Hydrolysis of organophosphorus nerve agent soman by the monoclonal antibodies elicited against an oxyphosphorane hapten.
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.
Yli-Kauhaluoma
J
J
VTT Technical Research Centre of Finland, Espoo.
Humppi
T
T
Yliniemelä
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000737:chemistry / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000737:chemistry; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D012999:Soman / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D006241:Haptens; D012999:Soman