Title

A comparison of flexible and constrained haptens in eliciting antibody catalysts for paraoxon hydrolysis

Document Type

Article

Publication Date

6-1-1999

Abstract

A new amine-oxide hapten was employed as an antigen, producing seven monoclonal antibodies (mAbs) from a panel of 20 that catalyzed paraoxon hydrolysis. The current hapten design differs from that previously described in that the molecule is inherently more flexible than its constrained predecessor. One of the seven antibody catalysts, mAb 1H9, showed the highest activity and was selected for detailed study. At pH=8.77, the catalytic hydrolysis of paraoxon by mAb 1H9 followed Michaelis-Menten kinetics affording a k(cat)=3.73x10-4min-1 and a K(m)=1.12mM with a rate acceleration k(cat)/k(uncat)=56. The hapten was found to be a competitive inhibitor of antibody-catalyzed paraoxon hydrolysis with a K(i)=0.54mM. A comparison of both the number and proficiency of antibody catalysts obtained when utilizing a flexible versus constrained hapten indicates that, for paraoxon hydrolysis, constrained haptens elicit superior catalysts, suggesting that further development should begin with the use of constrained haptens in producing more proficient antibody catalysts for paraoxon hydrolysis. Copyright (C) 1999 Elsevier Science Ltd.

Publication Source (Journal or Book title)

Bioorganic and Medicinal Chemistry

First Page

1145

Last Page

1150

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