title: Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase.
abstract: A biotinylated organophosphate could be useful for identifying proteins that react with organophosphorus toxicants (OP). FP-biotin, 10-(fluoroethoxyphosphinyl)-N-(biotinamidopentyl)decanamide, was synthesized and found to be stable in methanol and chloroform but less stable in water. Because acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) are known to be sensitive targets of OP, their reactivity with FP-biotin was tested. The rate constant for reaction with human AChE was 1.8 x 10(7) M(-1) min(-1), and for human BChE, it was 1.6 x 10(8) M(-1) min(-1). A phosphorus stereoisomer, constituting about 50% of the FP-biotin preparation, appeared to be the reactive species. The binding affinity was estimated to be >85 nM for AChE and >5.8 nM for BChE. It was concluded that FP-biotin is a potent OP, well-suited for searching for new biomarkers of OP exposure.
authors.affiliation: Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA. lmschopf@unmc.edu
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Schopfer
authors.forename: Troy
authors.initials: T
authors.lastname: Voelker
authors.forename: Cynthia F
authors.initials: CF
authors.lastname: Bartels
authors.forename: Charles M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Oksana
authors.initials: O
authors.lastname: Lockridge
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity
chemical_list: C403065:10-(fluoroethoxyphosphinyl)-N-(biotinamidopentyl)decanamide; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D001710:Biotin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase