IL87276A - Analog of tissue plasminogen activator comprising only the kringle 2 and protease domain dna encoding the same processes for the preparation thereof and pharmaceutical compositions containing the same - Google Patents

Analog of tissue plasminogen activator comprising only the kringle 2 and protease domain dna encoding the same processes for the preparation thereof and pharmaceutical compositions containing the same

Info

Publication number: IL87276A
Authority: IL; Israel
Prior art keywords: plasmid; dna; coli; dna fragment; amino acid
Prior art date: 1987-08-03

Application number

IL8727688A

Other languages

English (en)

Other versions

IL87276A0 (en

Original Assignee

Fujisawa Pharmaceutical Co

Priority date (The priority date 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 date listed.)

1987-08-03

Filing date

1988-07-31

Publication date

1995-07-31

1987-08-03 Priority claimed from GB878718298A external-priority patent/GB8718298D0/en

1987-10-26 Priority claimed from GB878725052A external-priority patent/GB8725052D0/en

1987-11-13 Priority claimed from GB878726683A external-priority patent/GB8726683D0/en

1988-07-31 Application filed by Fujisawa Pharmaceutical Co filed Critical Fujisawa Pharmaceutical Co

1988-12-30 Publication of IL87276A0 publication Critical patent/IL87276A0/xx

1995-07-31 Publication of IL87276A publication Critical patent/IL87276A/en

Links

238000000034 method Methods 0.000 title claims abstract description 22
102000003978 Tissue Plasminogen Activator Human genes 0.000 title claims abstract description 11
108090000373 Tissue Plasminogen Activator Proteins 0.000 title claims abstract description 11
229960000187 tissue plasminogen activator Drugs 0.000 title claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
238000002360 preparation method Methods 0.000 title description 7
108091005804 Peptidases Proteins 0.000 title description 4
239000004365 Protease Substances 0.000 title description 4
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title 1
108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 27
125000003275 alpha amino acid group Chemical group 0.000 claims abstract 6
108020004414 DNA Proteins 0.000 claims description 112
108050006955 Tissue-type plasminogen activator Proteins 0.000 claims description 109
102100033571 Tissue-type plasminogen activator Human genes 0.000 claims description 108
239000013604 expression vector Substances 0.000 claims description 15
235000015097 nutrients Nutrition 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
239000013598 vector Substances 0.000 claims description 3
238000012258 culturing Methods 0.000 claims description 2
230000000694 effects Effects 0.000 abstract description 13
102000009123 Fibrin Human genes 0.000 abstract description 7
108010073385 Fibrin Proteins 0.000 abstract description 7
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 abstract description 7
229950003499 fibrin Drugs 0.000 abstract description 7
208000007536 Thrombosis Diseases 0.000 abstract description 4
229940012957 plasmin Drugs 0.000 abstract description 4
102000013566 Plasminogen Human genes 0.000 abstract description 3
108010051456 Plasminogen Proteins 0.000 abstract description 3
239000003527 fibrinolytic agent Substances 0.000 abstract description 3
229960000103 thrombolytic agent Drugs 0.000 abstract description 3
239000013612 plasmid Substances 0.000 description 103
239000012634 fragment Substances 0.000 description 81
241000588724 Escherichia coli Species 0.000 description 59
238000010367 cloning Methods 0.000 description 47
238000010276 construction Methods 0.000 description 47
210000004027 cell Anatomy 0.000 description 37
102000012410 DNA Ligases Human genes 0.000 description 31
108010061982 DNA Ligases Proteins 0.000 description 31
150000001413 amino acids Chemical group 0.000 description 24
239000000203 mixture Substances 0.000 description 23
229960000723 ampicillin Drugs 0.000 description 22
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 22
241001452028 Escherichia coli DH1 Species 0.000 description 19
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 14
108091026890 Coding region Proteins 0.000 description 13
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 11
238000013507 mapping Methods 0.000 description 11
239000000243 solution Substances 0.000 description 11
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 10
108091008146 restriction endonucleases Proteins 0.000 description 10
