title: Recognition of oligosaccharide substrates by N-acetyl-glucosaminyltransferase-V.
abstract: Six analogs of the trisaccharide 8-methoxycarbonyloctyl 6-O-[2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-alpha-D-mannopyrano syl] -beta-D-mannopyranoside (3), a previously reported acceptor for N-acetylglucosaminyltransferase-V (GnT-V) have been chemically synthesized and evaluated as GnT-V acceptors. Replacement of the beta-D-man rho-O(CH2)8COOMe "reducing end" of 3 by beta-D-Glc rho-O(CH2)7 CH3 gave octyl 6-O-[2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl]-alpha-D- mannopyranosyl)-beta-D-glucopyranoside (5) whose activity was indistinguishable from that of 3. Removal of the 4-OH group of the beta-D-Glc residue in 5 had little effect on the activity, while the corresponding 4-O-methyl derivative was twice as active. Replacement of the C-6 pro-R hydrogen of the same residue by a methyl group gave the L-glycero-D-gluco derivative 8, whereas replacement of the corresponding pro-S hydrogen gave the D-glycero-D-gluco compound 9. Trisaccharide 8, whose rotameric distribution about the C-5-C-6 bond is sterically biased towards the gg conformation was less than half as active as 5 as a GnT-V acceptor, whereas 9, which is biased towards the gt conformation, was more than twice as active. These results provide evidence for the conformational control of oligosaccharide biosynthesis.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: O P
authors.initials: OP
authors.lastname: Srivastava
authors.forename: O
authors.initials: O
authors.lastname: Hindsgaul
authors.forename: M
authors.initials: M
authors.lastname: Shoreibah
authors.forename: M
authors.initials: M
authors.lastname: Pierce
mesh_terms: D000438:Alcohols; D002236:Carbohydrate Conformation; D005964:Glucosyltransferases / Q000378:metabolism*; D006031:Glycosylation; D015394:Molecular Structure; D009005:Monosaccharides; D017351:N-Acetylglucosaminyltransferases; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D000438:Alcohols; D009005:Monosaccharides; D014312:Trisaccharides; C058136:8-methoxycarbonyloctyl 6-O-(2-O-(2-acetamido-2-deoxyglucopyranosyl)mannopyranosyl)mannopyranoside; D005964:Glucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase