title: Synthesis of sugar-amino acid-nucleosides as potential glycosyltransferase inhibitors.
abstract: Sugar-amino acid-nucleosides (SAAN) were synthesized to mimic glycosyl nucleotide donors based on the hypothesis that a basic amino acid may interact with carboxylate groups of the enzyme in a manner similar to the diphosphate metal ion complex. C-Glycoside analogues of the d-galactopyranose or l-arabinofuranose ring systems, and four amino acids (lysine, glutamine, tryptophan, and histidine), were chosen for this study. The targets were synthesized and tested against GlfT2, a galactofuranosyltransferase essential for cell wall galactan biosynthesis in Mycobacterium tuberculosis. The inhibition assay showed that analogues containing histidine and tryptophan are moderate inhibitors of GlfT2.
authors.affiliation: Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6.
authors.forename: Kannan
authors.initials: K
authors.lastname: Vembaiyan
authors.forename: Jean A
authors.initials: JA
authors.lastname: Pearcey
authors.forename: Milan
authors.initials: M
authors.lastname: Bhasin
authors.forename: Todd L
authors.initials: TL
authors.lastname: Lowary
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016695:Glycosyltransferases / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D002241:Carbohydrates; D004791:Enzyme Inhibitors; D009705:Nucleosides; D016695:Glycosyltransferases