(672f) Surfactant-Mediated Polydispersities in the Synthesis of Self-Assembling, Amphipathic Polypeptides

Synthesizing a periodically-sequenced, useful, amphipathic peptide is challenging due to the polydispersity index increases of large molecular weight polypeptide systems. To overcome this, we designed synthetic amino acid dimers that are both amphipathic and water-soluble. When polymerized, these dimers give rise to a peptide with alternating hydrophilic/hydrophobic side groups: the typical periodicity for beta-sheet forming polypeptides. Using this approach, we can influence polydispersity in the growing polypeptide chains, controlling the kinetics of growth through transport-limited chain elongation. Our experiments show that in the absence of a micellular interface, standard bulk-phase condensation polymerization occurs. The amphipathic character of the peptide chain increases with increasing molecular weight, resulting in a polypeptide that partitions into surfactant micelles 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 mass spectrometry and define the evolving sheet-like secondary structure using circular dichroism for various peptides of differing amino acid pairs. Our results show that the peptides grown in the presence of micelles show significantly enhanced self-assembly and a narrowed polydispersity index. From this, we conclude that the transport-limited chain elongation polymerization method shows great promise in the manufacture of low-cost, interfacially assembling polypeptides.