239000006228 supernatant Substances 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 9
102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 9
230000029087 digestion Effects 0.000 description 9
229940124276 oligodeoxyribonucleotide Drugs 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
210000004962 mammalian cell Anatomy 0.000 description 8
239000002609 medium Substances 0.000 description 8
235000018102 proteins Nutrition 0.000 description 8
108090000623 proteins and genes Proteins 0.000 description 8
102000004169 proteins and genes Human genes 0.000 description 8
102000004190 Enzymes Human genes 0.000 description 7
108090000790 Enzymes Proteins 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
239000004202 carbamide Substances 0.000 description 7
229940088598 enzyme Drugs 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
102000002260 Alkaline Phosphatase Human genes 0.000 description 6
108020004774 Alkaline Phosphatase Proteins 0.000 description 6
241000894006 Bacteria Species 0.000 description 6
101100466198 Mus musculus Ptpra gene Proteins 0.000 description 6
108091034117 Oligonucleotide Proteins 0.000 description 6
229920002684 Sepharose Polymers 0.000 description 6
108020005038 Terminator Codon Proteins 0.000 description 6
238000003556 assay Methods 0.000 description 6
230000001580 bacterial effect Effects 0.000 description 6
238000002955 isolation Methods 0.000 description 6
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
229920000053 polysorbate 80 Polymers 0.000 description 6
230000009466 transformation Effects 0.000 description 6
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
108010053070 Glutathione Disulfide Proteins 0.000 description 5
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 5
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 5
108010076504 Protein Sorting Signals Proteins 0.000 description 5
108091081024 Start codon Proteins 0.000 description 5
244000309466 calf Species 0.000 description 5
238000005516 engineering process Methods 0.000 description 5
YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 5
230000000968 intestinal effect Effects 0.000 description 5
238000011160 research Methods 0.000 description 5
108700028146 Genetic Enhancer Elements Proteins 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
240000004808 Saccharomyces cerevisiae Species 0.000 description 4
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 4
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
238000005119 centrifugation Methods 0.000 description 4
239000002299 complementary DNA Substances 0.000 description 4
238000000502 dialysis Methods 0.000 description 4
BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
244000005700 microbiome Species 0.000 description 4
239000008188 pellet Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000011369 resultant mixture Substances 0.000 description 4
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
108700007698 Genetic Terminator Regions Proteins 0.000 description 3
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical group [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 3
102000035195 Peptidases Human genes 0.000 description 3
108020004511 Recombinant DNA Proteins 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
235000001014 amino acid Nutrition 0.000 description 3
125000000539 amino acid group Chemical group 0.000 description 3
210000004102 animal cell Anatomy 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
235000018417 cysteine Nutrition 0.000 description 3
229960003067 cystine Drugs 0.000 description 3
229960003180 glutathione Drugs 0.000 description 3
235000003969 glutathione Nutrition 0.000 description 3
235000011187 glycerol Nutrition 0.000 description 3
239000003102 growth factor Substances 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
239000008363 phosphate buffer Substances 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
239000000047 product Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
241000894007 species Species 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
238000012360 testing method Methods 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
108010039627 Aprotinin Proteins 0.000 description 2
HXWUJJADFMXNKA-BQBZGAKWSA-N Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O HXWUJJADFMXNKA-BQBZGAKWSA-N 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
108010017826 DNA Polymerase I Proteins 0.000 description 2
102000004594 DNA Polymerase I Human genes 0.000 description 2
