CN111647057B - 一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用 - Google Patents
一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用 Download PDFInfo
- Publication number
- CN111647057B CN111647057B CN202010378299.XA CN202010378299A CN111647057B CN 111647057 B CN111647057 B CN 111647057B CN 202010378299 A CN202010378299 A CN 202010378299A CN 111647057 B CN111647057 B CN 111647057B
- Authority
- CN
- China
- Prior art keywords
- protein
- salmonella typhi
- gly
- yncd
- vaccine
- 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
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 66
- 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
- 229940124857 Salmonella typhi vaccine Drugs 0.000 title claims abstract description 16
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 4
- 229960005486 vaccine Drugs 0.000 claims description 15
- 201000008297 typhoid fever Diseases 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000013598 vector Substances 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 4
- 125000003729 nucleotide group Chemical group 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 abstract description 45
- 239000013613 expression plasmid Substances 0.000 abstract description 15
- 230000014509 gene expression Effects 0.000 abstract description 15
- 241000699670 Mus sp. Species 0.000 abstract description 13
- 238000000746 purification Methods 0.000 abstract description 13
- 101100215887 Bacillus subtilis (strain 168) alr2 gene Proteins 0.000 abstract description 12
- 101100160358 Escherichia coli (strain K12) yncD gene Proteins 0.000 abstract description 12
- 239000013612 plasmid Substances 0.000 abstract description 9
- 101150014223 yncD gene Proteins 0.000 abstract description 8
- 241000607142 Salmonella Species 0.000 abstract description 7
- 241000894006 Bacteria Species 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 230000005847 immunogenicity Effects 0.000 abstract description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract description 4
- 238000010276 construction Methods 0.000 abstract description 4
- 230000006870 function Effects 0.000 abstract description 4
- 230000004083 survival effect Effects 0.000 abstract description 4
- 230000008506 pathogenesis Effects 0.000 abstract description 3
- 108090000301 Membrane transport proteins Proteins 0.000 abstract description 2
- 102000003939 Membrane transport proteins Human genes 0.000 abstract description 2
- 230000001419 dependent effect Effects 0.000 abstract description 2
- 229910052742 iron Inorganic materials 0.000 abstract description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 108020001507 fusion proteins Proteins 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 238000001514 detection method Methods 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 230000003053 immunization Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 235000019750 Crude protein Nutrition 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000002649 immunization Methods 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 208000037386 Typhoid Diseases 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 229930027917 kanamycin Natural products 0.000 description 5
- 229960000318 kanamycin Drugs 0.000 description 5
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 5
- 229930182823 kanamycin A Natural products 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 244000052769 pathogen Species 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000012474 protein marker Substances 0.000 description 5
- 229940126583 recombinant protein vaccine Drugs 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000002054 inoculum Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- 241000672609 Escherichia coli BL21 Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 206010039438 Salmonella Infections Diseases 0.000 description 3
- 241001052560 Thallis Species 0.000 description 3
- 108010047495 alanylglycine Proteins 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012148 binding buffer Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 108010028295 histidylhistidine Proteins 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 206010039447 salmonellosis Diseases 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 2
- QOIGKCBMXUCDQU-KDXUFGMBSA-N Ala-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N)O QOIGKCBMXUCDQU-KDXUFGMBSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 206010016952 Food poisoning Diseases 0.000 description 2
- 208000019331 Foodborne disease Diseases 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
- RTIRBWJPYJYTLO-MELADBBJSA-N Leu-Lys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N RTIRBWJPYJYTLO-MELADBBJSA-N 0.000 description 2
- 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 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 108010044940 alanylglutamine Proteins 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 108010008355 arginyl-glutamine Proteins 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000004927 fusion 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
- 108010050848 glycylleucine Proteins 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 108010090333 leucyl-lysyl-proline Proteins 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 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
- DVWVZSJAYIJZFI-FXQIFTODSA-N Ala-Arg-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O DVWVZSJAYIJZFI-FXQIFTODSA-N 0.000 description 1
- YAXNATKKPOWVCP-ZLUOBGJFSA-N Ala-Asn-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O YAXNATKKPOWVCP-ZLUOBGJFSA-N 0.000 description 1
- LGFCAXJBAZESCF-ACZMJKKPSA-N Ala-Gln-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O LGFCAXJBAZESCF-ACZMJKKPSA-N 0.000 description 1
- BGNLUHXLSAQYRQ-FXQIFTODSA-N Ala-Glu-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BGNLUHXLSAQYRQ-FXQIFTODSA-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
- 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
- OMDNCNKNEGFOMM-BQBZGAKWSA-N Ala-Met-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O OMDNCNKNEGFOMM-BQBZGAKWSA-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
- VQAVBBCZFQAAED-FXQIFTODSA-N Ala-Pro-Asn Chemical compound C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)N)C(=O)O)N VQAVBBCZFQAAED-FXQIFTODSA-N 0.000 description 1
- 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 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
- 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
- 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
- ISCYZXFOCXWUJU-KZVJFYERSA-N Ala-Thr-Met Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(O)=O ISCYZXFOCXWUJU-KZVJFYERSA-N 0.000 description 1
- CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 description 1
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 1
- AUFHLLPVPSMEOG-YUMQZZPRSA-N Arg-Gly-Glu Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AUFHLLPVPSMEOG-YUMQZZPRSA-N 0.000 description 1
- HAVKMRGWNXMCDR-STQMWFEESA-N Arg-Gly-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HAVKMRGWNXMCDR-STQMWFEESA-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
- UHFUZWSZQKMDSX-DCAQKATOSA-N Arg-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UHFUZWSZQKMDSX-DCAQKATOSA-N 0.000 description 1
- YKZJPIPFKGYHKY-DCAQKATOSA-N Arg-Leu-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YKZJPIPFKGYHKY-DCAQKATOSA-N 0.000 description 1
- NGTYEHIRESTSRX-UWVGGRQHSA-N Arg-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N NGTYEHIRESTSRX-UWVGGRQHSA-N 0.000 description 1
- RIQBRKVTFBWEDY-RHYQMDGZSA-N Arg-Lys-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RIQBRKVTFBWEDY-RHYQMDGZSA-N 0.000 description 1
- LCBSSOCDWUTQQV-SDDRHHMPSA-N Arg-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N LCBSSOCDWUTQQV-SDDRHHMPSA-N 0.000 description 1
- CZUHPNLXLWMYMG-UBHSHLNASA-N Arg-Phe-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=CC=C1 CZUHPNLXLWMYMG-UBHSHLNASA-N 0.000 description 1
- QHUOOCKNNURZSL-IHRRRGAJSA-N Arg-Tyr-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O QHUOOCKNNURZSL-IHRRRGAJSA-N 0.000 description 1
- CNBIWSCSSCAINS-UFYCRDLUSA-N Arg-Tyr-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CNBIWSCSSCAINS-UFYCRDLUSA-N 0.000 description 1
- PSUXEQYPYZLNER-QXEWZRGKSA-N Arg-Val-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PSUXEQYPYZLNER-QXEWZRGKSA-N 0.000 description 1
- HZPSDHRYYIORKR-WHFBIAKZSA-N Asn-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O HZPSDHRYYIORKR-WHFBIAKZSA-N 0.000 description 1
- NVGWESORMHFISY-SRVKXCTJSA-N Asn-Asn-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NVGWESORMHFISY-SRVKXCTJSA-N 0.000 description 1
- BHQQRVARKXWXPP-ACZMJKKPSA-N Asn-Asp-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N BHQQRVARKXWXPP-ACZMJKKPSA-N 0.000 description 1
- HUAOKVVEVHACHR-CIUDSAMLSA-N Asn-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N HUAOKVVEVHACHR-CIUDSAMLSA-N 0.000 description 1
- RAQMSGVCGSJKCL-FOHZUACHSA-N Asn-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(N)=O RAQMSGVCGSJKCL-FOHZUACHSA-N 0.000 description 1
- LSJQOMAZIKQMTJ-SRVKXCTJSA-N Asn-Phe-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O LSJQOMAZIKQMTJ-SRVKXCTJSA-N 0.000 description 1
- WLVLIYYBPPONRJ-GCJQMDKQSA-N Asn-Thr-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O WLVLIYYBPPONRJ-GCJQMDKQSA-N 0.000 description 1
- FMNBYVSGRCXWEK-FOHZUACHSA-N Asn-Thr-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O FMNBYVSGRCXWEK-FOHZUACHSA-N 0.000 description 1
- 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 1
- DPWDPEVGACCWTC-SRVKXCTJSA-N Asn-Tyr-Ser 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](CO)C(O)=O DPWDPEVGACCWTC-SRVKXCTJSA-N 0.000 description 1
- MYRLSKYSMXNLLA-LAEOZQHASA-N Asn-Val-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MYRLSKYSMXNLLA-LAEOZQHASA-N 0.000 description 1
- UGKZHCBLMLSANF-CIUDSAMLSA-N Asp-Asn-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O UGKZHCBLMLSANF-CIUDSAMLSA-N 0.000 description 1
- LKIYSIYBKYLKPU-BIIVOSGPSA-N Asp-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)N)C(=O)O LKIYSIYBKYLKPU-BIIVOSGPSA-N 0.000 description 1
- 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 1
- HAFCJCDJGIOYPW-WDSKDSINSA-N Asp-Gly-Gln Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O HAFCJCDJGIOYPW-WDSKDSINSA-N 0.000 description 1
- SVABRQFIHCSNCI-FOHZUACHSA-N Asp-Gly-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O SVABRQFIHCSNCI-FOHZUACHSA-N 0.000 description 1
- ICZWAZVKLACMKR-CIUDSAMLSA-N Asp-His-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CN=CN1 ICZWAZVKLACMKR-CIUDSAMLSA-N 0.000 description 1
- HJZLUGQGJWXJCJ-CIUDSAMLSA-N Asp-Pro-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJZLUGQGJWXJCJ-CIUDSAMLSA-N 0.000 description 1
- 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 1
- PDIYGFYAMZZFCW-JIOCBJNQSA-N Asp-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N)O PDIYGFYAMZZFCW-JIOCBJNQSA-N 0.000 description 1
- YODBPLSWNJMZOJ-BPUTZDHNSA-N Asp-Trp-Arg Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N YODBPLSWNJMZOJ-BPUTZDHNSA-N 0.000 description 1
- QOJJMJKTMKNFEF-ZKWXMUAHSA-N Asp-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O QOJJMJKTMKNFEF-ZKWXMUAHSA-N 0.000 description 1
- 206010004022 Bacterial food poisoning Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- KEBJBKIASQVRJS-WDSKDSINSA-N Cys-Gln-Gly Chemical compound C(CC(=O)N)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N KEBJBKIASQVRJS-WDSKDSINSA-N 0.000 description 1
- 101000760085 Daucus carota 21 kDa protein Proteins 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
- 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
- MINZLORERLNSPP-ACZMJKKPSA-N Gln-Asn-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N MINZLORERLNSPP-ACZMJKKPSA-N 0.000 description 1
- ULXXDWZMMSQBDC-ACZMJKKPSA-N Gln-Asp-Asp Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N ULXXDWZMMSQBDC-ACZMJKKPSA-N 0.000 description 1
- XEYMBRRKIFYQMF-GUBZILKMSA-N Gln-Asp-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O XEYMBRRKIFYQMF-GUBZILKMSA-N 0.000 description 1
- VSXBYIJUAXPAAL-WDSKDSINSA-N Gln-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O VSXBYIJUAXPAAL-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
- 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
- MLSKFHLRFVGNLL-WDCWCFNPSA-N Gln-Leu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MLSKFHLRFVGNLL-WDCWCFNPSA-N 0.000 description 1
- BJPPYOMRAVLXBY-YUMQZZPRSA-N Gln-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N BJPPYOMRAVLXBY-YUMQZZPRSA-N 0.000 description 1
- BZULIEARJFRINC-IHRRRGAJSA-N Gln-Phe-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N BZULIEARJFRINC-IHRRRGAJSA-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
- HLRLXVPRJJITSK-IFFSRLJSSA-N Gln-Thr-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HLRLXVPRJJITSK-IFFSRLJSSA-N 0.000 description 1
- CMFBOXUBWMZZMD-BPUTZDHNSA-N Gln-Trp-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N CMFBOXUBWMZZMD-BPUTZDHNSA-N 0.000 description 1
- CMBXOSFZCFGDLE-IHRRRGAJSA-N Gln-Tyr-Gln Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O CMBXOSFZCFGDLE-IHRRRGAJSA-N 0.000 description 1
- LJLPOZGRPLORTF-CIUDSAMLSA-N Glu-Asn-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O LJLPOZGRPLORTF-CIUDSAMLSA-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
- HVYWQYLBVXMXSV-GUBZILKMSA-N Glu-Leu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HVYWQYLBVXMXSV-GUBZILKMSA-N 0.000 description 1
