CHARACTERIZATION OF INHIBITORY ACTIVITIES AND BINDING MODE OF SYNTHETIC 6'-MODIFIED METHYL N-ACETYL-BETA-LACTOSAMINIDE TOWARD RAT-LIVER LACTOSIDE-(2-]6)-ALPHA-DEUTERIUM-SIALYLTRANSFERASE

6'-Deoxy (12), 6'-thio (13), and 6'-O-tetrahydropyranosyl (14) analogu es of methyl N-acetyl-beta-lactosaminide (3), were synthesized from la ctose. NOE experiments proved that they adopt the same conformation as that of 3. Inhibition studies using these synthetic analogues, includ ing the disulfide dimer 15, toward (2 --> 6)-alpha-sialyltransferase ( EC 2.4.99.1) revealed that the 6'-deoxy analogue 12 had remarkable inh ibitory activity as the first acceptor-analogue inhibitor for this enz yme. It is noteworthy that the disulfide 15 also behaves as an inhibit or. The results indicated that chemical modification at the 6'-positio n of 3 did not cause much decrease in the binding affinity to the sial yltransferase. Further, a novel possibility that the acceptor and the acceptor-analogue inhibitor can bind simultaneously to the sialyltrans ferase was proposed based on the inhibition studies with 12 and CMP.