1312592-18-9Relevant academic research and scientific papers
Design and synthesis of O-GlcNAcase inhibitors via 'click chemistry' and biological evaluations
Li, Tiehai,Guo, Lina,Zhang, Yan,Wang, Jiajia,Li, Zhonghua,Lin, Lin,Zhang, Zhenxing,Li, Lei,Lin, Jianping,Zhao, Wei,Li, Jing,Wang, Peng George
, p. 1083 - 1092 (2011/06/22)
Protein O-GlcNAcylation has been shown to play an important role in a number of biological processes, including regulation of the cell cycle, DNA transcription and translation, signal transduction, and protein degradation. O-GlcNAcase (OGA) is responsible for the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from serine or threonine residues, and thus plays a key role in O-GlcNAc metabolism. Potent OGA inhibitors are useful tools for studying the cellular processes of O-GlcNAc, and may be developed as drugs for the treatment neurodegenerative diseases. In this study, Cu(I)-catalyzed 'Click' cycloaddition reactions between glycosyl azides and alkynes were exploited to generate inhibitory candidates of OGA. Enzymatic kinetic screening revealed that compound 7 was a potent competitive inhibitor of human O-GlcNAcase (Ki = 185.6 μM). Molecular docking simulations of compound 7 into CpOGA (Clostridium perfringens OGA) suggested that strong π-π stacking interaction between the compound and W490 considerably contributed to improving the inhibitory activity. Crown Copyright
