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 su bphases. In the present study, we have examined peptide-amphiphiles co ntaining monoalkyl chain tails for similar self-assembly behaviors. Th e structure of a collagen-model peptide has been characterized with an d without an N-terminal hexanoic acid (C-6) modification. Evidence for a self-assembly process of both the peptide and peptide-amphiphile ha s been obtained from (a) circular dichroism spectra and melting curves characteristic of triple-helices, (b) one-dimensional NMR spectra ind icative of stable triple-helical structure at low temperatures and mel ted triple helices at high temperatures, and (c) pulsed-field gradient NMR experiments demonstrating different self-diffusion coefficients b etween proposed triple-helical and non-triple-helical species. The pep tide-amphiphile appeared to form monomeric triple helices. The thermal stability of the collagen-like structure:in the peptide-amphiphile wa s found to-increase as the monoalkyl tail chain length is increased ov er a range of C-6 to C-16 The assembly process driven by the hydrophob ic tail, albeit monoalkyl or dialkyl, may provide a general method for creating well-defined protein molecular architecture. Peptide-amphiph ile-structures possessing these alkyl moieties have the potential to b e used for biomaterial surface modification td improve biocompatibilit y or, by mimicing fusion of viral envelopes with cellular membranes; a s drug delivery vehicles.