ModulableSupramolecular Hydrogels via Co-AssemblyUsing Cyclic Dipeptides: Influence of One Methyl Group

Self-assembling peptide derivatives containing unnatural amino acids are promising for the modulation of the structure and function of supramolecular architectures consisting of natural peptide-based derivatives through co-assembly. In this study, we investigate the self-assembly of three cyclic dipeptides that contain synthetic α-methyl-l-phenylalanine as the unnatural amino acid in an aqueous medium. We reveal that one of the three synthesized cyclic dipeptides can form a supramolecular hydrogel and resolve the self-assembled architecture and the folded conformation at the atomic scale, where one methyl group introduced at the α-carbon of l-phenylalanine significantly influenced the properties of the hydrogel. Furthermore, we demonstrate that co-assembly with its natural counterpart enables modulation of the viscoelastic properties of supramolecular hydrogels. Thus, our study may facilitate the exploration of unnatural peptide-based self-assembling molecular libraries for the construction of supramolecular soft materials.