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Thromb Haemost 2007; 97(01): 139-145
DOI: 10.1160/TH06-06-0308
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Design and characterization of dipetacompinR10H, a dipetalogastin II-derived, classical competitive thrombin inhibitor

Thomas Bitter
1   Research Unit Pharmacological Haemostaseology, Medical Faculty, Friedrich-Schiller-University, Jena, Germany
,
Mercedes López
2   Instituto Venezolano de Investigaciones Científicas, Laboratorio de Trombosis Experimental, Centro de Biofísica y Bioquímica, Caracas, Venezuela
,
Goetz Nowak
1   Research Unit Pharmacological Haemostaseology, Medical Faculty, Friedrich-Schiller-University, Jena, Germany
› Author Affiliations
Further Information

Publication History

Received 06 June 2006

Accepted after resubmission 05 November 2006

Publication Date:
28 November 2017 (online)

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Summary

The design of small chimeric thrombin inhibitors based on the structure of dipetalogastin II has been previously described. These proteins are effective inhibitors of thrombin showing slow binding or slow, tight-binding kinetics. We report here about dipetacompinR10H, a new dipetalogastin II-derived chimeric thrombin inhibitor, which exhibits classical competitive kinetics. The dissociation constant Ki of dipetacompinR10H was determined to be 17.1 ± 0.8 pM. In various coagulation assays it showed a comparable anticoagulant activity like r-hirudin and r-dipetalogastin II. DipetacompinR10H’s inhibition of thrombin was specific, since no inhibition of other serine proteases like factor Xa, plasmin, trypsin or chymotrypsin has been observed.

Keywords

Thrombin inhibitor - Dipetalogastin - rational drug design - chimeric protein - classical competitive kinetics
 

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