NO302954B1 - Fremgangsmåte for fremstilling av et plasminogenaktiverende protein, DNA-sekvens som koder for proteinet, kloningsvektor inneholdende DNA-sekvensen, samt pattedyrcelle og bakteriecelle transfektert med kloningsvektoren - Google Patents
Fremgangsmåte for fremstilling av et plasminogenaktiverende protein, DNA-sekvens som koder for proteinet, kloningsvektor inneholdende DNA-sekvensen, samt pattedyrcelle og bakteriecelle transfektert med kloningsvektoren Download PDFInfo
- Publication number
- NO302954B1 NO302954B1 NO892976A NO892976A NO302954B1 NO 302954 B1 NO302954 B1 NO 302954B1 NO 892976 A NO892976 A NO 892976A NO 892976 A NO892976 A NO 892976A NO 302954 B1 NO302954 B1 NO 302954B1
- Authority
- NO
- Norway
- Prior art keywords
- protein
- plasminogen
- bat
- fibrin
- tpa
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title claims description 103
- 102000004169 proteins and genes Human genes 0.000 title claims description 80
- 102000013566 Plasminogen Human genes 0.000 title claims description 29
- 108010051456 Plasminogen Proteins 0.000 title claims description 29
- 108091028043 Nucleic acid sequence Proteins 0.000 title claims description 18
- 230000001580 bacterial effect Effects 0.000 title claims description 15
- 239000013599 cloning vector Substances 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title description 8
- 230000003213 activating effect Effects 0.000 title 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 61
- 229950003499 fibrin Drugs 0.000 claims description 61
- 108010073385 Fibrin Proteins 0.000 claims description 60
- 102000009123 Fibrin Human genes 0.000 claims description 60
- 210000004027 cell Anatomy 0.000 claims description 37
- 230000000694 effects Effects 0.000 claims description 32
- 150000001413 amino acids Chemical class 0.000 claims description 31
- 108020004414 DNA Proteins 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 20
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 17
- 239000013598 vector Substances 0.000 claims description 14
- 239000013604 expression vector Substances 0.000 claims description 12
- 102000010752 Plasminogen Inactivators Human genes 0.000 claims description 9
- 108010077971 Plasminogen Inactivators Proteins 0.000 claims description 9
- 239000002797 plasminogen activator inhibitor Substances 0.000 claims description 9
- 230000004913 activation Effects 0.000 claims description 7
- 108020001507 fusion proteins Proteins 0.000 claims description 6
- 102000037865 fusion proteins Human genes 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 6
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 5
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 3
- 229960000187 tissue plasminogen activator Drugs 0.000 claims description 2
- 235000018102 proteins Nutrition 0.000 description 69
- 102000001938 Plasminogen Activators Human genes 0.000 description 68
- 108010001014 Plasminogen Activators Proteins 0.000 description 68
- 229940127126 plasminogen activator Drugs 0.000 description 64
- 235000001014 amino acid Nutrition 0.000 description 33
- 108090000765 processed proteins & peptides Proteins 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 239000002299 complementary DNA Substances 0.000 description 22
- 102000004196 processed proteins & peptides Human genes 0.000 description 21
- 229920001184 polypeptide Polymers 0.000 description 18
- 239000012190 activator Substances 0.000 description 17
- 239000013612 plasmid Substances 0.000 description 17
- 230000009089 cytolysis Effects 0.000 description 16
- 210000002381 plasma Anatomy 0.000 description 14
- 108010088842 Fibrinolysin Proteins 0.000 description 12
- 229940012957 plasmin Drugs 0.000 description 12
- 210000003296 saliva Anatomy 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- 230000009471 action Effects 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000010367 cloning Methods 0.000 description 10
- 230000000875 corresponding effect Effects 0.000 description 10
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 10
- 241000288900 Desmodus rotundus Species 0.000 description 9
- 239000008188 pellet Substances 0.000 description 9
- 229920000136 polysorbate Polymers 0.000 description 9
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 8
