CN112362877B - 一种mbp重组蛋白以及其应用 - Google Patents
一种mbp重组蛋白以及其应用 Download PDFInfo
- Publication number
- CN112362877B CN112362877B CN202011167856.XA CN202011167856A CN112362877B CN 112362877 B CN112362877 B CN 112362877B CN 202011167856 A CN202011167856 A CN 202011167856A CN 112362877 B CN112362877 B CN 112362877B
- Authority
- CN
- China
- Prior art keywords
- mbp
- gly
- recombinant
- lys
- ser
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 title claims abstract description 25
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 title claims abstract description 24
- 238000001514 detection method Methods 0.000 claims abstract description 30
- 239000013612 plasmid Substances 0.000 claims description 38
- 238000011534 incubation Methods 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 108090000623 proteins and genes Proteins 0.000 claims description 22
- 238000007789 sealing Methods 0.000 claims description 13
- 230000000903 blocking effect Effects 0.000 claims description 10
- 210000002966 serum Anatomy 0.000 claims description 10
- 102000007562 Serum Albumin Human genes 0.000 claims description 8
- 108010071390 Serum Albumin Proteins 0.000 claims description 8
- 241001494479 Pecora Species 0.000 claims description 7
- 241000894006 Bacteria Species 0.000 claims description 6
- 241000283707 Capra Species 0.000 claims description 6
- 108700026244 Open Reading Frames Proteins 0.000 claims description 6
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 229920002866 paraformaldehyde Polymers 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 239000000427 antigen Substances 0.000 abstract description 8
- 102000036639 antigens Human genes 0.000 abstract description 8
- 108091007433 antigens Proteins 0.000 abstract description 8
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 238000005457 optimization Methods 0.000 abstract description 2
- 230000009466 transformation Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 44
- 239000000243 solution Substances 0.000 description 13
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- FEIWNULTQYHCDN-UHFFFAOYSA-N mbba Chemical compound C1=CC(CCCC)=CC=C1N=CC1=CC=C(OC)C=C1 FEIWNULTQYHCDN-UHFFFAOYSA-N 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 201000006417 multiple sclerosis Diseases 0.000 description 6
- 208000016192 Demyelinating disease Diseases 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 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 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 108010038633 aspartylglutamate Proteins 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002474 experimental method 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
- 239000007788 liquid Substances 0.000 description 4
- 108010064235 lysylglycine Proteins 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 150000007523 nucleic acids Chemical group 0.000 description 4
- 108010051242 phenylalanylserine Proteins 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 108010051110 tyrosyl-lysine Proteins 0.000 description 4
- 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 3
- HQRHFUYMGCHHJS-LURJTMIESA-N Gly-Gly-Arg Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N HQRHFUYMGCHHJS-LURJTMIESA-N 0.000 description 3
- 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 3
- 102000047918 Myelin Basic Human genes 0.000 description 3
- 102000006386 Myelin Proteins Human genes 0.000 description 3
- 108010083674 Myelin Proteins Proteins 0.000 description 3
- 101710107068 Myelin basic protein Proteins 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 108010050848 glycylleucine Proteins 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 108010048818 seryl-histidine Proteins 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- XVZCXCTYGHPNEM-IHRRRGAJSA-N (2s)-1-[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O XVZCXCTYGHPNEM-IHRRRGAJSA-N 0.000 description 2
- JAMAWBXXKFGFGX-KZVJFYERSA-N Ala-Arg-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JAMAWBXXKFGFGX-KZVJFYERSA-N 0.000 description 2
- LBFXVAXPDOBRKU-LKTVYLICSA-N Ala-His-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LBFXVAXPDOBRKU-LKTVYLICSA-N 0.000 description 2
- BTRULDJUUVGRNE-DCAQKATOSA-N Ala-Pro-Lys Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(O)=O BTRULDJUUVGRNE-DCAQKATOSA-N 0.000 description 2
- 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 2
- 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 2
- CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 description 2
- QEHMMRSQJMOYNO-DCAQKATOSA-N Arg-His-Asn Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N QEHMMRSQJMOYNO-DCAQKATOSA-N 0.000 description 2
- MSILNNHVVMMTHZ-UWVGGRQHSA-N Arg-His-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CN=CN1 MSILNNHVVMMTHZ-UWVGGRQHSA-N 0.000 description 2
- HBUJSDCLZCXXCW-YDHLFZDLSA-N Asn-Val-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HBUJSDCLZCXXCW-YDHLFZDLSA-N 0.000 description 2
- AXXCUABIFZPKPM-BQBZGAKWSA-N Asp-Arg-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O AXXCUABIFZPKPM-BQBZGAKWSA-N 0.000 description 2
- VBVKSAFJPVXMFJ-CIUDSAMLSA-N Asp-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N VBVKSAFJPVXMFJ-CIUDSAMLSA-N 0.000 description 2
- JUWZKMBALYLZCK-WHFBIAKZSA-N Asp-Gly-Asn Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O JUWZKMBALYLZCK-WHFBIAKZSA-N 0.000 description 2
- QNIACYURSSCLRP-GUBZILKMSA-N Asp-Lys-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O QNIACYURSSCLRP-GUBZILKMSA-N 0.000 description 2
- ZBYLEBZCVKLPCY-FXQIFTODSA-N Asp-Ser-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZBYLEBZCVKLPCY-FXQIFTODSA-N 0.000 description 2
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 description 2
- 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 2
- 206010012305 Demyelination Diseases 0.000 description 2
- LPJVZYMINRLCQA-AVGNSLFASA-N Gln-Cys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)N)N LPJVZYMINRLCQA-AVGNSLFASA-N 0.000 description 2
- 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 2
