Pasteur Institute-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" University of Rome, P.le Aldo Moro 5, I-00185 Rome, Italy.
Curr Med Chem. 2011;18(22):3335-42. doi: 10.2174/092986711796504619.
The HIV-1 integrase (IN) and reverse transcriptase (RT) are essential enzymes in the virus cycle. RT is crucial for the retrotranscription of the RNA viral genome, while IN is involved in the insertion in host chromosome of the proviral double strand DNA produced by RT. This enzyme has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H (RNase H). The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. Since the discovery that catalytic cores of both HIV-1 RNase H and IN are folded in a very similar way, have very similar active site geometries, and show the same DDE triad absolutely required for catalytic activity, some researches were devoted to study IN and RNase H dual inhibitor. Our decennial interest in design and synthesis of IN inhibitors led us to study the activity of our compounds also on RNase H activity. The results of the activities showed by pyrrolyl and quinolonyl diketo acids are reported and discussed.
HIV-1 整合酶（IN）和逆转录酶（RT）是病毒周期中的必需酶。RT 对于病毒 RNA 基因组的逆转录至关重要，而 IN 则参与 RT 产生的前病毒双链 DNA 插入宿主染色体。该酶具有两个相关功能：RNA 和 DNA 依赖性 DNA 聚合酶（RDDP 和 DDDP）和核糖核酸酶 H（RNase H）。RNase H 功能催化 RNA：DNA 杂交复制中间体中 RNA 链的选择性水解。自从发现 HIV-1 RNase H 和 IN 的催化核心以非常相似的方式折叠、具有非常相似的活性位点几何形状并且显示出相同的 DDE 三联体对于催化活性是绝对必需的，一些研究致力于研究 IN 和 RNase H 双重抑制剂。我们十年来对 IN 抑制剂的设计和合成的兴趣促使我们研究我们的化合物对 RNase H 活性的影响。报告并讨论了吡咯基和喹喔啉二酮酸的活性结果。
