(397b) Polydispersity Control In the Liquid Phase Synthesis of Amphipathic, Self-Assembling Polypeptides

Synthesizing a useful, periodically-sequenced, amphipathic polypeptide is a challenge because the polydispersity index increases with increasing molecular weight.  To circumvent this hurdle, we designed synthetic amino acid dimers that are both water-soluble and amphipathic.  The resulting peptide backbone has alternating hydrophilic/hydrophobic side groups, the typical periodicity for beta-sheet forming polypeptides.  Using this approach, we can influence the polydispersity of the growing polypeptide chains, controlling the kinetics of growth through transport-limited chain elongation.  Our experiments show that in the absence of an interface, standard bulk-phase condensation polymerization occurs.  With an interface present, the amphipathic character of the peptide chain increases with increasing molecular weight, resulting in a polypeptide that partitions to interface as a function of the degree of polymerization.  This type of kinetically limited growth serves to narrow the polydispersity of our periodically sequenced polypeptide. We quantify the dynamics of chain elongation and interfacial assembly using multi-angle light scattering, and we define the evolving sheet-like secondary structure using circular dichroism for various peptides of differing amino acid pairs.