Title : Toward antibody-catalyzed hydrolysis of organophosphorus poisons - Vayron_2000_Proc.Natl.Acad.Sci.U.S.A_97_7058 |
Author(s) : Vayron P , Renard PY , Taran F , Creminon C , Frobert Y , Grassi J , Mioskowski C |
Ref : Proc Natl Acad Sci U S A , 97 :7058 , 2000 |
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. |
PubMedSearch : Vayron_2000_Proc.Natl.Acad.Sci.U.S.A_97_7058 |
PubMedID: 10860971 |
Inhibitor | PhX |
Vayron P, Renard PY, Taran F, Creminon C, Frobert Y, Grassi J, Mioskowski C (2000)
Toward antibody-catalyzed hydrolysis of organophosphorus poisons
Proc Natl Acad Sci U S A
97 :7058
Vayron P, Renard PY, Taran F, Creminon C, Frobert Y, Grassi J, Mioskowski C (2000)
Proc Natl Acad Sci U S A
97 :7058