title: Total synthesis and biological evaluation of the antibiotic lysocin E and its enantiomeric, epimeric, and N-demethylated analogues.
abstract: Lysocin E, a macrocyclic peptide, exhibits potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) through a novel mechanism. The first total synthesis of lysocin E was achieved by applying a full solid-phase strategy. The developed approach also provides rapid access to the enantiomeric, epimeric, and N-demethylated analogues of lysocin E. Significantly, the antibacterial activity of the unnatural enantiomer was comparable to that of the natural isomer, suggesting the absence of chiral recognition in its mode of action.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Motoki
authors.initials: M
authors.lastname: Murai
authors.forename: Takuya
authors.initials: T
authors.lastname: Kaji
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kuranaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamamoto
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D056831:Coordination Complexes / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010165:Palladium / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D056831:Coordination Complexes; D010456:Peptides, Cyclic; C000597008:lysocin E; D010165:Palladium
keywords: antibiotics; natural products; solid-phase synthesis; structure-activity relationships; total synthesis