- 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 1
- QJVZSVUYZFYLFQ-CIUDSAMLSA-N Glu-Pro-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O QJVZSVUYZFYLFQ-CIUDSAMLSA-N 0.000 description 1
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 1
- UMZHHILWZBFPGL-LOKLDPHHSA-N Glu-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O UMZHHILWZBFPGL-LOKLDPHHSA-N 0.000 description 1
- CAQXJMUDOLSBPF-SUSMZKCASA-N Glu-Thr-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAQXJMUDOLSBPF-SUSMZKCASA-N 0.000 description 1
- HJTSRYLPAYGEEC-SIUGBPQLSA-N Glu-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCC(=O)O)N HJTSRYLPAYGEEC-SIUGBPQLSA-N 0.000 description 1
- PUUYVMYCMIWHFE-BQBZGAKWSA-N Gly-Ala-Arg Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PUUYVMYCMIWHFE-BQBZGAKWSA-N 0.000 description 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
- WKJKBELXHCTHIJ-WPRPVWTQSA-N Gly-Arg-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N WKJKBELXHCTHIJ-WPRPVWTQSA-N 0.000 description 1
- UXJHNZODTMHWRD-WHFBIAKZSA-N Gly-Asn-Ala Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O UXJHNZODTMHWRD-WHFBIAKZSA-N 0.000 description 1
- FUTAPPOITCCWTH-WHFBIAKZSA-N Gly-Asp-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FUTAPPOITCCWTH-WHFBIAKZSA-N 0.000 description 1
- FIQQRCFQXGLOSZ-WDSKDSINSA-N Gly-Glu-Asp Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FIQQRCFQXGLOSZ-WDSKDSINSA-N 0.000 description 1
- QPTNELDXWKRIFX-YFKPBYRVSA-N Gly-Gly-Gln Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O QPTNELDXWKRIFX-YFKPBYRVSA-N 0.000 description 1
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 1
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 1
- 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 1
- DGKBSGNCMCLDSL-BYULHYEWSA-N Gly-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN DGKBSGNCMCLDSL-BYULHYEWSA-N 0.000 description 1
- NSTUFLGQJCOCDL-UWVGGRQHSA-N Gly-Leu-Arg Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NSTUFLGQJCOCDL-UWVGGRQHSA-N 0.000 description 1
- 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 1
- IBYOLNARKHMLBG-WHOFXGATSA-N Gly-Phe-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IBYOLNARKHMLBG-WHOFXGATSA-N 0.000 description 1
- 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
- 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
- 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
- IROABALAWGJQGM-OALUTQOASA-N Gly-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)CN IROABALAWGJQGM-OALUTQOASA-N 0.000 description 1
- GWNIGUKSRJBIHX-STQMWFEESA-N Gly-Tyr-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)CN)O GWNIGUKSRJBIHX-STQMWFEESA-N 0.000 description 1
- 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
- BZKDJRSZWLPJNI-SRVKXCTJSA-N His-His-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O BZKDJRSZWLPJNI-SRVKXCTJSA-N 0.000 description 1
- XWUIHCZETFNRPA-IHPCNDPISA-N His-His-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CN=CN1 XWUIHCZETFNRPA-IHPCNDPISA-N 0.000 description 1
- YVCGJPIKRMGNPA-LSJOCFKGSA-N His-Met-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O YVCGJPIKRMGNPA-LSJOCFKGSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- QLRMMMQNCWBNPQ-QXEWZRGKSA-N Ile-Arg-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)O)N QLRMMMQNCWBNPQ-QXEWZRGKSA-N 0.000 description 1
- BGZIJZJBXRVBGJ-SXTJYALSSA-N Ile-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N BGZIJZJBXRVBGJ-SXTJYALSSA-N 0.000 description 1
- 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 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
- PNTWNAXGBOZMBO-MNXVOIDGSA-N Ile-Lys-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N PNTWNAXGBOZMBO-MNXVOIDGSA-N 0.000 description 1
- 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 1
- JODPUDMBQBIWCK-GHCJXIJMSA-N Ile-Ser-Asn Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O JODPUDMBQBIWCK-GHCJXIJMSA-N 0.000 description 1
- HXIDVIFHRYRXLZ-NAKRPEOUSA-N Ile-Ser-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)O)N HXIDVIFHRYRXLZ-NAKRPEOUSA-N 0.000 description 1
- KBDIBHQICWDGDL-PPCPHDFISA-N Ile-Thr-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N KBDIBHQICWDGDL-PPCPHDFISA-N 0.000 description 1
- KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-N 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- HXWALXSAVBLTPK-NUTKFTJISA-N Leu-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(C)C)N HXWALXSAVBLTPK-NUTKFTJISA-N 0.000 description 1
- WXHFZJFZWNCDNB-KKUMJFAQSA-N Leu-Asn-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WXHFZJFZWNCDNB-KKUMJFAQSA-N 0.000 description 1
- BPANDPNDMJHFEV-CIUDSAMLSA-N Leu-Asp-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O BPANDPNDMJHFEV-CIUDSAMLSA-N 0.000 description 1
- PJYSOYLLTJKZHC-GUBZILKMSA-N Leu-Asp-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(N)=O PJYSOYLLTJKZHC-GUBZILKMSA-N 0.000 description 1
- CIVKXGPFXDIQBV-WDCWCFNPSA-N Leu-Gln-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CIVKXGPFXDIQBV-WDCWCFNPSA-N 0.000 description 1
- QDSKNVXKLPQNOJ-GVXVVHGQSA-N Leu-Gln-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O QDSKNVXKLPQNOJ-GVXVVHGQSA-N 0.000 description 1
- QLDHBYRUNQZIJQ-DKIMLUQUSA-N Leu-Ile-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QLDHBYRUNQZIJQ-DKIMLUQUSA-N 0.000 description 1
- IRMLZWSRWSGTOP-CIUDSAMLSA-N Leu-Ser-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O IRMLZWSRWSGTOP-CIUDSAMLSA-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
- ILDSIMPXNFWKLH-KATARQTJSA-N Leu-Thr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ILDSIMPXNFWKLH-KATARQTJSA-N 0.000 description 1
- IXHKPDJKKCUKHS-GARJFASQSA-N Lys-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IXHKPDJKKCUKHS-GARJFASQSA-N 0.000 description 1
- FACUGMGEFUEBTI-SRVKXCTJSA-N Lys-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCCCN FACUGMGEFUEBTI-SRVKXCTJSA-N 0.000 description 1
- 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 1
- BVXXDMUMHMXFER-BPNCWPANSA-N Met-Ala-Tyr Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BVXXDMUMHMXFER-BPNCWPANSA-N 0.000 description 1
- WDTLNWHPIPCMMP-AVGNSLFASA-N Met-Arg-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O WDTLNWHPIPCMMP-AVGNSLFASA-N 0.000 description 1
- DGNZGCQSVGGYJS-BQBZGAKWSA-N Met-Gly-Asp Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O DGNZGCQSVGGYJS-BQBZGAKWSA-N 0.000 description 1
- LQMHZERGCQJKAH-STQMWFEESA-N Met-Gly-Phe Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 LQMHZERGCQJKAH-STQMWFEESA-N 0.000 description 1
- LRALLISKBZNSKN-BQBZGAKWSA-N Met-Gly-Ser Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LRALLISKBZNSKN-BQBZGAKWSA-N 0.000 description 1
