Assembly of peptide functionalized molecular architectures

Peptide-amphiphiles were designed as biological modules that are capable of self-assembly into a variety of aggregated structures leading to specific interactions with cellular ligands such as membrane proteins and DNA. These molecules contain a peptide head-group covalently lipidated with mono or di-alkyl tail-groups. Previous work with collagen-like peptides has shown this architecture can nucleate protein-like secondary structure and elicit function on bilayer surfaces. In addition, this amphiphilic character also allows us to study disperse phase aggregates and control assembled structures by manipulating their molecular construction. Peptide-amphiphiles with monoalkyl and dialykyl C₁₆-tails, as well as, a polymerizable hydrophobic tail have been studied with a variety of techniques to elucidate how molecular design influences self-assembled morphology and binding characteristics. Integrin binding sequences such as the triple-helical IVH1 and fibronectin derived RGD peptides have been included in vesicles and polymerized vesicles for drug delivery and biosensing applications. Also, a coiled-coil GCN4 peptide-amphiphiles is shown to direct the complexation with DNA, revealing fundamental details of the structure-function relationship. The ability to design peptide-amphiphiles as molecular building blocks capable of hierarchical assembly (hydrophobic collapse giving enhanced secondary structure) makes peptide-amphiphiles in aggregates a potential platform for protein models or therapeutic tools.