Catalytic antibodies hydrolysing organophosphorus esters.
Transition state stabilization is considered one means by which enzymes reduce free energy of activation. The transition state of phosphonic acid anhydrides acted on by OPA hydrolase is postulated to be pentacoordinate, which ordains either a square pyramid or a trigonal bipyramid structure. The advent of catalytic monoclonal antibodies has provided a system in which these assumptions can be tested. By immunizing mice with the protein conjugate of a trigonal bipyramid transition state analog, we have produced hybridomas secreting monoclonal antibodies which hydrolyze phosphonates. To date, activity has been shown toward pinacolyl methylphosphonofluoridic acid (soman). Preliminary results suggest that the antibody is an IgG2a with kappa light chain character. Our results support the trigonal bipyramidal transition state for this group of enzymes.
Brimfield
A A
AA
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Lenz
D E
DE
Maxwell
D M
DM
Broomfield
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D002384:Catalysis; D004952:Esters / Q000378:metabolism; D005260:Female; D006241:Haptens / Q000276:immunology; D006868:Hydrolysis; D007114:Immunization; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010753:Phosphoranes / Q000276:immunology / Q000378:metabolism; D012999:Soman / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004952:Esters; D006241:Haptens; D009943:Organophosphorus Compounds; D010753:Phosphoranes; D012999:Soman