Induction of protein-like molecular architecture by self-assembly processes

One of the most intriguing self-assembly processes is the folding of peptide chains into native protein structures. We have developed a method for building protein-like structural motifs that incorporate sequences of biological interest. A lipophilic moiety is attached onto an N-alpha-amino group of a peptide chain, resulting in a 'peptide-amphiphile'. The alignment of amphiphilic compounds at the lipid-solvent interface is used to facilitate peptide alignment and structure initiation and propagation. Peptide-amphiphiles containing potentially triple-helical structural motifs have been synthesized. The resultant head group structures have been characterized by circular dichroism and NMR spectroscopies. Evidence for a self-assembly process of peptide-amphiphiles has been obtained from: (a) circular dichroism spectra and melting curves characteristic of triple-helices, (b) one- and two-dimensional NMR spectra indicative of stable triple-helical structure at low temperatures and melted triple-helices at high temperatures, and (c) pulsed-field gradient NMR experiments demonstrating different self-diffusion coefficients between proposed triple-helical and non-triple-helical species. The peptide-amphiphiles described here provide a simple approach for building stable protein structural motifs using peptide head groups. (C) 1999 Elsevier Science Ltd. All rights reserved.