Molecular Recognition by Protein Kinases

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The focus of this research is the synthesis of poly-l-proline type II peptide mimics and the use of these mimics as kinase substrates with the goal of better defining the primary and secondary structure parameters which contribute to the substrate specificity of protein kinases. Construction of PPII mimics will utilize conformational control elements which define an all-proline PPII helix. This will involve the synthesis of modified proline analogs possessing the non-prolyl side chains on the proline backbone and the generation of oligopeptides from these modified prolines. With this new award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Jose S. Madalengoitia of the Department of Chemistry at the University of Vermont. Professor Madalengoitia will focus his work on probing the hypothesis that at least some protein kinases phosphorylate peptide strands in the PPII conformation, or in extended conformations resembling this geometry. High impact in an important area of current biology will occur with the success of this project.