The design and synthesis of a selective inhibitor of fucosyltransferase VI

Inversion of configuration of the C-2′ hydroxyl of methyl N-acetyllactosamine was accomplished by a two-step procedure involving oxidation to a ketone followed by reduction with NaBH₄. After deprotection, the resulting derivative 2 was examined as a substrate for α-(2,6)- and α-(2,3)-sialyltransferase and fucosyltransferase III, IV, V and VI. It was found that none of these enzymes could glycosylate 2. 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.