Potent and selective activity-based probes for GH27 human retaining α-galactosidases

Lianne I. Willems; Thomas J. M. Beenakker; Benjamin Murray; Saskia Scheij; Wouter W. Kallemeijn; Rolf G. Boot; Marri Verhoek; Wilma E. Donker-Koopman; Maria J. Ferraz; Erwin R. van Rijssel; Bogdan I. Florea; Jeroen D. C. Codée; Gijsbert A. van der Marel; Johannes M. F. G. Aerts; Herman S. Overkleeft

doi:10.1021/ja507040n

Potent and selective activity-based probes for GH27 human retaining α-galactosidases

Lianne I. Willems, Thomas J. M. Beenakker, Benjamin Murray, Saskia Scheij, Wouter W. Kallemeijn, Rolf G. Boot, Marri Verhoek, Wilma E. Donker-Koopman, Maria J. Ferraz, Erwin R. van Rijssel, Bogdan I. Florea, Jeroen D. C. Codée, Gijsbert A. van der Marel, Johannes M. F. G. Aerts, Herman S. Overkleeft

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

48 Citations (Scopus)

Abstract

Lysosomal degradation of glycosphingolipids is mediated by the consecutive action of several glycosidases. Malfunctioning of one of these hydrolases can lead to a lysosomal storage disorder such as Fabry disease, which is caused by a deficiency in α-galactosidase A. Herein we describe the development of potent and selective activity-based probes that target retaining α-galactosidases. The fluorescently labeled aziridine-based probes 3 and 4 inhibit the two human retaining α-galactosidases αGal A and αGal B covalently and with high affinity. Moreover, they enable the visualization of the endogenous activity of both α-galactosidases in cell extracts, thereby providing a means to study the presence and location of active enzyme levels in different cell types, such as healthy cells versus those derived from Fabry patients

Original language	English
Pages (from-to)	11622-11625
Journal	Journal of the American Chemical Society
Volume	136
Issue number	33
DOIs	https://doi.org/10.1021/ja507040n
Publication status	Published - 2014

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10.1021/ja507040n

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Willems, L. I., Beenakker, T. J. M., Murray, B., Scheij, S., Kallemeijn, W. W., Boot, R. G., Verhoek, M., Donker-Koopman, W. E., Ferraz, M. J., van Rijssel, E. R., Florea, B. I., Codée, J. D. C., van der Marel, G. A., Aerts, J. M. F. G., & Overkleeft, H. S. (2014). Potent and selective activity-based probes for GH27 human retaining α-galactosidases. Journal of the American Chemical Society, 136(33), 11622-11625. https://doi.org/10.1021/ja507040n

@article{d2a5f8755f90410b95c71b720fbe85d0,

title = "Potent and selective activity-based probes for GH27 human retaining α-galactosidases",

abstract = "Lysosomal degradation of glycosphingolipids is mediated by the consecutive action of several glycosidases. Malfunctioning of one of these hydrolases can lead to a lysosomal storage disorder such as Fabry disease, which is caused by a deficiency in α-galactosidase A. Herein we describe the development of potent and selective activity-based probes that target retaining α-galactosidases. The fluorescently labeled aziridine-based probes 3 and 4 inhibit the two human retaining α-galactosidases αGal A and αGal B covalently and with high affinity. Moreover, they enable the visualization of the endogenous activity of both α-galactosidases in cell extracts, thereby providing a means to study the presence and location of active enzyme levels in different cell types, such as healthy cells versus those derived from Fabry patients",

author = "Willems, {Lianne I.} and Beenakker, {Thomas J. M.} and Benjamin Murray and Saskia Scheij and Kallemeijn, {Wouter W.} and Boot, {Rolf G.} and Marri Verhoek and Donker-Koopman, {Wilma E.} and Ferraz, {Maria J.} and {van Rijssel}, {Erwin R.} and Florea, {Bogdan I.} and Cod{\'e}e, {Jeroen D. C.} and {van der Marel}, {Gijsbert A.} and Aerts, {Johannes M. F. G.} and Overkleeft, {Herman S.}",

year = "2014",

doi = "10.1021/ja507040n",

language = "English",

volume = "136",

pages = "11622--11625",

journal = "Journal of the American Chemical Society",

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publisher = "American Chemical Society",

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Willems, LI, Beenakker, TJM, Murray, B, Scheij, S, Kallemeijn, WW, Boot, RG, Verhoek, M, Donker-Koopman, WE, Ferraz, MJ, van Rijssel, ER, Florea, BI, Codée, JDC, van der Marel, GA, Aerts, JMFG & Overkleeft, HS 2014, 'Potent and selective activity-based probes for GH27 human retaining α-galactosidases', Journal of the American Chemical Society, vol. 136, no. 33, pp. 11622-11625. https://doi.org/10.1021/ja507040n

TY - JOUR

T1 - Potent and selective activity-based probes for GH27 human retaining α-galactosidases

AU - Willems, Lianne I.

AU - Beenakker, Thomas J. M.

AU - Murray, Benjamin

AU - Scheij, Saskia

AU - Kallemeijn, Wouter W.

AU - Boot, Rolf G.

AU - Verhoek, Marri

AU - Donker-Koopman, Wilma E.

AU - Ferraz, Maria J.

AU - van Rijssel, Erwin R.

AU - Florea, Bogdan I.

AU - Codée, Jeroen D. C.

AU - van der Marel, Gijsbert A.

AU - Aerts, Johannes M. F. G.

AU - Overkleeft, Herman S.

PY - 2014

Y1 - 2014

N2 - Lysosomal degradation of glycosphingolipids is mediated by the consecutive action of several glycosidases. Malfunctioning of one of these hydrolases can lead to a lysosomal storage disorder such as Fabry disease, which is caused by a deficiency in α-galactosidase A. Herein we describe the development of potent and selective activity-based probes that target retaining α-galactosidases. The fluorescently labeled aziridine-based probes 3 and 4 inhibit the two human retaining α-galactosidases αGal A and αGal B covalently and with high affinity. Moreover, they enable the visualization of the endogenous activity of both α-galactosidases in cell extracts, thereby providing a means to study the presence and location of active enzyme levels in different cell types, such as healthy cells versus those derived from Fabry patients

AB - Lysosomal degradation of glycosphingolipids is mediated by the consecutive action of several glycosidases. Malfunctioning of one of these hydrolases can lead to a lysosomal storage disorder such as Fabry disease, which is caused by a deficiency in α-galactosidase A. Herein we describe the development of potent and selective activity-based probes that target retaining α-galactosidases. The fluorescently labeled aziridine-based probes 3 and 4 inhibit the two human retaining α-galactosidases αGal A and αGal B covalently and with high affinity. Moreover, they enable the visualization of the endogenous activity of both α-galactosidases in cell extracts, thereby providing a means to study the presence and location of active enzyme levels in different cell types, such as healthy cells versus those derived from Fabry patients

U2 - 10.1021/ja507040n

DO - 10.1021/ja507040n

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SN - 0002-7863

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SP - 11622

EP - 11625

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

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