- GURIQZQSTBBHRV-SRVKXCTJSA-N Gln-Lys-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GURIQZQSTBBHRV-SRVKXCTJSA-N 0.000 description 2
- LXAUHIRMWXQRKI-XHNCKOQMSA-N Glu-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N)C(=O)O LXAUHIRMWXQRKI-XHNCKOQMSA-N 0.000 description 2
- IOUQWHIEQYQVFD-JYJNAYRXSA-N Glu-Leu-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IOUQWHIEQYQVFD-JYJNAYRXSA-N 0.000 description 2
- LURCIJSJAKFCRO-QWRGUYRKSA-N Gly-Asn-Tyr Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LURCIJSJAKFCRO-QWRGUYRKSA-N 0.000 description 2
- 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 2
- MVORZMQFXBLMHM-QWRGUYRKSA-N Gly-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 MVORZMQFXBLMHM-QWRGUYRKSA-N 0.000 description 2
- MHXKHKWHPNETGG-QWRGUYRKSA-N Gly-Lys-Leu Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O MHXKHKWHPNETGG-QWRGUYRKSA-N 0.000 description 2
- OJNZVYSGVYLQIN-BQBZGAKWSA-N Gly-Met-Asp Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O OJNZVYSGVYLQIN-BQBZGAKWSA-N 0.000 description 2
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 2
- DUAWRXXTOQOECJ-JSGCOSHPSA-N Gly-Tyr-Val Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O DUAWRXXTOQOECJ-JSGCOSHPSA-N 0.000 description 2
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 2
- UXSATKFPUVZVDK-KKUMJFAQSA-N His-Lys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CN=CN1)N UXSATKFPUVZVDK-KKUMJFAQSA-N 0.000 description 2
- KIMHKBDJQQYLHU-PEFMBERDSA-N Ile-Glu-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KIMHKBDJQQYLHU-PEFMBERDSA-N 0.000 description 2
- LPXHYGGZJOCAFR-MNXVOIDGSA-N Ile-Glu-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N LPXHYGGZJOCAFR-MNXVOIDGSA-N 0.000 description 2
- 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 2
- MASWXTFJVNRZPT-NAKRPEOUSA-N Ile-Met-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)O)N MASWXTFJVNRZPT-NAKRPEOUSA-N 0.000 description 2
- KBDIBHQICWDGDL-PPCPHDFISA-N Ile-Thr-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N KBDIBHQICWDGDL-PPCPHDFISA-N 0.000 description 2
- 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 2
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 2
- JDBQSGMJBMPNFT-AVGNSLFASA-N Leu-Pro-Val Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O JDBQSGMJBMPNFT-AVGNSLFASA-N 0.000 description 2
- AMSSKPUHBUQBOQ-SRVKXCTJSA-N Leu-Ser-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N AMSSKPUHBUQBOQ-SRVKXCTJSA-N 0.000 description 2
- QUYCUALODHJQLK-CIUDSAMLSA-N Lys-Asp-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O QUYCUALODHJQLK-CIUDSAMLSA-N 0.000 description 2
- TVHCDSBMFQYPNA-RHYQMDGZSA-N Lys-Thr-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O TVHCDSBMFQYPNA-RHYQMDGZSA-N 0.000 description 2
- WXHHTBVYQOSYSL-FXQIFTODSA-N Met-Ala-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O WXHHTBVYQOSYSL-FXQIFTODSA-N 0.000 description 2
- BQHLZUMZOXUWNU-DCAQKATOSA-N Met-Pro-Glu Chemical compound CSCC[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)O)N BQHLZUMZOXUWNU-DCAQKATOSA-N 0.000 description 2
- 108010079364 N-glycylalanine Proteins 0.000 description 2
- ZUQACJLOHYRVPJ-DKIMLUQUSA-N Phe-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 ZUQACJLOHYRVPJ-DKIMLUQUSA-N 0.000 description 2
- MVIJMIZJPHQGEN-IHRRRGAJSA-N Phe-Ser-Val Chemical compound CC(C)[C@@H](C([O-])=O)NC(=O)[C@H](CO)NC(=O)[C@@H]([NH3+])CC1=CC=CC=C1 MVIJMIZJPHQGEN-IHRRRGAJSA-N 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- ZSKJPKFTPQCPIH-RCWTZXSCSA-N Pro-Arg-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZSKJPKFTPQCPIH-RCWTZXSCSA-N 0.000 description 2
- KIGGUSRFHJCIEJ-DCAQKATOSA-N Pro-Asp-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O KIGGUSRFHJCIEJ-DCAQKATOSA-N 0.000 description 2
- SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 2
- SNSYSBUTTJBPDG-OKZBNKHCSA-N Pro-Trp-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N4CCC[C@@H]4C(=O)O SNSYSBUTTJBPDG-OKZBNKHCSA-N 0.000 description 2
- QGMLKFGTGXWAHF-IHRRRGAJSA-N Ser-Arg-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QGMLKFGTGXWAHF-IHRRRGAJSA-N 0.000 description 2
- WXUBSIDKNMFAGS-IHRRRGAJSA-N Ser-Arg-Tyr Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@H](CO)N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WXUBSIDKNMFAGS-IHRRRGAJSA-N 0.000 description 2
- UYLKOSODXYSWMQ-XGEHTFHBSA-N Ser-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CO)N)O UYLKOSODXYSWMQ-XGEHTFHBSA-N 0.000 description 2
- BCAVNDNYOGTQMQ-AAEUAGOBSA-N Ser-Trp-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(O)=O BCAVNDNYOGTQMQ-AAEUAGOBSA-N 0.000 description 2
- WLDUCKSCDRIVLJ-NUMRIWBASA-N Thr-Gln-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O WLDUCKSCDRIVLJ-NUMRIWBASA-N 0.000 description 2
- LIXBDERDAGNVAV-XKBZYTNZSA-N Thr-Gln-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O LIXBDERDAGNVAV-XKBZYTNZSA-N 0.000 description 2
- 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 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
- NSGZILIDHCIZAM-KKUMJFAQSA-N Tyr-Leu-Ser Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N NSGZILIDHCIZAM-KKUMJFAQSA-N 0.000 description 2
- UDLYXGYWTVOIKU-QXEWZRGKSA-N Val-Asn-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UDLYXGYWTVOIKU-QXEWZRGKSA-N 0.000 description 2
- ISERLACIZUGCDX-ZKWXMUAHSA-N Val-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N ISERLACIZUGCDX-ZKWXMUAHSA-N 0.000 description 2
- 108010044940 alanylglutamine Proteins 0.000 description 2
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 2
- 108010060035 arginylproline Proteins 0.000 description 2
- 108010047857 aspartylglycine Proteins 0.000 description 2
- 108010068265 aspartyltyrosine Proteins 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 2
- 108010038983 glycyl-histidyl-lysine Proteins 0.000 description 2
- 108010077435 glycyl-phenylalanyl-glycine Proteins 0.000 description 2
- 108010015792 glycyllysine Proteins 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000003007 myelin sheath Anatomy 0.000 description 2
- 210000000944 nerve tissue Anatomy 0.000 description 2
