Summary
The specific thrombin inhibitors r-hirudin and a synthetic peptide (I)
D
-FPRP(G)4-NGDFEEIPEEYL were compared in in vitro tests, r-hirudin proved to be the superior
compound with respect to inhibition of amidolytic small substrate turnover that is
catalysed by soluble and immobilised thrombin as well as to inhibition of fibrinogen
activation. In an in vitro clot model significantly higher molar concentrations of
peptide I are needed to achieve fibrin bound thrombin inhibition equivalent to that
of r-hirudin. Stable complexes consisting of thrombin and hirudin oppose labile complexes
containing the synthetic peptide. The latter leads to a regaining of thrombin activity
with subsequent additional fibrin accretion. Analyses of the mixtures of thrombin
and peptide I display a time dependent release of amino-terminal
D
-FPR peptide (III) exhibiting, similar to the residual fragment (peptide II), only
weak inhibitory activity. Peptide I and the carboxy-terminal fragment induce, within
a certain concentration range, an increase in thrombin activity and clot growth.
