CN104211802B - 人凝血因子轻链蛋白及其应用 - Google Patents
人凝血因子轻链蛋白及其应用 Download PDFInfo
- Publication number
- CN104211802B CN104211802B CN201310206823.5A CN201310206823A CN104211802B CN 104211802 B CN104211802 B CN 104211802B CN 201310206823 A CN201310206823 A CN 201310206823A CN 104211802 B CN104211802 B CN 104211802B
- Authority
- CN
- China
- Prior art keywords
- lhf
- albumen
- light chain
- blood coagulation
- human blood
- 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 60
- 230000023555 blood coagulation Effects 0.000 title claims abstract description 36
- 102000004169 proteins and genes Human genes 0.000 title abstract description 34
- 241000894006 Bacteria Species 0.000 claims abstract description 55
- 239000003814 drug Substances 0.000 claims abstract description 16
- 229940079593 drug Drugs 0.000 claims abstract description 14
- 208000037487 Endotoxemia Diseases 0.000 claims abstract description 9
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 7
- 239000013612 plasmid Substances 0.000 claims description 64
- 238000005215 recombination Methods 0.000 claims description 51
- 230000006798 recombination Effects 0.000 claims description 51
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 239000002158 endotoxin Substances 0.000 abstract description 31
- 102000015081 Blood Coagulation Factors Human genes 0.000 abstract description 8
- 108010039209 Blood Coagulation Factors Proteins 0.000 abstract description 8
- 239000003114 blood coagulation factor Substances 0.000 abstract description 8
- 229940019700 blood coagulation factors Drugs 0.000 abstract description 8
- 238000001514 detection method Methods 0.000 abstract description 8
- 208000002109 Argyria Diseases 0.000 abstract description 6
- 230000003385 bacteriostatic effect Effects 0.000 abstract description 5
- 238000001819 mass spectrum Methods 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 2
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 230000002000 scavenging effect Effects 0.000 abstract 1
- 230000009182 swimming Effects 0.000 description 33
- 241000699666 Mus <mouse, genus> Species 0.000 description 32
- 230000014509 gene expression Effects 0.000 description 26
- 241000588724 Escherichia coli Species 0.000 description 25
- 229920006008 lipopolysaccharide Polymers 0.000 description 25
- 238000012408 PCR amplification Methods 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- 239000012634 fragment Substances 0.000 description 21
- 239000013598 vector Substances 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 17
- 108091008146 restriction endonucleases Proteins 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 230000002068 genetic effect Effects 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 150000001413 amino acids Chemical group 0.000 description 14
- 230000000844 anti-bacterial effect Effects 0.000 description 12
- 239000002773 nucleotide Substances 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 239000012474 protein marker Substances 0.000 description 12
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 11
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 10
- 102000057593 human F8 Human genes 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229940047431 recombinate Drugs 0.000 description 10
- 230000004083 survival effect Effects 0.000 description 10
- 230000003115 biocidal effect Effects 0.000 description 9
- 230000029087 digestion Effects 0.000 description 9
- 239000003292 glue Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 9
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 description 8
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 8
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 8
- 239000008367 deionised water Substances 0.000 description 8
- 229910021641 deionized water Inorganic materials 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 8
