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Research Article

Inhibitors of HIV-1 Reverse Transcriptase and Fidelity of In Vitro DNA Replication

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Pages 35-46 | Received 02 Oct 1991, Published online: 27 Sep 2008
 

Abstract

Mechanisms of the effects of the dTTP analogues 3′-azido-3′-deoxythymidine 5′-triphosphate (AZTTP) and 3′-amino-3′-deoxythymidine 5′-triphosphate (NH2TTP) upon the HIV-1 reverse transcriptase (RT) are discussed. These compounds block the RT in vitro and do so by different kinetic mechanisms. Infidelity of replication is a hallmark of the HIV-1 RT, and replication errors by the enzyme on RNA and DNA templates are discussed. The enzyme's infidelity has ramifications for inhibition: On the one hand, the propensity to produce mutations enhances the ability of the virus to escape inhibitors whereas on the other hand, the infidelity of the reverse transcriptase may allow the development of imaginative inhibitor strategies.

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