods for the Treatment of Protein Aggregation Disorders | |
US20230234997A1 (en) | Compositions and Methods for the Treatment of Synucleinopathies | |
CN116685329A (zh) | 核酸构建体及其用于治疗脊髓性肌肉萎缩症的用途 | |
KR20220003566A (ko) | 신규한 유형의 효소 조성물 | |
US20240025954A1 (en) | Compositions and Methods for the Treatment of Alzheimer's Disease | |
KR20220131273A (ko) | 타우 발현을 억제시키기 위한 아연 핑거 단백질 전사 인자 | |
WO2023060248A1 (en) | Compositions and methods for the treatment of p53-mediated cancers | |
WO2023060221A2 (en) | Compositions and methods for the treatment of proteopathies | |
JP7482549B2 (ja) | 新規のマイクロジストロフィンおよび使用の関連する方法 | |
Dunckley et al. | Toward a gene therapy for duchenne muscular dystrophy | |
WO2024052413A1 (en) | Beta-hexosaminidase vectors | |
WO2024079292A1 (en) | Gene therapy treatment | |
CN116761812A (zh) | Neurod1和dlx2载体 | |
Al-Rafiah | PLASTIN3 AS A THERAPEUTIC TARGET IN SPINAL MUSCULAR ATROPHY | |
KR20210005612A (ko) | 산화성 스트레스에 대한 유전자 요법 |
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: 40092059 Country of ref document: HK |