UDP-6-deoxy-6-fluoro-alpha-D-galactose binds to two different galactosyltransferases, but neither can effectively catalyze transfer of the modified galactose to the appropriate acceptor

The effect of substitution of the HO-6 of D-galactose with fluorine on the ability of alpha-(1 --> 3)-galactosyltransferase (EC 2.4.1.151) and beta-(1 --> 4)-galactosyltransferase (EC 2.4.1.22) to catalyze its transfer from U DP to an appropriate acceptor was determined. HPLC analyses indicated that each transferase properly catalyzed formation of the expected product [beta -D-Gal-(1 --> 4)-D-GlcNAc for the beta-(1 --> 4)-galactosyltransferase and alpha-D-Gal-(1 --> 3)-beta-D-Gal-(1 --> 4)-D-GlcNAc for the alpha-(1 --> 3) -D-galactosyltransferase] when UDP-alpha-D-Gal was the substrate. When UDP- 6-deoxy-6-fluoro-alpha-D-galactose (6) was used in conjunction with each tr ansferase, no product indicative of transfer of 6-deoxy-6-fluoro-D-galactos e to its respective acceptor sugar was identified. 6-Deoxy-6-fluoro-D-galac tose (3) was obtained by hydrolysis of methyl 6-deoxy-6-fluoro-alpha-D-gala ctopyranoside, synthesized by the selective fluorination of methyl alpha-D- galactopyranoside with diethylaminosulfur trifluoride (DAST), with aqueous trifluoroacetic acid. Acetylation of 3 gave crystalline 1,2,3,4-tetra-O-ace tyl-6-deoxy-6-fluoro-beta-D-galactopyranose, which was converted to the cor responding 1-alpha-phosphate and used for the synthesis of 6. (C) 1999 Publ ished by Elsevier Science Ltd. All rights reserved.