Induction of protein-like molecular architecture by monoalkyl hydrocarbon chains

Numerous approaches have been described for creating relatively small folde d biomolecular structures. "Peptide-amphiphiles," whereby monoalkyl or dial kyl hydrocarbon chains are covalently linked to peptide sequences, have bee n shown previously to form specific molecular architecture of enhanced stab ility. The present study has examined the use of monoalkyl hydrocarbon chai ns as a more general method for inducing protein-like structures. Peptide a nd peptide-amphiphiles have been characterized by CD and one- and two-dimen sional nmr spectroscopic techniques. We have examined two structural elemen ts: alpha -helices and collagen-like triple helices. The alpha -helical pro pensity 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-resid ue peptide alone does not form a distinct structure in solution, whereas th e 16-residue peptide adopts predominantly an alpha -helical structure in so lution when a C-6 or C-16 monoalkyl hydrocarbon chain is N-terminally acyla ted. 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 agg regation induced by the respective hydrocarbon chains. Very similar results are seen using a 39-residue triple-helical model peptide, in that structur al thermal stability (a) is increasingly enhanced as alkyl chain length is increased and (b) correlates to the extent of peptide-amphiphile aggregatio n. Overall, structures as diverse as alpha -helices, triple helices, and tu rns/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 a s general tools for protein-like structure initiation and stabilization as well as biomaterial modification. (C) 2000 John Wiley & Sons, Inc.