title: Tuning the leaving group in 2-deoxy-2-fluoroglucoside results in improved activity-based retaining β-glucosidase probes.
abstract: The potency of 2-deoxy-2-fluoroglycosides in activity-based profiling of human acid β-glucosidase is drastically improved by introducing an N-phenyl trifluoroacetimidate leaving group at the anomeric center. Protonation by the general acid-base catalyst in the active site turned out to be a prerequisite, making the imidate probe a genuine mechanism-based glycosidase inactivator.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P. O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Marthe T C
authors.initials: MT
authors.lastname: Walvoort
authors.forename: Wouter W
authors.initials: WW
authors.lastname: Kallemeijn
authors.forename: Lianne I
authors.initials: LI
authors.lastname: Willems
authors.forename: Martin D
authors.initials: MD
authors.lastname: Witte
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Jeroen D C
authors.initials: JD
authors.lastname: Codée
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000378:metabolism; D005463:Fluoroacetates / Q000737:chemistry* / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D001617:beta-Glucosidase / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000081:Acetamides; D005463:Fluoroacetates; D006027:Glycosides; D015335:Molecular Probes; D001617:beta-Glucosidase