title: The design and synthesis of a selective inhibitor of fucosyltransferase VI.
abstract: Inversion of configuration of the C-2[prime or minute] hydroxyl of methyl N-acetyllactosamine was accomplished by a two-step procedure involving oxidation to a ketone followed by reduction with NaBH(4). After deprotection, the resulting derivative was examined as a substrate for [small alpha]-(2,6)- and [small alpha]-(2,3)-sialyltransferase and fucosyltransferase III, IV, V and VI. It was found that none of these enzymes could glycosylate. However, it showed exquisite selectivity for inhibition of fucosyltransferase VI. The kinetic data support an unusual mechanism in which the inhibitor can bind to the GDP-fucose complex as well as another enzyme form.
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens 30602, USA.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Galan
authors.forename: Andre P
authors.initials: AP
authors.lastname: Venot
authors.forename: Robert S
authors.initials: RS
authors.lastname: Phillips
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
mesh_terms: D000606:Amino Sugars / Q000737:chemistry* / Q000494:pharmacology; D002236:Carbohydrate Conformation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D016256:Lewis X Antigen
chemical_list: D000606:Amino Sugars; D004791:Enzyme Inhibitors; D016256:Lewis X Antigen; C000458:N-acetyllactosamine; C066693:FUT4 protein, human; D005647:Fucosyltransferases