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Potent Inhibitors of the Hepatitis C Virus NS3 Protease:  Design and Synthesis of Macrocyclic Substrate-Based β-Strand Mimics

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journal contribution
posted on 2004-09-17, 00:00 authored by Nathalie Goudreau, Christian Brochu, Dale R. Cameron, Jean-Simon Duceppe, Anne-Marie Faucher, Jean-Marie Ferland, Chantal Grand-Maître, Martin Poirier, Bruno Simoneau, Youla S. Tsantrizos
The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring β-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.