- ODFBIJXEWPWSAN-CYDGBPFRSA-N Met-Ile-Val Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O ODFBIJXEWPWSAN-CYDGBPFRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 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 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
- 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 1
- 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 1
- 108010047562 NGR peptide Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- UHRNIXJAGGLKHP-DLOVCJGASA-N Phe-Ala-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O UHRNIXJAGGLKHP-DLOVCJGASA-N 0.000 description 1
- DDYIRGBOZVKRFR-AVGNSLFASA-N Phe-Asp-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N DDYIRGBOZVKRFR-AVGNSLFASA-N 0.000 description 1
- OJUMUUXGSXUZJZ-SRVKXCTJSA-N Phe-Asp-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O OJUMUUXGSXUZJZ-SRVKXCTJSA-N 0.000 description 1
- BIYWZVCPZIFGPY-QWRGUYRKSA-N Phe-Gly-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CO)C(O)=O BIYWZVCPZIFGPY-QWRGUYRKSA-N 0.000 description 1
- YFXXRYFWJFQAFW-JHYOHUSXSA-N Phe-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](CC1=CC=CC=C1)N)O YFXXRYFWJFQAFW-JHYOHUSXSA-N 0.000 description 1
- 229920002538 Polyethylene Glycol 20000 Polymers 0.000 description 1
- KIZQGKLMXKGDIV-BQBZGAKWSA-N Pro-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 KIZQGKLMXKGDIV-BQBZGAKWSA-N 0.000 description 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
- SGCZFWSQERRKBD-BQBZGAKWSA-N Pro-Asp-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 SGCZFWSQERRKBD-BQBZGAKWSA-N 0.000 description 1
- WFHYFCWBLSKEMS-KKUMJFAQSA-N Pro-Glu-Phe Chemical compound N([C@@H](CCC(=O)O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C(=O)[C@@H]1CCCN1 WFHYFCWBLSKEMS-KKUMJFAQSA-N 0.000 description 1
- 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
- UUHXBJHVTVGSKM-BQBZGAKWSA-N Pro-Gly-Asn Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O UUHXBJHVTVGSKM-BQBZGAKWSA-N 0.000 description 1
- ULIWFCCJIOEHMU-BQBZGAKWSA-N Pro-Gly-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 ULIWFCCJIOEHMU-BQBZGAKWSA-N 0.000 description 1
- YDTUEBLEAVANFH-RCWTZXSCSA-N Pro-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 YDTUEBLEAVANFH-RCWTZXSCSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241001138501 Salmonella enterica Species 0.000 description 1
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 description 1
- 241000531795 Salmonella enterica subsp. enterica serovar Paratyphi A Species 0.000 description 1
- 241000577483 Salmonella enterica subsp. enterica serovar Paratyphi B Species 0.000 description 1
- 241000577475 Salmonella enterica subsp. enterica serovar Paratyphi C Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- HRNQLKCLPVKZNE-CIUDSAMLSA-N Ser-Ala-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O HRNQLKCLPVKZNE-CIUDSAMLSA-N 0.000 description 1
- VAUMZJHYZQXZBQ-WHFBIAKZSA-N Ser-Asn-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O VAUMZJHYZQXZBQ-WHFBIAKZSA-N 0.000 description 1
- TYYBJUYSTWJHGO-ZKWXMUAHSA-N Ser-Asn-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O TYYBJUYSTWJHGO-ZKWXMUAHSA-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
- LALNXSXEYFUUDD-GUBZILKMSA-N Ser-Glu-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LALNXSXEYFUUDD-GUBZILKMSA-N 0.000 description 1
- 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 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
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 description 1
- GZFAWAQTEYDKII-YUMQZZPRSA-N Ser-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO GZFAWAQTEYDKII-YUMQZZPRSA-N 0.000 description 1
- JFWDJFULOLKQFY-QWRGUYRKSA-N Ser-Gly-Phe Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JFWDJFULOLKQFY-QWRGUYRKSA-N 0.000 description 1
- 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
- CJINPXGSKSZQNE-KBIXCLLPSA-N Ser-Ile-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O CJINPXGSKSZQNE-KBIXCLLPSA-N 0.000 description 1
- MOINZPRHJGTCHZ-MMWGEVLESA-N Ser-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N MOINZPRHJGTCHZ-MMWGEVLESA-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
- VXYQOFXBIXKPCX-BQBZGAKWSA-N Ser-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CO)N VXYQOFXBIXKPCX-BQBZGAKWSA-N 0.000 description 1
- RXSWQCATLWVDLI-XGEHTFHBSA-N Ser-Met-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RXSWQCATLWVDLI-XGEHTFHBSA-N 0.000 description 1
- NERYDXBVARJIQS-JYBASQMISA-N Ser-Trp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CO)N)O NERYDXBVARJIQS-JYBASQMISA-N 0.000 description 1
- FHXGMDRKJHKLKW-QWRGUYRKSA-N Ser-Tyr-Gly Chemical compound OC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 FHXGMDRKJHKLKW-QWRGUYRKSA-N 0.000 description 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
- UKKROEYWYIHWBD-ZKWXMUAHSA-N Ser-Val-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O UKKROEYWYIHWBD-ZKWXMUAHSA-N 0.000 description 1
- LSHUNRICNSEEAN-BPUTZDHNSA-N Ser-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](CO)N LSHUNRICNSEEAN-BPUTZDHNSA-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
- YLXAMFZYJTZXFH-OLHMAJIHSA-N Thr-Asn-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O YLXAMFZYJTZXFH-OLHMAJIHSA-N 0.000 description 1
- 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 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
- ONNSECRQFSTMCC-XKBZYTNZSA-N Thr-Glu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O ONNSECRQFSTMCC-XKBZYTNZSA-N 0.000 description 1
- XPNSAQMEAVSQRD-FBCQKBJTSA-N Thr-Gly-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)NCC(O)=O XPNSAQMEAVSQRD-FBCQKBJTSA-N 0.000 description 1
- PAXANSWUSVPFNK-IUKAMOBKSA-N Thr-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N PAXANSWUSVPFNK-IUKAMOBKSA-N 0.000 description 1
- VTVVYQOXJCZVEB-WDCWCFNPSA-N Thr-Leu-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VTVVYQOXJCZVEB-WDCWCFNPSA-N 0.000 description 1
- QYDKSNXSBXZPFK-ZJDVBMNYSA-N Thr-Thr-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYDKSNXSBXZPFK-ZJDVBMNYSA-N 0.000 description 1
- CJEHCEOXPLASCK-MEYUZBJRSA-N Thr-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=C(O)C=C1 CJEHCEOXPLASCK-MEYUZBJRSA-N 0.000 description 1
- KPMIQCXJDVKWKO-IFFSRLJSSA-N Thr-Val-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KPMIQCXJDVKWKO-IFFSRLJSSA-N 0.000 description 1
- 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 1
- HQVKQINPFOCIIV-BVSLBCMMSA-N Trp-Arg-Tyr Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=C(O)C=C1 HQVKQINPFOCIIV-BVSLBCMMSA-N 0.000 description 1
- ADBFWLXCCKIXBQ-XIRDDKMYSA-N Trp-Asn-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N ADBFWLXCCKIXBQ-XIRDDKMYSA-N 0.000 description 1
- OGZRZMJASKKMJZ-XIRDDKMYSA-N Trp-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N OGZRZMJASKKMJZ-XIRDDKMYSA-N 0.000 description 1
