Self-Assembling Gemini-Type Amphiphiles From Helix-Loop-Helix Peptides

Amphiphilic peptides can be designed to self-assemble into various nanostructures, such as nanorods, nanotubes, and vesicles, depending on their sequence and secondary structure. We have designed a self-assembling amphiphilic peptide that folds into a hairpin-like helix-loop-helix (HLH) motif. The α-helical segments are rich in hydrophobic leucine residues, while the loop segment is positively charged. The morphology of the peptide self-assemblies can be controlled by the preparation method. When prepared from an ethanolic solution at room temperature, these amphiphilic HLHPs self-assemble into spherical particles with a diameter in the sub-100 nm range, with α-helical secondary structure and good long-term stability at 4°C and pH 3. When produced from an aqueous buffer using ultrasonication at elevated temperatures, peptides with a β-sheet secondary structure are obtained, forming disc-shaped particles which have a high tendency to fuse. The α-helical nanospheres have been shown to interact with hydrophobic molecules such as 1,6-diphenylhexatriene or Amplex Red. The structural stability of the self-assembling nanospheres is largely dependent on the loop sequence composition: higher charge density and lysine residues instead of arginine residues lead to markedly reduced stability of the spherical particles.