title: Chemoenzymatic synthesis of uridine diphosphate-GlcNAc and uridine diphosphate-GalNAc analogs for the preparation of unnatural glycosaminoglycans.
abstract: Eight N-acetylglucosamine-1-phosphate and N-acetylgalactosamine-1-phosphate analogs have been synthesized chemically and were tested for their recognition by the GlmU uridyltransferase enzyme. Among these, only substrates that have an amide linkage to the C-2 nitrogen were transferred by GlmU to afford their corresponding uridine diphosphate(UDP)-sugar nucleotides. Resin-immobilized GlmU showed comparable activity to nonimmobilized GlmU and provides a more facile final step in the synthesis of an unnatural UDP-donor. The synthesized unnatural UDP-donors were tested for their activity as substrates for glycosyltransferases in the preparation of unnatural glycosaminoglycans in vitro. A subset of these analogs was useful as donors, increasing the synthetic repertoire for these medically important polysaccharides.
authors.affiliation: Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Masuko
authors.forename: Smritilekha
authors.initials: S
authors.lastname: Bera
authors.forename: Dixy E
authors.initials: DE
authors.lastname: Green
authors.forename: Michel
authors.initials: M
authors.lastname: Weïwer
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Paul L
authors.initials: PL
authors.lastname: DeAngelis
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D058105:Polymerization; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
chemical_list: D029968:Escherichia coli Proteins; C520333:GlmU protein, E coli; D009097:Multienzyme Complexes; D014537:Uridine Diphosphate N-Acetylglucosamine