Thromb Haemost 1994; 71(03): 320-324
DOI: 10.1055/s-0038-1642437
Original Article
Schattauer GmbH Stuttgart

Inhibition of In Vitro Clot Growth by r-Hirudin Is More Effective and Longer Sustained than by an Analogous Peptide

Jürgen Römisch
The Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany
,
Hans-Arnold Stöhr
The Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany
,
Harald Stauß
The Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany
,
Rainer Koschinsky
The Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany
,
Werner Stüber
The Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany
,
Eric-Paul Pâques
The Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany
› Author Affiliations
Further Information

Publication History

Received: 28 June 1993

Accepted after revision 18 September 1993

Publication Date:
06 July 2018 (online)

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.