Vancomycin analogues containing monosaccharides exhibit improved antibiotic activity: a combined one-pot enzymatic glycosylation and chemical diversification strategy.
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.
Thayer
Desiree A
DA
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Wong
Chi-Huey
CH
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D016983:Enterococcus / Q000378:metabolism; D005944:Glucosamine / Q000737:chemistry; D006031:Glycosylation; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D009005:Monosaccharides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D002241:Carbohydrates; D009005:Monosaccharides; D010455:Peptides; D011134:Polysaccharides; D014640:Vancomycin; D005944:Glucosamine