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Hapten Design for Antibody-Catalyzed Decarboxylation and Ring-Opening Reactions of Benzisoxazoles |
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| Authors: | Masha V Sergeeva Vihra Yomtova Adrian Parkinson Marjolein Overgaauw Rikus Pomp Arjen Schots Anthony J Kirby Riet Hilhorst |
| Affiliation: | 1. Department of Biochemistry, Agricultural University, Dreijenlaan 3, 6703 HA Wageningen;2. University Chemical Laboratory, Cambridge CB2 1EW, UK;3. Laboratory for Monoclonal Antibodies, Agricultural University, Wageningen, The Netherlands;4. University Chemical Laboratory, Cambridge CB2 1EW, UK
Anthony J. Kirby, University Chemical Laboratory, Cambridge CB2 1EW, UK Riet Hilhorst, Department of Biochemistry, Agricultural University, Dreijenlaan 3, 6703 HA Wageningen;5. Department of Biochemistry, Agricultural University, Dreijenlaan 3, 6703 HA Wageningen Anthony J. Kirby, University Chemical Laboratory, Cambridge CB2 1EW, UK Riet Hilhorst, Department of Biochemistry, Agricultural University, Dreijenlaan 3, 6703 HA Wageningen |
| Abstract: | Three benzisoxazole haptens designed to elicit antibody binding sites with widely differing polarity have been synthesized and used to induce antibodies in mice. Monoclonal antibodies were prepared using hybridoma technology, and screened for catalysis of the ring-opening isomerization and/or decarboxylation of a series of related benzisoxazoles and their 3-carboxy-derivatives. No catalysis of decarboxylation was observed, but 4 of a total of 47 antibodies obtained against the three haptens catalyzed the isomerization process. Of 12 antibodies raised against the 3-acetylbenzisoxazole structure 5 none was catalytically active; but one of 24 raised against a 3-isopropenylbenzisoxazole 6 increased the rate of ring-opening of 6-nitrobenzisoxazole, and 5 of 11 antibodies 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 antibodies induced by the isopropenyl hapten do possess a recognizably hydrophobic binding site. |
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