@article{ref1,
title="Toward antibody-catalyzed hydrolysis of organophosphorus poisons",
journal="Proceedings of the National Academy of Sciences of the United States of America",
year="2000",
author="Vayron, P. and Renard, P. Y. and Taran, F. and Créminon, C. and Frobert, Y. and Grassi, J. and Mioskowski, C.",
volume="97",
number="13",
pages="7058-7063",
abstract="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>",
language="en",
issn="0027-8424",
doi="",
url="http://dx.doi.org/"
}