- 108700026244 Open Reading Frames Proteins 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 210000003079 salivary gland Anatomy 0.000 description 8
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 7
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000012134 supernatant fraction Substances 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 229960005356 urokinase Drugs 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 238000003752 polymerase chain reaction Methods 0.000 description 6
- 239000013615 primer Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000012588 trypsin Substances 0.000 description 6
- 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 5
- 229920002684 Sepharose Polymers 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 5
- 235000012434 pretzels Nutrition 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 4
- 241000288921 Desmodus Species 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 108010090665 Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase Proteins 0.000 description 4
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 4
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 208000034158 bleeding Diseases 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000003527 fibrinolytic agent Substances 0.000 description 4
- 230000002779 inactivation Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 241000288673 Chiroptera Species 0.000 description 3
- 108010049003 Fibrinogen Proteins 0.000 description 3
- 102000008946 Fibrinogen Human genes 0.000 description 3
- 108010054964 H-hexahydrotyrosyl-alanyl-arginine-4-nitroanilide Proteins 0.000 description 3
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 206010038563 Reocclusion Diseases 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 229940080469 phosphocellulose Drugs 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229960000103 thrombolytic agent Drugs 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108010043984 Erythrina caffra trypsin inhibitor Proteins 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 230000004988 N-glycosylation Effects 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000003024 amidolytic effect Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940106780 human fibrinogen Drugs 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000003153 stable transfection Methods 0.000 description 2
- 210000001913 submandibular gland Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 229960003766 thrombin (human) Drugs 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000003151 transfection method Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- GOOCRIHPADOQAS-ZNUXJMJHSA-N (4ar,5as,8ar,13as,15as,15br)-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2h-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinoline-14-one;sulfuric acid Chemical compound OS(O)(=O)=O.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 GOOCRIHPADOQAS-ZNUXJMJHSA-N 0.000 description 1
- LDMSFLLWFAFZAF-OALUTQOASA-N (4s)-5-[[2-[[(3s)-1-chloro-6-(diaminomethylideneamino)-2-oxohexan-3-yl]amino]-2-oxoethyl]amino]-4-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]-5-oxopentanoic acid Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)CCl LDMSFLLWFAFZAF-OALUTQOASA-N 0.000 description 1
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101001067249 Bos taurus Plasminogen Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108010058861 Fibrin Fibrinogen Degradation Products Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102000007625 Hirudins Human genes 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
- 101001046633 Homo sapiens Junctional adhesion molecule A Proteins 0.000 description 1
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
- 102100022304 Junctional adhesion molecule A Human genes 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 108091036407 Polyadenylation Proteins 0.000 description 1
- 101710118538 Protease Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 101000895926 Streptomyces plicatus Endo-beta-N-acetylglucosaminidase H Proteins 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 102000018690 Trypsinogen Human genes 0.000 description 1
