Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034.
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SUBMITTER: Madison V
PROVIDER: S-EPMC2394794 | biostudies-literature | 2008 May
REPOSITORIES: biostudies-literature
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Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034.
Madison Vincent V Prongay Andrew J AJ Guo Zhuyan Z Yao Nanhua N Pichardo John J Fischmann Thierry T Strickland Corey C Myers Joseph J Weber Patricia C PC Beyer Brian M BM Ingram Richard R Hong Zhi Z Prosise Winifred W WW Ramanathan Lata L Taremi S Shane SS Yarosh-Tomaine Taisa T Zhang Rumin R Senior Mary M Yang Rong Sheng RS Malcolm Bruce B Arasappan Ashok A Bennett Frank F Bogen Stephane L SL Chen Kevin K Jao Edwin E Liu Yi Tsung YT Lovey Raymond G RG Saksena Anil K AK Venkatraman Srikanth S Girijavallabhan Viyyoor V Njoroge F George FG
Journal of synchrotron radiation 20080418 Pt 3
The structures of both native and S139A holo-HCV NS3/4A protease domain were solved to high resolution. Subsequently, structures were determined for a series of ketoamide inhibitors in complex with the protease. The changes in the inhibitor potency were correlated with changes in the buried surface area upon binding the inhibitor to the active site. The largest contributions to the binding energy arise from the hydrophobic interactions of the P1 and P2 groups as they bind to the S1 and S2 pocket ...[more]
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