Water-soluble urokinase derivatives with increased affinity to the fibrin clot

The attachment of urokinase to fibrinogen via a "spacer" of aliphatic diamine increases the affinity of the modified enzyme to the fibrin clot. This provides increased (2.5-fold higher than for native urokinase) fibrinolytic activity of the modified urokinase. Modification of the enzyme does not affect its kinetic parameters, but increases its stability. It is shown that 1,12-dodecamethylenediamine is an optimal linking agent. Fibrinogen modified with diamines does not lose the ability to be co-polymerized in the three-dimensional fibrin clot under the action of thrombin and acquires increased stability towards proteolytic degradation. Use of fibrinogen as a carrier for thrombolytic drugs can increase their affinity to the injured site and enhance the local targeted action of therapeutic agent.