Structure-activity relationships of globomycin analogues as antibiotics

Toshihiro Kiho; Mizuka Nakayama; Kayo Yasuda; Shunichi Miyakoshi; Masatoshi Inukai; Hiroshi Kogen

doi:10.1016/j.bmc.2003.10.055

Structure-activity relationships of globomycin analogues as antibiotics

Bioorg Med Chem. 2004 Jan 15;12(2):337-61. doi: 10.1016/j.bmc.2003.10.055.

Authors

Toshihiro Kiho¹, Mizuka Nakayama, Kayo Yasuda, Shunichi Miyakoshi, Masatoshi Inukai, Hiroshi Kogen

Affiliation

¹ Exploratory Chemistry Research Laboratories, Sankyo Co. Ltd., 2-58 Hiromachi 1-chome, Sinagawa-ku, Tokyo 140-8710, Japan.

PMID: 14723954
DOI: 10.1016/j.bmc.2003.10.055

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.

MeSH terms

Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Biochemistry / methods
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Magnetic Resonance Spectroscopy
Microbial Sensitivity Tests
Peptides / chemistry*
Peptides / pharmacology
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Peptides
globomycin