期刊
CHEMMEDCHEM
卷 9, 期 8, 页码 1869-1879出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201402015
关键词
antiviral agents; dual inhibitors; enzymes; HIV-1; molecular modeling; RNase H
资金
- RAS (Regione Autonoma della Sardegna) [LR 7/2007 CRP2 450, CRP-24915]
- Istituto Superiore di Sanita [RF-PAD-2009-1304305 n.40H98]
- Fondazione Banco di Sardegna
- RAS
- PO Sardinia FSE [7/2007, CRP2 683]
A small library of 1,3-diarylpropenones was designed and synthesized as dual inhibitors of both HIV-1 reverse transcriptase (RT) DNA polymerase (DP) and ribonuclease H (RNase H) associated functions. Compounds were assayed on these enzyme activities, which highlighted dual inhibition properties in the low-micromolar range. Interestingly, mutations in the non-nucleoside RT inhibitor binding pocket strongly affected RNase H inhibition by the propenone derivatives without decreasing their capacity to inhibit DP activity, which suggests long-range RT structural effects. Biochemical and computational studies indicated that the propenone derivatives bind two different interdependent allosteric pockets.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据