alpha-Glucopyranoimidazolines as intermediate analogue inhibitors of family 20 beta-N-acetylglucosaminidases.
The alpha-glucopyranoimidazolines, 2-methyl-(1,2-dideoxy-alpha-d-glucopyrano)[2,1-d]-1-imidazolines 1 and 2, have been synthesized and evaluated as inhibitors of beta-N-acetylglucosaminidases (NAGs). Compounds 1 and 2, mimicking the oxazolinium ion intermediate in enzyme catalysis, served as potent and competitive inhibitors of family 20 NAGs with K(i) as low as 0.1 microM, but showed no inhibitory activities toward family 3 NAGs. Due to structural and electrostatic resemblance to the oxazolinium ion intermediate, the alpha-glucopyranoimidazolines may lead to novel and selective inhibitors of mechanistically related glycosidases such as family 18 chitinases.
Kato
Masahiro
M
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
Uno
Tetsuya
T
Hiratake
Jun
J
Sakata
Kanzo
K
D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048288:Imidazolines / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
D004791:Enzyme Inhibitors; D048288:Imidazolines; D000118:Acetylglucosaminidase