- 108010084525 phenylalanyl-phenylalanyl-glycine Proteins 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108010031719 prolyl-serine Proteins 0.000 description 2
- 108010015796 prolylisoleucine Proteins 0.000 description 2
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 2
- 108010026333 seryl-proline Proteins 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 108700004896 tripeptide FEG Proteins 0.000 description 2
- 108010020532 tyrosyl-proline Proteins 0.000 description 2
- 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
- LZRNYBIJOSKKRJ-XVYDVKMFSA-N Ala-Asp-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N LZRNYBIJOSKKRJ-XVYDVKMFSA-N 0.000 description 1
- PAIHPOGPJVUFJY-WDSKDSINSA-N Ala-Glu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O PAIHPOGPJVUFJY-WDSKDSINSA-N 0.000 description 1
- OMMDTNGURYRDAC-NRPADANISA-N Ala-Glu-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OMMDTNGURYRDAC-NRPADANISA-N 0.000 description 1
- SMCGQGDVTPFXKB-XPUUQOCRSA-N Ala-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N SMCGQGDVTPFXKB-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
- 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
- HJWQFFYRVFEWRM-SRVKXCTJSA-N Arg-Arg-Met Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(O)=O HJWQFFYRVFEWRM-SRVKXCTJSA-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
- HGKHPCFTRQDHCU-IUCAKERBSA-N Arg-Pro-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HGKHPCFTRQDHCU-IUCAKERBSA-N 0.000 description 1
- PBSQFBAJKPLRJY-BYULHYEWSA-N Asn-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N PBSQFBAJKPLRJY-BYULHYEWSA-N 0.000 description 1
- SPCONPVIDFMDJI-QSFUFRPTSA-N Asn-Ile-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O SPCONPVIDFMDJI-QSFUFRPTSA-N 0.000 description 1
- DOURAOODTFJRIC-CIUDSAMLSA-N Asn-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N DOURAOODTFJRIC-CIUDSAMLSA-N 0.000 description 1
- WUQXMTITJLFXAU-JIOCBJNQSA-N Asn-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N)O WUQXMTITJLFXAU-JIOCBJNQSA-N 0.000 description 1
- POTCZYQVVNXUIG-BQBZGAKWSA-N Asp-Gly-Pro Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O POTCZYQVVNXUIG-BQBZGAKWSA-N 0.000 description 1
- LDGUZSIPGSPBJP-XVYDVKMFSA-N Asp-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)O)N LDGUZSIPGSPBJP-XVYDVKMFSA-N 0.000 description 1
- LNENWJXDHCFVOF-DCAQKATOSA-N Asp-His-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)O)N LNENWJXDHCFVOF-DCAQKATOSA-N 0.000 description 1
- JUWISGAGWSDGDH-KKUMJFAQSA-N Asp-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=CC=C1 JUWISGAGWSDGDH-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
- BWJZSLQJNBSUPM-FXQIFTODSA-N Asp-Pro-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O BWJZSLQJNBSUPM-FXQIFTODSA-N 0.000 description 1
- DRCOAZZDQRCGGP-GHCJXIJMSA-N Asp-Ser-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DRCOAZZDQRCGGP-GHCJXIJMSA-N 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- XOKGKOQWADCLFQ-GARJFASQSA-N Gln-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XOKGKOQWADCLFQ-GARJFASQSA-N 0.000 description 1
- GMGKDVVBSVVKCT-NUMRIWBASA-N Gln-Asn-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GMGKDVVBSVVKCT-NUMRIWBASA-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
- XSBGUANSZDGULP-IUCAKERBSA-N Gln-Gly-Lys Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O XSBGUANSZDGULP-IUCAKERBSA-N 0.000 description 1
- 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 1
- ZEEPYMXTJWIMSN-GUBZILKMSA-N Gln-Lys-Ser Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ZEEPYMXTJWIMSN-GUBZILKMSA-N 0.000 description 1
- SRZLHYPAOXBBSB-HJGDQZAQSA-N Glu-Arg-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SRZLHYPAOXBBSB-HJGDQZAQSA-N 0.000 description 1
- MUSGDMDGNGXULI-DCAQKATOSA-N Glu-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O MUSGDMDGNGXULI-DCAQKATOSA-N 0.000 description 1
- 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 1
- WRNAXCVRSBBKGS-BQBZGAKWSA-N Glu-Gly-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O WRNAXCVRSBBKGS-BQBZGAKWSA-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
- 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
- UCZXXMREFIETQW-AVGNSLFASA-N Glu-Tyr-Asn 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](CC(N)=O)C(O)=O UCZXXMREFIETQW-AVGNSLFASA-N 0.000 description 1
- ZYRXTRTUCAVNBQ-GVXVVHGQSA-N Glu-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZYRXTRTUCAVNBQ-GVXVVHGQSA-N 0.000 description 1
- RJIVPOXLQFJRTG-LURJTMIESA-N Gly-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N RJIVPOXLQFJRTG-LURJTMIESA-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
- UTYGDAHJBBDPBA-BYULHYEWSA-N Gly-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)CN UTYGDAHJBBDPBA-BYULHYEWSA-N 0.000 description 1
- 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 1
- 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 1
- IGOYNRWLWHWAQO-JTQLQIEISA-N Gly-Phe-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IGOYNRWLWHWAQO-JTQLQIEISA-N 0.000 description 1
- YLEIWGJJBFBFHC-KBPBESRZSA-N Gly-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 YLEIWGJJBFBFHC-KBPBESRZSA-N 0.000 description 1
- BMWFDYIYBAFROD-WPRPVWTQSA-N Gly-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN BMWFDYIYBAFROD-WPRPVWTQSA-N 0.000 description 1
- VNNRLUNBJSWZPF-ZKWXMUAHSA-N Gly-Ser-Ile Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNNRLUNBJSWZPF-ZKWXMUAHSA-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
- MUGLKCQHTUFLGF-WPRPVWTQSA-N Gly-Val-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)CN MUGLKCQHTUFLGF-WPRPVWTQSA-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
- WGVPDSNCHDEDBP-KKUMJFAQSA-N His-Asp-Phe Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O WGVPDSNCHDEDBP-KKUMJFAQSA-N 0.000 description 1
- PYNUBZSXKQKAHL-UWVGGRQHSA-N His-Gly-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O PYNUBZSXKQKAHL-UWVGGRQHSA-N 0.000 description 1
- FYTCLUIYTYFGPT-YUMQZZPRSA-N His-Gly-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FYTCLUIYTYFGPT-YUMQZZPRSA-N 0.000 description 1
- 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
