Abstract
Thrombin plays a key role in thrombosis and haemostasis. Amongst other functions, thrombin effects thrombus formation through conversion of fibrinogen into fibrin and induction of platelet aggregation. Thrombin has therefore been implicated in various disease processes such as myocardial infarction, stroke or pulmonary embolism. In such cases, the quick administration of selective thrombin inhibitors might offer an attractive means of antithrombotic therapy1. Apart from a few natural protein inhibitors such as antithrombin III and hirudin, a large number of synthetic inhibitors have been found’. Some of these inhibitors (in particular MQPA = MD805, see Figure 1) are already in clinical trials. The recent availability of experimental thrombin structures10,11 allows rationalization of these screening results with respect to substitution effects, conformation and shape19,23. In conjunction with interactive graphics and new computational methods, such experimental structures now offer the unique possibility of tailoring existing drugs, or of designing new compounds and elaborating them into drugs.
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Bode, W. (1993). X-Ray Crystal Structures of Thrombin in Complex with D-Phe-Pro-Arg and with Small Benzamidine- and Arginine-Based “Non-Peptidic” Inhibitors. In: Claeson, G., Scully, M.F., Kakkar, V.V., Deadman, J. (eds) The Design of Synthetic Inhibitors of Thrombin. Advances in Experimental Medicine and Biology, vol 340. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-2418-6_2
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