Crystal Structures of HIV-1 Reverse Transcriptase with Etravirine (TMC125) and Rilpivirine (TMC278): Implications for Drug Design

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• 作者：Eric B. Lansdon ; Katherine M. Brendza ; Magdeleine Hung ; Ruth Wang ; Susmith Mukund ; Debi Jin ; Gabriel Birkus ; Nilima Kutty ; Xiaohong Liu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：May 27, 2010
• 年：2010
• 卷：53
• 期：10
• 页码：4295-4299
• 全文大小：844K
• 年卷期：v.53,no.10(May 27, 2010)
• ISSN：1520-4804

文摘

Diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitors (NNRTIs) have inherent flexibility, helping to maintain activity against a wide range of resistance mutations. Crystal structures were determined with wild-type and K103N HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278). These structures reveal a similar binding mode for TMC125 and TMC278, whether bound to wild-type or K103N RT. Comparison to previously published structures reveals differences in binding modes for TMC125 and differences in protein conformation for TMC278.