Conformation Preservation of α-Helical Peptides within Supramolecular Filamentous Assemblies.

Hydrogen-bonded β-sheets are the most commonly explored building motifs for creating peptide-based filamentous nanostructures; however, most bioactive epitopes must assume an α-helix conformation to exert their functions. Incorporating α-helical sequences into β-sheet-forming peptides often involves the use of a flexible spacer to alleviate the steric impact of the intermolecular hydrogen bonding on the α-helical conformation. In this context, we report our findings on the alkylation-regulated conformation preservation of α-helical peptides within their filamentous assemblies. We found that the chemical conjugation of two short linear hydrocarbons (octanoic acids, C8) can retain the α-helical conformation of two protein A-derived peptide sequences while effectively driving their assembly into filamentous nanostructures. In contrast, the use of a single palmitoyl tail (C16) of similar hydrophobicity would lead to formation of β-sheet assemblies. Our studies further demonstrated that the length of the conjugated hydrocarbon also plays an important role in partially preserving the native α-helical conformation, with longer ones promoting β-sheet formation and short ones stabilizing α-helices to some extent. We believe that these findings offer important guiding principles for the alkylation of self-assembling peptides containing α-helical sequences.