Dataset Information

Detection of Active Mammalian GH31 ?-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes.

ABSTRACT: The development of small molecule activity-based probes (ABPs) is an evolving and powerful area of chemistry. There is a major need for synthetically accessible and specific ABPs to advance our understanding of enzymes in health and disease. ?-Glucosidases are involved in diverse physiological processes including carbohydrate assimilation in the gastrointestinal tract, glycoprotein processing in the endoplasmic reticulum (ER), and intralysosomal glycogen catabolism. Inherited deficiency of the lysosomal acid ?-glucosidase (GAA) causes the lysosomal glycogen storage disorder, Pompe disease. Here, we design a synthetic route for fluorescent and biotin-modified ABPs for in vitro and in situ monitoring of ?-glucosidases. We show, through mass spectrometry, gel electrophoresis, and X-ray crystallography, that ?-glucopyranose configured cyclophellitol aziridines label distinct retaining ?-glucosidases including GAA and ER ?-glucosidase II, and that this labeling can be tuned by pH. We illustrate a direct diagnostic application in Pompe disease patient cells, and discuss how the probes may be further exploited for diverse applications.

SUBMITTER: Jiang J

PROVIDER: S-EPMC4882745 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Detection of Active Mammalian GH31 α-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes.

Jiang Jianbing J Kuo Chi-Lin CL Wu Liang L Franke Christian C Kallemeijn Wouter W WW Florea Bogdan I BI van Meel Eline E van der Marel Gijsbert A GA Codée Jeroen D C JD Boot Rolf G RG Davies Gideon J GJ Overkleeft Herman S HS Aerts Johannes M F G JM

ACS central science 20160426 5

The development of small molecule activity-based probes (ABPs) is an evolving and powerful area of chemistry. There is a major need for synthetically accessible and specific ABPs to advance our understanding of enzymes in health and disease. α-Glucosidases are involved in diverse physiological processes including carbohydrate assimilation in the gastrointestinal tract, glycoprotein processing in the endoplasmic reticulum (ER), and intralysosomal glycogen catabolism. Inherited deficiency of the l ...[more]

PMID: 27280170

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Dataset Information

Detection of Active Mammalian GH31 ?-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes.

Publications

Detection of Active Mammalian GH31 α-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes.

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