title: Comparing Cyclophellitol N-Alkyl and N-Acyl Cyclophellitol Aziridines as Activity-Based Glycosidase Probes.
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.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands).
authors.forename: Jianbing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands).
authors.forename: Thomas J M
authors.initials: TJ
authors.lastname: Beenakker
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands).
authors.forename: Wouter W
authors.initials: WW
authors.lastname: Kallemeijn
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands).
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands).
authors.forename: Hans
authors.initials: H
authors.lastname: van den Elst
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands).
authors.forename: Jeroen D C
authors.initials: JD
authors.lastname: Codée
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands).
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA Leiden (The Netherlands). h.s.overkleeft@chem.leidenuniv.nl.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
mesh_terms: D000818:Animals; D001388:Aziridines / Q000737:chemistry*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003511:Cyclohexanols / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005456:Fluorescent Dyes / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000032:analysis*; D005644:alpha-L-Fucosidase / Q000032:analysis*; D001617:beta-Glucosidase / Q000032:analysis*
chemical_list: D001388:Aziridines; D003511:Cyclohexanols; D005456:Fluorescent Dyes; C063285:cyclophellitol; C033132:aziridine; D000520:alpha-Glucosidases; D001617:beta-Glucosidase; D005644:alpha-L-Fucosidase
keywords: activity-based protein profiling; aziridine; biological activity; chemical biology; glycosidases