Induction of protein-like molecular architecture by monoalkyl hydrocarbon chains

Abstract

Numerous approaches have been described for creating relatively small folded biomolecular structures. "Peptide-amphiphiles," whereby monoalkyl or dialkyl hydrocarbon chains are covalently linked to peptide sequences, have been shown previously to form specific molecular architecture of enhanced stability. The present study has examined the use of monoalkyl hydrocarbon chains as a more general method for inducing protein-like structures. Peptide and peptide-amphiphiles have been characterized by CD and one- and two-dimensional nmr spectroscopic techniques. We have examined two structural elements: alpha-helices and collagen-like triple helices. The alpha-helical propensity of a 16-residue peptide either unmodified or acylated with a C(6) or C(16) monoalkyl hydrocarbon chain has been examined initially. The 16-residue peptide alone does not form a distinct structure in solution, whereas the 16-residue peptide adopts predominantly an alpha-helical structure in solution when a C(6) or C(16) monoalkyl hydrocarbon chain is N-terminally acylated. The thermal stability of the alpha-helix is greater upon addition of the C(16) compared with the C(6) chain, which correlates to the extent of aggregation induced by the respective hydrocarbon chains. Very similar results are seen using a 39-residue triple-helical model peptide, in that structural thermal stability (a) is increasingly enhanced as alkyl chain length is increased and (b) correlates to the extent of peptide-amphiphile aggregation. Overall, structures as diverse as alpha-helices, triple helices, and turns/loops have been shown to be induced and/or stabilized by alkyl chains. Increasing alkyl chain length enhances stability of the structural element and induces aggregates of defined sizes. Hydrocarbon chains may be useful as general tools for protein-like structure initiation and stabilization as well as biomaterial modification.