From covalent glycosidase inhibitors to activity-based glycosidase probes

Lianne I. Willems; Jianbing Jiang; Kah-Yee Li; Martin D. Witte; Wouter W. Kallemeijn; Thomas J.N. Beenakker; Sybrin P Schröder; Johannes M F G Aerts; Gijsbert A. Van Der Marel; Jeroen D C Codée; Hermen S. Overkleeft

doi:10.1002/chem.201404014

From covalent glycosidase inhibitors to activity-based glycosidase probes

Lianne I. Willems, Jianbing Jiang, Kah-Yee Li, Martin D. Witte, Wouter W. Kallemeijn, Thomas J.N. Beenakker, Sybrin P Schröder, Johannes M F G Aerts, Gijsbert A. Van Der Marel, Jeroen D C Codée, Hermen S. Overkleeft^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Activity-based protein profiling has emerged as a powerful discovery tool in chemical biology and medicinal chemistry research. Success of activity-based protein profiling hinges on the presence of compounds that can covalently and irreversibly bind to enzymes, do so selectively in the context of complex biological samples, and subsequently report on the selected pool of proteins. Such tagged molecules featuring an electrophilic trap, termed activity-based probes, have been developed with most success for serine hydrolases and various protease families (serine proteases, cysteine proteases, proteasomes). This concept presents the current progress and future directions in the design of activity-based probes targeting retaining glycosidases, enzymes that employ a double displacement mechanism in the hydrolysis of glycosidic bonds with overall retention. In contrast to inverting glycosidases, retaining glycosidases form a covalent intermediate with their substrates during the catalytic process and are therefore amenable to activity-based protein profiling studies.

Original language	English
Pages (from-to)	10864-10872
Number of pages	9
Journal	Chemistry : A European Journal
Volume	20
Issue number	35
DOIs	https://doi.org/10.1002/chem.201404014
Publication status	Published - 25 Aug 2014

Keywords

enzymes
glycobiology
glycosidases
protein profiling
proteins

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10.1002/chem.201404014

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title = "From covalent glycosidase inhibitors to activity-based glycosidase probes",

abstract = "Activity-based protein profiling has emerged as a powerful discovery tool in chemical biology and medicinal chemistry research. Success of activity-based protein profiling hinges on the presence of compounds that can covalently and irreversibly bind to enzymes, do so selectively in the context of complex biological samples, and subsequently report on the selected pool of proteins. Such tagged molecules featuring an electrophilic trap, termed activity-based probes, have been developed with most success for serine hydrolases and various protease families (serine proteases, cysteine proteases, proteasomes). This concept presents the current progress and future directions in the design of activity-based probes targeting retaining glycosidases, enzymes that employ a double displacement mechanism in the hydrolysis of glycosidic bonds with overall retention. In contrast to inverting glycosidases, retaining glycosidases form a covalent intermediate with their substrates during the catalytic process and are therefore amenable to activity-based protein profiling studies.",

keywords = "enzymes, glycobiology, glycosidases, protein profiling, proteins",

author = "Willems, {Lianne I.} and Jianbing Jiang and Kah-Yee Li and Witte, {Martin D.} and Kallemeijn, {Wouter W.} and Beenakker, {Thomas J.N.} and Schr{\"o}der, {Sybrin P} and Aerts, {Johannes M F G} and {Van Der Marel}, {Gijsbert A.} and Cod{\'e}e, {Jeroen D C} and Overkleeft, {Hermen S.}",

year = "2014",

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doi = "10.1002/chem.201404014",

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AU - Jiang, Jianbing

AU - Li, Kah-Yee

AU - Witte, Martin D.

AU - Kallemeijn, Wouter W.

AU - Beenakker, Thomas J.N.

AU - Schröder, Sybrin P

AU - Aerts, Johannes M F G

AU - Van Der Marel, Gijsbert A.

AU - Codée, Jeroen D C

AU - Overkleeft, Hermen S.

PY - 2014/8/25

Y1 - 2014/8/25

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AB - Activity-based protein profiling has emerged as a powerful discovery tool in chemical biology and medicinal chemistry research. Success of activity-based protein profiling hinges on the presence of compounds that can covalently and irreversibly bind to enzymes, do so selectively in the context of complex biological samples, and subsequently report on the selected pool of proteins. Such tagged molecules featuring an electrophilic trap, termed activity-based probes, have been developed with most success for serine hydrolases and various protease families (serine proteases, cysteine proteases, proteasomes). This concept presents the current progress and future directions in the design of activity-based probes targeting retaining glycosidases, enzymes that employ a double displacement mechanism in the hydrolysis of glycosidic bonds with overall retention. In contrast to inverting glycosidases, retaining glycosidases form a covalent intermediate with their substrates during the catalytic process and are therefore amenable to activity-based protein profiling studies.

KW - enzymes

KW - glycobiology

KW - glycosidases

KW - protein profiling

KW - proteins

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JO - Chemistry : A European Journal

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From covalent glycosidase inhibitors to activity-based glycosidase probes

Abstract

Keywords

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