Selective Small Molecules Blocking HIV-1 Tat and Coactivator PCAF Association
Journal of the American Chemical Society2005Vol. 127(8), pp. 2376–2377
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Lei Zeng, Jiaming Li, Michaela Müller, S.X. Yan, Shiraz Mujtaba, Chongfeng Pan, Zhiyong Wang, Ming‐Ming Zhou
Abstract
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.
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