Comparison of hirudin and hirudin PA C-terminal fragments and related analogs as antithrombin agents.

ABSTRACT

Hirudin PA54-66 and related hirudin fragment analogs were synthesized and assessed for their inhibition of thrombin-induced fibrin-clot formation in plasma. Pro58 and Ala63-Tyr64 modifications in the hirudin sequence resulted in increased antithrombin potency, whereas Asp62, Ala63 and Tyr64 individual substitutions each resulted in a loss of potency.