Fluorescent-tagged sp2-iminosugars with potent β-glucosidase inhibitory activity

被引：20

作者：

Aguilar-Moncayo, Matilde ^{[2
]}

Garcia-Moreno, M. Isabel ^{[2
]}

Stuetz, Arnold E. ^{[1
]}

Fernandez, Jose M. Garcia ^{[3
]}

Wrodnigg, Tanja M. ^{[1
]}

Mellet, Carmen Ortiz ^{[2
]}

机构：

[1] Graz Univ Technol, Glycogrp, Inst Organ Chem, A-8010 Graz, Austria

[2] Univ Seville, Fac Quim, Dept Quim Organ, E-41012 Seville, Spain

[3] Univ Seville, CSIC, Inst Invest Quim, E-41092 Seville, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 21期

关键词：

Glycosidase inhibitors; Fluorescence resonance energy transfer (FRET); Iminosugars; Photolabeling; GLYCOSIDASE; GLYCOMIMETICS; INDOLIZIDINE; STRATEGIES; ANALOGS;

D O I：

10.1016/j.bmc.2010.09.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

New fluorescently-labelled sp(2)-iminosugars based on the 5N,6S-[N'-(4-aminobutyl)iminomethylidene]-6-thionojirimycin skeleton have been synthesized as photoprobes to monitor glycosidase binding. Dansyl, dapoxyl and coumarin fluorophores were appended to the terminal amino group at the N'-substituent by either sulfonamide or amide bridging reaction. All the conjugates behaved as strong (low micromolar to nanomolar) and selective inhibitors of beta-glucosidases (almonds and bovine liver) and naringinase, in agreement with the inhibition pattern previously encountered for related iso(thio)urea-type bicyclic sp(2)-iminosugars. The presence of the fluorescent probe allows real-time and continuous monitoring of beta-glucosidase inhibition by fluorescence resonance energy transfer (FRET), taking advantage of the intrinsic tryptophan-associated fluorescence of the protein. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7439 / 7445

页数：7

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