Synthesizing and Self-Assembling Periodically Sequenced Polypeptides

Constructing a periodically sequenced amphipathic polypeptide is a challenge because the polydispersity index increases with increasing molecular weight.  To circumvent this hurdle, we are designing synthetic amino acid dimers that are both water-soluble and amphipathic.  The resulting peptide backbone will have alternating hydrophilic/hydrophobic side groups, which is 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 the 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.