- XKIYNCLILDLGRS-QWRGUYRKSA-N His-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 XKIYNCLILDLGRS-QWRGUYRKSA-N 0.000 description 1
- WSWAUVHXQREQQG-JYJNAYRXSA-N His-Tyr-Gln Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O WSWAUVHXQREQQG-JYJNAYRXSA-N 0.000 description 1
- 101001018318 Homo sapiens Myelin basic protein Proteins 0.000 description 1
- VQUCKIAECLVLAD-SVSWQMSJSA-N Ile-Cys-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N VQUCKIAECLVLAD-SVSWQMSJSA-N 0.000 description 1
- NHJKZMDIMMTVCK-QXEWZRGKSA-N Ile-Gly-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N NHJKZMDIMMTVCK-QXEWZRGKSA-N 0.000 description 1
- KFVUBLZRFSVDGO-BYULHYEWSA-N Ile-Gly-Asp Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O KFVUBLZRFSVDGO-BYULHYEWSA-N 0.000 description 1
- DFFTXLCCDFYRKD-MBLNEYKQSA-N Ile-Gly-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N DFFTXLCCDFYRKD-MBLNEYKQSA-N 0.000 description 1
- HPCFRQWLTRDGHT-AJNGGQMLSA-N Ile-Leu-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O HPCFRQWLTRDGHT-AJNGGQMLSA-N 0.000 description 1
- UDBPXJNOEWDBDF-XUXIUFHCSA-N Ile-Lys-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)O)N UDBPXJNOEWDBDF-XUXIUFHCSA-N 0.000 description 1
- SNHYFFQZRFIRHO-CYDGBPFRSA-N Ile-Met-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)O)N SNHYFFQZRFIRHO-CYDGBPFRSA-N 0.000 description 1
- LRAUKBMYHHNADU-DKIMLUQUSA-N Ile-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)CC)CC1=CC=CC=C1 LRAUKBMYHHNADU-DKIMLUQUSA-N 0.000 description 1
- CIDLJWVDMNDKPT-FIRPJDEBSA-N Ile-Phe-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)N CIDLJWVDMNDKPT-FIRPJDEBSA-N 0.000 description 1
- YKZAMJXNJUWFIK-JBDRJPRFSA-N Ile-Ser-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)O)N YKZAMJXNJUWFIK-JBDRJPRFSA-N 0.000 description 1
- WLRJHVNFGAOYPS-HJPIBITLSA-N Ile-Ser-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N WLRJHVNFGAOYPS-HJPIBITLSA-N 0.000 description 1
- APQYGMBHIVXFML-OSUNSFLBSA-N Ile-Val-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N APQYGMBHIVXFML-OSUNSFLBSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ULXYQAJWJGLCNR-YUMQZZPRSA-N Leu-Asp-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O ULXYQAJWJGLCNR-YUMQZZPRSA-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
- 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
- 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
- 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
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 1
- AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 description 1
- HQVDJTYKCMIWJP-YUMQZZPRSA-N Lys-Asn-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O HQVDJTYKCMIWJP-YUMQZZPRSA-N 0.000 description 1
- YEIYAQQKADPIBJ-GARJFASQSA-N Lys-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)N)C(=O)O YEIYAQQKADPIBJ-GARJFASQSA-N 0.000 description 1
- NRQRKMYZONPCTM-CIUDSAMLSA-N Lys-Asp-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O NRQRKMYZONPCTM-CIUDSAMLSA-N 0.000 description 1
- LXNPMPIQDNSMTA-AVGNSLFASA-N Lys-Gln-His Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 LXNPMPIQDNSMTA-AVGNSLFASA-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
- DTUZCYRNEJDKSR-NHCYSSNCSA-N Lys-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN DTUZCYRNEJDKSR-NHCYSSNCSA-N 0.000 description 1
- JYXBNQOKPRQNQS-YTFOTSKYSA-N Lys-Ile-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JYXBNQOKPRQNQS-YTFOTSKYSA-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
- 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
- MIMXMVDLMDMOJD-BZSNNMDCSA-N Lys-Tyr-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O MIMXMVDLMDMOJD-BZSNNMDCSA-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
- 101150028955 MBP gene Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- MSSJHBAKDDIRMJ-SRVKXCTJSA-N Met-Lys-Gln Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O MSSJHBAKDDIRMJ-SRVKXCTJSA-N 0.000 description 1
- CULGJGUDIJATIP-STQMWFEESA-N Met-Tyr-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 CULGJGUDIJATIP-STQMWFEESA-N 0.000 description 1
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- FIRWJEJVFFGXSH-RYUDHWBXSA-N Phe-Glu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 FIRWJEJVFFGXSH-RYUDHWBXSA-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
- WFHRXJOZEXUKLV-IRXDYDNUSA-N Phe-Gly-Tyr Chemical compound C([C@H](N)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 WFHRXJOZEXUKLV-IRXDYDNUSA-N 0.000 description 1
- RGZYXNFHYRFNNS-MXAVVETBSA-N Phe-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N RGZYXNFHYRFNNS-MXAVVETBSA-N 0.000 description 1
- OSBADCBXAMSPQD-YESZJQIVSA-N Phe-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N OSBADCBXAMSPQD-YESZJQIVSA-N 0.000 description 1
- RMKGXGPQIPLTFC-KKUMJFAQSA-N Phe-Lys-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O RMKGXGPQIPLTFC-KKUMJFAQSA-N 0.000 description 1
- WLYPRKLMRIYGPP-JYJNAYRXSA-N Phe-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 WLYPRKLMRIYGPP-JYJNAYRXSA-N 0.000 description 1
- AUJWXNGCAQWLEI-KBPBESRZSA-N Phe-Lys-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O AUJWXNGCAQWLEI-KBPBESRZSA-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
- IWZRODDWOSIXPZ-IRXDYDNUSA-N Phe-Phe-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(O)=O)C1=CC=CC=C1 IWZRODDWOSIXPZ-IRXDYDNUSA-N 0.000 description 1
- RBRNEFJTEHPDSL-ACRUOGEOSA-N Phe-Phe-Lys Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 RBRNEFJTEHPDSL-ACRUOGEOSA-N 0.000 description 1
- BSKMOCNNLNDIMU-CDMKHQONSA-N Phe-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O BSKMOCNNLNDIMU-CDMKHQONSA-N 0.000 description 1
- JTKGCYOOJLUETJ-ULQDDVLXSA-N Phe-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 JTKGCYOOJLUETJ-ULQDDVLXSA-N 0.000 description 1
- MWQXFDIQXIXPMS-UNQGMJICSA-N Phe-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC1=CC=CC=C1)N)O MWQXFDIQXIXPMS-UNQGMJICSA-N 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- LANQLYHLMYDWJP-SRVKXCTJSA-N Pro-Gln-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O LANQLYHLMYDWJP-SRVKXCTJSA-N 0.000 description 1
