Design and characterization of dipetacompinR10H, a dipetalogastin II-derived, classical competitive thrombin inhibitor.
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.
Bitter
Thomas
T
Research Unit Pharmacological Haemostaseology, Medical Faculty, Friedrich-Schiller-University, Jena, Germany. Th.Bitter@web.de
López
Mercedes
M
Nowak
Goetz
G
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D001780:Blood Coagulation Tests; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000187:drug effects; D013379:Substrate Specificity; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D012697:Serine Endopeptidases; D013917:Thrombin