CONFORMATIONALLY CONSTRAINED PROTEIN POLYMERS

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The proposed research will entail the design, modeling, synthesis, and characterization of repeating polypeptide sequences incorporating non-natural amino acids. A particular emphasis will be the in vivo expression of protein polymers that include the methionine analog homoallylglycine, or "Hag". The presence of the alkene chemical functionality in these polymers will be exploited to create novel macromolecular materials with tailored properties. Artificial genes encoding alpha-helical protein polymers that include Hag residues in a repeating i to i + 4 pattern will be expressed in an E. coli methionine auxotroph. Following purification, the terminal alkene groups of the Hag sidechains will be subjected to ring-closing metathesis. This reaction will generate 19-membered ring macrocycles that will tether the protein secondary structure. The anticipated product is a monodisperse rigid-rod polymer. The biophysical and materials properties of this polymer will be investigated, with particular attention to the thermal stability of the alpha- helical structure. The behavior of the polymers will be modeled by molecular dynamics simulations. Characterization of these polymers will provide advances in materials science through the precise spatial patterning of novel chemical functionalities, and will provide advances in protein biophysics through an enhanced understanding of the forces that control the formation of protein secondary structure.