TY - JOUR
T1 - Synthesis and inhibitory activity of oligosaccharide thiazolines as a class of mechanism-based inhibitors for endo-β-N-acetylglucosaminidases
AU - Li, Bing
AU - Takegawa, Kaoru
AU - Suzuki, Tadashi
AU - Yamamoto, Kenji
AU - Wang, Lai Xi
N1 - Funding Information:
The work was supported by the National Institutes of Health (R01 GM073717 and R01 GM080374).
PY - 2008/4/15
Y1 - 2008/4/15
N2 - A facile synthesis of oligosaccharide-thiazoline derivatives of N-glycans as a novel class of inhibitors for endo-β-N-acetylglucosaminidases was described. It was found that the external sugar residues on the N-glycan core could enhance the inhibitory potency. While the Manβ1,4GlcNAc- and Man3GlcNAc-thiazolines were only moderate inhibitors, the large Man9GlcNAc-thiazoline demonstrated potent inhibitory activity, with an IC50 of 0.22 and 0.42 μM against the Arthrobacter enzyme (Endo-A) and the human endo-β-N-acetylglycosaminidase (hENGase), respectively. It was also observed that the oligosaccharide thiazolines could differentially inhibit endo-β-N-acetylglucosaminidases from different sources. These oligosaccharide thiazolines represent the first class of endo-β-N-acetylglucosaminidase inhibitors.
AB - A facile synthesis of oligosaccharide-thiazoline derivatives of N-glycans as a novel class of inhibitors for endo-β-N-acetylglucosaminidases was described. It was found that the external sugar residues on the N-glycan core could enhance the inhibitory potency. While the Manβ1,4GlcNAc- and Man3GlcNAc-thiazolines were only moderate inhibitors, the large Man9GlcNAc-thiazoline demonstrated potent inhibitory activity, with an IC50 of 0.22 and 0.42 μM against the Arthrobacter enzyme (Endo-A) and the human endo-β-N-acetylglycosaminidase (hENGase), respectively. It was also observed that the oligosaccharide thiazolines could differentially inhibit endo-β-N-acetylglucosaminidases from different sources. These oligosaccharide thiazolines represent the first class of endo-β-N-acetylglucosaminidase inhibitors.
UR - http://www.scopus.com/inward/record.url?scp=42149195630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42149195630&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2008.02.032
DO - 10.1016/j.bmc.2008.02.032
M3 - Article
C2 - 18304822
AN - SCOPUS:42149195630
SN - 0968-0896
VL - 16
SP - 4670
EP - 4675
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 8
ER -