Structure-based design of conformationally flexible reverse transcriptase inhibitors to combat resistant HIV.

Abstract:

:Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 RT agents that have improved potency and efficacy against the wild-type (WT) RT, but also target resistant RT forms. Previous crystal complex structures of HIV-1 RT revealed the interaction mechanism between the enzyme and inhibitors, which promoted the exploitation of inhibitor that had sufficient conformational flexibility to combat resistance. Hence, the potential flexibility of a drug should be part of the strategy considered in the early stages of designing drugs that are intended to be broadly effective against mutated targets associated with drug resistance. This review provides an overview of the state of the art in this field, including design strategies and challenges for medicinal chemists.

journal_name

Curr Pharm Des

authors

Hao GF,Yang SG,Yang GF

doi

10.2174/138161282005140214163439

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

725-39

issue

5

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-20130513-4

journal_volume

20

pub_type

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