title: Natural product disaccharide engineering through tandem glycosyltransferase catalysis reversibility and neoglycosylation.
abstract: A two-step strategy for disaccharide modulation using vancomycin as a model is reported. The strategy relies upon a glycosyltransferase-catalyzed 'reverse' reaction to enable the facile attachment of an alkoxyamine-bearing sugar to the vancomycin core. Neoglycosylation of the corresponding aglycon led to a novel set of vancomycin 1,6-disaccharide variants. While the in vitro antibacterial properties of corresponding vancomycin 1,6-disaccharide analogs were equipotent to the parent antibiotic, the chemoenzymatic method presented is expected to be broadly applicable.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, Wisconsin Center for Natural Products Research, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.
authors.forename: Pauline
authors.initials: P
authors.lastname: Peltier-Pain
authors.forename: Karen
authors.initials: K
authors.lastname: Marchillo
authors.forename: Maoquan
authors.initials: M
authors.lastname: Zhou
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism*; D015394:Molecular Structure; D014640:Vancomycin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D004187:Disaccharides; D014640:Vancomycin; D016695:Glycosyltransferases