Abstract
A computational algorithm was used to design automatically novel thrombin inhibitors that are available from a single-step chemical reaction. The compounds do not contain amide bonds, are achiral and have a molecular weight below 400. Of the 10 compounds that were synthesized, five bind to thrombin with a Ki in the nanomolar range. Subsequent X-ray structure determination of the thrombin-inhibitor complex for the best compound (Ki=95 nM) confirms the predicted binding mode. The novel algorithm is applicable to a broad range of chemical reactions.
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Böhm, HJ., Banner, D.W. & Weber, L. Combinatorial docking and combinatorial chemistry: Design of potent non-peptide thrombin inhibitors. J Comput Aided Mol Des 13, 51–56 (1999). https://doi.org/10.1023/A:1008040531766
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DOI: https://doi.org/10.1023/A:1008040531766