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ID: ALA1132772

Journal: Bioorg Med Chem Lett

Title: NMR line-broadening and transferred NOESY as a medicinal chemistry tool for studying inhibitors of the hepatitis C virus NS3 protease domain.

Authors: LaPlante SR, Aubry N, Bonneau PR, Kukolj G, Lamarre D, Lefebvre S, Li H, Llinàs-Brunet M, Plouffe C, Cameron DR.

Abstract: This work describes the use of NMR as a medicinal chemistry tool for better understanding the binding characteristics of inhibitors of the HCV NS3 protease. The protease-bound structure of a tetrapeptide-like inhibitor that has an acid C-terminus, a norvaline at P1 and a naphthylmethoxy proline at P2 is described. Conformational comparisons are made with a similar compound having a 1-amino-cyclopropylcarboxylic acid at P1 and with a hexapeptide inhibitor. Differences between the free and bound states are identified. 19F NMR also helped in determining that a single complex is observed when an inhibitor is added to the protease at a 1:1 ratio.

CiteXplore: 11055336

DOI: 10.1016/s0960-894x(00)00466-2