Immunologically driven antibodies chemical engineering: design and synthesis of a hapten aimed at nerve agent hydrolysis

In this letter, we describe the design and the synthesis of an organophosphorus hapten aimed at a mixed biotechnological-chemical strategy for the mild decontamination of exceedingly toxic nerve agent VX. Hapten will be used to raise and select monoclonal antibodies (mAbs) able to bind both the nerve agent, and an oxime, derived from pyridinaldoxime, able to specifically hydrolyze its P-S bond. In order to significantly increase the hydrolysis reaction rate, the controlled respective positioning of the oxime and of the substrate will be achieved through the immunization, and in a second step, the oxime will be bound to the mAb in a reactive position towards the reactive thiophosphate functionality of the substrate.