CA1041449A - Ion exchange purification of urokinase - Google Patents
Ion exchange purification of urokinaseInfo
- Publication number
- CA1041449A CA1041449A CA236,744A CA236744A CA1041449A CA 1041449 A CA1041449 A CA 1041449A CA 236744 A CA236744 A CA 236744A CA 1041449 A CA1041449 A CA 1041449A
- Authority
- CA
- Canada
- Prior art keywords
- urokinase
- solution
- ion exchange
- resin
- exchange resin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 title claims abstract description 48
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 title claims abstract description 48
- 229960005356 urokinase Drugs 0.000 title claims abstract description 48
- 238000005342 ion exchange Methods 0.000 title claims description 6
- 238000000746 purification Methods 0.000 title abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 22
- 239000000243 solution Substances 0.000 claims description 23
- 239000011347 resin Substances 0.000 claims description 11
- 229920005989 resin Polymers 0.000 claims description 11
- 239000003957 anion exchange resin Substances 0.000 claims description 7
- 150000001412 amines Chemical group 0.000 claims description 5
- 239000011324 bead Substances 0.000 claims description 5
- 239000012535 impurity Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 239000012736 aqueous medium Substances 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 239000007791 liquid phase Substances 0.000 claims description 2
- QHQZEEGNGSZBOL-UHFFFAOYSA-N 2-(aminomethyl)-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(CO)(CO)CO QHQZEEGNGSZBOL-UHFFFAOYSA-N 0.000 claims 1
- 229920005654 Sephadex Polymers 0.000 abstract description 8
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)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)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 abstract 1
- 102000002262 Thromboplastin Human genes 0.000 abstract 1
- 108010000499 Thromboplastin Proteins 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FZGDMLUTCCXACJ-UHFFFAOYSA-N 1-[3-(chloromethyl)pentan-3-ylamino]propan-2-ol Chemical compound CCC(CC)(CCl)NCC(C)O FZGDMLUTCCXACJ-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 239000003104 tissue culture media Substances 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
- 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
- C12N9/6462—Plasminogen activators u-Plasminogen activator (3.4.21.73), i.e. urokinase
-
- 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)
- C12Y304/21073—Serine endopeptidases (3.4.21) u-Plasminogen activator (3.4.21.73), i.e. urokinase
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/814—Enzyme separation or purification
- Y10S435/815—Enzyme separation or purification by sorption
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/525,334 US3957582A (en) | 1974-11-20 | 1974-11-20 | Purification of urokinase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1041449A true CA1041449A (en) | 1978-10-31 |
Family
ID=24092806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA236,744A Expired CA1041449A (en) | 1974-11-20 | 1975-09-30 | Ion exchange purification of urokinase |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US3957582A (en, 2012) |
| JP (1) | JPS5167787A (en, 2012) |
| AR (1) | AR208000A1 (en, 2012) |
| BE (1) | BE835330A (en, 2012) |
| CA (1) | CA1041449A (en, 2012) |
| CH (1) | CH608021A5 (en, 2012) |
| DE (1) | DE2551966C3 (en, 2012) |
| DK (1) | DK140555B (en, 2012) |
| FR (1) | FR2291983A1 (en, 2012) |
| GB (1) | GB1493018A (en, 2012) |
| NL (1) | NL162657B (en, 2012) |
| SE (1) | SE431226B (en, 2012) |
| ZA (1) | ZA756197B (en, 2012) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE29980E (en) * | 1975-07-04 | 1979-05-01 | Asahi Kasei Kogyo Kabushiki Kaisha | Method of obtaining urokinase |