241001131785 Escherichia coli HB101 Species 0.000 description 2
LLEUXCDZPQOJMY-AAEUAGOBSA-N Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(O)=O)=CNC2=C1 LLEUXCDZPQOJMY-AAEUAGOBSA-N 0.000 description 2
108010024636 Glutathione Proteins 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
102000016943 Muramidase Human genes 0.000 description 2
108010014251 Muramidase Proteins 0.000 description 2
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
108091000080 Phosphotransferase Proteins 0.000 description 2
101100153172 Pisum sativum TIC32 gene Proteins 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
102100033237 Pro-epidermal growth factor Human genes 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
229920004890 Triton X-100 Polymers 0.000 description 2
239000013504 Triton X-100 Substances 0.000 description 2
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
PDSLRCZINIDLMU-QWRGUYRKSA-N Tyr-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PDSLRCZINIDLMU-QWRGUYRKSA-N 0.000 description 2
108010050025 alpha-glutamyltryptophan Proteins 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
229960004405 aprotinin Drugs 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
235000011148 calcium chloride Nutrition 0.000 description 2
229940041514 candida albicans extract Drugs 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
239000000385 dialysis solution Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
238000001802 infusion Methods 0.000 description 2
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
229960000274 lysozyme Drugs 0.000 description 2
239000004325 lysozyme Substances 0.000 description 2
235000010335 lysozyme Nutrition 0.000 description 2
229910001629 magnesium chloride Inorganic materials 0.000 description 2
235000011147 magnesium chloride Nutrition 0.000 description 2
239000003550 marker Substances 0.000 description 2
230000035772 mutation Effects 0.000 description 2
208000010125 myocardial infarction Diseases 0.000 description 2
102000039446 nucleic acids Human genes 0.000 description 2
108020004707 nucleic acids Proteins 0.000 description 2
150000007523 nucleic acids Chemical class 0.000 description 2
YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
102000020233 phosphotransferase Human genes 0.000 description 2
230000008488 polyadenylation Effects 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000006152 selective media Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
230000002537 thrombolytic effect Effects 0.000 description 2
238000001890 transfection Methods 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
239000012138 yeast extract Substances 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
WPANETAWYGDRLL-UHFFFAOYSA-N 4-aminobenzenecarboximidamide Chemical compound NC(=N)C1=CC=C(N)C=C1 WPANETAWYGDRLL-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
208000031104 Arterial Occlusive disease Diseases 0.000 description 1
QJMCHPGWFZZRID-BQBZGAKWSA-N Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O QJMCHPGWFZZRID-BQBZGAKWSA-N 0.000 description 1
244000063299 Bacillus subtilis Species 0.000 description 1
235000014469 Bacillus subtilis Nutrition 0.000 description 1
101100067721 Caenorhabditis elegans gly-3 gene Proteins 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
230000006820 DNA synthesis Effects 0.000 description 1
206010051055 Deep vein thrombosis Diseases 0.000 description 1
102100031681 DnaJ homolog subfamily C member 3 Human genes 0.000 description 1
239000006145 Eagle's minimal essential medium Substances 0.000 description 1
102000010911 Enzyme Precursors Human genes 0.000 description 1
108010062466 Enzyme Precursors Proteins 0.000 description 1
101800003838 Epidermal growth factor Proteins 0.000 description 1
241000588722 Escherichia Species 0.000 description 1
108010049003 Fibrinogen Proteins 0.000 description 1
102000008946 Fibrinogen Human genes 0.000 description 1
102000016359 Fibronectins Human genes 0.000 description 1
108010067306 Fibronectins Proteins 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
VPZXBVLAVMBEQI-VKHMYHEASA-N Glycyl-alanine Chemical compound OC(=O)[C@H](C)NC(=O)CN VPZXBVLAVMBEQI-VKHMYHEASA-N 0.000 description 1
101000845898 Homo sapiens DnaJ homolog subfamily C member 3 Proteins 0.000 description 1
101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
NDYNTQWSJLPEMK-WDSKDSINSA-N Met-Cys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CS)C(O)=O NDYNTQWSJLPEMK-WDSKDSINSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 1
