STRATEGIES FOR DEVELOPMENT OF NOVEL ANTITHROMBOTICS - MODULATING THROMBINS PROCOAGULANT AND ANTICOAGULANT PROPERTIES

Thrombin is a serine proteinase that can interact with a large number of diverse macromolecular substrates, which results in either a procoa gulant or anticoagulant effect. These divergent properties are physiol ogically regulated by the endogenous protein thrombomodulin. This revi ew summarizes recent work on a variety of methods used to exploit the allosteric nature of the enzyme. The procoagulant and anticoagulant fu nctions of thrombin can be modulated by sodium binding, site-directed mutagenesis, and a small synthetic molecule. Modulation of thrombin's intrinsic properties represents a novel approach to the development of unique antithrombotic agents.