Hydrolysis of organophosphorus nerve agent soman by the monoclonal antibodies elicited against an oxyphosphorane hapten

Acta Chem Scand (Cph). 1999 Jul;53(7):473-9. doi: 10.3891/acta.chem.scand.53-0473.

Abstract

The antibody-mediated hydrolysis of the nerve agent O-1,2,2-trimethylpropyl methylphosphonofluoridate (soman) 1 has now been established with two monoclonal antibodies raised against the cyclic pentacovalent methyloxyphosphorane hapten 10 that mimics the pentacoordinated trigonal bipyramidal transition-state of the reaction. The hydrolysis reaction was studied using molecular orbital methods at the MP2/6-31 + G*/(/)HF/6-31 + G* level of accuracy. According to the ab initio calculations, the reaction seems to proceed via three separate transition-states. The calculations are in good agreement with the experimental results. The 1,3-dioxabenzophosphole hapten 10 was synthesized, coupled to the carrier protein and the antibodies were obtained by the hybridoma technique. Two antibodies, DB-108P and DB-108Q were found to enhance the rate of soman hydrolysis and they were kinetically characterised.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Chemical Warfare Agents / chemistry
  • Chemical Warfare Agents / metabolism*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / immunology
  • Cholinesterase Inhibitors / metabolism
  • Haptens / chemistry
  • Hydrolysis
  • Kinetics
  • Mice
  • Models, Molecular
  • Soman / chemistry
  • Soman / immunology*
  • Soman / metabolism*

Substances

  • Antibodies, Monoclonal
  • Chemical Warfare Agents
  • Cholinesterase Inhibitors
  • Haptens
  • Soman