UDP-N-TRIFLUOROACETYLGLUCOSAMINE AS AN ALTERNATIVE SUBSTRATE IN N-ACETYLGLUCOSAMINYLTRANSFERASE REACTIONS

The synthesis of UDP-N-trifluoroacetylglucosamine [uridine -trifluoroa cetamido-2-deoxy-alpha-D-glucopyranosyl diphosphate, UDP-GlcNAc-F-3] i s reported. The compound is found to serve as a substrate for the 'cor e-2' GlcNAc transferase (EC 2.4.1.102) that is involved in the biosynt hesis, of O-linked glycoproteins and for the GlcNAcT-V transferase (EC 2.4. 1.155) that is a key biosynthetic enzyme controlling the branchi ng pattern of cell surface complex Asn-linked oligosaccharides. The tr isaccharide beta-o-Gal p-(1 --> 3)-[beta-D-GlcpNAc-F-3(1 --> 6)]alpha- D-GalpNAc-OR [R = (CH2)(8)CO2Me] was prepared from beta-D-Galp-(1 --> 3)-alpha-D-GalpNAc-OR using the 'core-2' GlcNAc transferase. The tetra saccharide beta-D-GlcpNAc-(1 --> 2)-[beta-D-GlcpNAc-F-3-(1 --> 6)]-alp ha-D-Manp-(1 --> 6)-beta-D-Glcp-OR [R = (CH2)(7)CH3] was prepared from beta-D-GlcpNAc-(1 --> 2)-alpha-D-Manp-(1 --> 6)-beta-D-Glcp-OR [R = ( CH2)(7)CH3] using the GlcNAcT-V transferase. Removal of the trifluoroa cetyl group was achieved under mild basic conditions to give the corre sponding glucosamine containing tetrasaccharide. These examples demons trate the feasibility of introducing masked forms of glucosamine resid ues into oligosaccharides using GlcNAc-specific transferases. The requ irement for the trifluoroacetamido group as a specific recognition ele ment was evident in the observation that neither UDP-glucosamine nor U DP-glucose served as a donor substrates for the 'core-2' GlcNAc transf erase. (C) 1998 Elsevier Science Ltd. All rights reserved.