title: Antimicrobial activities of chemically modified thiazolyl peptide antibiotic MDL 62,879 (GE2270A).
abstract: MDL 62,879 (GE2270A) 1 is a new inhibitor of elongation factor-Tu (EF-Tu) and belongs to the class of thiazolyl peptide antibiotics. Controlled acid hydrolysis of 1 followed by treatment with base resulted in the lost of the two terminal amino acids and in the formation of water-soluble MDL 62,935 2. Although less active in vitro than its parent compound, 2 was able to inhibit by 50% an Escherichia coli cell-free protein synthesis system at roughly the same concentration of 1. MDL 62,935 2 was subjected to further modification at the beta-phenylserine residue. Derivatives obtained from 2 were less active in both antimicrobial (MIC) and enzymatic (IC50) assays. This suggests that beta-phenylserine plays an important role for the inhibition of EF-Tu by 1 and 2.
authors.affiliation: Biosearch Italia S.p.A., Gerenzano (Va), Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lociuro
authors.forename: P
authors.initials: P
authors.lastname: Tavecchia
authors.forename: E
authors.initials: E
authors.lastname: Marzorati
authors.forename: P
authors.initials: P
authors.lastname: Landini
authors.forename: B P
authors.initials: BP
authors.lastname: Goldstein
authors.forename: M
authors.initials: M
authors.lastname: Denaro
authors.forename: R
authors.initials: R
authors.lastname: Ciabatti
mesh_terms: D000107:Acetylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010444:Peptide Elongation Factor Tu / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; D013844:Thiazoles; D010444:Peptide Elongation Factor Tu; C068122:GE 2270 A