- XYHMFGGWNOFUOU-QXEWZRGKSA-N Pro-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 XYHMFGGWNOFUOU-QXEWZRGKSA-N 0.000 description 1
- HBBBLSVBQGZKOZ-GUBZILKMSA-N Pro-Met-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O HBBBLSVBQGZKOZ-GUBZILKMSA-N 0.000 description 1
- SEZGGSHLMROBFX-CIUDSAMLSA-N Pro-Ser-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O SEZGGSHLMROBFX-CIUDSAMLSA-N 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 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
- XWCYBVBLJRWOFR-WDSKDSINSA-N Ser-Gln-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O XWCYBVBLJRWOFR-WDSKDSINSA-N 0.000 description 1
- MIJWOJAXARLEHA-WDSKDSINSA-N Ser-Gly-Glu Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O MIJWOJAXARLEHA-WDSKDSINSA-N 0.000 description 1
- QGAHMVHBORDHDC-YUMQZZPRSA-N Ser-His-Gly Chemical compound OC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CN=CN1 QGAHMVHBORDHDC-YUMQZZPRSA-N 0.000 description 1
- IOVBCLGAJJXOHK-SRVKXCTJSA-N Ser-His-His Chemical compound C([C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 IOVBCLGAJJXOHK-SRVKXCTJSA-N 0.000 description 1
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 1
- OWCVUSJMEBGMOK-YUMQZZPRSA-N Ser-Lys-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O OWCVUSJMEBGMOK-YUMQZZPRSA-N 0.000 description 1
- LRWBCWGEUCKDTN-BJDJZHNGSA-N Ser-Lys-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LRWBCWGEUCKDTN-BJDJZHNGSA-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
- LLSLRQOEAFCZLW-NRPADANISA-N Ser-Val-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LLSLRQOEAFCZLW-NRPADANISA-N 0.000 description 1
- IMULJHHGAUZZFE-MBLNEYKQSA-N Thr-Gly-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IMULJHHGAUZZFE-MBLNEYKQSA-N 0.000 description 1
- MPUMPERGHHJGRP-WEDXCCLWSA-N Thr-Gly-Lys Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N)O MPUMPERGHHJGRP-WEDXCCLWSA-N 0.000 description 1
- UYTYTDMCDBPDSC-URLPEUOOSA-N Thr-Ile-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N UYTYTDMCDBPDSC-URLPEUOOSA-N 0.000 description 1
- FLPZMPOZGYPBEN-PPCPHDFISA-N Thr-Leu-Ile 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)CC)C(O)=O FLPZMPOZGYPBEN-PPCPHDFISA-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
- UQCNIMDPYICBTR-KYNKHSRBSA-N Thr-Thr-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O UQCNIMDPYICBTR-KYNKHSRBSA-N 0.000 description 1
- BBPCSGKKPJUYRB-UVOCVTCTSA-N Thr-Thr-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O BBPCSGKKPJUYRB-UVOCVTCTSA-N 0.000 description 1
- PELIQFPESHBTMA-WLTAIBSBSA-N Thr-Tyr-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 PELIQFPESHBTMA-WLTAIBSBSA-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
- NSTPFWRAIDTNGH-BZSNNMDCSA-N Tyr-Asn-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NSTPFWRAIDTNGH-BZSNNMDCSA-N 0.000 description 1
- 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
- CTDPLKMBVALCGN-JSGCOSHPSA-N Tyr-Gly-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O CTDPLKMBVALCGN-JSGCOSHPSA-N 0.000 description 1
- PGEFRHBWGOJPJT-KKUMJFAQSA-N Tyr-Lys-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O PGEFRHBWGOJPJT-KKUMJFAQSA-N 0.000 description 1
- ZTKGDWOUYRRAOQ-ULQDDVLXSA-N Val-His-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)N ZTKGDWOUYRRAOQ-ULQDDVLXSA-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
- SSKKGOWRPNIVDW-AVGNSLFASA-N Val-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N SSKKGOWRPNIVDW-AVGNSLFASA-N 0.000 description 1
- JSOXWWFKRJKTMT-WOPDTQHZSA-N Val-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N JSOXWWFKRJKTMT-WOPDTQHZSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 1
- 108010072405 glycyl-aspartyl-glycine Proteins 0.000 description 1
- 108010062266 glycyl-glycyl-argininal Proteins 0.000 description 1
- 108010010147 glycylglutamine Proteins 0.000 description 1
- 108010037850 glycylvaline Proteins 0.000 description 1
- 108010092114 histidylphenylalanine Proteins 0.000 description 1
- 108010085325 histidylproline Proteins 0.000 description 1
- 102000054064 human MBP Human genes 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 108010012988 lysyl-glutamyl-aspartyl-glycine Proteins 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108010016686 methionyl-alanyl-serine Proteins 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 1
- 108010071207 serylmethionine Proteins 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 108010017949 tyrosyl-glycyl-glycine Proteins 0.000 description 1
- 108010035534 tyrosyl-leucyl-alanine Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
- G01N33/6857—Antibody fragments
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Hematology (AREA)
- Pathology (AREA)
- Urology & Nephrology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明提供一种MBP重组蛋白以及其应用，通过抗原结构优化和细胞亚定位改造，提高了MBP重组蛋白在CBA试剂盒产品的稳定性，以及对MBP抗体检测的灵敏度和检测速率，特异性达到100％。
Description
技术领域
本申请涉及生物技术领域，具体涉及一种MBP重组蛋白以及其应用。
背景技术
多发性硬化症(Multiple sclerosis，MS)是人类中枢神经系统(Central NervousSystem，CNS)的一种后天性脱髓鞘疾病。该疾病的遗传易感性或抗性被认为与位于第六条染色体短臂上的HLA-DR-DQ区域内或附近的基因有关。自身免疫机制在MS相关的脱髓鞘疾病过程中起重要作用，属于特异性抗原介导的细胞免疫和体液免疫共同参与的炎性脱髓鞘疾病。目前尚无证据说明何种抗原在MS的病因中最为重要，但有力证据表明髓鞘碱性蛋白(Myelin Basic Protein，MBP)比较关键，MS患者由于免疫功能的异常，使 MBP具有自身抗原性，引起T淋巴细胞致敏活化和B细胞克隆扩增、表达效应功能，产生了MBP抗体(MyelinBasic Protein Antibody，MBPA)，这些抗体在T细胞参与下，作用于MBP和其它完整的髓鞘磷脂蛋白，故认为MBP 及MBPA在MS的发病机制中起关健作用。
MBP是构成髓鞘的主要成分之一，具有神经组织特异性。当神经组织受损时，游离MBP进入脑脊液(Cerebrospinal Fluid，CSF)或(和)血液，导致体液MBP含量增高并可能刺激机体产生MBPA自身抗体。国内外学者曾对急性脑外伤、脑血管疾病、多发性硬化、脑炎和脑膜炎等患者CSF和血清 MBP含量进行研究，一致认为CSF和血清MBP是在一定程度上反映了CNS 有无实质性损害，特别是有无髓鞘脱失的一个较为特异性的生化指标，对判断病情严重程度和预后有重要意义。
由于MS的可靠特征是增加了血脑屏障(blood-brain barrier，BBB)IgG 的合成，因此以前的研究集中于针对髓磷脂蛋白的潜在人体自身免疫机制。 MBPA经常在患有急性视神经炎和活动性MS的患者的脑脊液(CSF)以及 MS患者的CNS组织中发现。人类MBP分子上的抗MBP表位范围已通过合成肽研究进行了估算。
由于MBP是一种封闭的自身抗原，当MBP暴露或释放至CSF中时，可引起免疫应答，并刺激机体产生MBPA自身抗体。已在MS患者血清和CSF 中发现针对MBP的特异抗体。这些抗体在T细胞参与下，作用于MBP和其它完整的髓鞘磷脂蛋白，导致多种神经系统疾病产生。故CSF或血清MBP 及其抗体含量测定可作为急性脑损害和急性脱髓鞘的特异生化指标，其含量的高低反映了损害的范围和严重程度。另外，由于MBP属机体隐蔽性抗原， MBP的释放入血可诱发自身免疫性炎症反应，进一步引起髓鞘的破坏。通过测定不同疾病的血清MBP水平，有助于了解疾病的进展，因此，在神经损伤时测定血清MBP水平具有重要价值。
目前血清MBP检测手段众多，诸如ELISA，膜条法等。不过由于血液样本成分复杂，有些成分与ELISA板产生非特异性结合，导致ELISA检测法的假阳性率较高；膜条法仅能检测识别线性区域的抗体，导致膜条法检出率偏低。因此，目前常用的检测手段，如免疫荧光、ELISA、免疫印迹、免疫组化等，都有检测过程耗时较长，步骤繁琐，抗体需求量大，成本高，灵敏度不高等缺点，利用这些方法很难一次性对大批量样本同时检测或针对某一个样本进行反复检测。