- 229960002260 meropenem Drugs 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 229930182555 Penicillin Natural products 0.000 description 7
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 231100000636 lethal dose Toxicity 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 229940049954 penicillin Drugs 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 241000193830 Bacillus <bacterium> Species 0.000 description 6
- 108010077805 Bacterial Proteins Proteins 0.000 description 6
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 6
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000013467 fragmentation Methods 0.000 description 6
- 238000006062 fragmentation reaction Methods 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 230000003321 amplification Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 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 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 230000009465 prokaryotic expression Effects 0.000 description 5
- 238000001742 protein purification Methods 0.000 description 5
- 230000017854 proteolysis Effects 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000000246 agarose gel electrophoresis Methods 0.000 description 4
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000007758 minimum essential medium Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 125000003345 AMP group Chemical group 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 101150006005 VII gene Proteins 0.000 description 3
- 101150003160 X gene Proteins 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 229920006227 ethylene-grafted-maleic anhydride Polymers 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000004153 renaturation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000588923 Citrobacter Species 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 241000588697 Enterobacter cloacae Species 0.000 description 2
- 101001091385 Homo sapiens Kallikrein-6 Proteins 0.000 description 2
- 102100034866 Kallikrein-6 Human genes 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 241000588770 Proteus mirabilis Species 0.000 description 2
- 241000588767 Proteus vulgaris Species 0.000 description 2
- 241000607720 Serratia Species 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 229910001870 ammonium persulfate Inorganic materials 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
- 229960000723 ampicillin Drugs 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000007910 cell fusion Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000010985 leather Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 201000009240 nasopharyngitis Diseases 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 229940007042 proteus vulgaris Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000607528 Aeromonas hydrophila Species 0.000 description 1
- 101710134784 Agnoprotein Proteins 0.000 description 1
- 108700042778 Antimicrobial Peptides Proteins 0.000 description 1
- 102000044503 Antimicrobial Peptides Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101710163092 D-lysergyl-peptide-synthetase subunit 1 Proteins 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 102100037642 Elongation factor G, mitochondrial Human genes 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000892865 Heros Species 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000880344 Homo sapiens Elongation factor G, mitochondrial Proteins 0.000 description 1
- 101150108210 IX gene Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 241000233855 Orchidaceae Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 229920002538 Polyethylene Glycol 20000 Polymers 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 238000012181 QIAquick gel extraction kit Methods 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 241000607764 Shigella dysenteriae Species 0.000 description 1
