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Toward the First Nonpeptidic Molecular Tong Inhibitor of Wild‐Type and Mutated HIV‐1 Protease Dimerization
Author(s) -
Vidu Anamaria,
Dufau Laure,
Bannwarth Ludovic,
Soulier JeanLouis,
Sicsic Sames,
Piarulli Umberto,
ReboudRavaux Michèle,
Ongeri Sandrine
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000308
Subject(s) - proteases , peptidomimetic , protease , hiv 1 protease , chemistry , protease inhibitor (pharmacology) , stereochemistry , enzyme inhibitor , wild type , molecular model , inhibitory postsynaptic potential , human immunodeficiency virus (hiv) , biochemistry , in vitro , enzyme , biology , peptide , mutant , virology , gene , antiretroviral therapy , viral load , neuroscience
Herein we describe the synthesis and HIV‐1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV‐1 wild‐type and multimutated ANAM‐11 proteases obtained to date for this class of molecules (∼40 n M for wild‐type PR and 100 n M for ANAM‐11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained.