Active site and allosteric inhibitors of the ribonuclease H activity of HIV reverse transcriptase

被引：50

作者：

Corona, Angela ^{[1
]}

Masaoka, Takashi ^{[2
]}

Tocco, Graziella ^{[3
]}

Tramontano, Enzo ^{[1
]}

Le Grice, Stuart F. J. ^{[2
]}

机构：

[1] Univ Cagliari, Dept Life & Environm Sci, Unit Biomed, I-09124 Cagliari, Italy

[2] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA

[3] Univ Cagliari, Dept Life & Environm Sci, Unit Drug Sci, I-09124 Cagliari, Italy

来源：

FUTURE MEDICINAL CHEMISTRY | 2013年 / 5卷 / 18期

关键词：

SMALL-MOLECULE INHIBITORS; CELL-BASED ASSAYS; RNASE-H; DNA-POLYMERASE; DUAL INHIBITORS; INTEGRASE INHIBITORS; STRAND TRANSFER; STRUCTURAL BASIS; DIKETO ACID; VIRUS;

D O I：

10.4155/fmc.13.178

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Despite the wealth of information available for the reverse transcriptase (RT)-associated ribonuclease H (RNaseH) domain of lentiviruses, gammaretroviruses and long terminal repeat containing retrotransposons, exploiting this information in the form of an RNaseH inhibitor with high specificity and low cellular toxicity has been disappointing. However, it is now becoming increasingly evident that the two-subunit HIV-1 RT is a highly versatile enzyme, undergoing major structural alterations in order to interact with, position and ultimately hydrolyze the RNA component of an RNA/DNA hybrid. Thus, in addition to targeting the RNaseH active site, identifying small molecules that bind elsewhere and disrupt catalysis allosterically by impairing conformational flexibility is gaining increased attention. This review summarizes current progress towards development of both active site and allosteric RNaseH inhibitors.

引用

页码：2127 / 2139

页数：13

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