Effect of a synthetic thrombin-inhibitor MD805 on the reaction between thrombin and plasma antithrombin-III |
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Authors: | Akiko Hijikata-Okunomiya Shosuke Okamoto Keiko Wanaka |
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Affiliation: | a School of Allied Medical Sciences, Kobe University, Kobe 654, Japan b Research Projects on Thrombosis and Haemostasis, Saiseikai Hospital, Kobe 651, Japan |
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Abstract: | MD805, a synthetic thrombin-inhibitor, effectively retarded the time-dependent inactivation of thrombin which was generated endogeneously or added exogeneously in human plasma. The kinetical study of the time-dependent inactivation indicated that the type of inhibition was competitive and the obtained Ki of MD805 for thrombin was 3 × 10−8M. MD805 also inhibited the formation of thrombin-ATIII complex. These results indicated that the active site of thrombin was involved in the reaction between thrombin and ATIII, and that MD805 competed with ATIII for thrombin in exactly the same manner as it competed with fibrinogen or synthetic peptide substrates. As a result, MD805 would serve as a protective agent for ATIII from being consumed, in addition to its potent thrombin-inhibitory activity without the aid of ATIII. By contrast, heparin accelerated the time-dependent inactivation rate of thrombin and the formation of thrombin-ATIII complex, which indicates that heparin accelerates the consumption of ATIII. |
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Keywords: | Author Keywords: synthetic inhibitor thrombin ATIII heparin |
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