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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| Published in: | Journal of organic chemistry Vol. 69; no. (19) ; 09, 2004 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
30-06-2008
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| 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. |
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| AbstractList | 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. |
| Author | Grand-Maître, Chantal Brochu, Christian Goudreau, Nathalie Ferland, Jean-Marie Simoneau, Bruno Tsantrizos, Youla S. Cameron, Dale R. Faucher, Anne-Marie Duceppe, Jean-Simon Poirier, Martin |
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| BackLink | https://www.osti.gov/biblio/1008760$$D View this record in Osti.gov |
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| Snippet | The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis,... |
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| SubjectTerms | DESIGN ENZYMES HEPATITIS INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY LIFE CYCLE LIVER PATHOGENS SUBSTRATES SYNTHESIS |
| Title | Potent Inhibitors of the Hepatitis C Virus NS3 Protease: Design and Synthesis of Macrocyclic Substrate-Based [beta]-Strand Mimics |
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