| JPS527485A (en) * | 1975-07-04 | 1977-01-20 | Asahi Chem Ind Co Ltd | Isolation of urokinase |
| JPS53113080A (en) * | 1977-03-10 | 1978-10-03 | Sumitomo Chem Co Ltd | Purification of urokinase |
| DE2812609A1 (de) * | 1977-04-09 | 1978-10-19 | Tanabe Seiyaku Co | Verfahren zur reinigung roher urokinase |
| JPS5935B2 (ja) * | 1977-06-03 | 1984-01-05 | 住友化学工業株式会社 | ウロキナ−ゼの精製法 |
| FR2444465A1 (fr) * | 1978-12-22 | 1980-07-18 | Green Cross Corp | Procede de production d'une preparation thrombolytique |
| GB2121050B (en) * | 1979-07-05 | 1986-03-26 | Genentech Inc | Preparation of functional human urokinase proteins |
| CY1382A (en) * | 1979-11-13 | 1987-12-18 | Syed Shaukat Husain | Isolation of plasminogen activators useful as therapeutic and diagnostic agents |
| USRE32271E (en) * | 1979-11-13 | 1986-10-28 | Isolation of plasminogen activators useful as therapeutic and diagnostic agents | |
| US4558010A (en) * | 1980-04-03 | 1985-12-10 | Abbott Laboratories | Recombinant deoxyribonucleic acid which codes for plasminogen activator and method of making plasminogen activator protein therefrom |
| US4370417A (en) * | 1980-04-03 | 1983-01-25 | Abbott Laboratories | Recombinant deoxyribonucleic acid which codes for plasminogen activator |
| US5112755A (en) * | 1982-04-15 | 1992-05-12 | Genentech, Inc. | Preparation of functional human urokinase proteins |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3755083A (en) * | 1971-08-30 | 1973-08-28 | Rand Labor Inc | Method for recovering urokinase from urine containing the same |
| BE789189A (fr) * | 1971-09-24 | 1973-03-22 | Choay Sa | Perfectionnements aux procedes de preparation, de depyrogenation et de stabilisation de l'urokinase et compositions obtenues |
| FR2190413A2 (en) * | 1972-06-30 | 1974-02-01 | Choay Sa | Stable,pyrogen-free urokinase prepns - from human urine |
| DE2428248B2 (de) * | 1973-07-24 | 1978-01-12 | Serna Ag, Glarus (Schweiz) | Verfahren zur herstellung von pyrogenfreier urokinase |
| US3897309A (en) * | 1974-02-15 | 1975-07-29 | Merck & Co Inc | Process for removing pyrogenic material from aqueous solutions |
-
1974
- 1974-11-20 US US05/525,334 patent/US3957582A/en not_active Expired - Lifetime
-
1975
- 1975-01-01 AR AR261023A patent/AR208000A1/es active
- 1975-09-30 ZA ZA00756197A patent/ZA756197B/xx unknown
- 1975-09-30 CA CA236,744A patent/CA1041449A/en not_active Expired
- 1975-10-03 GB GB40641/75A patent/GB1493018A/en not_active Expired
- 1975-10-08 NL NL7511803.A patent/NL162657B/xx not_active IP Right Cessation
- 1975-10-31 JP JP50130576A patent/JPS5167787A/ja active Pending
- 1975-11-07 BE BE2054648A patent/BE835330A/xx not_active IP Right Cessation
- 1975-11-07 FR FR7534180A patent/FR2291983A1/fr active Granted
- 1975-11-14 CH CH1482075A patent/CH608021A5/xx not_active IP Right Cessation
- 1975-11-19 SE SE7513027A patent/SE431226B/xx unknown
- 1975-11-19 DE DE2551966A patent/DE2551966C3/de not_active Expired
- 1975-11-19 DK DK521375AA patent/DK140555B/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH608021A5 (en, 2012) | 1978-12-15 |
| GB1493018A (en) | 1977-11-23 |
| DK140555C (en, 2012) | 1980-03-03 |
| FR2291983A1 (fr) | 1976-06-18 |
| AR208000A1 (es) | 1976-11-22 |
| DE2551966B2 (de) | 1977-10-13 |
| DK140555B (da) | 1979-10-01 |
| NL7511803A (nl) | 1976-05-24 |
| AU8545075A (en) | 1977-04-07 |
| US3957582A (en) | 1976-05-18 |
| JPS5167787A (en, 2012) | 1976-06-11 |
| FR2291983B1 (en, 2012) | 1979-03-30 |
| NL162657B (nl) | 1980-01-15 |
| DE2551966C3 (de) | 1978-06-01 |
| ZA756197B (en) | 1976-09-29 |
| BE835330A (fr) | 1976-05-07 |
| SE431226B (sv) | 1984-01-23 |
| DE2551966A1 (de) | 1976-05-26 |
| SE7513027L (sv) | 1976-05-21 |
| DK521375A (en, 2012) | 1976-05-21 |
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