Departments of Biochemistry and Molecular Biology, and ‡Chemistry, Simon Fraser University , 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada.
J Am Chem Soc. 2017 Aug 9;139(31):10625-10628. doi: 10.1021/jacs.7b05065. Epub 2017 Jul 26.
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 α-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.
在糖科学研究中，共价抑制剂的设计对于化学生物学探针的发展非常重要。在这里，我们报告了一种新型碳环基于机制的α-葡萄糖苷酶共价抑制剂的合成。该酶通过烯丙基阳离子或正离子过渡态有效地催化其烷基化。我们表明，这种烯丙基共价抑制剂对假糖基化和去糖基化具有不同的催化效率。这些抑制剂有可能成为有用的化学生物学工具。
