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Immunologically driven antibodies chemical engineering: design and synthesis of a hapten aimed at nerve agent hydrolysis |
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| Authors: | Florence Jovic Charles Mioskowski |
| Affiliation: | a Service de Marquage moléculaire et de Chimie Bioorganique, CEA Saclay F-91191 Gif sur Yvette cedex, France b Institut de Recherche en Chimie Organique Fine, Laboratoire d’Hétérochimie Organique, CNRS UMR 6014, Université de Rouen et INSA de Rouen, Rue Tesnière F-76131 Mont Saint Aignan cedex, France c Laboratoire de Synthèse Bioorganique, CNRS UMR 7514, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 74, Route du Rhin BP 24, F-67401 Illkirch-Graffenstaden, France |
| Abstract: | 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. |
| Keywords: | Catalytic antibodies Bioorganic chemistry Organophosphorus chemistry Nerve agent |
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