- 101100226845 Strongylocentrotus purpuratus EGF2 gene Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 229960000182 blood factors Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013373 clone screening Methods 0.000 description 1
- 229910001429 cobalt ion Inorganic materials 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- 210000001520 comb Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229960000027 human factor ix Drugs 0.000 description 1
- 229940099816 human factor vii Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 229960001614 levamisole Drugs 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000001374 post-anti-biotic effect Effects 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229940007046 shigella dysenteriae Drugs 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 230000008470 skin growth Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical class [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21006—Coagulation factor Xa (3.4.21.6)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21021—Coagulation factor VIIa (3.4.21.21)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
-
- 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)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310206823.5A CN104211802B (zh) | 2013-05-29 | 2013-05-29 | 人凝血因子轻链蛋白及其应用 |
| US14/894,415 US9782461B2 (en) | 2013-05-29 | 2014-05-22 | Human coagulation factor light chain protein and use of the same |
| JP2016515629A JP6441906B2 (ja) | 2013-05-29 | 2014-05-22 | ヒト凝固因子軽鎖タンパク質及びその使用 |
| PCT/CN2014/078108 WO2014190871A1 (zh) | 2013-05-29 | 2014-05-22 | 人凝血因子轻链蛋白及其应用 |
| EP14804149.4A EP3006461A4 (en) | 2013-05-29 | 2014-05-22 | Human coagulation factor light-chain protein and application of same |
| CN201480042517.5A CN105473611B (zh) | 2013-05-29 | 2014-05-22 | 人凝血因子轻链蛋白及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310206823.5A CN104211802B (zh) | 2013-05-29 | 2013-05-29 | 人凝血因子轻链蛋白及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104211802A CN104211802A (zh) | 2014-12-17 |
| CN104211802B true CN104211802B (zh) | 2018-07-27 |
Family
ID=51987992
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310206823.5A Active CN104211802B (zh) | 2013-05-29 | 2013-05-29 | 人凝血因子轻链蛋白及其应用 |
| CN201480042517.5A Active CN105473611B (zh) | 2013-05-29 | 2014-05-22 | 人凝血因子轻链蛋白及其应用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480042517.5A Active CN105473611B (zh) | 2013-05-29 | 2014-05-22 | 人凝血因子轻链蛋白及其应用 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US9782461B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP3006461A4 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6441906B2 (cg-RX-API-DMAC7.html) |
| CN (2) | CN104211802B (cg-RX-API-DMAC7.html) |
| WO (1) | WO2014190871A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111272889B (zh) * | 2020-02-10 | 2022-02-25 | 济宁学院 | 基于蛋白质组学定量技术分析嗜水气单胞菌感染日本沼虾血细胞差异表达蛋白质的方法 |
| CN116539893A (zh) * | 2023-04-23 | 2023-08-04 | 天津医科大学总医院 | 一种细胞内凝血因子ⅹ的质谱检测方法、应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103079588A (zh) * | 2010-07-22 | 2013-05-01 | 德国杰特贝林生物制品有限公司 | 祖先丝氨酸蛋白酶凝血级联在早期免疫防御中发挥新功能 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5940799A (en) * | 1994-10-24 | 2000-02-17 | Novo Nordisk A/S | Modified factor VII |
| CA2450127A1 (en) * | 2001-06-14 | 2002-12-27 | Shujian Wu | Polynucleotide encoding a novel human growth factor with homology to epidermal growth factor, bgs-8, expressed highly in immune tissue |
| US6861236B2 (en) * | 2002-05-24 | 2005-03-01 | Applied Nanosystems B.V. | Export and modification of (poly)peptides in the lantibiotic way |
| CA2528239A1 (en) * | 2003-06-05 | 2004-12-16 | Canadian Blood Services | Mutants of the factor vii epidermal growth factor domain |
| WO2004111242A1 (en) * | 2003-06-19 | 2004-12-23 | Maxygen Holdings Ltd. | FACTOR VII OR VIIa GLA DOMAIN VARIANTS |
