Thrombin and anhydrothrombin with modified carboxyl groups

Details Thrombin and anhydrothrombin with modified carboxyl groups Thrombin and anhydrothrombin with modified carboxyl groups

C - Chemistry, Metallurgy

07

K

C07K 14/745 (2006.01) A61K 38/36 (2006.01) A61K 38/48 (2006.01) A61P 7/02 (2006.01) A61P 43/00 (2006.01) C07K 1/22 (2006.01) C12N 9/74 (2006.01) G01N 33/86 (2006.01)

Patent

CA 2441201

Thrombin derivatives having a lowered fibrinogen activity and anhydrothrombin derivatives having a lowered fibrinogen activity are provided. Namely, thrombin derivatives wherein carboxyl of thrombin is modified; and anhydrothrombin derivatives wherein carboxyl of anhydrothrombin is modified. Because of having a lowered affinity for fibrinogen, these thrombin derivatives are usable as platelet agglutination-inducing compositions and specific coagulation reaction reagents for clinical tests, etc. By affinity chromatography with the use of anhydrothrombin as a ligand bonded to carboxyl, blood coagulation factor VIII can be more selectively purified. The anhydrothrombin derivatives having modified carboxyl exert a sufficient antithrombotic effect in a smaller amount than conventional anhydrothrombin does, which makes them usable as thrombosis inhibitors.

L'invention porte sur des dérivés de thrombine et d'anhydrothrombine dont l'activité du fibrinogène est réduite. Il est à noter que les dérivés de thrombine présentent un carboxyle modifié, de même que les dérivés d'anhydrothrombine. Du fait d'une faible affinité pour le fibrinogène, les dérivés de thrombine peuvent être utilisés comme compositions induisant l'agrégation plaquettaire et comme réactifs spécifiques dans la réaction de coagulation dans les tests cliniques, etc. Par la chromatographie d'affinité avec l'anhydrothrombine utilisée comme ligand lié à carboxyle, il est possible de purifier de manière plus sélective le facteur VIII de coagulation sanguine. Les dérivés d'anhydrothrombine présentant un carboxyle modifié exercent, dans une plus petite quantité, un effet antithrombotique suffisant que ne le ferait l'anhydrothrombine traditionnelle, ce qui permet de les utiliser comme inhibiteurs de thrombose.

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