Selective Small Molecules Blocking HIV-1 Tat and Coactivator PCAF Association

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• 作者：Lei Zeng ; Jiaming Li ; Michaela Muller ; Sherry Yan ; Shiraz Mujtaba ; Chongfeng Pan ; Zhiyong Wang ; and Ming-Ming Zhou
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：March 2, 2005
• 年：2005
• 卷：127
• 期：8
• 页码：2376 - 2377
• 全文大小：125K
• 年卷期：v.127,no.8(March 2, 2005)
• ISSN：1520-5126

文摘

Development of drug resistance from mutations in the targeted viral proteins leads to continuation of viral production by chronically infected cells, contributing to HIV-mediated immune dysfunction. Targeting a host cell protein essential for viral reproduction, rather than a viral protein, may minimize the viral drug resistance problem as observed with HIV protease inhibitors. We report here the development of a novel class of N1-aryl-propane-1,3-diamine compounds using a structure-based approach that selectively inhibit the activity of the bromodomain of the human transcriptional co-activator PCAF, of which association with the HIV trans-activator Tat is essential for transcription and replication of the integrated HIV provirus.