Dimerization inhibitors of HIV-1 protease.
By targeting the highly conserved antiparallel beta-sheet formed by the interdigitation of the N- and C-terminal strands of each monomer, dimerization inhibitors of HIV-1 protease may be useful to overcome the drug resistance observed with current active-site directed antiproteases. Sequestration of the monomer by the inhibitor (or disruption of the dimer interface) prevents the correct assembly of the inactive monomers to active enzyme. Strategies for the design of drugs targeting the dimer interface are described. Various dimerization inhibitors are reported including N- and C-terminal mimetics, lipopeptides and cross-linked interface peptides.
Boggetto
Nicole
N
Département de Biologie Cellulaire, Institut Jacques Monod, UMR 7592, CNRS-Université Paris 6, France.
Reboud-Ravaux
Michèle
M
D019281:Dimerization; D015195:Drug Design; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry
D017320:HIV Protease Inhibitors; D016333:HIV Protease