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利用光诱导电子转移测定亚氨基糖-酶复合物的质子化状态

Determination of protonation states of iminosugar-enzyme complexes using photoinduced electron transfer.

作者信息

Wang Bo, Olsen Jacob Ingemar, Laursen Bo W, Navarro Poulsen Jens Christian, Bols Mikael

机构信息

Department of Chemistry , University of Copenhagen , Universitetsparken 5 , DK-2100 Copenhagen Ø , Denmark . Email:

出版信息

Chem Sci. 2017 Nov 1;8(11):7383-7393. doi: 10.1039/c7sc01540b. Epub 2017 Sep 14.

DOI:10.1039/c7sc01540b
PMID:29163889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5672842/
Abstract

A series of -alkylated analogues of 1-deoxynojirimycin containing a fluorescent 10-chloro-9-anthracene group in the -alkyl substituent were prepared. The anthracene group acted as a reporting group for protonation at the nitrogen in the iminosugar because an unprotonated amine was found to quench fluorescence by photoinduced electron transfer. The new compounds were found to inhibit β-glucosidase from and α-glucosidase from , with values in the low micro- to nanomolar range. Fluorescence and inhibition pH studies of the β-glucosidase-iminosugar complexes revealed that the amino group in the inhibitor is unprotonated when bound, while one of the active site carboxylates is protonated.

摘要

制备了一系列1-脱氧野尻霉素的β-烷基化类似物，其β-烷基取代基中含有一个荧光10-氯-9-蒽基团。蒽基团作为亚氨基糖中氮原子质子化的报告基团，因为发现未质子化的胺通过光诱导电子转移淬灭荧光。发现这些新化合物可抑制来自[具体来源1]的β-葡萄糖苷酶和来自[具体来源2]的α-葡萄糖苷酶，IC50值在低微摩尔至纳摩尔范围内。对β-葡萄糖苷酶-亚氨基糖复合物的荧光和抑制pH研究表明，抑制剂中的氨基在结合时未质子化，而活性位点的一个羧酸盐质子化。

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