UDP-6-deoxy-6-fluoro-α-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 α-(1→3)-galactosyltransferase (EC 2.4.1.151) and β-(1→4)-galactosyltransferase (EC 2.4.1.22) to catalyze its transfer from UDP to an appropriate acceptor was determined. HPLC analyses indicated that each transferase properly catalyzed formation of the expected product [β-D-Gal-(1→4)-D-GlcNAc] for the β-(1→4)-galactosyltransferase and α-D-Gal-(1→3)-β-D-Gal-(1→4)-D-GlcNAc for the α-(1→3)-D-galactosyltransferase] when UDP-α-D-Gal was the substrate. When UDP-6-deoxy-6-fluoro-α-D-galactose (6) was used in conjunction with each transferase, no product indicative of transfer of 6-deoxy-6-fluoro-D-galactose to its respective acceptor sugar was identified. 6-Deoxy-6-fluoro-D-galactose (3) was obtained by hydrolysis of methyl 6-deoxy-6-fluoro-α-D-galactopyranoside, synthesized by the selective fluorination of methyl α-D-galactopyranoside with diethylaminosulfur trifluoride (DAST), with aqueous trifluoroacetic acid. Acetylation of 3 gave crystalline 1,2,3,4-tetra-O-acetyl-6-deoxy-6-fluoro-β-D-galactopyranose, which was converted to the corresponding 1-α-phosphate and used for the synthesis of 6. Copyright (C) 1999 Elsevier Science Ltd.