Electrostatic and Aromatic Interaction-Directed Supramolecular Self-Assembly of a Designed Fmoc-Tripeptide into Helical Nanoribbons

Supramolecular self-assembly offers an efficient pathway for creating macroscopically chiral structures in biology and materials science. Here, a new peptide consisting of an <i>N</i>-(9-fluorenylmethoxycarbonyl) headgroup connected to an aromatic phenylalanine-tryptophan dipeptide and terminated with zwitterionic lysine (Fmoc-FWK) and its cationic form (Fmoc-FWK-NH₂) were designed for self-assembly into chiral structures. It was found that the Fmoc-FWK peptide self-assembled into left-handed helical nanoribbons at pH 11.2–11.8, whereas it formed nanofibers at pH 5 and 12 and large flat ribbons composed of many nanofibers in the pH range of 6–11. However, only nanofibers were observed in the cases of Fmoc-FWK-NH₂ at different values. A series of structural characterizations based on CD, FTIR, UV–vis and fluorescence spectroscopy reveal that the electrostatic and aromatic interactions and the associated hydrogen bonding direct the self-assembly into various structures. The enhanced π–π stacking and hydrogen bonding were found in the helical nanoribbons. This difference in intermolecular interactions should be derived from the ionization of carboxyl and amino groups from lysine residues at different pH values. Furthermore, we performed molecular dynamics simulations to gain insight into the assembly mechanisms. The results imply that a relatively rigid molecular conformation and the strong intramolecular aromatic interaction between Trp and Fmoc groups favor chiral self-assembly. This study is the first attempt to design a Fmoc-tripeptide for the fabrication of helical structures with macroscopic chirality, which provides a successful example and allows us to create new peptide-based chiral assembly systems