Enzymes hydrolyzing organophosphates as potential catalytic scavengers against organophosphate poisoning

Patrick Masson, Denis Josse, Oksana Lockridge, Nathalie Viguié, Claire Taupin, Cyril Buhler

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Enzymes hydrolyzing organophosphates could be used as catalytic scavengers for treatment of organophosphate poisoning and for decontamination. Two organophosphorus hydrolases (OPH) were selected: the Flavobacterium sp/Pseudomonas diminuta phosphotriesterase (PTE) and human paraoxonase (HuPON). Genes encoding these enzymes were cloned and functional recombinant enzymes expressed. PTE was expressed in E. coli. Natural HuPON was purified from human plasma; recombinant HuPON was expressed in human embryonic kidney 293 T cells. Although HuPON displays interesting catalytic properties, a site-directed mutagenesis program was undertaken to improve its catalytic efficiency. PTE has high efficiency in hydrolysis of organophosphates, including nerve agents. PTE injected in rat has a half- life of 100 min. However, to overcome pharmacokinetic problems of injected OPH and/or immunological incompatibility, the model enzyme (recombinant PTE) was immobilized onto a hollow-fiber reactor. This reactor designed for extracorporeal blood circulation is under experimentation for post-exposure detoxification.

Original languageEnglish (US)
Pages (from-to)357-362
Number of pages6
JournalJournal of Physiology Paris
Volume92
Issue number5-6
DOIs
StatePublished - Jan 1 1998

Fingerprint

Phosphoric Triester Hydrolases
Organophosphate Poisoning
Aryldialkylphosphatase
Organophosphates
Enzymes
Immunological Models
Flavobacterium
Extracorporeal Circulation
Decontamination
Blood Circulation
Site-Directed Mutagenesis
Pseudomonas
Half-Life
Hydrolysis
Pharmacokinetics
Escherichia coli
T-Lymphocytes
Kidney
Genes

Keywords

  • Organophosphate poisoning
  • Organophosphorus hydrolase (OPH)
  • Paraoxonase (PON)
  • Phosphotriesterase (PTE)
  • Scavenger

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology (medical)

Cite this

Enzymes hydrolyzing organophosphates as potential catalytic scavengers against organophosphate poisoning. / Masson, Patrick; Josse, Denis; Lockridge, Oksana; Viguié, Nathalie; Taupin, Claire; Buhler, Cyril.

In: Journal of Physiology Paris, Vol. 92, No. 5-6, 01.01.1998, p. 357-362.

Research output: Contribution to journalArticle

Masson, Patrick ; Josse, Denis ; Lockridge, Oksana ; Viguié, Nathalie ; Taupin, Claire ; Buhler, Cyril. / Enzymes hydrolyzing organophosphates as potential catalytic scavengers against organophosphate poisoning. In: Journal of Physiology Paris. 1998 ; Vol. 92, No. 5-6. pp. 357-362.
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