TY  - JOUR
PY  - 2000//
TI  - Toward antibody-catalyzed hydrolysis of organophosphorus poisons
JO  - Proceedings of the National Academy of Sciences of the United States of America
A1  - Vayron, P.
A1  - Renard, P. Y.
A1  - Taran, F.
A1  - Créminon, C.
A1  - Frobert, Y.
A1  - Grassi, J.
A1  - Mioskowski, C.
SP  - 7058
EP  - 7063
VL  - 97
IS  - 13
N2  - We report here our preliminary results on the use of catalytic antibodies as an approach to neutralizing organophosphorus chemical weapons. A first-generation hapten, methyl-alpha-hydroxyphosphinate Ha, was designed to mimic the approach of an incoming water molecule for the hydrolysis of exceedingly toxic methylphosphonothioate VX (1a). A moderate protective activity was first observed on polyclonal antibodies raised against Ha. The results were further confirmed by using a mAb PAR 15 raised against phenyl-alpha-hydroxyphosphinate Hb, which catalyzes the hydrolysis of PhX (1b), a less toxic phenylphosphonothioate analog of VX with a rate constant of 0.36 M(-1) x min(-1) at pH 7.4 and 25 degrees C, which corresponds to a catalytic proficiency of 14,400 M(-1) toward the rate constant for the uncatalyzed hydrolysis of 1b. This is a demonstration on the organophosphorus poisons themselves that mAbs can catalytically hydrolyze nerve agents, and a significant step toward the production of therapeutically active abzymes to treat poisoning by warfare agents.<p /> <p>Language: en</p>
LA  - en
SN  - 0027-8424
UR  - http://dx.doi.org/
ID  - ref1
ER  -