Inhibitors of HIV-Protease from Computational Design. A History of Theory and Synthesis Still to be Fully Appreciated

Author(s): Federico Berti, Vladimir Frecer, Stanislav Miertus.

Journal Name: Current Pharmaceutical Design

Volume 20 , Issue 21 , 2014

Abstract:

Despite the fact that HIV-Protease is an over 20 years old target, computational approaches to rational design of its inhibitors still have a great potential to stimulate the synthesis of new compounds and the discovery of new, potent derivatives, ever capable to overcome the problem of drug resistance. This review deals with successful examples of inhibitors identified by computational approaches, rather than by knowledge-based design. Such methodologies include the development of energy and scoring functions, docking protocols, statistical models, virtual combinatorial chemistry. Computations addressing drug resistance, and the development of related models as the substrate envelope hypothesis are also reviewed. In some cases, the identified structures required the development of synthetic approaches in order to obtain the desired target molecules; several examples are reported.

Keywords: AIDS, HIV protease, protease inhibitors, structure-based drug design, computational chemistry, molecular modelling, pseudopeptide synthesis.

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Article Details

VOLUME: 20
ISSUE: 21
Year: 2014
Page: [3398 - 3411]
Pages: 14
DOI: 10.2174/13816128113199990628
Price: $58

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