Nanomolar affinity, iminosugar-based chemical probes for specific labeling of lysosomal glucocerebrosidase

被引：25

作者：

van Scherpenzeel, Monique ^{[1
]}

van den Berg, Richard J. B. H. N. ^{[2
]}

Donker-Koopman, Wilma E. ^{[3
]}

Liskamp, Rob M. J. ^{[1
]}

Aerts, Johannes M. F. G. ^{[3
]}

Overkleeft, Herman S. ^{[2
]}

Pieters, Roland J. ^{[1
]}

机构：

[1] Univ Utrecht, Dept Med Chem & Chem Biol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands

[2] Leiden Univ, Gorlaeus Labs, Dept Bioorgan Synth, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands

[3] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 01期

关键词：

Glucosidases; Proteomics probes; Photolabeling; BETA-GLUCOSIDASE; GAUCHER-DISEASE; PROTEIN IDENTIFICATION; MASS-SPECTROMETRY; GALECTIN-3; INHIBITORS; GLYCOSIDASES; MECHANISM; DEOXYNOJIRIMYCIN; PROTEOMICS;

D O I：

10.1016/j.bmc.2009.10.060

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：

Three different photoprobes were synthesized to label beta-glucosidases; one probe was based on glucose, two probes on the iminosugar deoxynojirimycin. The affinity of the probes for three different beta-glucosidases was determined. Furthermore, their labeling efficiencies, binding specificities through competition with deoxynojirimycin, and binding specificities in the presence of cell lysate, were evaluated. Especially one showed very high affinity towards non-lysosomal glucoceramidase (IC50 = 20 nM). (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：267 / 273

页数：7

共 34 条

[1] PATHOGENESIS OF LYSOSOMAL STORAGE DISORDERS AS ILLUSTRATED BY GAUCHER DISEASE [J].