Minimal lipidation stabilizes protein-like molecular architecture

Peptide-amphiphiles with collagen-model head groups and dialkyl chain tails have been shown previously to self-assemble into highly ordered polyPro II-like triple-helical structures when dissolved in aqueous subphases. In the present study, we have examined peptide-amphiphiles containing monoalkyl chain tails for similar self-assembly behaviors. The structure of a collagen-model peptide has been characterized with and without an N-terminal hexanoic acid (C-6) modification. Evidence for a self-assembly process of both the peptide and peptide-amphiphile has been obtained from (a) circular dichroism spectra and melting curves characteristic of triple-helices, (b) one-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-amphiphile appeared to form monomeric triple helices. The thermal stability of the collagen-like structure:in the peptide-amphiphile was found to-increase as the monoalkyl tail chain length is increased over a range of C-6 to C-16 The assembly process driven by the hydrophobic tail, albeit monoalkyl or dialkyl, may provide a general method for creating well-defined protein molecular architecture. Peptide-amphiphile-structures possessing these alkyl moieties have the potential to be used for biomaterial surface modification td improve biocompatibility or, by mimicing fusion of viral envelopes with cellular membranes; as drug delivery vehicles.