- NLLARHRWSFNEMH-NUTKFTJISA-N Trp-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N NLLARHRWSFNEMH-NUTKFTJISA-N 0.000 description 1
- MPYZGXUYLNPSNF-NAZCDGGXSA-N Trp-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N)O MPYZGXUYLNPSNF-NAZCDGGXSA-N 0.000 description 1
- TVOGEPLDNYTAHD-CQDKDKBSSA-N Tyr-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 TVOGEPLDNYTAHD-CQDKDKBSSA-N 0.000 description 1
- HSVPZJLMPLMPOX-BPNCWPANSA-N Tyr-Arg-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O HSVPZJLMPLMPOX-BPNCWPANSA-N 0.000 description 1
- ZNFPUOSTMUMUDR-JRQIVUDYSA-N Tyr-Asn-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZNFPUOSTMUMUDR-JRQIVUDYSA-N 0.000 description 1
- RYSNTWVRSLCAJZ-RYUDHWBXSA-N Tyr-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RYSNTWVRSLCAJZ-RYUDHWBXSA-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
- 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
- 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
- CWVHKVVKAQIJKY-ACRUOGEOSA-N Tyr-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=C(C=C2)O)N CWVHKVVKAQIJKY-ACRUOGEOSA-N 0.000 description 1
- WYOBRXPIZVKNMF-IRXDYDNUSA-N Tyr-Tyr-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(O)=O)C1=CC=C(O)C=C1 WYOBRXPIZVKNMF-IRXDYDNUSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AZSHAZJLOZQYAY-FXQIFTODSA-N Val-Ala-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O AZSHAZJLOZQYAY-FXQIFTODSA-N 0.000 description 1
- WKWJJQZZZBBWKV-JYJNAYRXSA-N Val-Arg-Tyr Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@@H](N)C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WKWJJQZZZBBWKV-JYJNAYRXSA-N 0.000 description 1
- ZMDCGGKHRKNWKD-LAEOZQHASA-N Val-Asn-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZMDCGGKHRKNWKD-LAEOZQHASA-N 0.000 description 1
- XLDYBRXERHITNH-QSFUFRPTSA-N Val-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)C(C)C XLDYBRXERHITNH-QSFUFRPTSA-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
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 1
- BZMIYHIJVVJPCK-QSFUFRPTSA-N Val-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N BZMIYHIJVVJPCK-QSFUFRPTSA-N 0.000 description 1
- VXDSPJJQUQDCKH-UKJIMTQDSA-N Val-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](C(C)C)N VXDSPJJQUQDCKH-UKJIMTQDSA-N 0.000 description 1
- OTJMMKPMLUNTQT-AVGNSLFASA-N Val-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N OTJMMKPMLUNTQT-AVGNSLFASA-N 0.000 description 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
- SJRUJQFQVLMZFW-WPRPVWTQSA-N Val-Pro-Gly Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O SJRUJQFQVLMZFW-WPRPVWTQSA-N 0.000 description 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
- AEFJNECXZCODJM-UWVGGRQHSA-N Val-Val-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)NCC([O-])=O AEFJNECXZCODJM-UWVGGRQHSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 1
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 1
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- 108010045350 alanyl-tyrosyl-alanine Proteins 0.000 description 1
- 108010041407 alanylaspartic acid Proteins 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 108010009111 arginyl-glycyl-glutamic acid Proteins 0.000 description 1
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008956 bacterial persistence Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 108010008237 glutamyl-valyl-glycine Proteins 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- 108010019832 glycyl-asparaginyl-glycine Proteins 0.000 description 1
- 108010062266 glycyl-glycyl-argininal Proteins 0.000 description 1
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 1
- 108010038983 glycyl-histidyl-lysine Proteins 0.000 description 1
- 108010077435 glycyl-phenylalanyl-glycine Proteins 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 108010037850 glycylvaline Proteins 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 208000011140 intestinal infectious disease Diseases 0.000 description 1
- 108010051673 leucyl-glycyl-phenylalanine Proteins 0.000 description 1
- 108010047926 leucyl-lysyl-tyrosine Proteins 0.000 description 1
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 108010016686 methionyl-alanyl-serine Proteins 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 108010018625 phenylalanylarginine Proteins 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108010004914 prolylarginine Proteins 0.000 description 1
- 108010029020 prolylglycine Proteins 0.000 description 1
- 108010090894 prolylleucine Proteins 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 108010005834 tyrosyl-alanyl-glycine Proteins 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 206010048282 zoonosis Diseases 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
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/255—Salmonella (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/025—Enterobacteriales, e.g. Enterobacter
- A61K39/0275—Salmonella
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明公开了一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用，该重组蛋白包括如SEQ ID NO.1所示的氨基酸序列。制备方法包括：构建yncD表达质粒，对yncD表达质粒诱导表达和纯化；所述构建yncD表达质粒采用如SEQ ID NO.3和如SEQ ID NO.4所示的引物做PCR，获得yncD基因全序列，连接到表达质粒，得到重组质粒。本发明的重组蛋白包括具有良好免疫原性的靶蛋白，位于沙门菌表面；其是一个涉及铁摄取的TonB依赖性外膜转运体，为细菌体内生存和致病所必需；蛋白的氨基酸序列保守，广泛存在于目前已测序的伤寒沙门菌菌株中，且其基因功能在不同伤寒沙门菌菌株中是一致的，具有良好的免疫原性，对免疫小鼠具有良好的保护效果。
Description
技术领域
本发明涉及生物技术领域，尤其涉及一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用。
背景技术
沙门菌属细菌包括2500多个血清型，其中部分血清型(伤寒沙门菌、甲型、乙型和丙型副伤寒沙门菌)可以引起人类的传染病，即肠热症(伤寒或副伤寒)；另外部分沙门菌是人畜共患病的病原体，可引起人类食物中毒或者败血症(如鼠伤寒沙门菌、猪霍乱沙门菌、肠炎沙门菌等)。沙门菌引起的疾病发病率高，危害严重，例如作为肠道传染病的伤寒和副伤寒，据世界卫生组织估计，全球每年有1600-3300万感染者，死亡病例在50-60万左右。伤寒病例长期位居我国法定传染病的前10位，各地每年仍有大量散发病例，还时有局部的爆发流行，严重威胁着人们的身体健康。而由沙门菌引起的食物中毒则更为常见，是我国细菌性食物中毒的最常见病原之一。因此对于沙门菌感染的控制是一件非常重要的课题。沙门菌感染的控制需要采取综合措施，包括改善卫生条件以及有效疫苗的使用。通过疫苗刺激机体产生针对沙门菌的特异性免疫反应是一种有效的低成本预防策略。
接种疫苗的基本目的是诱导机体的免疫反应，进而对病原体的感染起到免疫保护的作用。这一目的可以通过重组蛋白疫苗的接种而实现。重组蛋白疫苗是指将病原体的目的抗原基因构建在表达载体上诱导表达，通过纯化后制备的疫苗。此类疫苗制备工艺简便、安全性好，疫苗不存在毒力回复等问题。重组蛋白疫苗还可以根据需要进行适当组合，从而实现一次接种免疫多种疾病的目的。
对于重组蛋白疫苗研制的关键是找到具有良好免疫原性的靶蛋白。良好的蛋白疫苗候选应该具有以下几个特征：
1、一般位于致病菌表面，具有良好的免疫原性；
2、蛋白功能对于致病菌致病至关重要；
3、蛋白的氨基酸序列保守，且存在于该致病菌绝大多数菌株中。
基于此，研究一种符合上述特征的重组蛋白疫苗，成为本领域技术人员亟待解决的技术问题。
发明内容
为解决上述技术问题，本发明实施例提出一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用。
本发明实施例所公开的一种伤寒沙门菌疫苗重组蛋白，其包括如SEQ ID NO.1所示的氨基酸序列。
本发明实施例还公开了一种编码上述的伤寒沙门菌疫苗重组蛋白的基因。
进一步地，所述基因包括如SEQ ID NO.2所示的核苷酸序列。
本发明实施例还公开了一种重组载体，其包括上述的基因。
本发明实施例还公开了一种重组菌株，所述重组菌株含有上述的重组载体。
进一步地，所述菌株为大肠杆菌。
本发明实施例还公开了一种制备伤寒沙门菌疫苗重组蛋白的方法，其包括：
构建yncD表达质粒，对yncD表达质粒诱导表达和纯化；
其中，所述构建yncD表达质粒采用如SEQ ID NO.3和如SEQ ID NO.4所示的引物做PCR，获得yncD基因全序列，连接到表达质粒，得到重组质粒；所述对yncD表达质粒诱导表达包括将所述重组质粒在大肠杆菌BL21中进行诱导表达。
进一步地，所述表达质粒为PET28a。
进一步地，所述构建yncD表达质粒包括采用SacΙ酶切所述表达质粒。
本发明一些实施例还公开了上述的伤寒沙门菌疫苗重组蛋白、上述的基因、上述的重组载体、上述的重组菌株，以及上述的制备伤寒沙门菌疫苗重组蛋白的方法在制备用于预防伤寒沙门菌感染的疫苗中的应用。
