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

Thomas Bitter; Mercedes López; Goetz Nowak

doi:10.1160/TH06-06-0308

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

Autor*innen

Thomas Bitter

¹Research Unit Pharmacological Haemostaseology, Medical Faculty, Friedrich-Schiller-University, Jena, Germany
Mercedes López

²Instituto Venezolano de Investigaciones Científicas, Laboratorio de Trombosis Experimental, Centro de Biofísica y Bioquímica, Caracas, Venezuela
Goetz Nowak

¹Research Unit Pharmacological Haemostaseology, Medical Faculty, Friedrich-Schiller-University, Jena, Germany

Abstract

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 K_i 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

Volltext

Referenzen

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