108010079364 N-glycylalanine Proteins 0.000 description 1
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
241001045988 Neogene Species 0.000 description 1
241000577979 Peromyscus spicilegus Species 0.000 description 1
102000001938 Plasminogen Activators Human genes 0.000 description 1
108010001014 Plasminogen Activators Proteins 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
208000010378 Pulmonary Embolism Diseases 0.000 description 1
239000012506 Sephacryl® Substances 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
WBAXJMCUFIXCNI-WDSKDSINSA-N Ser-Pro Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WBAXJMCUFIXCNI-WDSKDSINSA-N 0.000 description 1
102000012479 Serine Proteases Human genes 0.000 description 1
108010022999 Serine Proteases Proteins 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
208000006011 Stroke Diseases 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
108090000190 Thrombin Proteins 0.000 description 1
206010046865 Vaccinia virus infection Diseases 0.000 description 1
206010047249 Venous thrombosis Diseases 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000012190 activator Substances 0.000 description 1
238000000246 agarose gel electrophoresis Methods 0.000 description 1
238000013019 agitation Methods 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
208000021328 arterial occlusion Diseases 0.000 description 1
108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 1
235000015278 beef Nutrition 0.000 description 1
PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000005018 casein Substances 0.000 description 1
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
235000021240 caseins Nutrition 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
210000002421 cell wall Anatomy 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
101150108293 cla gene Proteins 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
230000030609 dephosphorylation Effects 0.000 description 1
238000006209 dephosphorylation reaction Methods 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
229940116977 epidermal growth factor Drugs 0.000 description 1
239000013613 expression plasmid Substances 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
229940012952 fibrinogen Drugs 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 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
210000005260 human cell Anatomy 0.000 description 1
239000000413 hydrolysate Substances 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
238000011835 investigation Methods 0.000 description 1
JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
229960000318 kanamycin Drugs 0.000 description 1
229930027917 kanamycin Natural products 0.000 description 1
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 1
229930182823 kanamycin A Natural products 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
CJWXCNXHAIFFMH-AVZHFPDBSA-N n-[(2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5r)-2-acetamido-4,5,6-trihydroxy-1-oxohexan-3-yl]oxy-3,5-dihydroxy-6-methyloxan-4-yl]acetamide Chemical compound C[C@H]1O[C@@H](O[C@@H]([C@@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O)[C@H](O)[C@@H](NC(C)=O)[C@@H]1O CJWXCNXHAIFFMH-AVZHFPDBSA-N 0.000 description 1
101150091879 neo gene Proteins 0.000 description 1
235000008935 nutritious Nutrition 0.000 description 1
125000001477 organic nitrogen group Chemical group 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
229940127126 plasminogen activator Drugs 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
208000019585 progressive encephalomyelitis with rigidity and myoclonus Diseases 0.000 description 1
101150079601 recA gene Proteins 0.000 description 1
230000003362 replicative effect Effects 0.000 description 1
108010073863 saruplase Proteins 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
108010026333 seryl-proline Proteins 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
229940063673 spermidine Drugs 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000012085 test solution Substances 0.000 description 1
DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
208000007089 vaccinia Diseases 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
-1 vitamin Bl) Natural products 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6456—Plasminogen activators
- C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
- 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)
- C12Y304/21069—Protein C activated (3.4.21.69)