综上，目前市场上多发性硬化症检测试剂盒稀缺，而且常规检测方法局限性。因此，亟需一种经济、快速、易操作的检测试剂盒，为疑似脱髓鞘患者定制检测方案，以达到精准的用药和治疗需求。有鉴于此，特提出本发明。
发明内容
本申请提供一种MBP重组蛋白，其特征在于，氨基酸序列如SEQ ID No.1 所示，或与该氨基酸序列有至少80％一致性的氨基酸序列。
另一方面，本发明提供了一种编码权利要求1所述MBP重组蛋白的基因。
在一些具体实施方案中，所述基因为核酸序列如SEQ ID No.2所示，或与该核酸序列有至少80％一致性的核酸序列。
另一方面，本发明还提供了一种含权利要求2或3所述基因的重组质粒。
在一些具体实施方案中，所述重组质粒采用mEGFP标记MBP重组蛋白的完整开放阅读框架。
另一方面，本发明还提供了一种上述重组质粒的细胞株或重组菌，优选的，细胞株为上述重组质粒转染AD293细胞所得。
另一方面，本发明还提供了一种检测MBP抗体的试剂盒，包括权利要求 4-5任一所述重组质粒，或权利要求6所述的细胞株或重组菌；更优选的，所述试剂盒还包括AD293细胞株、2％多聚甲醛、5％的羊血清白蛋白的PBS 溶液、标记的山羊抗人IgG。
另一方面，本发明还提供了一种MBP抗体检测试剂的制备方法，方法包括：对权利要求6所述的细胞株进行培养，以及固定、封闭、孵育和封片步骤。
在一些具体实施方案中，所述固定步骤为当细胞密度为70-80％时，采用 2-5％多聚甲醛20-30℃固定10min，优选地，细胞密度为75％时采用2％多聚甲醛25℃固定。
在一些具体实施方案中，所述封闭步骤为采用5％的羊血清白蛋白的PBS 溶液20-30℃封闭1h，优选地，采用5％的羊血清白蛋白的PBS溶液25℃封闭。
在一些具体实施方案中，所述孵育步骤包括一抗孵育、二抗孵育，其中一抗孵育为加入采用封闭液倍增稀释的待测血清(1:20)，3-5℃孵育14-20h，优选地，一抗孵育采用4℃孵育15h；二抗孵育为采用标记的山羊抗人IgG 避光20-30℃孵育50-60min，优选地，二抗孵育采用25℃孵育60min。
另一方面，本发明还提供了一种检测MBP抗体的方法，所述方法包括权利要求8-11任一所述方法，并进一步包括荧光检测步骤。
另一方面，本发明还提供了权利要求1所述蛋白、权利要求2-3任一所述基因、权利要求4-5任一所述重组质粒，或权利要求6所述的细胞株或重组菌在制备MBP抗体检测试剂中的应用。
本申请的具体试验方法如下：
1、构建重组质粒：根据设计的基因序列，合成嵌合基因，连接到载体 pcDNA3.1上，构建出用mEGFP标记MBP重组蛋白的完整开放阅读框架的真核表达载体，得到MBP重组蛋白并携带mEGFP的质粒；
2、质粒转染：将上述质粒转染培养好的AD293细胞，得到携带重组质粒的AD293细胞；
3、细胞培养：将经多聚赖氨酸处理96孔细胞培养板中，加入携带重组质粒的AD293细胞，并进行培养；
4、细胞固定：当携带重组质粒的AD293细胞的密度为70％～80％时，采用2％多聚甲醛固定液室温固定10min；
5、封闭：细胞固定完毕后，采用封闭液室温封闭1.0h；其中，封闭液是含质量分数为5％的羊血清白蛋白的PBS溶液；
6、一抗孵育：封闭完毕后，加入采用封闭液倍增稀释法稀释的待测血清，然后4℃孵育过夜；
7、二抗孵育：一抗孵育完毕后，采用Alex594标记的山羊抗人IgG避光室温孵育1.0h；
8、封片荧光显微镜拍照：荧光二抗孵育完毕后，采用荧光显微镜进行观察，红色荧光呈现明显的细胞膜染色定位结果，则判断为阳性，从而检测出 MBPA。
本申请有益的技术效果：
1、本发明提供一种新型MBP重组蛋白以及其应用，通过目的抗原的细胞亚定位改造，提高了对MBP抗体检测的灵敏度和检测速率；
2、本发明针对性的优化抗原结构，构建了一种全新的优化质粒，提高了 MBP重组蛋白在CBA试剂盒产品的稳定性；
3、本发明提供的MBP蛋白抗体的检测方法，特异性几乎达到100％，为多性硬化症患者的诊治提供了必要的实验依据，对多发性硬化症患者的诊治提供了新的方向，具有重要的意义；
4、本发明通过优化固定、封闭等等条件参数，提高了整个CBA检测试剂盒的有效性和灵敏度。
附图说明
为了更清楚地说明本申请具体实施方式或现有技术中的技术方案，下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图是本申请的一些实施方式，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1：mEGFP标记MBP重组蛋白基因结构示意图；
图2：抗体检测结果(使用的是含未改造的MBP试剂盒)；
图3：抗体检测结果(使用的是生产并保存一个月的含未改造的MBP试剂盒)；
图4：抗体检测结果(使用的是含本发明重组质粒的试剂盒)；
图5：抗体检测结果(使用的是生产并保存一个月的含本发明重组质粒的试剂盒)。
具体实施方式
下面将结合实施例对本申请的实施方案进行详细描述，但是本领域技术人员将会理解，下列实施例仅用于说明本申请，而不应视为限制本申请的范围。实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市购买获得的常规产品。
实施例1 MBP重组蛋白和质粒构建
为MBP基因序列添加信号肽序列和跨膜结构域序列，构建MBP重组蛋白，其中MBP重组蛋白氨基酸序列如SEQ ID No.1所示，核酸序列如 SEQ ID No.2。融合蛋白表达后定位在细胞膜上面，并通过免疫荧光实验证明其蛋白结构正常，嵌合基因结构如图1所示。
实施例2携带重组质粒的AD293细胞的构建
1)构建MBP重组质粒：选用pcDNA3.1质粒，构建出增强型绿色荧光蛋白(monomericEnhanced green fluorescent protein，mEGFP)的真核表达载体，用mEGFP标记MBP重组蛋白的完整开放阅读框架(Open Reading frame，ORF)，同时让目的蛋白在AD293细胞中充分表达，作为抗原进行后续检测研究。
2)AD293细胞的培养：采用常规实验方法培养AD293细胞。
3)质粒转染：首先根据lipofectamine 3000转染试剂说明书摸索DNA 与lipofectamine 3000最佳浓度比，从而获得最佳转染效果。本发明通过24 孔细胞培养板摸索浓度，最终发现DNA与lipofectamine 3000最佳浓度比为 1:2.5，本发明得到的野生型质粒的浓度为1000μg/mL，空白组质粒浓度为 7.08μg/μL，分别将两种质粒转染至2个12孔细胞培养板进行预实验。
实施例3细胞免疫荧光法检测MBP抗体
本发明经过反复体系优化，最终确立如下方法体系：
1、培养：将经多聚赖氨酸处理的细胞爬片置于24孔细胞培养板中，然后加入携带重组质粒的AD293细胞进行培养。
2、固定：当携带重组质粒的AD293细胞的密度为75％时，采用2％多聚甲醛固定液室温固定10min。
3、封闭：细胞固定完毕后，采用封闭液室温封闭1h；其中，封闭液是含质量分数为5％的羊血清白蛋白的PBS溶液。
4、一抗孵育：封闭完毕后，加入采用封闭液倍增稀释法稀释的待测血清 (1:20)，然后4℃孵育过夜。
5、荧光二抗孵育：一抗孵育完毕后，采用Alex594标记的山羊抗人IgG 避光室温孵育1h。
6、封片荧光显微镜拍照：每份样品重复两次的操作。荧光二抗孵育完毕后，采用荧光显微镜进行观察。荧光显微镜激发光波长分别为蓝光(420～490 nm)和绿光(535～550nm)，产生绿色荧光和红色荧光，有绿色荧光并且红色荧光呈现明显膜结构，则判读为阳性。每组设置阴性和阳性对照。测试结果的评价要借助于阳性和阴性质控的评价。所以拍照原始结果必须保存以备追溯。阳性对照在任何情况下必须是阳性。阳性对照确保实验是正确操作且各种组分正常。如果阳性对照结果不好则不能读取实验数据。
实施例4MBP重组质粒功能评价
本实施例中，采用本发明所述MBP重组质粒，以及未经改进的MBP重组质粒，其中未经改进的MBP重组质粒为将mEGFP标记MBP完整开放阅读框架构成表达载体，得到表达重组MBP，其氨基酸序列为SEQ ID No.3，核酸序列为SEQ ID No.4。
材料与方法材料：
方法：具体为AD293细胞的培养、质粒转染、培养、固定、封闭、一抗孵育、荧光二抗孵育、封片荧光显微镜拍照，具体步骤如实施例2中2、3步以及实施例3所述方法。
结果：图1展示为未改造的MBP蛋白表达和抗体检测结果，绿色荧光是与目的蛋白一同表达的mEGFP，红色荧光是使用MBP自身抗体阳性的血液样本染色结果，有绿色荧光且有红色荧光的为阳性细胞，阳性细胞形态与背景细胞(无绿色荧光但有红的荧光的细胞)形态相似，则在样本中该抗体滴度较低时往往影响判读结果。
图3展示为改造后MBP重组蛋白表达和抗体检测结果，绿色荧光是与目的蛋白一同表达的mEGFP，红色荧光是使用MBP自身抗体阳性的血液样本染色结果，此时呈现膜表达结构，有绿色荧光且有红色荧光的为阳性细胞，阳性细胞形态与背景细胞区分明显。
可见改进后的MBP重组蛋白在MBP检测中的优异效果，拍片中阳性细胞形态与背景细胞区分明显，易于区分判断；并且，本发明提供的检测方法准确性几乎达到100％(因抗原抗体一一对应)，为这一类患者的诊治提供了必要的实验室依据。
实施例5MBP重组质粒试剂盒稳定性评价
本实施例中，采用本发明试剂盒，以及未经改进的MBP试剂盒。将两种试剂盒均保存一个月后同步进行试验，进行试剂盒稳定性评价。
本发明试剂盒成分：细胞基质板(含SEQ ID No.1重组质粒)、Anti-Human IgG AF-594、抗体稀释液(5％的羊血清白蛋白的PBS溶液)、PBS。
未经改进的MBP试剂盒成分：细胞基质板(含SEQ ID No.3重组质粒)、 Anti-HumanIgG AF-594、抗体稀释液(5％的羊血清白蛋白的PBS溶液)、 PBS。
材料与方法见实施例4II材料与方法。
结果：图2展示为未经改进的MBP试剂盒的抗体检测结果，结果使用的是生产并保存一个月的试剂盒，绿色荧光是与目的蛋白一同表达的mEGFP，红色荧光是使用MBP自身抗体阳性的血液样本染色结果，此时红色荧光不清晰，很难做阴阳性判读，说明此试剂的稳定性不佳。
图4展示为本发明所述试剂盒的抗体检测结果，结果使用的是生产和保存一个月的试剂盒，绿色荧光是与目的蛋白一同表达的mEGFP，红色荧光是使用MBP自身抗体阳性的血液样本染色结果，此时呈现膜表达结构，有绿色荧光且有红色荧光的为阳性细胞，阳性细胞荧光仍清晰可见。
可见本发明试剂盒在稳定性方面的优异效果，在保存一个月之久，拍片中阳性细胞形态与背景细胞依旧区分明显，易于区分判断，而未经改进的试剂盒，由于稳定性较差，红色荧光不清晰，很难做阴阳性判读。试剂盒的稳定进一步保障了在试剂盒的生产、运输和储存中不会降低其功效，保证了后续实验室检测中的准确性。
最后应说明的是：以上各实施例仅用以说明本申请的技术方案，而非对其限制；尽管参照前述各实施例对本申请进行了详细的说明，但本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分或者全部技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本申请各实施例技术方案的范围。
序列表
<110> 江苏先声医学诊断有限公司
江苏先声医疗器械有限公司
江苏先声诊断技术有限公司
<120> 一种MBP重组蛋白以及其应用
<160> 4
<170> SIPOSequenceListing 1.0
<210> 1
<211> 464
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 1
Met Tyr Gly Lys Ile Ile Phe Val Leu Leu Leu Ser Glu Ile Val Ser
1 5 10 15
Ile Ser Ala Gly Ser Gly Ser Gly Ser Met Ala Ser Gln Lys Arg Pro
20 25 30
Ser Gln Arg His Gly Ser Lys Tyr Leu Ala Thr Ala Ser Thr Met Asp
35 40 45
His Ala Arg His Gly Phe Leu Pro Arg His Arg Asp Thr Gly Ile Leu
50 55 60
Asp Ser Ile Gly Arg Phe Phe Gly Gly Asp Arg Gly Ala Pro Lys Arg
65 70 75 80
Gly Ser Gly Lys Asp Ser His His Pro Ala Arg Thr Ala His Tyr Gly
85 90 95
Ser Leu Pro Gln Lys Ser His Gly Arg Thr Gln Asp Glu Asn Pro Val
100 105 110
Val His Phe Phe Lys Asn Ile Val Thr Pro Arg Thr Pro Pro Pro Ser
115 120 125
Gln Gly Lys Gly Arg Gly Leu Ser Leu Ser Arg Phe Ser Trp Gly Ala
130 135 140
Glu Gly Gln Arg Pro Gly Phe Gly Tyr Gly Gly Arg Ala Ser Asp Tyr
145 150 155 160
Lys Ser Ala His Lys Gly Phe Lys Gly Val Asp Ala Gln Gly Thr Leu
165 170 175
Ser Lys Ile Phe Lys Leu Gly Gly Arg Asp Ser Arg Ser Gly Ser Pro
180 185 190
Met Ala Arg Arg Gly Ser Gly Ser Gly Ser Ile Thr Leu Ile Ile Phe
195 200 205
