CATALYTIC ANTIBODIES HYDROLYZING ORGANOPHOSPHORUS ESTERS

Transition state stabilization is considered one means by which enzyme s reduce free energy of activation. The transition state of phosphonic acid anhydrides acted on by OPA hydrolase is postulated to be pentaco ordinate, which ordains either a square pyramid or a trigonal bipyrami d structure. The advent of catalytic monoclonal antibodies has provide d a system in which these assumptions can be tested. By immunizing mic e with the protein conjugate of a trigonal bipyramid transition state analog, we have produced hybridomas secreting monoclonal antibodies wh ich hydrolyze phosphonates. To date, activity has been shown toward pi nacolyl methylphosphonofluoridic acid (soman). Preliminary results sug gest that the antibody is an IgG2a with kappa light chain character. O ur results support the trigonal bipyramidal transition state for this group of enzymes.