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Genetics & Genomics (AREA)
Zoology (AREA)
Wood Science & Technology (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
General Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
Molecular Biology (AREA)
Microbiology (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Physics & Mathematics (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Biophysics (AREA)
Plant Pathology (AREA)
Vascular Medicine (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Urology & Nephrology (AREA)
Hematology (AREA)
Diabetes (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Enzymes And Modification Thereof (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Peptides Or Proteins (AREA)
Saccharide Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

IL8727688A 1987-08-03 1988-07-31 Analog of tissue plasminogen activator comprising only the kringle 2 and protease domain dna encoding the same processes for the preparation thereof and pharmaceutical compositions containing the same IL87276A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB878718298A GB8718298D0 (en)	1987-08-03	1987-08-03	Tissue plasminogen activator
GB878725052A GB8725052D0 (en)	1987-10-26	1987-10-26	Tissue plasminogen activator
GB878726683A GB8726683D0 (en)	1987-11-13	1987-11-13	Tissue plasminogen activator

Publications (2)

Publication Number	Publication Date
IL87276A0 IL87276A0 (en)	1988-12-30
IL87276A true IL87276A (en)	1995-07-31

Family

ID=27263535

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL8727688A IL87276A (en)	1987-08-03	1988-07-31	Analog of tissue plasminogen activator comprising only the kringle 2 and protease domain dna encoding the same processes for the preparation thereof and pharmaceutical compositions containing the same

Country Status (11)

Country	Link
US (2)	US5648250A (de)
EP (1)	EP0302456B1 (de)
JP (3)	JP2561708B2 (de)
KR (1)	KR970001237B1 (de)
AT (1)	ATE108206T1 (de)
AU (1)	AU623340B2 (de)
CA (1)	CA1341458C (de)
DE (1)	DE3850531T2 (de)
DK (1)	DK174413B1 (de)
ES (1)	ES2056082T3 (de)
IL (1)	IL87276A (de)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL87276A (en) *	1987-08-03	1995-07-31	Fujisawa Pharmaceutical Co	Analog of tissue plasminogen activator comprising only the kringle 2 and protease domain dna encoding the same processes for the preparation thereof and pharmaceutical compositions containing the same
IL88247A0 (en) *	1987-11-06	1989-06-30	Genentech Inc	Novel human tissue-type plasminogen activator variant
US5094953A (en) *	1988-03-21	1992-03-10	Genentech, Inc.	Human tissue plasminogen activator variants
US5262170A (en) *	1988-09-02	1993-11-16	Genentech, Inc.	Tissue plasminogen activator having zymogenic or fibrin specific properties and substituted at amino acid positions 296-299, DNA molecules encoding them, vectors, and host cells
DE3903581A1 (de) *	1989-02-07	1990-08-16	Boehringer Mannheim Gmbh	Gewebs-plasminogenaktivator-derivat
US5676947A (en) *	1989-02-07	1997-10-14	Boehringer Manneheim Gmbh	Method for treating thromboembolic conditions using thrombolytically active proteins
DE3923339A1 (de) *	1989-05-31	1990-12-06	Boehringer Mannheim Gmbh	Gewebs-plasminogen-aktivator-derivat
US5242688A (en) *	1990-12-24	1993-09-07	Eli Lilly And Company	Method of treating thromboembolic disorders by administration of diglycosylated t-pa variants
GB9204439D0 (en)	1992-02-27	1992-04-15	Fujisawa Pharmaceutical Co	A new cephalosporin c acylase
DE4440892A1 (de) *	1994-11-17	1996-05-23	Gruenenthal Gmbh	Proteine mit fibrinolytischen und gerinnungshemmenden Eigenschaften
DE19937219A1 (de) *	1999-08-06	2001-02-08	Aventis Behring Gmbh	Verfahren zur Reindarstellung der den Blutgerinnungsfaktor VII aktivierenden Protease, ihres Proenzyms oder eines Gemisches beider Proteine mittels Ionenaustauscherchromatographie
DE19937218A1 (de) *	1999-08-06	2001-02-08	Aventis Behring Gmbh	Verfahren zur Reindarstellung der den Blutgerinnungsfaktor VII aktivierenden Protease, ihres Proenzyms oder eines Gemisches beider Proteine mittels Affinitätschromatographie
US6821755B2 (en) *	2000-07-27	2004-11-23	Boehringer Ingelheim International Gmbh	Preparation of a recombinant protein in a prokaryotic host cell
GB0027779D0 (en) *	2000-11-14	2000-12-27	Boehringer Ingelheim Int	Methods for large scale production of recombinant dna-derived tpa or k2s molecules
US7087412B2 (en)	2000-11-14	2006-08-08	Boehringer Ingelheim International Gmbh	Methods for large scale protein production in prokaryotes
US6955910B2 (en)	2000-11-14	2005-10-18	Boehringer Ingelheim International Gmbh	Method for large scale production of recombinant DNA-derived TPA or K2S molecules
GB0029001D0 (en) *	2000-11-28	2001-01-10	Isis Innovation	Assay
DE10153601A1 (de) *	2001-11-02	2003-05-22	Paion Gmbh	DSPA zur Behandlung von Schlaganfall
US20080057050A1 (en) *	2003-05-02	2008-03-06	Paion Deutschland Gmbh	Intravenous injection of plasminogen non-neurotoxic activators for treating cerebral stroke
TWI482628B (zh) *	2007-10-18	2015-05-01	Lundbeck & Co As H	新穎之血栓溶解病患次群
KR100855024B1 (ko)	2008-04-30	2008-08-28	가톨릭대학교 산학협력단	크링글 도메인 １ 및 ２ 로 이루어진 비-글리코실화 재조합단백질
EP2289542A1 (de) *	2009-08-31	2011-03-02	PAION Deutschland GmbH	Behandlung von neurologischen und neurodegenerativen Erkrankungen
EP4713445A2 (de) *	2023-05-18	2026-03-25	Versiti Blood Research Institute Foundation, Inc.	Fragmente des rekombinanten gewebeplasminogenaktivators (tpa) und verwendungen davon

