Document Detail

Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates.
MedLine Citation:
PMID:  22095519     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Novel indolylarylsulfones (IASs), designed through rational structure-based molecular modelling and docking approaches, have been recently characterized as effective inhibitors of the wild-type and drug-resistant mutant HIV-1 reverse transcriptase (RT).
METHODS: Here, we studied the interaction of selected halo- and nitro-substituted IAS derivatives, with the RT enzyme carrying the single resistance mutations K103N and Y181I through steady-state kinetic experiments.
RESULTS: The studied compounds exhibited high selectivity to the mutant RT in complex with its substrates, behaving as uncompetitive inhibitors. The presence of the K103N mutation, and to a lesser extent the Y181I, stabilized the drug interactions with the viral RT, when both its substrates were bound.
CONCLUSIONS: The characterization of these mutation-specific effects on inhibitor binding might be relevant to the design of more effective new generation non-nucleoside reverse transcriptase inhibitors, with better resilience towards drug resistant mutants.
Alberta Samuele; Sara Bisi; Alexandra Kataropoulou; Giuseppe La Regina; Francesco Piscitelli; Valerio Gatti; Romano Silvestri; Giovanni Maga
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Publication Detail:
Type:  Journal Article     Date:  2011-11-17
Journal Detail:
Title:  Antiviral chemistry & chemotherapy     Volume:  22     ISSN:  2040-2066     ISO Abbreviation:  Antivir. Chem. Chemother.     Publication Date:  2011  
Date Detail:
Created Date:  2011-11-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9009212     Medline TA:  Antivir Chem Chemother     Country:  England    
Other Details:
Languages:  eng     Pagination:  107-18     Citation Subset:  IM    
Department of DNA Enzymology and Molecular Virology, Institute of Molecular Genetics - National Research Council, IGM-CNR, Pavia, Italy.
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