Work on this project will be in the following topical areas: 1. Full nuclear Overhauser effect characterization of template-nucleated alanine helices through study of deuterium-labeled derivatives. 2. Determination for the first time of the experimental length-dependence of the CD ellipticities for short alanine-derived helices. 3. Measurements of the energetics and stabilization/ destabilization of helices by the twenty amino acid residues, using template-nucleated helices. These measurements should resolve the current controversies concerning the magnitudes and independence of s values (helix propagation constants). 4. Design, synthesis, and study of maximally nucleating helix templates. 5. Measurement in templated systems of the magnitudes of polar stabilization effects. With this award, the Organic Synthesis Program will support the research of Dr. Daniel S. Kemp at Massachusetts Institute of Technology. The research will develop structural models that will facilitate the evaluation of parameters which control the formation of secondary and tertiary structure in peptide chains. This information is crucial to the understanding of protein chemistry and the design of biologically active molecules for biochemistry and medicine, as well as in the chemical industry.
