HAPTEN DESIGN FOR ANTIBODY-CATALYZED DECARBOXYLATION AND RING-OPENINGREACTIONS OF BENZISOXAZOLES

Three benzisoxazole haptens designed to elicit antibody binding sites with widely differing polarity have been synthesized and used to induc e antibodies in mice. Monoclonal antibodies were prepared using hybrid oma technology, and screened for catalysis of the ring-opening isomeri zation and/or decarboxylation of a series of related benzisoxazoles an d their 3-carboxy-derivatives. No catalysis of decarboxylation was obs erved, but 3 of a total of 47 antibodies obtained against the three ha ptens catalyzed the isomerization process. Of 12 antibodies raised aga inst the 3-acetylbenzisoxazole structure 5 none was catalytically acti ve; but one of 24 raised against a 3-isopropenylbenzisoxazole 6 increa sed the rate of ring-opening of 6-nitrobenzisoxazole, and 5 of 11 anti bodies raised against a benzisoxazole 7 with a 3-amidinium group were moderately active against either 6-nitro or 6-acylaminobenzisoxazoles. Competitive binding studies suggest that at least some of the antibod ies induced by the isopropenyl hapten do possess a recognizably hydrop hobic binding site.