title: Alpha-ketoamide Phe-Pro isostere as a new core structure for the inhibition of HIV protease.
abstract: Studies on the inhibition of HIV-1 protease utilizing a core isostere with replacement of the scissle bond for an alpha-amino-ketone have resulted in the development of an alpha-keto-amide isosteric replacement of the Phe-Pro scissle amide bond. The simple dipeptide isostere was shown to be a promising new core structure for the development of the enzyme inhibitors. The Ki of this core structure was determined to be 6 microM, compared to 230 microM and > 50 microM for the corresponding phosphinic acid and hydroxyethylamine isosteres.
authors.affiliation: Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: B
authors.initials: B
authors.lastname: Munoz
authors.forename: C Z
authors.initials: CZ
authors.lastname: Giam
authors.forename: C H
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors
chemical_list: D000577:Amides; D000588:Amines; D004151:Dipeptides; D017320:HIV Protease Inhibitors; D007659:Ketones; D011993:Recombinant Fusion Proteins; D010649:Phenylalanine; D011392:Proline