title: Molecular tongs containing amino acid mimetic fragments: new inhibitors of wild-type and mutated HIV-1 protease dimerization.
abstract: We have designed, synthesized, and evaluated the inhibitory activity and metabolic stability of new peptidomimetic molecular tongs based on a naphthalene scaffold for inhibiting HIV-1 protease dimerization. Peptidomimetic motifs were inserted into one peptidic strand to make it resistant to proteolysis. The peptidic character of the molecular tongs can be decreased without changing the way they inhibit dimerization. Mutated HIV-1 proteases are also vulnerable to dimerization inhibitors, and the multimutated protease ANAM-11 is twice as sensitive to the inhibitor compared to wild-type protease. Thus, the metabolic stability of antidimeric molecular tongs can be increased without compromising their ability to inhibit wild-type and mutated HIV-1 proteases in vitro.
authors.affiliation: Université de Paris-Sud XI, IFR 141, Biocis, UMR-CNRS 8076, Faculté de Pharmacie, 5 Rue J. B. Clément, F-92296 Châtenay-Malabry Cedex, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Bannwarth
authors.forename: Albane
authors.initials: A
authors.lastname: Kessler
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pèthe
authors.forename: Bruno
authors.initials: B
authors.lastname: Collinet
authors.forename: Naïma
authors.initials: N
authors.lastname: Merabet
authors.forename: Nicole
authors.initials: N
authors.lastname: Boggetto
authors.forename: Sames
authors.initials: S
authors.lastname: Sicsic
authors.forename: Michèle
authors.initials: M
authors.lastname: Reboud-Ravaux
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ongeri
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D019281:Dimerization; D004355:Drug Stability; D016333:HIV Protease / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D006868:Hydrolysis; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D009154:Mutation; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000596:Amino Acids; D017320:HIV Protease Inhibitors; D009281:Naphthalenes; D010455:Peptides; D011725:Pyridines; D016333:HIV Protease