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

共 37 条

[1] Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring [J].

Aguilar-Moncayo, Matilde ;

Gloster, Tracey M. ;

Turkenburg, Johan P. ;

Isabel Garcia-Moreno, M. ;

Ortiz Mellet, Carmen ;

Davies, Gideon J. ;

Garcia Fernandez, Jose M. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2009, 7 (13) :2738-2747

[2]

[Anonymous], 2007, IMINOSUGARS SYNTHESI

[3]

BENTILFA M, 2008, BIOORG MED CHEM LETT, V18, P2805

[4]

Bisson AP, 1998, CHEM-EUR J, V4, P845, DOI 10.1002/(SICI)1521-3765(19980515)4:5<845::AID-CHEM845>3.3.CO

[5]

2-R

[6] Synthesis and recognition properties of aromatic amide oligomers: Molecular zippers [J].

Bisson, AP ;

Carver, FJ ;

Eggleston, DS ;

Haltiwanger, RC ;

Hunter, CA ;

Livingstone, DL ;

McCabe, JF ;

Rotger, C ;

Rowan, AE .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (37) :8856-8868

[7]

Blanco JLJ, 1997, CHEM COMMUN, P1969

[8] 1-aza sugars, apparent transition state analogues of equatorial glycoside formation/cleavage [J].

Bols, M .

ACCOUNTS OF CHEMICAL RESEARCH, 1998, 31 (01) :1-8

[9] 6-Amino-6-deoxy-5,6-di-N-(N′-octyliminomethylidene)nojirimycin: Synthesis, Biological Evaluation, and Crystal Structure in Complex with Acid β-Glucosidase [J].

Brumshtein, Boris ;

Aguilar-Moncayo, Matilde ;

Isabel Garcia-Moreno, M. ;

Ortiz Mellet, Carmen ;

Garcia Fernandez, Jose M. ;

Silman, Israel ;

Shaaltiel, Yoseph ;

Aviezer, David ;

Sussman, Joel L. ;

Futerman, Anthony H. .

CHEMBIOCHEM, 2009, 10 (09) :1480-1485

[10] Pharmacotherapeutic strategies using small molecules for the treatment of glycolipid lysosomal storage disorders [J].

Butters, Terry D. .

EXPERT OPINION ON PHARMACOTHERAPY, 2007, 8 (04) :427-435

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