| CN101384613A (zh) * | 2006-02-10 | 2009-03-11 | 德玛根股份公司 | 新型抗微生物肽及其应用 |
| US7968683B1 (en) * | 2008-05-07 | 2011-06-28 | Schering Corporation | Factor IXa crystals, related complexes and methods |
| FR2972114B1 (fr) * | 2011-03-01 | 2013-03-15 | Univ Grenoble 1 | Un nouveau leurre moleculaire procoagulant pour le traitement des hemophiles a ou b avec ou sans inhibiteur |
| CN102875685B (zh) * | 2012-09-29 | 2013-12-25 | 郑骏年 | 嵌合抗原受体hFⅦL-CD8-OX40-CD3ζ及其用途 |
-
2013
- 2013-05-29 CN CN201310206823.5A patent/CN104211802B/zh active Active
-
2014
- 2014-05-22 WO PCT/CN2014/078108 patent/WO2014190871A1/zh not_active Ceased
- 2014-05-22 EP EP14804149.4A patent/EP3006461A4/en active Pending
- 2014-05-22 JP JP2016515629A patent/JP6441906B2/ja active Active
- 2014-05-22 US US14/894,415 patent/US9782461B2/en active Active
- 2014-05-22 CN CN201480042517.5A patent/CN105473611B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103079588A (zh) * | 2010-07-22 | 2013-05-01 | 德国杰特贝林生物制品有限公司 | 祖先丝氨酸蛋白酶凝血级联在早期免疫防御中发挥新功能 |
Non-Patent Citations (5)
| Title |
|---|
| Blood coagulation factor activity in experimental endotoxemia;R L West;《Ann Surg.》;19660430;第163卷(第4期);567–572 * |
| No.1O5D_L;NCBI;《GenBank》;20121010 * |
| No.AAA51981.1，;NCBI;《GenBank》;19941101 * |
| No.XP_004054811.1;NCBI;《GenBank》;20121203 * |
| 凝血系统在细菌感染性疾病中的临床意义;李婧;《中华医学会第七次全国检验医学学术会议资料汇编》;20080501;384-385 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3006461A4 (en) | 2017-01-25 |
| US20160106818A1 (en) | 2016-04-21 |
| CN105473611B (zh) | 2020-03-20 |
| WO2014190871A1 (zh) | 2014-12-04 |
| US9782461B2 (en) | 2017-10-10 |
| CN104211802A (zh) | 2014-12-17 |
| CN105473611A (zh) | 2016-04-06 |
| JP2016521685A (ja) | 2016-07-25 |
| JP6441906B2 (ja) | 2018-12-19 |
| EP3006461A1 (en) | 2016-04-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2962555B2 (ja) | 溶菌ペプチドによる真核性病原体と新生物の抑制及び繊維芽細胞とリンパ球の刺激 | |
| Seo et al. | Purification and characterization of YFGAP, a GAPDH-related novel antimicrobial peptide, from the skin of yellowfin tuna, Thunnus albacares | |
| CN106282216B (zh) | 一种重组长效鸡干扰素α的制备方法 | |
| CN104211799B (zh) | 人源egf结构域蛋白及其应用 | |
| CN111304181B (zh) | 一种基因工程改造后的副溶血性弧菌噬菌体裂解酶及其制备方法和应用 | |
| JPS60120990A (ja) | ウサギ癌壊死因子をコ−ドするクロ−ン化ｄνａ | |
| CN108396030A (zh) | 凡纳滨对虾抗菌肽基因Lv-BigPEN及其重组蛋白和应用 | |
| CN104211802B (zh) | 人凝血因子轻链蛋白及其应用 | |
| CN109627316A (zh) | 草鱼IFN-γ2基因及其编码的重组蛋白和应用 | |
| CN109134635A (zh) | 一种具有复合生物活性的抗菌肽及其制备方法与应用 | |
| CN108264548B (zh) | 鳜鱼伽玛干扰素相关因子及其重组蛋白和应用 | |
| CN106432459B (zh) | 花姬蛙抗菌肽及其基因和在制药中的应用 | |
| CN112480227B (zh) | 一种提高鲟鱼抵抗病原菌能力的蛋白及其制备方法与应用 | |
| Green et al. | Inhibition of mumps virus multiplication by a synthetic polypeptide | |
| CN118165126B (zh) | 一种重组猪干扰素λ1、猪干扰素γ和猪Fc（KiH）的融合蛋白及其应用 | |
| CN113754750A (zh) | 一种抗菌肽及其在水产养殖中的应用 | |
| CN110669114B (zh) | 一种羊毛硫肽前体肽amyA6及其制备方法和应用 | |
| CN102406929A (zh) | 一种共表达分子佐剂加强型二价口蹄疫蛋白工程疫苗 | |
| CN106479987B (zh) | 一种可溶性家蝇MdproPO1重组蛋白的制备方法及其应用 | |
| JP6709395B2 (ja) | 冷水病ワクチン及び冷水病の予防方法 | |
| CN112941040B (zh) | 斑节对虾E3泛素连接酶TRIM50-like蛋白及其应用 | |
| EP2128172B1 (en) | Preparation process of recombinant human p43 protein | |
| WO1998052972A1 (en) | Novel protein, its gene, reagents for inducing apoptosis, and anticancer agents | |
| CN107827986B (zh) | 猪O/Mya98和O/PanAsia型口蹄疫基因工程灭活疫苗 | |
| Konishi et al. | Molecular cloning and multifunctional characterization of host defense peptides from the bullfrog Harderian gland with special reference to catesbeianalectin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20151208 Address after: Science Park Road Chengdu city Sichuan province 610041 No. 9 of No. 2 East Building 2 floor Applicant after: CHENGDU ORIGIN BIOTECHNOLOGY CO., LTD. Address before: 610065 Wuhou District, Chengdu, South Ring Road, No. 1, No. 1, Sichuan Applicant before: Sichuan University |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |