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Science 15 December 1995:
Vol. 270. no. 5243, pp. 1775 - 1783
DOI: 10.1126/science.270.5243.1775
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Research Articles

Reactive Immunization

Peter Wirsching,  Jon A. Ashley,  Chih-Hung L. Lo,  Kim D. Janda (1),  Richard A. Lerner (1)

For almost 200 years inert antigens have been used for initiating the process of immunization. A procedure is now described in which the antigen used is so highly reactive that a chemical reaction occurs in the antibody combining site during immunization. An organophosphorus diester hapten was used to illustrate this concept coined ``reactive immunization.'' The organophosphonate recruited chemical potential from the immune response that resembled the way these compounds recruit the catalytic power of the serine hydrolases. During this recruitment, a large proportion of the isolated antibodies catalyzed the formation and cleavage of phosphonylated intermediates and subsequent ester hydrolysis. Reactive immunization can augment traditional immunization and enhance the scope of catalytic antibody chemistry. Among the compounds anticipated to be effective are those that contain appropriate reactive functionalities or those that are latently reactive, as in the mechanism-based inhibitors of enzymes.


The authors are at the Scripps Research Institute, Departments of Molecular Biology and Chemistry, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
(1) To whom correspondence should be addressed.


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