title: Structure-activity relationships of globomycin analogues as antibiotics.
abstract: Globomycin (1a), a signal peptidase II inhibitor, and its derivatives show potent antibacterial activity against Gram-negative bacteria. The synthesis and antimicrobial activity of novel globomycin analogues are reported. The hydroxyl group in the L-Ser residue was essential for the antimicrobial activity and the length of the alkyl side chain greatly influenced the activity. In addition, derivatives that had a modified cyclic core exhibited weak activity. One of the analogues showed a wider antimicrobial spectrum, effective against not only Gram-negative but also Gram-positive bacteria.
authors.affiliation: Exploratory Chemistry Research Laboratories, Sankyo Co. Ltd., 2-58 Hiromachi 1-chome, Sinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kiho
authors.forename: Mizuka
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kayo
authors.initials: K
authors.lastname: Yasuda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyakoshi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inukai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; C017339:globomycin