- 108010027252 Trypsinogen Proteins 0.000 description 1
- 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 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000003277 amino acid sequence analysis Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000002823 anti-activator Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 230000008275 binding mechanism Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 125000000837 carbohydrate group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000002596 correlated effect Effects 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
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000003241 endoproteolytic effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000000208 fibrin degradation product Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 229940116978 human epidermal growth factor Drugs 0.000 description 1
- 230000000951 immunodiffusion Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 1
- 230000012432 negative regulation of plasminogen activation Effects 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(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](CC=1C=CC(O)=CC=1)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](CCCCN)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)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)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=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 229940099990 ogen Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000012514 protein characterization Methods 0.000 description 1
- 239000012521 purified sample Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical group 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
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005406 washing Methods 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
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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
-
- 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)
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Plant Pathology (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22169788A | 1988-07-20 | 1988-07-20 | |
| US37722189A | 1989-07-13 | 1989-07-13 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO892976D0 NO892976D0 (no) | 1989-07-20 |
| NO892976L NO892976L (no) | 1990-01-22 |
| NO302954B1 true NO302954B1 (no) | 1998-05-11 |
Family
ID=26916041
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO892976A NO302954B1 (no) | 1988-07-20 | 1989-07-20 | Fremgangsmåte for fremstilling av et plasminogenaktiverende protein, DNA-sekvens som koder for proteinet, kloningsvektor inneholdende DNA-sekvensen, samt pattedyrcelle og bakteriecelle transfektert med kloningsvektoren |
| NO19970603A NO314548B1 (no) | 1988-07-20 | 1997-02-10 | Fremgangsmåte for rensing av et plasminogenaktiverende protein fra vampyrflaggermus |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19970603A NO314548B1 (no) | 1988-07-20 | 1997-02-10 | Fremgangsmåte for rensing av et plasminogenaktiverende protein fra vampyrflaggermus |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5830849A (fi) |
| EP (1) | EP0352119B1 (fi) |
| JP (1) | JP2713467B2 (fi) |
| KR (1) | KR0138997B1 (fi) |
| AT (1) | ATE126269T1 (fi) |
| AU (1) | AU621389B2 (fi) |
| CA (1) | CA1341090C (fi) |
| DE (1) | DE68923741T2 (fi) |
| DK (1) | DK176140B1 (fi) |
| ES (1) | ES2076965T3 (fi) |
| FI (1) | FI100403B (fi) |
| GR (1) | GR3017587T3 (fi) |
| IE (1) | IE69054B1 (fi) |
| IL (1) | IL91059A (fi) |
| NO (2) | NO302954B1 (fi) |
| NZ (1) | NZ230017A (fi) |
| PT (1) | PT91236B (fi) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01500322A (ja) * | 1986-03-28 | 1989-02-09 | クリエイティブ バイオモレクレス，インコーポレーテッド | 組織プラスミノーゲンアクテイベーター類縁蛋白質 |
| JP2904918B2 (ja) * | 1989-02-13 | 1999-06-14 | シェーリング アクチェンゲゼルシャフト | 新規血栓溶解剤 |
| US6008019A (en) * | 1989-02-13 | 1999-12-28 | Schering Aktiengesellschaft | Plasminogen activator from saliva of the vampire bat |
| DE3943241A1 (de) * | 1989-12-22 | 1991-06-27 | Schering Ag | Thrombolytisch wirkendes kombinationspraeparat |
| EP0455424A3 (en) * | 1990-05-02 | 1992-04-29 | Merck & Co. Inc. | Mammalian inducible promoter cascade system |
