title: Structure-activity relationship of boronic acid derivatives of tyropeptin: proteasome inhibitors.
abstract: The structure-activity relationship of the boronic acid derivatives of tyropeptin, a proteasome inhibitor, was studied. Based on the structure of a previously reported boronate analog of tyropeptin (2), 41 derivatives, which have varying substructure at the N-terminal acyl moiety and P2 position, were synthesized. Among them, 3-phenoxyphenylacetamide 6 and 3-fluoro picolinamide 22 displayed the most potent inhibitory activity toward chymotryptic activity of proteasome and cytotoxicity, respectively. The replacement of the isopropyl group in the P2 side chain to H or Me had negligible effects on the biological activities examined in this study.
authors: Institute of Microbial Chemistry, Tokyo, Tokyo 141-0021, Japan. twatanabe@bikaken.or.jp
authors: Takumi
authors: T
authors: Watanabe
authors: Hikaru
authors: H
authors: Abe
authors: Isao
authors: I
authors: Momose
authors: Yoshikazu
authors: Y
authors: Takahashi
authors: Daishiro
authors: D
authors: Ikeda
authors: Yuzuru
authors: Y
authors: Akamatsu
mesh_terms: D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D001896:Boron Compounds; D001897:Boronic Acids; D004151:Dipeptides; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D061988:Proteasome Inhibitors; C449021:tyropeptin A; D046988:Proteasome Endopeptidase Complex