本发明一些实施例还公开了一种用于预防伤寒沙门菌感染的疫苗，所述疫苗含有上述的伤寒沙门菌重组蛋白作为活性成分。
进一步地，所述疫苗还含有药学上可接受的佐剂。
本发明一些实施例还公开了一种药物，其特征在于，所述药物含有上述的伤寒沙门菌重组蛋白作为活性成分；
优选地，所述药物还含有药学上可接受的佐剂。
采用上述技术方案，本发明至少具有如下有益效果：
本发明公开的的伤寒沙门菌重组蛋白包括具有良好免疫原性的靶蛋白，位于沙门菌表面(细菌外膜)；其是一个涉及铁摄取的TonB依赖性外膜转运体，为细菌体内生存和致病所必需；蛋白的氨基酸序列保守，广泛存在于目前已测序的伤寒沙门菌菌株中，且其基因功能在不同伤寒沙门菌菌株中是一致的。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例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，下面描述中的附图仅仅是本发明的一些实施例，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为融合蛋白表达小试SDS-PAGE分析图。
图2为融合蛋白镍琼脂糖亲和层析纯化SDS-PAGE分析图。
图3为融合蛋白离子柱纯化SDS-PAGE分析图。
图4为最终纯化蛋白SDS-PAGE分析图。
图5为最终纯化蛋白Western Blot分析图。
图6、图7为YncD蛋白免疫小鼠感染伤寒沙门菌后肝脾带菌。
图8为伤寒沙门菌yncD基因相似性Blast结果。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚明白，以下结合具体实施例，并参照附图，对本发明实施例进一步详细说明。
需要说明的是，本发明实施例中所有使用“第一”和“第二”的表述均是为了区分两个相同名称非相同的实体或者非相同的参量，可见“第一”“第二”仅为了表述的方便，不应理解为对本发明实施例的限定，后续实施例对此不再一一说明。
本发明所用试剂材料：
实验中所用试剂除DNA连接酶和试剂盒外，均为Takara公司产品；
LB培养基配方：氯化钠1％，胰蛋白胨1％，酵母提取物0.5％；配制固体培养基，加入琼脂1.4％，121℃高压蒸汽灭菌后使用；
DNA连接酶购自Promega公司，胶回收试剂盒和质粒提取试剂盒购自Omega公司，引物合成和DNA片段测序由华大公司完成
卡那霉素培养基：即在普通LB培养基基础上加入终浓度100μg/ml的卡那霉素；
氨苄青霉素培养基：即在普通LB培养基基础上加入终浓度100μg/ml的氨苄青霉素。
本发明所用主要仪器：
凝胶成像仪(Bio-rad-T2a)、电转仪(Bio-rad gene-pluserII)、分光光度计(Bio-radsmartspeec 3000)、电泳仪(Bio-rad 72BR5008)、PCR仪(Bio-rad580B5502)、水浴(上海生工HH-2A)、金属浴(杭州博日CHB-A4-HH)、摇床(zhicheng ZHWY-100B恒温摇床)、离心机(Thermo LEGEND Micro21)。
实施例1 yncD表达质粒的构建
以伤寒沙门菌ty2野生株基因组DNA为模板，用PCR方式获得yncD基因全序列(去除该基因前端信号肽序列)，连接到PET28a表达质粒上，得到如SEQ ID NO.2所示的核苷酸序列，经验证序列无误后，电转入大肠埃希菌BL21中，诱导表达YncD重组蛋白的氨基酸序列如SEQ ID NO.1所示。
1.1 PCR：根据yncD基因序列设计引物K1，K2(如表1所示)，做PCR。
表1引物序列
PCR方法如下：
反应条件：
94℃顶盖预热5min；94℃解链30s，55℃退火40s，72℃延长3min，共35个循环。
1.2将所得PCR产物电泳做胶回收，标记为pcr1。用PET28a做单酶切。
体系：
PET28a 43μl
SacΙ 2μl
10×缓冲溶液 5μl
总体积 50μl
条件：37℃水浴过夜。
将酶切产物跑凝胶电泳后胶回收，并测定浓度，标记为L1。用L1和pcr1做无缝克隆反应构建表达载体，记为PET28a-yncD，条件如下：
体系：
反应条件：37℃金属浴30分钟。
1.3将PET28a-yncD电转入大肠埃希菌BL21中复制、扩增、提取质粒(卡那霉素抗性)，送华大公司进行测序鉴定。对测序获得的序列与网上公布的相应序列对比。结果成功构建表达载体，测序结果表明克隆的基因序列完全正确。
实施例2yncD表达质粒的诱导表达和纯化
将测序鉴定正确的PET28a-yncD重组质粒在BL21中进行诱导表达，将表达产物进行纯化，最后通过SDS-PAGE以及Western Blot验证重组YncD蛋白纯化效果。主要材料与试剂、主要缓冲液、主要仪器如表2，表3，表4所示。
表2主要材料与试剂
表3主要缓冲液
表4主要仪器
2.1实验步骤
2.1.1蛋白表达
转化：将重组质粒转入大肠埃希菌感受态细胞，热激后涂布在含有100μg/ml卡那霉素的平板上，培养；
活化：挑取单克隆到含有100μg/ml卡那霉素的液体培养基中培养；
诱导：当OD值达到0.6时，添加诱导剂IPTG，继续培养，分别于20℃条件下培养过夜、37℃条件下培养过夜，未添加诱导剂的为阴性对照；
收集菌体：离心，弃上清，收集菌体；
表达检测：在收集到的菌体中加入缓冲液A悬浮，使用超声破碎仪使其充分溶解并离心，离心后的沉淀使用缓冲液B进行溶解，分别对上清和沉淀处理，制样，准备SDS-PAGE检测。
2.1.2蛋白纯化
2.1.2.1一步纯化——Ni柱
收集粗蛋白：细胞菌体用缓冲液C溶解、超声破碎。离心去上清，沉淀用缓冲液D溶解，超声破碎、离心收集上清粗蛋白。
平衡：采用5ml Ni-NTA柱料，用5倍柱床体积的Binding buffer 1清洗平衡柱子，流速5ml/min；
孵育：将粗蛋白与平衡后的柱填料孵育1h；
上柱：将孵育后的产物上柱，收集流出；
平衡：用Binding buffer 1清洗平衡柱子；
洗杂：用Washing buffer 1洗柱子，并收集流出；
洗脱：用Elution buffer 1洗脱，收集流出；
纯化检测：对粗蛋白、洗杂流出、洗脱流出分别处理，制样，准备SDS-PAGE检测。
透析浓缩：将纯度较好的组分3透析到4M Urea，50mM Tris，pH 8.0中，准备过离子柱。
2.1.2.2二次纯化——离子柱
平衡：采用5ml Q Sefinose FF柱料，用10倍柱床体积的Binding buffer 2清洗平衡柱子，流速5ml/min；
孵育：将粗蛋白与平衡后的柱填料孵育1h；
上柱：将样品上柱，收集流出；
洗杂：用Washing buffer 2洗柱子，并收集流出；
洗脱：用Elution buffer 2洗脱，收集流出；
纯化检测：对粗蛋白、洗杂流出、洗脱流出分别处理，制样，准备SDS-PAGE检测。
透析浓缩：将纯度较好的组分5、6透析到50mM Tris，300mM NaCl，0.1％SKL，10％Glycerol，pH 8.0中，透析结束后用PEG20000浓缩，0.22μm滤膜过滤后分装1ml/tube，-80℃保存。
2.1.2.3目的蛋白检测
SDS-PAGE检测：对纯化后蛋白进行处理，制样，跑胶，检测分子量。Western Blot验证：对纯化后蛋白进行处理，制样，使用标签抗体进行验证。
2.2实验结果
2.2.1序列信息
2.2.1.1表达氨基酸序列(融合YncD蛋白氨基酸序列)SEQ ID NO.1
Protein Length＝722MW＝79453.2
Predicted pI＝6.31
MGSSHHHHHHSSGLVPRGSHMASMTGGQQMGRGSEFASAPNEQTMIVTATPQTVSELDTPAAVSVIEGEDMRLATPRVNLSESLTSVPGLQVQNRQNYAQDLQISIRGFGSRSAFGVRGIRLYVDGIPATMPDGQGQISNIDINSIQNVEVLRGPFSALYGNASGGVINVTTETGRQPPTLEASSYYGSYGSWRYGLKATGAMGDGTQPGDVDYTVSTTRFTTHGYRDHSGARKNLANAKLGVRLDDVSKLSLIFNSVDIKADDPGGLTESEWKADPQQAPRAEQYNTRKTIKQTQAGLRYERQLSAQDDISVMAYAGERETTQYQSIPLVAQLKPAQAGGVITLQRHYQGIDSRWTHRGELGVPVTFTGGLNYENMSENRKGYNNFRLNNGTPEFGHKGDLRRDERNLMWNVDPYLQTQWQLTQKLSLDAGVRYSSVWFDSNDHYIAPGNGDDSGDASYHHWLPAGSLKYALTDAWNLYLAAGRGFETPTINELSYRADGQSGFNFDLKPSTNDTVEVGSKTRIGNGLLTAALFQTDTDDEIVVASSMGGRTTYKNAGKTRRQGAELALDQRFAGDWRVKASWTWLDATYRSNVCQGQNCDGNRMPGIARNMGFASLGFIPDEGWYAGTDVRYMGDIMANDENTAKAPSYTVVGLNTGYKFNYSQLTVDIFGRVDNLFDEEYIGSVIVNESNGRYYEPAPGRNYGVGINLAWQFEHHHHHH
2.2.1.2质粒基因序列(YncD融合蛋白基因DNA序列)SEQ ID NO.2
ATGGGCAGCAGCCATCATCATCATCATCACAGCAGCGGCCTGGTGCCGCGCGGCAGCCATATGGCTAGCATGACTGGTGGACAGCAAATGGGTCGCGGATCCGAATTCGCCAGCGCGCCCAATGAACAAACCATGATAGTCACCGCAACGCCGCAAACCGTATCCGAGCTGGATACACCTGCCGCCGTTAGCGTCATTGAGGGAGAAGACATGCGTCTGGCGACGCCGCGCGTTAATTTATCTGAGTCTTTAACCAGCGTCCCGGGATTGCAGGTGCAGAACCGGCAGAACTACGCGCAGGATCTGCAAATCTCTATCCGTGGATTTGGCTCGCGTTCCGCCTTTGGCGTGCGCGGCATTCGTCTGTATGTTGATGGCATTCCCGCCACCATGCCGGATGGACAAGGCCAGATTTCAAATATTGATATTAACAGCATACAAAACGTTGAAGTGTTACGCGGCCCCTTCTCAGCGCTATACGGCAATGCTTCCGGCGGCGTGATAAATGTCACCACCGAAACCGGGAGACAGCCGCCCACCCTTGAGGCCAGCAGCTACTACGGCAGTTATGGAAGCTGGCGCTATGGGTTAAAAGCCACGGGCGCGATGGGGGACGGCACACAGCCTGGCGACGTGGATTACACGGTATCGACTACCCGTTTCACCACCCACGGCTACCGCGATCACAGCGGCGCGCGAAAAAATCTGGCTAATGCCAAACTGGGCGTGCGCCTTGACGATGTCAGTAAACTTTCGCTGATTTTTAATAGTGTGGACATTAAGGCGGACGATCCCGGCGGACTTACCGAATCTGAATGGAAAGCCGATCCGCAGCAGGCGCCGCGCGCTGAACAGTACAATACGCGTAAAACCATCAAACAAACTCAGGCAGGATTGCGTTATGAACGTCAGCTCAGCGCGCAGGATGATATCAGCGTGATGGCCTACGCCGGAGAGCGGGAAACCACGCAATACCAGTCTATTCCCCTGGTGGCACAGCTAAAACCAGCCCAGGCTGGCGGCGTAATTACACTGCAACGCCACTATCAGGGAATTGATTCCCGCTGGACTCACCGGGGAGAATTAGGTGTGCCGGTCACCTTCACTGGCGGGTTAAACTATGAAAACATGAGCGAAAACCGCAAGGGTTACAATAATTTCCGTCTCAACAACGGCACCCCTGAGTTCGGGCATAAAGGCGATTTACGGCGGGATGAGCGTAACCTGATGTGGAATGTCGATCCTTATCTGCAAACCCAGTGGCAGCTTACGCAAAAACTCTCGCTGGATGCTGGCGTGCGCTACAGTTCCGTGTGGTTCGATTCTAACGATCACTATATCGCGCCCGGCAATGGCGATGACAGCGGCGACGCCAGCTATCACCACTGGCTACCCGCCGGATCGCTAAAATATGCGTTAACTGACGCCTGGAATCTCTATCTTGCTGCCGGTCGCGGATTTGAAACTCCCACTATCAATGAACTTTCTTATCGCGCTGACGGCCAAAGCGGGTTCAACTTTGACCTCAAACCGTCGACCAATGATACGGTGGAAGTCGGCAGTAAAACGCGGATTGGCAATGGCTTGTTGACCGCCGCGTTATTTCAAACCGATACCGATGATGAAATTGTCGTCGCCAGTAGTATGGGAGGACGCACTACCTACAAAAACGCGGGCAAAACGCGCCGCCAGGGCGCAGAGCTCGCGTTGGACCAGCGCTTCGCCGGCGACTGGCGGGTGAAAGCATCATGGACCTGGCTGGATGCGACCTATCGCAGTAACGTTTGTCAGGGGCAAAACTGTGATGGAAACCGGATGCCCGGCATCGCCCGTAATATGGGATTCGCCTCATTAGGTTTTATCCCGGATGAGGGGTGGTACGCCGGAACAGACGTTCGGTATATGGGCGATATCATGGCCAATGATGAAAATACCGCCAAAGCGCCTTCGTATACCGTTGTTGGACTAAATACAGGGTATAAATTTAATTACAGTCAGCTTACCGTCGATATTTTTGGGCGGGTAGATAATCTATTTGATGAAGAATATATCGGTTCGGTGATCGTTAATGAATCTAATGGCCGATATTATGAGCCAGCGCCAGGGCGTAACTATGGCGTGGGGATTAATCTGGCATGGCAATTTGAACACCACCACCACCACCACTGA
其中，
ATGGGCAGCAGCCATCATCATCATCATCACAGCAGCGGCCTGGTGCCGCGCGGCAGCCATATGGCTAGCATGACTGGTGGACAGCAAATGGGTCGCGGATCCGAATTC和CACCACCACCACCACCACTGA为pet28a质粒序列，其余为无信号肽，无终止密码子TAA的YncD蛋白序列。
2.2.2蛋白表达检测
如图1所示为融合蛋白表达小试SDS-PAGE分析图，其中，
M：Protein Marker；1：诱导前总蛋白；2：20℃上清；3：20℃沉淀；4：37℃上清；5：37℃沉淀。
2.2.3蛋白纯化检测
2.2.3.1一步纯化
如图2所示为融合蛋白镍琼脂糖亲和层析纯化SDS-PAGE分析图，其中，
M：Protein marker；1：上样；2：流出；3-4：20mM Imidazole洗脱组分；5：50mMImidazole洗脱组分；6：500mM Imidazole洗脱组分。
2.2.3.2二次纯化
如图3所示为融合蛋白离子柱纯化SDS-PAGE分析图，其中，
M：Protein marker；1：上样；2：流出；3-4：50mM NaCl洗脱组分；5：100mM NaCl洗脱组分；6：200mM NaCl洗脱组分；7：500mM NaCl洗脱组分。
