Kirschberg Thorsten A, Balakrishnan Mini, Squires Neil H, Barnes Tiffany, Brendza Katherine M, Chen Xiaowu, Eisenberg Eugene J, Jin Weili, Kutty Nilima, Leavitt Stephanie, Liclican Albert, Liu Qi, Liu Xiaohong, Mak John, Perry Jason K, Wang Michael, Watkins William J, Lansdon Eric B
Department of Medicinal Chemistry, Gilead Sciences, Foster City, California 94404, USA.
J Med Chem. 2009 Oct 8;52(19):5781-4. doi: 10.1021/jm900597q.
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.
嘧啶醇羧酸被设计为HIV-1核糖核酸酶H功能的抑制剂。这些分子可以与核糖核酸酶H活性位点中的两个二价金属离子配位。通过生化测定法测量酶活性的抑制情况，但未观察到抗病毒作用。通过HIV-1逆转录酶分离的p15-Ec结构域的固态结构证明了结合情况，该结构显示抑制剂和两个锰（II）离子与核糖核酸酶H活性位点结合。