Gly Val Met Ala Gly Val Ile Gly Thr Ile Leu Leu Ile Ser Tyr Gly
210 215 220
Ile Met Val Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile
225 230 235 240
Leu Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser
245 250 255
Gly Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe
260 265 270
Ile Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr
275 280 285
Thr Leu Thr Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met
290 295 300
Lys Gln His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln
305 310 315 320
Glu Arg Thr Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala
325 330 335
Glu Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys
340 345 350
Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu
355 360 365
Tyr Asn Tyr Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys
370 375 380
Asn Gly Ile Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly
385 390 395 400
Ser Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp
405 410 415
Gly Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Lys
420 425 430
Leu Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu
435 440 445
Phe Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys
450 455 460
<210> 2
<211> 1395
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 2
atgtatggaa aaataatctt tgtattacta ttgtcagaaa ttgtgagcat atcagcaggc 60
agcggcagcg gcagcatggc gtcacagaag agaccctccc agaggcacgg atccaagtac 120
ctggccacag caagtaccat ggaccatgcc aggcatggct tcctcccaag gcacagagac 180
acgggcatcc ttgactccat cgggcgcttc tttggcggtg acaggggtgc gcccaagcgg 240
ggctctggca aggactcaca ccacccggca agaactgctc actacggctc cctgccccag 300
aagtcacacg gccggaccca agatgaaaac cccgtagtcc acttcttcaa gaacattgtg 360
acgcctcgca caccaccccc gtcgcaggga aaggggagag gactgtccct gagcagattt 420
agctgggggg ccgaaggcca gagaccagga tttggctacg gaggcagagc gtccgactat 480
aaatcggctc acaagggatt caagggagtc gatgcccagg gcacgctttc caaaattttt 540
aagctgggag gaagagatag tcgctctgga tcacccatgg ctagacgcgg cagcggcagc 600
ggcagcataa cactcattat ttttggggtg atggctggtg ttattggaac gatcctctta 660
atttcttacg gtattatggt gagcaagggc gaggagctgt tcaccggggt ggtgcccatc 720
ctggtcgagc tggacggcga cgtaaacggc cacaagttca gcgtgtccgg cgagggcgag 780
ggcgatgcca cctacggcaa gctgaccctg aagttcatct gcaccaccgg caagctgccc 840
gtgccctggc ccaccctcgt gaccaccctg acctacggcg tgcagtgctt cagccgctac 900
cccgaccaca tgaagcagca cgacttcttc aagtccgcca tgcccgaagg ctacgtccag 960
gagcgcacca tcttcttcaa ggacgacggc aactacaaga cccgcgccga ggtgaagttc 1020
gagggcgaca ccctggtgaa ccgcatcgag ctgaagggca tcgacttcaa ggaggacggc 1080
aacatcctgg ggcacaagct ggagtacaac tacaacagcc acaacgtcta tatcatggcc 1140
gacaagcaga agaacggcat caaggtgaac ttcaagatcc gccacaacat cgaggacggc 1200
agcgtgcagc tcgccgacca ctaccagcag aacaccccca tcggcgacgg ccccgtgctg 1260
ctgcccgaca accactacct gagcacccag tccaagctga gcaaagaccc caacgagaag 1320
cgcgatcaca tggtcctgct ggagttcgtg accgccgccg ggatcactct cggcatggac 1380
gagctgtaca agtaa 1395
<210> 3
<211> 410
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 3
Met Ala Ser Gln Lys Arg Pro Ser Gln Arg His Gly Ser Lys Tyr Leu
1 5 10 15
Ala Thr Ala Ser Thr Met Asp His Ala Arg His Gly Phe Leu Pro Arg
20 25 30
His Arg Asp Thr Gly Ile Leu Asp Ser Ile Gly Arg Phe Phe Gly Gly
35 40 45
Asp Arg Gly Ala Pro Lys Arg Gly Ser Gly Lys Asp Ser His His Pro
50 55 60
Ala Arg Thr Ala His Tyr Gly Ser Leu Pro Gln Lys Ser His Gly Arg
65 70 75 80
Thr Gln Asp Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Val Thr
85 90 95
Pro Arg Thr Pro Pro Pro Ser Gln Gly Lys Gly Arg Gly Leu Ser Leu
100 105 110
Ser Arg Phe Ser Trp Gly Ala Glu Gly Gln Arg Pro Gly Phe Gly Tyr
115 120 125
Gly Gly Arg Ala Ser Asp Tyr Lys Ser Ala His Lys Gly Phe Lys Gly
130 135 140
Val Asp Ala Gln Gly Thr Leu Ser Lys Ile Phe Lys Leu Gly Gly Arg
145 150 155 160
Asp Ser Arg Ser Gly Ser Pro Met Ala Arg Arg Met Val Ser Lys Gly
165 170 175
Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly
180 185 190
Asp Val Asn Gly His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp
195 200 205
Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys
210 215 220
Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val
225 230 235 240
Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys Gln His Asp Phe Phe
245 250 255
Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Phe Phe
260 265 270
Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly
275 280 285
Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu
290 295 300
Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His
305 310 315 320
Asn Val Tyr Ile Met Ala Asp Lys Gln Lys Asn Gly Ile Lys Val Asn
325 330 335
Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp
340 345 350
His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro
355 360 365
Asp Asn His Tyr Leu Ser Thr Gln Ser Lys Leu Ser Lys Asp Pro Asn
370 375 380
Glu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly
385 390 395 400
Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys
405 410
<210> 4
<211> 1233
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 4
atggcgtcac agaagagacc ctcccagagg cacggatcca agtacctggc cacagcaagt 60
accatggacc atgccaggca tggcttcctc ccaaggcaca gagacacggg catccttgac 120
tccatcgggc gcttctttgg cggtgacagg ggtgcgccca agcggggctc tggcaaggac 180
tcacaccacc cggcaagaac tgctcactac ggctccctgc cccagaagtc acacggccgg 240
acccaagatg aaaaccccgt agtccacttc ttcaagaaca ttgtgacgcc tcgcacacca 300
cccccgtcgc agggaaaggg gagaggactg tccctgagca gatttagctg gggggccgaa 360
ggccagagac caggatttgg ctacggaggc agagcgtccg actataaatc ggctcacaag 420
ggattcaagg gagtcgatgc ccagggcacg ctttccaaaa tttttaagct gggaggaaga 480
gatagtcgct ctggatcacc catggctaga cgcatggtga gcaagggcga ggagctgttc 540
accggggtgg tgcccatcct ggtcgagctg gacggcgacg taaacggcca caagttcagc 600
gtgtccggcg agggcgaggg cgatgccacc tacggcaagc tgaccctgaa gttcatctgc 660
accaccggca agctgcccgt gccctggccc accctcgtga ccaccctgac ctacggcgtg 720
cagtgcttca gccgctaccc cgaccacatg aagcagcacg acttcttcaa gtccgccatg 780
cccgaaggct acgtccagga gcgcaccatc ttcttcaagg acgacggcaa ctacaagacc 840
cgcgccgagg tgaagttcga gggcgacacc ctggtgaacc gcatcgagct gaagggcatc 900
gacttcaagg aggacggcaa catcctgggg cacaagctgg agtacaacta caacagccac 960