2.2.4融合目的蛋白验证
如图4所示，融合蛋白经过纯化，SDS-PAGE电泳分析在理论分子量相应位置出现明显条带，可初步确定融合蛋白成功得到了纯化。其中，
M：Protein marker；1：融合目的蛋白。
为进一步确定纯化获得的蛋白为目的蛋白，如图5所示，按照Western Blot步骤用TMB显色试剂盒显色。结果显示在相应位置出现明显条带，表明该蛋白为目的蛋白。其中，
M：Protein marker；1：融合目的蛋白。
综上所述，成功纯化出目的蛋白。
实施例3 YncD蛋白动物免疫效果
3.1实验步骤：
3.1.1将纯化的YncD蛋白和完全弗氏佐剂按1:1的比例混合并反复研磨直至形成油包水样的悬液；
3.1.2分别在第0、2、4周的时候，用悬液对BALB/c雌鼠进行皮下接种，蛋白接种量为50μg/只，共50只。同时设置PBS免疫对照组35只；
3.1.3BALB/c雌鼠在第6周末时(即42天)，分别腹腔接种ty2野生株细菌。接种菌量分别为2.5x101cfu、2.5x102cfu、5.0x102cfu、2.5x103cfu、5.0x103cfu，每个浓度10只小鼠，同时设置PBS免疫对照组，接种细菌量为2.5x101cfu、2.5x102cfu、5.0x102cfu每个浓度10只，2.5x103cfu浓度5只；
3.1.4接种细菌的小鼠禁食喂水72小时，并及时观察记录小鼠存活情况和取出死亡小鼠。
3.2实验结果：
如表5所示为YncD蛋白小鼠免疫效果，其中，
YNCD：YncD蛋白免疫组；PBS：PBS对照组。
表5 YncD蛋白小鼠免疫效果
结果显示：YncD蛋白免疫组相较于对照组具有更高的存活率，伤寒沙门菌对二者的半数致死量分别为6.09x102CFU和9.05x101CFU，相差大约7倍。说明YncD蛋白免疫接种对小鼠具有显著的免疫保护效果。
实施例4小鼠免疫与肝脾带菌量
4.1实验步骤：
4.1.1将纯化的YncD蛋白和完全弗氏佐剂按1:1的比例混合并反复研磨直至形成油包水样的悬液；
4.1.2分别在第0,2,4周的时候，用悬液对BALB/c雌鼠进行皮下接种，蛋白接种量为50μg/只；
4.1.3 BALB/c雌鼠在第6周末时(即42天)，分别腹腔接种ty2野生株细菌。接种菌量分别为2.5x104cfu、2.5x105cfu、2.5x106cfu，每个浓度三只小鼠，同时设置PBS对照组；
4.1.4接种细菌的小鼠正常饲养一周(7天)后，处死并分别摘取肝脏和脾脏；
4.1.5将每只小鼠的肝脏和脾脏分别破碎并用1ml无菌超纯水混悬，破碎液用无菌超纯水进行适当稀释，并取各梯度稀释液100μl涂布PLB平板，37℃孵育过夜；
4.1.6计数平板上的菌落并分析；
4.2实验结果：
如图6，图7所示，结果显示，免疫组的肝脾载菌量显著低于对照组，在2.5x104CFU剂量组甚至无细菌存留。说明小鼠经YncD蛋白免疫接种后，对伤寒沙门菌具有更好的免疫耐受力和清除能力。
实施例5 yncD基因在伤寒沙门菌中的相似度分析
对已测序的伤寒沙门菌的yncD基因序列进行相似度比对。伤寒沙门菌yncD基因相似性Blast结果参见图8。分析表明，yncD基因序列在伤寒沙门菌中有高度的保守性，相似度为100％，高度的保守性表明其基因功能在不同伤寒沙门菌菌株中是一致的。
综上所述，本发明提供的可用作伤寒疫苗的重组蛋白，具有良好的免疫原性和免疫保护性，YncD蛋白免疫组对实验动物具有显著的免疫保护作用。因此，可作为一种良好的疫苗预防伤寒沙门菌感染；同时本发明的重组蛋白可以较低成本大规模生产，具有良好的市场前景。
需要特别指出的是，上述各个实施例中的各个组件或步骤均可以相互交叉、替换、增加、删减，因此，这些合理的排列组合变换形成的组合也应当属于本发明的保护范围，并且不应将本发明的保护范围局限在所述实施例之上。
以上是本发明公开的示例性实施例，上述本发明实施例公开的顺序仅仅为了描述，不代表实施例的优劣。但是应当注意，以上任何实施例的讨论仅为示例性的，并非旨在暗示本发明实施例公开的范围(包括权利要求)被限于这些例子，在不背离权利要求限定的范围的前提下，可以进行多种改变和修改。根据这里描述的公开实施例的方法权利要求的功能、步骤和/或动作不需以任何特定顺序执行。此外，尽管本发明实施例公开的元素可以以个体形式描述或要求，但除非明确限制为单数，也可以理解为多个。
所属领域的普通技术人员应当理解：以上任何实施例的讨论仅为示例性的，并非旨在暗示本发明实施例公开的范围(包括权利要求)被限于这些例子；在本发明实施例的思路下，以上实施例或者不同实施例中的技术特征之间也可以进行组合，并存在如上所述的本发明实施例的不同方面的许多其它变化，为了简明它们没有在细节中提供。因此，凡在本发明实施例的精神和原则之内，所做的任何省略、修改、等同替换、改进等，均应包括在本发明实施例的保护范围之内。
序列表
<110> 西南医科大学附属中医医院
<120> 一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用
<141> 2020-05-07
<160> 4
<170> SIPOSequenceListing 1.0
<210> 1
<211> 722
<212> PRT
<213> 人工合成(Artificial synthesis)
<400> 1
Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro
1 5 10 15
Arg Gly Ser His Met Ala Ser Met Thr Gly Gly Gln Gln Met Gly Arg
20 25 30
Gly Ser Glu Phe Ala Ser Ala Pro Asn Glu Gln Thr Met Ile Val Thr
35 40 45
Ala Thr Pro Gln Thr Val Ser Glu Leu Asp Thr Pro Ala Ala Val Ser
50 55 60
Val Ile Glu Gly Glu Asp Met Arg Leu Ala Thr Pro Arg Val Asn Leu
65 70 75 80
Ser Glu Ser Leu Thr Ser Val Pro Gly Leu Gln Val Gln Asn Arg Gln
85 90 95
Asn Tyr Ala Gln Asp Leu Gln Ile Ser Ile Arg Gly Phe Gly Ser Arg
100 105 110
Ser Ala Phe Gly Val Arg Gly Ile Arg Leu Tyr Val Asp Gly Ile Pro
115 120 125
Ala Thr Met Pro Asp Gly Gln Gly Gln Ile Ser Asn Ile Asp Ile Asn
130 135 140
Ser Ile Gln Asn Val Glu Val Leu Arg Gly Pro Phe Ser Ala Leu Tyr
145 150 155 160
Gly Asn Ala Ser Gly Gly Val Ile Asn Val Thr Thr Glu Thr Gly Arg
165 170 175
Gln Pro Pro Thr Leu Glu Ala Ser Ser Tyr Tyr Gly Ser Tyr Gly Ser
180 185 190
Trp Arg Tyr Gly Leu Lys Ala Thr Gly Ala Met Gly Asp Gly Thr Gln
195 200 205
Pro Gly Asp Val Asp Tyr Thr Val Ser Thr Thr Arg Phe Thr Thr His
210 215 220
Gly Tyr Arg Asp His Ser Gly Ala Arg Lys Asn Leu Ala Asn Ala Lys
225 230 235 240
Leu Gly Val Arg Leu Asp Asp Val Ser Lys Leu Ser Leu Ile Phe Asn
245 250 255
Ser Val Asp Ile Lys Ala Asp Asp Pro Gly Gly Leu Thr Glu Ser Glu
260 265 270
Trp Lys Ala Asp Pro Gln Gln Ala Pro Arg Ala Glu Gln Tyr Asn Thr
275 280 285
Arg Lys Thr Ile Lys Gln Thr Gln Ala Gly Leu Arg Tyr Glu Arg Gln
290 295 300
Leu Ser Ala Gln Asp Asp Ile Ser Val Met Ala Tyr Ala Gly Glu Arg
305 310 315 320
Glu Thr Thr Gln Tyr Gln Ser Ile Pro Leu Val Ala Gln Leu Lys Pro
325 330 335
Ala Gln Ala Gly Gly Val Ile Thr Leu Gln Arg His Tyr Gln Gly Ile
340 345 350
Asp Ser Arg Trp Thr His Arg Gly Glu Leu Gly Val Pro Val Thr Phe
355 360 365
Thr Gly Gly Leu Asn Tyr Glu Asn Met Ser Glu Asn Arg Lys Gly Tyr
370 375 380
Asn Asn Phe Arg Leu Asn Asn Gly Thr Pro Glu Phe Gly His Lys Gly
385 390 395 400
Asp Leu Arg Arg Asp Glu Arg Asn Leu Met Trp Asn Val Asp Pro Tyr
405 410 415
Leu Gln Thr Gln Trp Gln Leu Thr Gln Lys Leu Ser Leu Asp Ala Gly
420 425 430
Val Arg Tyr Ser Ser Val Trp Phe Asp Ser Asn Asp His Tyr Ile Ala
435 440 445
Pro Gly Asn Gly Asp Asp Ser Gly Asp Ala Ser Tyr His His Trp Leu
450 455 460
Pro Ala Gly Ser Leu Lys Tyr Ala Leu Thr Asp Ala Trp Asn Leu Tyr
465 470 475 480
Leu Ala Ala Gly Arg Gly Phe Glu Thr Pro Thr Ile Asn Glu Leu Ser
485 490 495
Tyr Arg Ala Asp Gly Gln Ser Gly Phe Asn Phe Asp Leu Lys Pro Ser
500 505 510
Thr Asn Asp Thr Val Glu Val Gly Ser Lys Thr Arg Ile Gly Asn Gly
515 520 525
Leu Leu Thr Ala Ala Leu Phe Gln Thr Asp Thr Asp Asp Glu Ile Val
530 535 540
Val Ala Ser Ser Met Gly Gly Arg Thr Thr Tyr Lys Asn Ala Gly Lys
545 550 555 560
Thr Arg Arg Gln Gly Ala Glu Leu Ala Leu Asp Gln Arg Phe Ala Gly
565 570 575
Asp Trp Arg Val Lys Ala Ser Trp Thr Trp Leu Asp Ala Thr Tyr Arg
580 585 590
Ser Asn Val Cys Gln Gly Gln Asn Cys Asp Gly Asn Arg Met Pro Gly
595 600 605
Ile Ala Arg Asn Met Gly Phe Ala Ser Leu Gly Phe Ile Pro Asp Glu
610 615 620
Gly Trp Tyr Ala Gly Thr Asp Val Arg Tyr Met Gly Asp Ile Met Ala
625 630 635 640
Asn Asp Glu Asn Thr Ala Lys Ala Pro Ser Tyr Thr Val Val Gly Leu
645 650 655
Asn Thr Gly Tyr Lys Phe Asn Tyr Ser Gln Leu Thr Val Asp Ile Phe
660 665 670
Gly Arg Val Asp Asn Leu Phe Asp Glu Glu Tyr Ile Gly Ser Val Ile
675 680 685
Val Asn Glu Ser Asn Gly Arg Tyr Tyr Glu Pro Ala Pro Gly Arg Asn
690 695 700
Tyr Gly Val Gly Ile Asn Leu Ala Trp Gln Phe Glu His His His His
705 710 715 720
His His
<210> 2
<211> 2169
<212> DNA
<213> 人工合成(Artificial synthesis)
<400> 2
atgggcagca gccatcatca tcatcatcac agcagcggcc tggtgccgcg cggcagccat 60
atggctagca tgactggtgg acagcaaatg ggtcgcggat ccgaattcgc cagcgcgccc 120
aatgaacaaa ccatgatagt caccgcaacg ccgcaaaccg tatccgagct ggatacacct 180
gccgccgtta gcgtcattga gggagaagac atgcgtctgg cgacgccgcg cgttaattta 240
tctgagtctt taaccagcgt cccgggattg caggtgcaga accggcagaa ctacgcgcag 300
gatctgcaaa tctctatccg tggatttggc tcgcgttccg cctttggcgt gcgcggcatt 360
cgtctgtatg ttgatggcat tcccgccacc atgccggatg gacaaggcca gatttcaaat 420
attgatatta acagcataca aaacgttgaa gtgttacgcg gccccttctc agcgctatac 480
ggcaatgctt ccggcggcgt gataaatgtc accaccgaaa ccgggagaca gccgcccacc 540
cttgaggcca gcagctacta cggcagttat ggaagctggc gctatgggtt aaaagccacg 600
ggcgcgatgg gggacggcac acagcctggc gacgtggatt acacggtatc gactacccgt 660
ttcaccaccc acggctaccg cgatcacagc ggcgcgcgaa aaaatctggc taatgccaaa 720
ctgggcgtgc gccttgacga tgtcagtaaa ctttcgctga tttttaatag tgtggacatt 780
aaggcggacg atcccggcgg acttaccgaa tctgaatgga aagccgatcc gcagcaggcg 840