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AR241654A1 (es) *	1982-05-05	1992-10-30	Genentech Inc	Procedimiento para producir activador de plasminogeno de tejido humano.
WO1984001786A1 (en) *	1982-10-28	1984-05-10	Beecham Group Plc	Enzyme derivatives and their use in the treatment of thrombosis
US4753879A (en) *	1984-08-27	1988-06-28	Biogen N.V.	Modified tissue plasminogen activators
US4577584A (en) *	1984-12-24	1986-03-25	Shih Nan C	Bell lock (II)
EP0201153A3 (de) *	1985-02-09	1987-10-07	Beecham Group Plc	Modifiziertes Enzym und Verfahren zu dessen Herstellung
GB8508717D0 (en) *	1985-04-03	1985-05-09	Beecham Group Plc	Composition
HU206520B (en) *	1985-04-22	1992-11-30	Genentech Inc	Process for producing new human tissue plasminogen activator /tpa/ mutants and pharmaceutical compositions containing them
DK43387A (da) *	1986-01-29	1987-07-30	Beecham Group Plc	Fibrinolytisk enzym
PT84588B (en) *	1986-04-02	1989-05-09	Beecham Group Plc	Process for preparing a fibrinolytic enzyme
AU1295088A (en) *	1987-01-30	1988-08-24	American Home Products Corporation	Des-epidermal growth factor plasminogen activators
IL87276A (en) *	1987-08-03	1995-07-31	Fujisawa Pharmaceutical Co	Analog of tissue plasminogen activator comprising only the kringle 2 and protease domain dna encoding the same processes for the preparation thereof and pharmaceutical compositions containing the same

