title: Organophosphorus hydrolase as an in vivo catalytic nerve agent bioscavenger.
abstract: The use of proteins as a treatment for organophosphorus intoxication has been investigated since A. R. Main demonstrated protective efficacy against parathion with an exogenously administered arylesterase in the late 1950s. His experiments spurred over 60 years of research and progress in the development of enzymes as potential bioscavengers of nerve agents and pesticides. Efforts have been made to broaden the specificity of enzymes to make a universal scavenger that would protect against multiple compounds, and an understanding of the differential isomer toxicity of these compounds has provided the impetus for rational and random mutagenic approaches in the stereospecific design of enzymes. As improved candidate enzymes are continually developed, our understanding of the contributions of the catalytic parameters (k(cat) , K(M) and catalytic efficiency) to efficacy expands. In addition to the scavenging properties of the proteins, another important aspect of development is the pharmacokinetic profile of the drug product. Immunogenicity, absorption, distribution and elimination contribute significantly to the level of protection afforded by the protein. A review of the development of organophosphorus hydrolase (OPH) for use as in vivo catalytic bioscavengers is presented here.
authors.affiliation: Department of Biochemistry & Biophysics, Texas A&M University, College Station, TX 77842, USA. m-wales@tamu.edu
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Wales
authors.forename: Tony E
authors.initials: TE
authors.lastname: Reeves
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D006801:Humans; D009943:Organophosphorus Compounds / Q000633:toxicity*
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D043303:Aryldialkylphosphatase