Active Site and Allosteric Inhibitors of the Ribonuclease H Activity of HIV Reverse Transcriptase

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2013 Nov 23

PMID 24261890

Citations 28

Authors

Angela Corona

Takashi Masaoka

Graziella Tocco

Enzo Tramontano

Stuart F J Le Grice

Affiliations

Soon will be listed here.

Abstract

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.

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