Synthesis and inhibitory activity of oligosaccharide thiazolines as a class of mechanism-based inhibitors for endo-β-N-acetylglucosaminidases
- 作者：Bing Li ; Kaoru Takegawa ; Tadashi Suzuki ; Kenji Yamamoto ; Lai-Xi Wang
- 关键词：Oligosaccharide thiazoline ; Endoglycosidase ; endo-β ; -N-Acetylglucosaminidase ; Sugar oxazoline ; Transition state analog ; Enzyme inhibitor
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 April 2008
- 卷：16
- 期：8
- 页码：4670-4675
- 文件大小：523 K
摘要
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.