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Binding Mode Determination of Benzimidazole Inhibitors of the Hepatitis C Virus RNA Polymerase by a Structure and Dynamics Strategy
Author(s) -
LaPlante Steven R.,
Jakalian Araz,
Aubry Norman,
Bousquet Yves,
Ferland JeanMarie,
Gillard James,
Lefebvre Sylvain,
Poirier Martin,
Tsantrizos Youla S.,
Kukolj George,
Beaulieu Pierre L.
Publication year - 2004
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200460326
Subject(s) - benzimidazole , polymerase , hepatitis c virus , rna polymerase , virology , rational design , dynamics (music) , chemistry , binding site , computational biology , stereochemistry , virus , combinatorial chemistry , biochemistry , rna , biology , enzyme , genetics , physics , organic chemistry , gene , acoustics
A novel strategy involving NMR, medicinal chemistry, and molecular modeling is described for determining the binding mode of ligands and the binding roles of their substituents. The first solution structure of an inhibitor bound to hepatitis C virus (HCV) polymerase (see picture) provides practical information for the rational design of potential therapeutics against HCV infections.