Vancomycin analogues containing monosaccharides exhibit improved antibiotic activity: a combined one-pot enzymatic glycosylation and chemical diversification strategy

Chem Asian J. 2006 Sep 18;1(3):445-52. doi: 10.1002/asia.200600084.

Abstract

Many natural products contain carbohydrate moieties that contribute to their biological activity. Manipulation of the carbohydrate domain of natural products through multiple glycosylations to identify new derivatives with novel biological activities has been a difficult and impractical process. We report a practical one-pot enzymatic approach with regeneration of cosubstrates to synthesize analogues of vancomycin that contain an N-alkyl glucosamine, which exhibited marked improvement in antibiotic activity against a vancomycin-resistant strain of Enterococcus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Carbohydrates / chemistry
  • Catalysis
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Enterococcus / metabolism
  • Glucosamine / chemistry
  • Glycosylation*
  • Microbial Sensitivity Tests
  • Models, Chemical
  • Monosaccharides / chemistry*
  • Peptides / chemistry
  • Polysaccharides / chemistry
  • Technology, Pharmaceutical / methods*
  • Vancomycin / analogs & derivatives*
  • Vancomycin / chemical synthesis
  • Vancomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Carbohydrates
  • Monosaccharides
  • Peptides
  • Polysaccharides
  • Vancomycin
  • Glucosamine