Studies in antibody catalysis: I. Preparation and evaluation of an insulin prodrug. II. Physiological roles for the antibody-catalyzed oxidation of water.

摘要

The work described in this thesis investigates the catalytic ability of antibody molecules. In the first chapter, work is presented that demonstrates an application of a tailor-made catalytic antibody for the treatment of a metabolic deficiency. Specifically, insulin deactivation/reactivation is demonstrated as the basis for a novel insulin delivery system for the maintenance of basal blood glucose in the treatment of diabetes mellitus. In the second chapter, work is presented that explores the catalytic oxidation potential of all antibodies. This chemistry, along with what is known about the chemistry of the phagosome, suggests that antibodies can participate chemically in the destruction of foreign particles. This process is explored and characterized in the killing of Gram-negative bacteria, including pathogenic E. coli and S. typhimurium. Finally, the third chapter extends the studies on antibody-mediated oxidation to the subject of inflammatory disease. Specifically, the question as to whether antibody-mediated oxidation occurs and whether it has any effect on the progression of tissue damage during ischemia/reperfusion injury as modeled by the Langendorff method is investigated.