Systematic syntheses and inhibitory activities of bisubstrate-type inhibitors of sialyltransferases.
Bisubstrate-type sialyltransferase inhibitors 1/2a-e, having CMP-NeuAc and N-acetyllactosamine (or lactose) moieties connected by an alkanedithiol linker, were synthesized systematically. A uniform synthetic strategy was adopted that consists of consecutive couplings of three components (N-acetyllactosamine or lactose, sialic acid, and CMP), followed by oxidation. Due to the sensitivity of the compounds under alkaline conditions, final deprotection required careful monitoring by (1)H NMR. The inhibitory activities of 1/2a-e toward ST6N and ST3N indicated that both the structure of the acceptor moiety and the distance between donor and acceptor moieties were important.
Hinou
Hiroshi
H
RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Sun
Xue-Long
XL
Ito
Yukishige
Y
D000606:Amino Sugars / Q000737:chemistry; D003432:Cross-Linking Reagents; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000737:chemistry; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D012799:Sialyltransferases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000606:Amino Sugars; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; C000458:N-acetyllactosamine; D012799:Sialyltransferases