Monoclonal Catalytic Antibodies Directed Towards Organophosphorus Agents

The hapten molecule CF3(CH3)P(OR)3 which mimics the transition state for hydrolysis of organophosphates such as soman will be synthesized. A protein conjugate will be used for monoclonal catalytic antibody production. A key element of the hapten is that it is a phosphorane (pentacoordinate phosphorus) and contains the CF3PCH3 group. The synthesis depends upon new chemistry which we have discovered for phosphoranes and trifluoromethyl phosphorus compounds. The highly electronegative CF3 mimics an anionic oxygen bond to phosphorus and also stabilizes the phosphorane hapten towards hydrolytic decomposition. This novel hapten represents a closely proximate model for the transition state in organophosphate hydrolytic cleavage and should enable production of a highly effective catalytic antibody for organophosphate neutralization. The project is a collaborative effort between Steroids, Ltd which will do the synthesis, conjugation and haptn-protein ratio determination, and USAMRICD with will generate monoclonal catalytic antibodies and determine their activity towards hydrolytic cleavage of soman.