Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase

Lawrence M Schopfer, Troy Voelker, Cynthia F. Bartels, Charles M. Thompson, Oksana Lockridge

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 × 107 M-1 min-1, and for human BChE, it was 1.6 × 108 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.

Original languageEnglish (US)
Pages (from-to)747-754
Number of pages8
JournalChemical Research in Toxicology
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2005

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Butyrylcholinesterase
Acetylcholinesterase
Reaction kinetics
Stereoisomerism
Organophosphates
Cholinesterases
Biomarkers
Chloroform
Phosphorus
Methanol
Rate constants
10-(fluoroethoxyphosphinyl)-N-(biotinamidopentyl)decanamide
Water
Proteins

ASJC Scopus subject areas

  • Toxicology

Cite this

Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase. / Schopfer, Lawrence M; Voelker, Troy; Bartels, Cynthia F.; Thompson, Charles M.; Lockridge, Oksana.

In: Chemical Research in Toxicology, Vol. 18, No. 4, 01.04.2005, p. 747-754.

Research output: Contribution to journalArticle

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