| ES2082465T3 (es) * | 1991-04-16 | 1996-03-16 | Boehringer Mannheim Gmbh | Unidad farmaceutica de envasado que contiene activadores de plasminogeno para la administracion multiple de bolos. |
| US5910481A (en) * | 1995-11-13 | 1999-06-08 | Immuno Ag | Hybrid proteins with modified activity |
| US5945432A (en) * | 1995-12-22 | 1999-08-31 | The University Of Vermont And State Agricultural College | Thrombolytic agents and thienopyridine derivatives in acute stroke |
| US5731186A (en) * | 1996-02-05 | 1998-03-24 | Schering Aktiengesellschaft | Method for the production of rDSPA α1 |
| DE10153601A1 (de) * | 2001-11-02 | 2003-05-22 | Paion Gmbh | DSPA zur Behandlung von Schlaganfall |
| PL1622639T3 (pl) * | 2003-05-02 | 2013-06-28 | Lundbeck H As | Dożylne wstrzyknięcie nieneurotoksycznych aktywatorów plazminogenu do leczenia udaru mózgu |
| WO2004096267A1 (de) * | 2003-05-02 | 2004-11-11 | Paion Gmbh | Intravenöse injektion nicht-neurotoxischer plasminogen-aktivatoren zur behandlung von schlaganfall |
| US20060135425A1 (en) * | 2003-05-02 | 2006-06-22 | Paion Deutschland Gmbh | Intravenous injection of plasminogen non-neurotoxic activators for treating cerebral stroke |
| DE10342518A1 (de) * | 2003-09-12 | 2005-05-12 | Paion Gmbh | Plasminogen-Aktivatoren mit verringerter Lysin-Bindungskapazität |
| AR068914A1 (es) * | 2007-10-18 | 2009-12-16 | Paion Deutschland Gmbh | Uso de un activador de plasminogeno para la preparacion de un medicamento para el tratamiento de apoplejia |
| EP2289541A1 (en) | 2009-08-31 | 2011-03-02 | PAION Deutschland GmbH | Treatment of neurological or neurodegenerative disorders |
| EP2289542A1 (en) | 2009-08-31 | 2011-03-02 | PAION Deutschland GmbH | Treatment of neurological or neurodegenerative disorders |
| SG11201906530TA (en) | 2017-02-03 | 2019-08-27 | Acticor Biotech | Inhibition of platelet aggregation using anti-human gpvi antibodies |
| JP2020520386A (ja) | 2017-05-16 | 2020-07-09 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 急性虚血性脳卒中の処置のための方法及び医薬組成物 |
| WO2019238933A1 (en) | 2018-06-15 | 2019-12-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of pi3kc2b inhibitors for the preservation of vascular endothelial cell barrier integrity |
| WO2021148439A1 (en) | 2020-01-21 | 2021-07-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for stimulating cerebrovascular function |
| US20240207190A1 (en) | 2020-06-09 | 2024-06-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fucoidan-functionalized polysaccharide particles with t-pa for targeted thrombolytic therapy |
| WO2023156683A1 (en) | 2022-02-21 | 2023-08-24 | Acticor Biotech | Treatment of cardiovascular diseases using anti-human gpvi antibodies |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4766075A (en) * | 1982-07-14 | 1988-08-23 | Genentech, Inc. | Human tissue plasminogen activator |
| US5010002A (en) * | 1983-01-19 | 1991-04-23 | Genentech, Inc. | Human t-PA production using vectors coding DHFR protein |
| ATE90967T1 (de) * | 1986-03-28 | 1993-07-15 | Creative Biomolecules Inc | Proteinanaloge des gewebs-plasminogenaktivators. |
| JPH01132377A (ja) * | 1987-10-09 | 1989-05-24 | Monsanto Co | 修正型組織プラスミノーゲンアクチベーター |
| JP2904918B2 (ja) * | 1989-02-13 | 1999-06-14 | シェーリング アクチェンゲゼルシャフト | 新規血栓溶解剤 |
-
1989
- 1989-07-19 DK DK198903575A patent/DK176140B1/da not_active IP Right Cessation
- 1989-07-19 IE IE235489A patent/IE69054B1/en not_active IP Right Cessation
- 1989-07-19 FI FI893500A patent/FI100403B/fi active IP Right Grant
- 1989-07-20 DE DE68923741T patent/DE68923741T2/de not_active Expired - Lifetime
- 1989-07-20 AT AT89307411T patent/ATE126269T1/de not_active IP Right Cessation
- 1989-07-20 JP JP1188673A patent/JP2713467B2/ja not_active Expired - Lifetime
- 1989-07-20 NZ NZ230017A patent/NZ230017A/en unknown
- 1989-07-20 NO NO892976A patent/NO302954B1/no not_active IP Right Cessation
- 1989-07-20 EP EP89307411A patent/EP0352119B1/en not_active Expired - Lifetime
- 1989-07-20 ES ES89307411T patent/ES2076965T3/es not_active Expired - Lifetime
- 1989-07-20 CA CA000606185A patent/CA1341090C/en not_active Expired - Lifetime
- 1989-07-20 PT PT91236A patent/PT91236B/pt not_active IP Right Cessation
- 1989-07-20 IL IL9105989A patent/IL91059A/en unknown
- 1989-07-20 KR KR1019890010264A patent/KR0138997B1/ko not_active IP Right Cessation
- 1989-07-25 AU AU38915/89A patent/AU621389B2/en not_active Expired
-
1995
- 1995-06-06 US US08/467,966 patent/US5830849A/en not_active Expired - Lifetime
- 1995-09-29 GR GR950402700T patent/GR3017587T3/el unknown
-
1997
- 1997-02-10 NO NO19970603A patent/NO314548B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ES2076965T3 (es) | 1995-11-16 |
| DE68923741D1 (de) | 1995-09-14 |
| KR910003094A (ko) | 1991-02-26 |
| AU3891589A (en) | 1990-01-25 |
| PT91236A (pt) | 1990-02-08 |
| JPH02167075A (ja) | 1990-06-27 |
| FI893500A (fi) | 1990-01-21 |
| FI100403B (fi) | 1997-11-28 |
| GR3017587T3 (en) | 1995-12-31 |
| DK176140B1 (da) | 2006-09-25 |
| DE68923741T2 (de) | 1996-02-15 |
| US5830849A (en) | 1998-11-03 |
| IL91059A0 (en) | 1990-02-09 |
| EP0352119A2 (en) | 1990-01-24 |
| CA1341090C (en) | 2000-08-29 |
| IE69054B1 (en) | 1996-08-07 |
| DK357589D0 (da) | 1989-07-19 |
| NO892976D0 (no) | 1989-07-20 |
| ATE126269T1 (de) | 1995-08-15 |
| NZ230017A (en) | 1992-05-26 |
| NO970603L (no) | 1990-01-22 |
| NO314548B1 (no) | 2003-04-07 |
| IL91059A (en) | 1995-06-29 |
| IE892354L (en) | 1990-01-20 |
| JP2713467B2 (ja) | 1998-02-16 |
| EP0352119B1 (en) | 1995-08-09 |
| NO892976L (no) | 1990-01-22 |
| EP0352119A3 (en) | 1990-07-04 |
| NO970603D0 (no) | 1997-02-10 |
| FI893500A0 (fi) | 1989-07-19 |
| DK357589A (da) | 1990-01-23 |
| AU621389B2 (en) | 1992-03-12 |
| KR0138997B1 (ko) | 1998-04-30 |
| PT91236B (pt) | 1995-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO302954B1 (no) | Fremgangsmåte for fremstilling av et plasminogenaktiverende protein, DNA-sekvens som koder for proteinet, kloningsvektor inneholdende DNA-sekvensen, samt pattedyrcelle og bakteriecelle transfektert med kloningsvektoren | |
| Holmes et al. | Cloning and expression of the gene for pro-urokinase in Escherichia coli | |
| NO305562B1 (no) | FremgangsmÕte for fremstilling av en plasminogenanalog, syntetisk eller rekombinant nukleinsyre som koder for den, vektorer som omfatter en slik nukleinsyresekvens, samt celler eller cellelinjer som kan fremstille plasminogenanalogen | |
| DK174236B1 (da) | Fremgangsmåde til fremstilling af et protein som har human vævsplasminogenaktivatorfunktion, fremgangsmåde til fremstilling af et farmaceutisk præparat indeholdende proteinet, DNA-isolat, som koder for proteinet, rekombinante klonings- og ...... | |
| DK175958B1 (da) | Vævsplasminoaktivator-(t-PA)-variant med zymogene eller fibrinspecifikke eller plasmakoagel-specifikke egenskaber, fremgangsmåde til fremstilling deraf, DNA-sekvens, som koder for varianten, replicerbar udtrykkelsesvektor for denne og værtsceller tran | |
| NO308708B1 (no) | FremgangsmÕte for fremstilling av et trombolytisk protein, samt isolert DNA, mikroorganisme og fremgangsmÕte for fremstilling av et farmasøytisk preparat | |
| RU2143490C1 (ru) | Бифункциональный вариант урокиназы, плазмида, содержащая синтетический структурный ген, кодирующий бифункциональную урокиназу, плазмида (варианты), способ получения плазмиды, способ получения бифункционального варианта урокиназы, тромболитическое средство | |
| Wang et al. | Glycosylation of prourokinase produced by Pichia pastoris impairs enzymatic activity but not secretion | |
| JP2728240B2 (ja) | ヒトプロテインｃ変異体及びその製造方法 | |
| JPH03502526A (ja) | ヒトプロウロキナーゼの製造 | |
| NO317661B1 (no) | Trombinaktiverbare plasminogenanaloger, anvendelse av forbindelsene ved fremstilling av et farmasoytisk middel, preparater som omfatter forbindelsene, samt nukleinsyre | |
| EP0316068A1 (en) | Modified low molecular weight plasminogen activator and method of preparation | |
| GB2246133A (en) | Amidated human pro-urokinase enzymes and their precursors | |
| FI100406B (fi) | Menetelmä vampyyrilepakon syljen plasminogeeniaktivaattoreiden valmist amiseksi | |
| NL8701021A (nl) | Humane t-pa(u-pa) substitutie-mutant eiwitten, daarvoor coderend recombinant dna, getransfecteerde gastheercellen, bereiding van de mutant eiwitten, en farmaceutische preparaten. | |
| BG60507B2 (bg) | Човешки тъканен плазминогенен активатор | |
| JP2000504941A (ja) | トロンビンによって活性化され得るプラスミノーゲンアクチベーター | |
| Collen et al. | Recombinant Protein Drugs 107 ed. by P. Buckel© 2001 Birkhäuser Verlag/Switzerland |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |