Antimicrobial activities of chemically modified thiazolyl peptide antibiotic MDL 62,879 (GE2270A)

J Antibiot (Tokyo). 1997 Apr;50(4):344-9. doi: 10.7164/antibiotics.50.344.

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.

Publication types

  • Comparative Study

MeSH terms

  • Acetylation
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Chromatography, High Pressure Liquid
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Peptide Elongation Factor Tu / antagonists & inhibitors*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology

Substances

  • Anti-Bacterial Agents
  • Peptides, Cyclic
  • Thiazoles
  • Peptide Elongation Factor Tu
  • GE 2270 A