New Class of Glycoside Hydrolase Mechanism-Based Covalent Inhibitors: Glycosylation Transition State Conformations

被引：20

作者：

Abadi, Saeideh Shamsi Kazem ^{[1
]}

Tran, Michael ^{[2
]}

Yadav, Anuj K. ^{[2
]}

Adabala, Pal John Pal ^{[2
]}

Chaldadar, Saswati ^{[2
]}

Bennet, Andrew J. ^{[2
]}

机构：

[1] Simon Fraser Univ, Dept Biochem & Mol Biol, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada

[2] Simon Fraser Univ, Dept Chem, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2017年 / 139卷 / 31期

基金：

加拿大自然科学与工程研究理事会;

关键词：

ACTIVITY-BASED PROBES; ALPHA; CYCLOPROPYLCARBINYL; GLUCOSIDASE; DERIVATIVES; HYDROLYSIS; STABILITY; CHEMISTRY; CATALYSIS; ENZYMES;

D O I：

10.1021/jacs.7b05065

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The design of covalent inhibitors in glycoscience research is important for the development of chemical biology probes. Here we report the synthesis of a new carbocyclic mechanism-based covalent inhibitor of an alpha-glucosidase. The enzyme efficiently catalyzes its alkylation via either an allylic cation or a cationic transition state. We show this allylic covalent inhibitor has different catalytic proficiencies for pseudoglycosylation and deglycosylation. Such inhibitors have the potential to be useful chemical biology tools.

引用

收藏

页码：10625 / 10628

页数：4

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