title: Identification of constrained peptidomimetic chemotypes as HIV protease inhibitors.
abstract: Small-molecule peptidomimetic inhibitors that already showed activity towards Secreted aspartic protease 2 as anti-Candida agents are herein presented as candidate HIV protease inhibitors. A library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was screened towards HIV protease, resulting in the identification of hit compounds possessing IC50 in the sub-micromolar range, and showing the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues.
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy. Electronic address: chiara.calugi@unifi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Calugi
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Guarna
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy. Electronic address: andrea.trabocchi@unifi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Trabocchi
mesh_terms: D004305:Dose-Response Relationship, Drug; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D017320:HIV Protease Inhibitors; D057786:Peptidomimetics; D054852:Small Molecule Libraries; D016333:HIV Protease
keywords: AIDS; Amino acid; Drug design; Enzyme; Molecular docking; Small molecule