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

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 inhibiti...

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Bibliographic Details
Published in:	Journal of organic chemistry Vol. 69; no. (19) ; 09, 2004
Main Authors:	Goudreau, Nathalie, Brochu, Christian, Cameron, Dale R., Duceppe, Jean-Simon, Faucher, Anne-Marie, Ferland, Jean-Marie, Grand-Maître, Chantal, Poirier, Martin, Simoneau, Bruno, Tsantrizos, Youla S.
Format:	Journal Article
Language:	English
Published:	United States 30-06-2008
Subjects:	DESIGN ENZYMES HEPATITIS INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY LIFE CYCLE LIVER PATHOGENS SUBSTRATES SYNTHESIS
Online Access:	Get full text
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Summary:	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.
Bibliography:	USDOE
ISSN:	0022-3263 1520-6904
DOI:	10.1021/jo049288r