| Autor: |
Willems LI; Leiden Institute of Chemistry and The Netherlands Proteomics Centre, Leiden University , P.O. Box 9502, 2300 RA Leiden, The Netherlands., Beenakker TJ, Murray B, Scheij S, Kallemeijn WW, Boot RG, Verhoek M, Donker-Koopman WE, Ferraz MJ, van Rijssel ER, Florea BI, Codée JD, van der Marel GA, Aerts JM, Overkleeft HS |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2014 Aug 20; Vol. 136 (33), pp. 11622-5. Date of Electronic Publication: 2014 Aug 11. |
| DOI: |
10.1021/ja507040n |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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