Enzymes hydrolyzing organophosphates as potential catalytic scavengers against organophosphate poisoning

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

doi:10.1016/S0928-4257(99)80005-9

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 journal › Article › peer-review

70 Scopus citations

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 language	English (US)
Pages (from-to)	357-362
Number of pages	6
Journal	Journal of Physiology Paris
Volume	92
Issue number	5-6
DOIs	https://doi.org/10.1016/S0928-4257(99)80005-9
State	Published - 1998

Keywords

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

ASJC Scopus subject areas

Neuroscience(all)
Physiology (medical)

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10.1016/S0928-4257(99)80005-9

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title = "Enzymes hydrolyzing organophosphates as potential catalytic scavengers against organophosphate poisoning",

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.",

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author = "Patrick Masson and Denis Josse and Oksana Lockridge and Nathalie Vigui{\'e} and Claire Taupin and Cyril Buhler",

note = "Funding Information: Supported by the Service de Sante des ArmCes (France) and by grants from the Direction des Systemes de Forces et de la Prospective (DRET No 96/02 and 97/08).",

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AU - Taupin, Claire

AU - Buhler, Cyril

N1 - Funding Information: Supported by the Service de Sante des ArmCes (France) and by grants from the Direction des Systemes de Forces et de la Prospective (DRET No 96/02 and 97/08).

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N2 - 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.

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Enzymes hydrolyzing organophosphates as potential catalytic scavengers against organophosphate poisoning

Abstract

Keywords

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