Synthesis and inhibitory activity of oligosaccharide thiazolines as a class of mechanism-based inhibitors for endo-beta-N-acetylglucosaminidases.
A facile synthesis of oligosaccharide-thiazoline derivatives of N-glycans as a novel class of inhibitors for endo-beta-N-acetylglucosaminidases was described. It was found that the external sugar residues on the N-glycan core could enhance the inhibitory potency. While the Manbeta1,4GlcNAc- and Man3GlcNAc-thiazolines were only moderate inhibitors, the large Man9GlcNAc-thiazoline demonstrated potent inhibitory activity, with an IC(50) of 0.22 and 0.42 microM against the Arthrobacter enzyme (Endo-A) and the human endo-beta-N-acetylglycosaminidase (hENGase), respectively. It was also observed that the oligosaccharide thiazolines could differentially inhibit endo-beta-N-acetylglucosaminidases from different sources. These oligosaccharide thiazolines represent the first class of endo-beta-N-acetylglucosaminidase inhibitors.
Li
Bing
B
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Takegawa
Kaoru
K
Suzuki
Tadashi
T
Yamamoto
Kenji
K
Wang
Lai-Xi
LX
D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D013844:Thiazoles; D000118:Acetylglucosaminidase