1997 年 55 巻 4 号 p. 325-333
In order to create specific inhibitors against glycosyltransferases, tethering glycosyl donor to acceptor was planned. Mono-O-methylated UDP-Gal and related analogues were synthesized, and their behaviors toward β-1, 4-galactosyltransferase were examined. The allowance for the O-methylation of Gal moiety was decreased in the following order : 2-, 3-, 4- and 6-positions and it was suggested that the modification at the 2-position does not affect the affinity but retards the reaction rate by preventing the conformational change to the transition state, which develops so-called dynamic binding. Modification of the glycosyl acceptor (G1cNAc) moiety showed the tethering probability in the 3' - and 6' - positions. Bisubstrate tricomponent analogues linked through 2, 6' -methylene and 2, 6' -ethylene groups were synthesized and found to be potent inhibitors against bovine G1cNAc : β-1, 4-galactosyltransferase, with Ki values of 1.35 and 1.95 μM, respectively, for the acceptor.