Abstract
The natural product heparin has turned out to be an important lead for the research on antithrombotics. By systematic modification of synthetic heparin fragments new derivatives were discovered. One of them, the synthetic counterpart of the antithrombin III binding pentasaccharide 1, is now being tested clinically. Recently, the structure elucidation of a number of blood coagulation proteins initiated a new breakthrough in the anticoagulant research. Molecular modelling of the crucial antithrombin III — heparin — thrombin complex inspired the design and synthesis of a novel class of anticoagulants. Their anticoagulant properties can be adjusted in a rational way leading to compounds with unprecedented characteristics. The heparin story illustrates the weaknesses and strengths of molecular modelling and structure-based design in drug discovery.
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Grootenhuis, P.D.J., van Boeckel, C.A.A. (1998). Structure-Based Design of Novel Heparin-Like Anticoagulants. In: Codding, P.W. (eds) Structure-Based Drug Design. NATO ASI Series, vol 352. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9028-0_15
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DOI: https://doi.org/10.1007/978-94-015-9028-0_15
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