ccgcgcgctg aacagtacaa tacgcgtaaa accatcaaac aaactcaggc aggattgcgt 900
tatgaacgtc agctcagcgc gcaggatgat atcagcgtga tggcctacgc cggagagcgg 960
gaaaccacgc aataccagtc tattcccctg gtggcacagc taaaaccagc ccaggctggc 1020
ggcgtaatta cactgcaacg ccactatcag ggaattgatt cccgctggac tcaccgggga 1080
gaattaggtg tgccggtcac cttcactggc gggttaaact atgaaaacat gagcgaaaac 1140
cgcaagggtt acaataattt ccgtctcaac aacggcaccc ctgagttcgg gcataaaggc 1200
gatttacggc gggatgagcg taacctgatg tggaatgtcg atccttatct gcaaacccag 1260
tggcagctta cgcaaaaact ctcgctggat gctggcgtgc gctacagttc cgtgtggttc 1320
gattctaacg atcactatat cgcgcccggc aatggcgatg acagcggcga cgccagctat 1380
caccactggc tacccgccgg atcgctaaaa tatgcgttaa ctgacgcctg gaatctctat 1440
cttgctgccg gtcgcggatt tgaaactccc actatcaatg aactttctta tcgcgctgac 1500
ggccaaagcg ggttcaactt tgacctcaaa ccgtcgacca atgatacggt ggaagtcggc 1560
agtaaaacgc ggattggcaa tggcttgttg accgccgcgt tatttcaaac cgataccgat 1620
gatgaaattg tcgtcgccag tagtatggga ggacgcacta cctacaaaaa cgcgggcaaa 1680
acgcgccgcc agggcgcaga gctcgcgttg gaccagcgct tcgccggcga ctggcgggtg 1740
aaagcatcat ggacctggct ggatgcgacc tatcgcagta acgtttgtca ggggcaaaac 1800
tgtgatggaa accggatgcc cggcatcgcc cgtaatatgg gattcgcctc attaggtttt 1860
atcccggatg aggggtggta cgccggaaca gacgttcggt atatgggcga tatcatggcc 1920
aatgatgaaa ataccgccaa agcgccttcg tataccgttg ttggactaaa tacagggtat 1980
aaatttaatt acagtcagct taccgtcgat atttttgggc gggtagataa tctatttgat 2040
gaagaatata tcggttcggt gatcgttaat gaatctaatg gccgatatta tgagccagcg 2100
ccagggcgta actatggcgt ggggattaat ctggcatggc aatttgaaca ccaccaccac 2160
caccactga 2169
<210> 3
<211> 39
<212> DNA
<213> 人工合成(Artificial synthesis)
<400> 3
gtcgcggatc cgaattcgcc agcgcgccca atgaacaaa 39
<210> 4
<211> 34
<212> DNA
<213> 人工合成(Artificial synthesis)
<400> 4
gcaagcttgt cgacgttatt caaattgcca tgcc 34
Claims (3)
1.一种伤寒沙门菌疫苗重组蛋白、编码伤寒沙门菌疫苗重组蛋白的基因、包含编码伤寒沙门菌疫苗重组蛋白基因的重组载体、含有编码伤寒沙门菌疫苗重组蛋白基因的重组载体的重组菌株在制备用于预防伤寒沙门菌感染的疫苗中的应用；
所述伤寒沙门菌疫苗重组蛋白的氨基酸序列如SEQ ID NO.1所示；
所述基因的核苷酸序列如SEQ ID NO.2所示。
2.一种用于预防伤寒沙门菌感染的疫苗，其特征在于，所述疫苗含有氨基酸序列如SEQID NO.1所示的伤寒沙门菌重组蛋白作为活性成分。
3.根据权利要求2所述的疫苗，其特征在于：所述疫苗还含有药学上可接受的佐剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010378299.XA CN111647057B (zh) | 2020-05-07 | 2020-05-07 | 一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010378299.XA CN111647057B (zh) | 2020-05-07 | 2020-05-07 | 一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111647057A CN111647057A (zh) | 2020-09-11 |
| CN111647057B true CN111647057B (zh) | 2022-09-13 |
Family
ID=72341787
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010378299.XA Active CN111647057B (zh) | 2020-05-07 | 2020-05-07 | 一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111647057B (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009014259A1 (en) * | 2007-07-24 | 2009-01-29 | Ajinomoto Co., Inc. | A METHOD FOR PRODUCING AN L-AMINO ACID USING A BACTERIUM OF THE ENTEROBACTERIACEAE FAMILY WITH ATTENUATED EXPRESSION OF THE yncD GENE |
| CN102172399A (zh) * | 2011-02-25 | 2011-09-07 | 中国人民解放军第三军医大学 | 沙门菌yncD基因敲除载体及其制备方法及制备的沙门菌减毒疫苗 |
| CN104474539A (zh) * | 2014-11-17 | 2015-04-01 | 中国人民解放军第三军医大学 | 敲除yncD-aroC双基因的甲型副伤寒沙门菌减毒疫苗 |
| WO2017011340A2 (en) * | 2015-07-10 | 2017-01-19 | Epitopix, Llc. | Proteins and immunizing compositions containing klebsiella proteins and methods of use |
| CN110885809A (zh) * | 2019-12-04 | 2020-03-17 | 中国农业大学 | α-L-岩藻糖苷酶及其相关生物材料与应用 |
-
2020
- 2020-05-07 CN CN202010378299.XA patent/CN111647057B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009014259A1 (en) * | 2007-07-24 | 2009-01-29 | Ajinomoto Co., Inc. | A METHOD FOR PRODUCING AN L-AMINO ACID USING A BACTERIUM OF THE ENTEROBACTERIACEAE FAMILY WITH ATTENUATED EXPRESSION OF THE yncD GENE |
| CN102172399A (zh) * | 2011-02-25 | 2011-09-07 | 中国人民解放军第三军医大学 | 沙门菌yncD基因敲除载体及其制备方法及制备的沙门菌减毒疫苗 |
| CN104474539A (zh) * | 2014-11-17 | 2015-04-01 | 中国人民解放军第三军医大学 | 敲除yncD-aroC双基因的甲型副伤寒沙门菌减毒疫苗 |
| WO2017011340A2 (en) * | 2015-07-10 | 2017-01-19 | Epitopix, Llc. | Proteins and immunizing compositions containing klebsiella proteins and methods of use |
| CN110885809A (zh) * | 2019-12-04 | 2020-03-17 | 中国农业大学 | α-L-岩藻糖苷酶及其相关生物材料与应用 |
Non-Patent Citations (4)
| Title |
|---|
| Crystallization and preliminary crystallographic analysis of a chitinase from Clonostachys rosea;Zhongwei Gan等;《Acta Crystallogr Sect F Struct Biol Cryst Commun.》;20090401;第386-387页第2.1小节 * |
| Deletion of yncD gene in Salmonella enterica ssp. enterica serovar Typhi leads to attenuation in mouse model;Kun Xiong等;《FEMS Microbiol Lett》;20120110;第70-77页 * |
| TonB-dependent receptor YncD [Salmonella enterica subsp. enterica serovar Typhi];NCBI;《Genbank database》;20150613;Accession NO. CGZ99707.1 * |
| 伤寒沙门菌外膜蛋白YncD 的重组表达、纯化及其免疫保护作用观察;丛延广等;《免疫学杂志》;20201130;第36卷(第11期);第951-955页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111647057A (zh) | 2020-09-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8173773B2 (en) | Mycobacterium tuberculosis fusion protein and uses thereof | |
| CN104844712B (zh) | 肺炎链球菌蛋白抗原及其制备方法和应用 | |
| Feng et al. | Identification and characterization of a novel conserved 46 kD maltoporin of Aeromonas hydrophila as a versatile vaccine candidate in European eel (Anguilla anguilla) | |
| CN109293750B (zh) | 一种铜绿假单胞菌疫苗重组蛋白sbp及其制备方法及应用 | |
| CN108126190A (zh) | 分枝杆菌噬菌体裂解酶Lysin-Guo1的制备与应用 | |
| CN108066755A (zh) | 一种抗羊包虫病感染的基因工程亚单位疫苗及其制备方法和应用 | |
| CN108794584B (zh) | 一种胸膜肺炎放线杆菌免疫保护性抗原蛋白apjl_1380及其应用 | |
| CN104861050B (zh) | 鲍曼不动杆菌锌依赖寡肽a1s_1610蛋白及其制备方法和应用 | |
| CN101747416B (zh) | 拟态弧菌OmpU蛋白B细胞抗原多表位串联肽及其构建方法与用途 | |
| CN105669844B (zh) | 一种铜绿假单胞菌重组蛋白Vac33的纯化方法 | |
| CN111647057B (zh) | 一种伤寒沙门菌疫苗重组蛋白及其编码基因和它们的应用 | |
| CN108314718A (zh) | 一种家蝇抗菌肽maf-1a肽聚体、其编码基因及其表达和应用 | |
| CN110746496B (zh) | 一种鲍曼不动杆菌的pal重组蛋白及其编码基因和它们的应用 | |
| CN106117365B (zh) | 抗猪链球菌病且具有自身免疫活性的融合蛋白及其制备和应用 | |
| Zhao et al. | Cloning, expressing, and hemolysis of tdh, trh and tlh genes of Vibrio parahaemolyticus | |
| CN108822192B (zh) | 一种胸膜肺炎放线杆菌免疫保护性抗原蛋白apjl_1976及其应用 | |
| CN112402598A (zh) | 针对鸭疫里默氏杆菌感染引起的通用型亚单位疫苗 | |
| CN105647894A (zh) | 铜绿假单胞菌疫苗重组蛋白Vac11的纯化方法 | |
| CN108840913A (zh) | 一种胸膜肺炎放线杆菌免疫保护性抗原蛋白apjl_0922及其应用 | |
| CN112316130B (zh) | 一种SARS-CoV2粘膜免疫疫苗及其应用 | |
| CN110922456B (zh) | 铜绿假单胞菌疫苗重组蛋白reSBP-ExoU及制备方法和应用 | |
| CN113121672A (zh) | 猫干扰素γ的可溶性原核表达和纯化方法及应用 | |
| CN105622734A (zh) | 铜绿假单胞菌疫苗重组蛋白Vac14的纯化方法 | |
| CN101845084B (zh) | 一种作为a群链球菌四价疫苗保护性抗原的重组多肽 | |
| CN117603320A (zh) | 伤寒沙门菌YncE蛋白的重组蛋白及其制备方法和用途 |
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 | ||
| CB03 | Change of inventor or designer information |
Inventor after: Cong Yanguang Inventor after: Wang Jia Inventor after: Yu Yue Inventor after: He Jinrui Inventor before: Cong Yanguang Inventor before: Xiong Kun Inventor before: Chen Zhijin Inventor before: Wang Jia Inventor before: Yu Yue Inventor before: He Jinrui |