NMR Spectroscopic Investigation of Peptide Aggregation

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This Faculty Early Career Development (CAREER) project is in the general area of analytical and surface chemistry and in the subfield of bioanalytical chemistry. During the tenure of this three-year continuing grant, Professor Larive and her students at the University of Kansas will pursue research designed to provide a detailed understanding of the relationships between peptide primary structure, three-dimensional conformation, and aggregation. These studies will involve five specific aims, namely (1) to understand the importance of primary structure in aggregation; (2) to perform peptide conformation analysis; (3) to measure peptide diffusion coefficients; (4) to develop an aggregation model; and (5) to test the model by examining aggregation under various conditions of solvent, temperature, pH, and ionic strength. A family of synthetic peptides based on systematic alteration of primary structure of a sixteen-residue sequence will be examined using a suite of experimental techniques featuring nuclear magnetic resonance (NMR) and circular dichroism (CD). The results of these studies should indicate the relative contributions of hydrogen bonding, dipolar interactions, and hydrophobic contacts to the stabilization of aggregates of these peptides. Also during this grant period, Professor Larive will pursue an educational development plan that includes the reorganization and revitalization of the undergraduate analytical chemistry laboratory, introduction of an environmental option for chemistry majors, and increasing the involvement of undergraduates in research. Peptide and protein aggregation is a fundamentally and practically important problem. By exploring the effects of solution conditions such as solvent, pH, and ionic strength, this CAREER research project will produce a foundation of experimental results which will be useful in controlling aggregation of proteins expressed for research, therapeutic, or commercial purposes. The educational developmen t aspects of this CAREER project will enrich and broaden the undergraduate analytical chemistry curriculum at the University of Kansas.