title: N-Alkylated aziridines are easily-prepared, potent, specific and cell-permeable covalent inhibitors of human β-glucocerebrosidase.
abstract: β-Glucocerebrosidase deficiency leads to Gaucher disease and is a potential marker of Parkinson's disease. We have identified N-octyl conduritol aziridine as a potent and specific covalent inactivator of GBA1 in living cells. This compound is a promising lead towards a positron emission tomography probe intended to image GBA1 activity.
authors.affiliation: Thunder Bay Regional Research Institute, 290 Munro Street, Thunder Bay, Ontario, CanadaP7A 7T1. phenixc@tbh.net.
authors.forename: B T
authors.initials: BT
authors.lastname: Adams
authors.forename: S
authors.initials: S
authors.lastname: Niccoli
authors.forename: M A
authors.initials: MA
authors.lastname: Chowdhury
authors.forename: A N K
authors.initials: AN
authors.lastname: Esarik
authors.forename: S J
authors.initials: SJ
authors.lastname: Lees
authors.forename: B P
authors.initials: BP
authors.lastname: Rempel
authors.forename: C P
authors.initials: CP
authors.lastname: Phenix
mesh_terms: D000478:Alkylation; D001388:Aziridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005776:Gaucher Disease / Q000201:enzymology; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D050112:Imino Pyranoses / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007294:Inositol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010300:Parkinson Disease / Q000201:enzymology
chemical_list: D001388:Aziridines; D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; C060863:conduritol aziridine; D007294:Inositol; D005962:Glucosylceramidase