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.