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Inhibition of HIV‐1 Reverse Transcriptase Dimerization by Small Molecules
Author(s) -
Tintori Cristina,
Corona Angela,
Esposito Francesca,
Brai Annalaura,
Grandi Nicole,
Ceresola Elisa Rita,
Clementi Massimo,
Canducci Filippo,
Tramontano Enzo,
Botta Maurizio
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500668
Subject(s) - reverse transcriptase , chemistry , enzyme , docking (animal) , small molecule , rational design , in vitro , protein subunit , polymerase , rnase h , ribonuclease , human immunodeficiency virus (hiv) , biochemistry , stereochemistry , biology , rna , virology , genetics , gene , medicine , nursing
Because HIV‐1 reverse transcriptase is an enzyme whose catalytic activity depends on its heterodimeric structure, this system could be a target for inhibitors that perturb the interactions between the protein subunits, p51 and p66. We previously demonstrated that the small molecule MAS0 reduced the association of the two RT subunits and simultaneously inhibited both the polymerase and ribonuclease H activities. In this study, some analogues of MAS0 were rationally selected by docking studies and evaluated in vitro for their ability to disrupt dimeric assembly. Two inhibitors were identified with improved activity compared to MAS0. This study lays the basis for the rational design of more potent inhibitors of RT dimerization.