Peptide-Amphiphile Induction of α-Helical and Triple-Helical Structures

Abstract

Protein-like molecular architecture has often been created by utilizing the ability of peptides to self-assemble and form higher order three-dimensional structures. We have attached pseudo-lipids onto Nα-amino groups of peptide chains to create "peptide-amphiphiles." The alignment of amphiphilic compounds at the lipid-solvent interface is used to facilitate peptide alignment and structure initiation and propagation. CD and NMR spectroscopies have been used to examine the secondary or super-secondary structures of a series of peptides both with and without lipophilic hydrocarbon "tails." Overall, the tails (a) do not disrupt the structures of the peptide "head groups," but in fact enhance structure thermal stability and (b) significantly reduce the necessary length for a peptide to have predominantly an α-helical or triple-helical structure in solution. The extent of peptide-amphiphile aggregation appears to be correlated to hydrocarbon tail length. The peptide-amphiphiles described here provide a simple approach for building stable protein structural motifs using peptide head groups, and have potential as therapeutics and for improving biomaterial biocompatibility.