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Abstract

Monoclonal antibodies elicited to haptens that are analogs of the transition state for hydrolysis of carboxylic esters behaved as enzymic catalysts with the appropriate substrates. These substrates are distinguished by the structural congruence of both hydrolysis products with haptenic fragments. The haptens were potent inhibitors of this esterolytic activity, in agreement with their classification as transition state analogs. Mechanisms are proposed to account for the different chemical behavior of these antibodies with two types of ester substrates. The generation of an artificial enzyme through transition state stabilization by antibodies was thus demonstrated. These studies indicate a potentially general approach to catalyst design.

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Published In

Science
Volume 234 | Issue 4783
19 December 1986

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Published in print: 19 December 1986

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Alfonso Tramontano
Department of Molecular Biology, The Research Institute of Scripps Clinic, La Jolla, CA 92037.
Kim D. Janda
Department of Molecular Biology, The Research Institute of Scripps Clinic, La Jolla, CA 92037.
Richard A. Lerner
Department of Molecular Biology, The Research Institute of Scripps Clinic, La Jolla, CA 92037.

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