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
Department of Chemistry, Boehringer Ingelheim Ltd., Research and Development, 2100 Cunard Street, Laval, Quebec, Canada H7S 2G5.
J Org Chem. 2004 Sep 17;69(19):6185-201. doi: 10.1021/jo049288r.
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.
病毒编码的NS3蛋白酶对于丙型肝炎病毒(HCV)的生命周期至关重要,HCV是一种重要的人类病原体,可导致慢性肝炎、肝硬化和肝细胞癌。本文将描述能够抑制HCV NS3蛋白酶与其多聚蛋白底物之间相互作用的15元环β-链模拟物的设计与合成。通过核磁共振(NMR)和分子动力学研究了大环配体与该酶之间的结合相互作用,并建立了配体/酶复合物的模型。