Transition State-Based Sialyltransferase Inhibitors: Mimicking Oxocarbenium Ion by Simple Amide

In
the new transition-state based sialyltransferase inhibitors,
an amide group was placed at the corresponding C-2 position of CMP-sialic
acid to mimic the geometry and charge distribution in the transition
state, and simple aromatic or aliphatic rings were used instead of
the sialic acid moiety. All synthetic compounds exhibited excellent
α­(2-6)-sialyltransferase inhibition, resulting in up to a 2600-fold
higher affinity for the enzyme than CMP-Neu5Ac, suggesting that amide
is a key element for simulating transition-state features.