2004•The Journal of Organic ChemistryRequires access
Potent Inhibitors of the Hepatitis C Virus NS3 Protease: Design and Synthesis of Macrocyclic Substrate-Based β-Strand Mimics
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
Open publisher page 58 citations
Abstract
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 beta-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.