title: Oligosaccharides as inhibitors of mycobacterial arabinosyltransferases. Di- and trisaccharides containing C-3 modified arabinofuranosyl residues.
abstract: The assembly of the arabinan portions of cell wall polysaccharides in mycobacteria involves a family of arabinosyltransferases (AraT's) that promote the polymerization of decaprenolphosphoarabinose. Mycobacterial viability depends upon the ability of the organism to synthesize an intact arabinan and thus compounds that inhibit these AraT's are both useful biochemical tools as well as potential lead compounds for new anti-tuberculosis agents. We describe here the preparation of oligosaccharide fragments of mycobacterial arabinan that contain arabinofuranosyl residues modified at C-3 by the replacement of the hydroxyl group with an amino, azido or methoxy functionality. Subsequent testing of these oligosaccharides as inhibitors of mycobacterial AraT's revealed that all inhibited the enzymes, but to varying degrees. In further studies, each compound was shown to have only low activity as an inhibitor of mycobacterial growth.
authors.affiliation: Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA.
authors.forename: Oana M
authors.initials: OM
authors.lastname: Cociorva
authors.forename: Sudagar S
authors.initials: SS
authors.lastname: Gurcha
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Todd L
authors.initials: TL
authors.lastname: Lowary
mesh_terms: D002240:Carbohydrate Sequence; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000201:enzymology*; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D010430:Pentosyltransferases; C101967:arabinosyltransferase