INHIBITION OF IN-VITRO CLOT GROWTH BY R-HIRUDIN IS MORE EFFECTIVE ANDLONGER SUSTAINED THAN BY AN ANALOGOUS PEPTIDE

The specific thrombin inhibitors r-hirudin and a synthetic peptide (I) D-FPRP(G)4-NGDFEEIPEEYL were compared in in vitro tests. r-hirudin pr oved to be the superior compound with respect to inhibition of amidoly tic small substrate turnover that is catalysed by soluble and immobili sed thrombin as well as to inhibition of fibrinogen activation. In an in vitro clot model significantly higher molar concentrations of pepti de I are needed to achieve fibrin bound thrombin inhibition equivalent to that of r-hirudin. Stable complexes consisting of thrombin and hir udin oppose labile complexes containing the synthetic peptide. The lat ter leads to a regaining of thrombin activity with subsequent addition al fibrin accretion. Analyses of the mixtures of thrombin and peptide I display a time dependent release of amino-terminal D-FPR peptide (II I) exhibiting, similar to the residual fragment (peptide II), only wea k inhibitory activity. Peptide I and the carboxyl-terminal fragment in duce, within a certain concentration range, an increase in thrombin ac tivity and clot growth.