Synthesis of Catalytic Antibodies

Scripps Research Institute, The, La Jolla CA

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Abstract

In the past, we have exploited the natural genetic diversity of the humoral immune system to make highly selective catalysts, to test fundamental notions of biological catalysis, and to analyze the molecular basis for germline polyspecificity and affinity maturation. Here we propose to extend these efforts to the generation of antibodies with engineered metal binding sites. These studies will likely facilitate both chemical and therapeutic applications of antibodies. In addition, we will pursue two additional efforts that have evolved from work in antibody catalysis. The first focuses on the evolution of novel protein structures and functions by the combinatorial association and subsequent mutation of bacterial secondary structural elements. The second focuses on novel redox activities associated with membrane bound receptors[unreadable]specifically human growth factor and related receptors. These latter projects will provide new insights into the evolution of protein structure and function, and the role of redox processes in biological recognition and cell signaling, respectively.