aacgtctata tcatggccga caagcagaag aacggcatca aggtgaactt caagatccgc 1020
cacaacatcg aggacggcag cgtgcagctc gccgaccact accagcagaa cacccccatc 1080
ggcgacggcc ccgtgctgct gcccgacaac cactacctga gcacccagtc caagctgagc 1140
aaagacccca acgagaagcg cgatcacatg gtcctgctgg agttcgtgac cgccgccggg 1200
atcactctcg gcatggacga gctgtacaag taa 1233
Claims (10)
1.一种MBP重组蛋白，其特征在于，所述MBP重组蛋白的氨基酸序列如SEQ ID No.1所示。
2.一种编码权利要求1所述MBP重组蛋白的基因；所述基因序列如SEQ ID No.2所示。
3.一种含权利要求2所述基因的重组质粒；所述重组质粒采用mEGFP标记MBP重组蛋白的完整开放阅读框架。
4.一种含权利要求3所述重组质粒的细胞株或重组菌。
5.一种检测MBP抗体的试剂盒，其特征在于，包括权利要求3所述重组质粒，或权利要求4所述的细胞株或重组菌。
6.一种MBP抗体检测试剂的制备方法，其特征在于，包括对权利要求4所述的细胞株或重组菌进行培养步骤，以及固定步骤、封闭步骤、孵育步骤和封片步骤。
7.权利要求6所述的制备方法，其特征在于，所述固定步骤为当细胞密度为70-80％时，采用2-5％多聚甲醛20-30℃固定10min。
8.权利要求6所述的制备方法，其特征在于，所述封闭步骤为采用5％的羊血清白蛋白的PBS溶液20-30℃封闭1h。
9.权利要求6所述的制备方法，其特征在于，所述孵育步骤包括一抗孵育、二抗孵育，其中所述一抗孵育为加入采用封闭液1:20倍增稀释的待测血清，3-5℃孵育14-20h；所述二抗孵育为采用标记的山羊抗人IgG避光20-30℃孵育50-60min。
10.权利要求1所述的MBP重组蛋白、权利要求2所述的基因、权利要求3所述的重组质粒，或权利要求4所述的细胞株或重组菌在制备MBP抗体检测试剂中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011167856.XA CN112362877B (zh) | 2020-10-27 | 2020-10-27 | 一种mbp重组蛋白以及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011167856.XA CN112362877B (zh) | 2020-10-27 | 2020-10-27 | 一种mbp重组蛋白以及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112362877A CN112362877A (zh) | 2021-02-12 |
| CN112362877B true CN112362877B (zh) | 2024-04-12 |
Family
ID=74511039
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011167856.XA Active CN112362877B (zh) | 2020-10-27 | 2020-10-27 | 一种mbp重组蛋白以及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112362877B (zh) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002355035A (ja) * | 2001-05-08 | 2002-12-10 | Inst Of Physical & Chemical Res | スフィンゴミエリン検出プローブ |
| CN1991366A (zh) * | 2005-12-29 | 2007-07-04 | 财团法人工业技术研究院 | 诊断重症肌无力症的方法及其所用的试剂盒 |
| WO2011085081A2 (en) * | 2010-01-08 | 2011-07-14 | Bayhill Therapeutics, Inc. | Methods of selecting ms patients for antigen specific therapy |
| WO2012154215A1 (en) * | 2011-05-04 | 2012-11-15 | Cellular Technology, Ltd. | Cns antigen-specific b cell, t cell and antibody assays and their uses in diagnosis and treatment of multiple sclerosis |
| CN104099357A (zh) * | 2013-04-12 | 2014-10-15 | 中国科学院上海生命科学研究院 | 检测蛋白质稳定性的方法及其应用 |
| CN108845127A (zh) * | 2018-04-13 | 2018-11-20 | 四川农业大学 | 基于vp2或vp4重组蛋白抗原的dhav-3抗体的间接elisa检测方法及应用 |
| CN109862909A (zh) * | 2016-08-19 | 2019-06-07 | 赛门蒂斯有限公司 | 病毒疫苗 |
| CN111089972A (zh) * | 2019-12-18 | 2020-05-01 | 天津天海新域生物科技有限公司 | 一种用于检测抗人体髓鞘碱性蛋白抗体的试剂盒及其应用 |
| CN111272998A (zh) * | 2020-01-09 | 2020-06-12 | 天津天海新域生物科技有限公司 | 一种同时检测中枢脱髓鞘自身抗体aqp4、mog和mbp的方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020111312A1 (en) * | 1991-10-22 | 2002-08-15 | The Governors Of The University Of Alberta | Peptide specificity of anti-myelin basic protein and the administration of myelin basic protein peptides to multiple sclerosis patients |
-
2020
- 2020-10-27 CN CN202011167856.XA patent/CN112362877B/zh active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002355035A (ja) * | 2001-05-08 | 2002-12-10 | Inst Of Physical & Chemical Res | スフィンゴミエリン検出プローブ |
| CN1991366A (zh) * | 2005-12-29 | 2007-07-04 | 财团法人工业技术研究院 | 诊断重症肌无力症的方法及其所用的试剂盒 |
| WO2011085081A2 (en) * | 2010-01-08 | 2011-07-14 | Bayhill Therapeutics, Inc. | Methods of selecting ms patients for antigen specific therapy |
| WO2012154215A1 (en) * | 2011-05-04 | 2012-11-15 | Cellular Technology, Ltd. | Cns antigen-specific b cell, t cell and antibody assays and their uses in diagnosis and treatment of multiple sclerosis |
| CN104099357A (zh) * | 2013-04-12 | 2014-10-15 | 中国科学院上海生命科学研究院 | 检测蛋白质稳定性的方法及其应用 |
| CN109862909A (zh) * | 2016-08-19 | 2019-06-07 | 赛门蒂斯有限公司 | 病毒疫苗 |
| CN108845127A (zh) * | 2018-04-13 | 2018-11-20 | 四川农业大学 | 基于vp2或vp4重组蛋白抗原的dhav-3抗体的间接elisa检测方法及应用 |
| CN111089972A (zh) * | 2019-12-18 | 2020-05-01 | 天津天海新域生物科技有限公司 | 一种用于检测抗人体髓鞘碱性蛋白抗体的试剂盒及其应用 |
| CN111272998A (zh) * | 2020-01-09 | 2020-06-12 | 天津天海新域生物科技有限公司 | 一种同时检测中枢脱髓鞘自身抗体aqp4、mog和mbp的方法 |
Non-Patent Citations (4)
| Title |
|---|
| Myelin Basic Protein and a Multiple Sclerosis-related MBP-peptide Bind to Oligonucleotides;Guido Tomás Rozenblum 等;Mol Ther Nucleic Acids;3(9);全文 * |
| Variation within MBP gene predicts disease course in multiple sclerosis;Yuan Zhou 等;Brain Behav;7(4);全文 * |
| 多发性硬化患者抗髓鞘碱性蛋白抗体的检测及其意义;李群彦;郝洪军;高枫;袁锦楣;;免疫学杂志(S1);全文 * |
| 血清抗髓鞘碱性蛋白抗体对多发性硬化的诊断价值;高枫, 李群彦, 郝洪军, 袁锦楣;中国康复理论与实践(05);全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112362877A (zh) | 2021-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Grissom et al. | Identification of a novel light intermediate chain (D2LIC) for mammalian cytoplasmic dynein 2 | |
| CN106432508B (zh) | 一种pla2r‑thsd7a融合蛋白及其应用和试剂盒 | |
| CN106243211A (zh) | 神经自身免疫疾病的诊断 | |
| US20220153865A1 (en) | Synthetic peptide, relative artificial antigen, relative anti-ehd2 antibody and preparation method thereof and use thereof | |
| CN108728526A (zh) | 神经自身免疫疾病的诊断 | |
| CN114019161B (zh) | 抗camk2a自身抗体的试剂在制备诊断神经系统症状相关疾病的试剂盒中的应用 | |
| US20100035360A1 (en) | Reagent for detection of autoantibody and kit for diagnosis of autoimmune disease | |
| CN112362877B (zh) | 一种mbp重组蛋白以及其应用 | |
| EP3011008B1 (en) | Method of detecting the presence or absence of autoantibodies | |
| CN113214373B (zh) | 新包虫病抗原Murinoglobulin-2蛋白 | |
| CN102047113A (zh) | 用于检测神经损伤的组合物、试剂盒及方法 | |
| CN114075270B (zh) | 一种人源包虫病抗原的重组蛋白及其应用 | |
| CN108845134A (zh) | 细胞分析法检测低密度脂蛋白受体相关蛋白4抗体 | |
| CN114075271B (zh) | 一种人源包虫病抗原的重组蛋白及其应用 | |
| Hoefges et al. | Antibody landscape of C57BL/6 mice cured of B78 melanoma via immunotherapy | |
| CN109777833A (zh) | T细胞特异接头蛋白slp-76类泛素化的方法及相应的体外高效鉴定 | |
| CN113214374B (zh) | 一种包虫病新抗原Cystatin蛋白 | |
| CN113687067B (zh) | 针对AChR单亚基抗体的检测试剂盒及其应用 | |
| CN115856323A (zh) | 一种抗非膜蛋白的自身抗体检测试剂、制备方法及其应用 | |
| KR102466369B1 (ko) | 자가면역 뇌염의 진단 방법 | |
| CN115850424A (zh) | 一种up蛋白片段及其在人源包虫病中的应用 | |
| CN115850425A (zh) | 一种spon1-1蛋白片段及其在人源包虫病中的应用 | |
| CN102047112A (zh) | 用于检测老化、及伴随有血管障碍的疾病的组合物、试剂盒及方法 | |
| CN115850423A (zh) | 一种psap-3蛋白片段及其在人源包虫病中的应用 | |
| CN115825431A (zh) | 原发性膜性肾病诊断试剂盒的研发与应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |