1. Comparing Cyclophellitol N-Alkyl and N-Acyl Cyclophellitol Aziridines as Activity-Based Glycosidase Probes.
- Author
-
Jiang J, Beenakker TJ, Kallemeijn WW, van der Marel GA, van den Elst H, Codée JD, Aerts JM, and Overkleeft HS
- Subjects
- Animals, COS Cells, Cell Line, Chlorocebus aethiops, Electrophoresis, Polyacrylamide Gel, Aziridines chemistry, Cyclohexanols chemistry, Fluorescent Dyes chemistry, alpha-Glucosidases analysis, alpha-L-Fucosidase analysis, beta-Glucosidase analysis
- Abstract
The synthesis and evaluation as activity-based probes (ABPs) of three configurationally distinct, fluorescent N-alkyl cyclophellitol aziridine isosteres for profiling GH1 β-glucosidase (GBA), GH27 α-galactosidase (GLA) and GH29 α-fucosidase (FUCA) is described. In comparison with the corresponding acyl aziridine ABPs reported previously, the alkyl aziridine ABPs are synthesized easily and are more stable in mild acidic and basic media, and are thus easier to handle. The β-glucose-configured alkyl aziridine ABP proves equally effective in labeling GBA as its N-acyl counterpart, whereas the N-acyl aziridines targeting GLA and FUCA outperform their N-alkyl counterparts. Alkyl aziridines can therefore be an attractive alternative in retaining glycosidase ABP design, but in targeting a new retaining glycosidase both N-alkyl and N-acyl aziridines are best considered at the onset of a new study., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
- View/download PDF