RNase H Active Site Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Design, Biochemical Activity, and Structural Information
RNase H Active Site Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Design, Biochemical Activity, and Structural Information
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DOI：
10.1021/jm900597q
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发表时间：
2009-10-08
影响因子：
7.3
通讯作者：
Lansdon, Eric B.
中科院分区：
文献类型：
--
作者：
Kirschberg, Thorsten A.;Balakrishnan, Mini;Lansdon, Eric B.
设计了嘧啶酚羧酸作为HIV-1核糖核酸酶H功能的抑制剂。这些分子可以与RNaseH活性中心上的两个二价金属离子配位。生物化学方法检测到对酶活性的抑制，但没有观察到抗病毒作用。通过分离的HIV-1RT的p15-EC结构域的固态结构显示抑制物和两个Mn(II)离子与RNaseH活性部位结合，证明了结合WITS。
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 wits 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.