In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 α-l-fucosidases† †Electronic supplementary information (ESI) available: Experimental part including synthesis procedures, characterization data, copies of NMR spectra of new compounds, supporting biological figures and crystallographic information. See DOI: 10.1039/c4sc03739a
| Autor: | Jiang, Jianbing, Kallemeijn, Wouter W., Wright, Daniel W., van den Nieuwendijk, Adrianus M. C. H., Rohde, Veronica Coco, Folch, Elisa Colomina, van den Elst, Hans, Florea, Bogdan I., Scheij, Saskia, Donker-Koopman, Wilma E., Verhoek, Marri, Li, Nan, Schürmann, Martin, Mink, Daniel, Boot, Rolf G., Codée, Jeroen D. C., van der Marel, Gijsbert A., Davies, Gideon J., Aerts, Johannes M. F. G., Overkleeft, Herman S. |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6539 2041-6520 |
| Popis: | Development of probes for active GH29 α-l-fucosidases. GH29 α-l-fucosidases catalyze the hydrolysis of α-l-fucosidic linkages. Deficiency in human lysosomal α-l-fucosidase (FUCA1) leads to the recessively inherited disorder, fucosidosis. Herein we describe the development of fucopyranose-configured cyclophellitol aziridines as activity-based probes (ABPs) for selective in vitro and in vivo labeling of GH29 α-l-fucosidases from bacteria, mice and man. Crystallographic analysis on bacterial α-l-fucosidase confirms that the ABPs act by covalent modification of the active site nucleophile. Competitive activity-based protein profiling identified l-fuconojirimycin as the single GH29 α-l-fucosidase inhibitor from eight configurational isomers. |
| Databáze: | OpenAIRE |
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