RNase H Active Site Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Design, Biochemical Activity, and Structural Information

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• 作者：Thorsten A. Kirschberg ; Mini Balakrishnan ; Neil H. Squires ; Tiffany Barnes ; Katherine M. Brendza ; Xiaowu Chen ; Eugene J. Eisenberg ; Weili Jin ; Nilima Kutty ; Stephanie Leavitt ; Albert Liclican ; Qi Liu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：October 8, 2009
• 年：2009
• 卷：52
• 期：19
• 页码：5781-5784
• 全文大小：759K
• 年卷期：v.52,no.19(October 8, 2009)
• ISSN：1520-4804

文摘

Pyrimidinol carboxylic acids were designed as inhibitors of HIV-1 RNase H function. These molecules can coordinate to two divalent metal ions in the RNase H active site. Inhibition of enzymatic activity was measured in a biochemical assay, but no antiviral effect was observed. Binding was demonstrated via a solid state structure of the isolated p15-Ec domain of HIV-1 RT showing inhibitor and two Mn(II) ions bound to the RNase H active site.