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
收藏
页码：7439 / 7445
页数：7
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