Enzymatic deacylation of teicoplanin followed by reductive alkylation: synthesis and antibacterial activity of new glycopeptides

J Antibiot (Tokyo). 1998 Oct;51(10):945-51. doi: 10.7164/antibiotics.51.945.

Abstract

Novel glycopeptides derived from teicoplanin were prepared and evaluated for activity against antibiotic-resistant gram-positive pathogens. Removal of the fatty acid sidechains of teicoplanin was accomplished by enzymatic deacylation. The resulting deacylated teicoplanin was subjected to reductive alkylation resulting in mono- and di-alkylated compounds at the 2 possible primary amines. Deacylated teicoplanin was less active than teicoplanin against enterococci and staphylococci (MIC > or =32 microg/ml). All mono- and di-alkylated products regained some activity, and some had potent activity against both staphylococci and glycopeptide-resistant enterococci. MICs of the most potent di-alkylated compounds ranged from 0.25 approximately 2 microg/ml against glycopeptide-resistant enterococci.

MeSH terms

  • Alkylation
  • Amidohydrolases / chemistry
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Chromatography, High Pressure Liquid
  • Drug Evaluation, Preclinical
  • Drug Resistance, Microbial
  • Echinocandins
  • Enterococcus / drug effects
  • Fatty Acids / chemistry
  • Fungal Proteins*
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Peptides*
  • Peptides, Cyclic*
  • Staphylococcus / drug effects
  • Structure-Activity Relationship
  • Teicoplanin / analogs & derivatives*
  • Teicoplanin / chemistry*

Substances

  • Anti-Bacterial Agents
  • Echinocandins
  • Fatty Acids
  • Fungal Proteins
  • Peptides
  • Peptides, Cyclic
  • Teicoplanin
  • echinocandin B
  • Amidohydrolases