title: Applications of 3-aminolactams: design, synthesis, and biological evaluation of a library of potential dimerisation inhibitors of HIV1-protease.
abstract: In the context of our studies on the applications of 3-aminolactams as conformationally restricted pseudodipeptides, we report here the synthesis of a library of potential dimerisation inhibitors of HIV1-protease. Two of the pseudopeptides were active on the wild type virus (HIV1) at micromolar levels (EC(50)). Although the peptides showed lower anti-viral activity than previously reported dimerisation inhibitors, our results demonstrate that the piperidone moiety does not prevent cell penetration, and hence that such derivatization is compatible with potential anti-HIV treatment.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, 08028-Barcelona, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Pinyol
authors.forename: Silvia
authors.initials: S
authors.lastname: Frutos
authors.forename: Dolors
authors.initials: D
authors.lastname: Grillo-Bosch
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Jose A
authors.initials: JA
authors.lastname: Esté
authors.forename: Anna
authors.initials: A
authors.lastname: Diez
mesh_terms: D000588:Amines / Q000737:chemistry*; D019281:Dimerization; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary
chemical_list: D000588:Amines; D017320:HIV Protease Inhibitors; D007769:Lactams; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1