1988
- 1988-07-31 IL IL8727688A patent/IL87276A/en not_active IP Right Cessation
- 1988-08-01 JP JP63192320A patent/JP2561708B2/ja not_active Expired - Fee Related
- 1988-08-02 AT AT88112569T patent/ATE108206T1/de not_active IP Right Cessation
- 1988-08-02 EP EP88112569A patent/EP0302456B1/de not_active Expired - Lifetime
- 1988-08-02 ES ES88112569T patent/ES2056082T3/es not_active Expired - Lifetime
- 1988-08-02 KR KR1019880009836A patent/KR970001237B1/ko not_active Expired - Lifetime
- 1988-08-02 DE DE3850531T patent/DE3850531T2/de not_active Expired - Lifetime
- 1988-08-02 CA CA000573585A patent/CA1341458C/en not_active Expired - Lifetime
- 1988-08-02 DK DK198804319A patent/DK174413B1/da not_active IP Right Cessation
- 1988-08-03 AU AU20361/88A patent/AU623340B2/en not_active Expired
1994
- 1994-10-21 JP JP6257008A patent/JP2570633B2/ja not_active Expired - Fee Related
1995
- 1995-03-29 US US08/412,859 patent/US5648250A/en not_active Expired - Lifetime
1996
- 1996-01-12 JP JP8003853A patent/JP2606620B2/ja not_active Expired - Lifetime
1997
- 1997-03-05 US US08/811,949 patent/US5840533A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
ATE108206T1 (de)	1994-07-15
DK174413B1 (da)	2003-02-17
JP2606620B2 (ja)	1997-05-07
EP0302456A1 (de)	1989-02-08
CA1341458C (en)	2004-10-12
AU623340B2 (en)	1992-05-14
JPH08228773A (ja)	1996-09-10
DK431988D0 (da)	1988-08-02
KR970001237B1 (ko)	1997-02-04
DE3850531T2 (de)	1994-11-24
JP2570633B2 (ja)	1997-01-08
EP0302456B1 (de)	1994-07-06
JP2561708B2 (ja)	1996-12-11
ES2056082T3 (es)	1994-10-01
DE3850531D1 (de)	1994-08-11
KR890003952A (ko)	1989-04-19
JPH01104167A (ja)	1989-04-21
AU2036188A (en)	1989-02-09
US5840533A (en)	1998-11-24
JPH07163346A (ja)	1995-06-27
IL87276A0 (en)	1988-12-30
US5648250A (en)	1997-07-15
DK431988A (da)	1989-02-04

Legal Events

Date	Code	Title
1996-05-14	KB	Patent renewed
1998-12-27	KB	Patent renewed
2001-06-14	RH	Patent void
2002-09-12	KB	Patent renewed
2006-09-05	KB	Patent renewed
2009-02-11	EXP	Patent expired
2010-04-14	EXP	Patent expired

Publication	Publication Date	Title
CA1341458C (en)	2004-10-12	Modified human t-pa
US5342775A (en)	1994-08-30	Plasminogen activator
Sumi et al.	1995	A unique strong fibrinolytic enzyme (katsuwokinase) in skipjack “Shiokara” a Japanese traditional fermented food
IE950235L (en)	1983-10-15	Preparation of functional human urokinase proteins.
JPH03500724A (ja)	1991-02-21	組織プラスミノーゲン活性化因子の誘導体
DK175938B1 (da)	2005-07-25	Plasminogenaktivator-varianter, DNA-sekvenser, vektorer, celler og cellekulturer, der omfatter DNA-sekvenser, der koder for sådanne varianter, samt sammensætninger til behandling af karsygdom eller -tilstand, der omfatter en sådan variant
US5747291A (en)	1998-05-05	Bifunctional urokinase variants with improved fibrinolytic characteristics and thrombin inhibiting effect
US7070958B2 (en)	2006-07-04	Methods of making pro-urokinase mutants
US5866358A (en)	1999-02-02	Production of human prourokinase
EP0241210B1 (de)	1992-07-08	Modifiziertes Enzym
FI114102B (fi)	2004-08-13	Menetelmä trombiinin vaikutuksesta pilkkoutuvan plasminogeenianalogin valmistamiseksi
IE913070A1 (en)	1992-03-11	Novel compounds
GB2246133A (en)	1992-01-22	Amidated human pro-urokinase enzymes and their precursors
AU637781B2 (en)	1993-06-10	New tissue plasminogen activator
US5973118A (en)	1999-10-26	Mutant of the Erythrina caffra type inhibitor and the use of the said mutant for purifying serine proteases
CA2262751A1 (en)	1998-02-12	Plasminogen activator capable of being activated by thrombin
AU624869B2 (en)	1992-06-25	Production of human prourokinase
CA2185436C (en)	2000-08-01	Use of a recombinant inhibitor from erythrina caffra for purifying serine proteases
BG60507B2 (bg)	1995-06-30	Човешки тъканен плазминогенен активатор
IE861054L (en)	1986-10-22	Protease resistant single-chain urokinase
MXPA99000966A (en)	1999-09-20	Plasminogen activator capable of being activated by thrombin
JPH0361482A (ja)	1991-03-18	新規な組織プラスミノーゲン活性化因子