Modulable supramolecular hydrogels via co-assembly using 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 new cyclic dipeptides that contain synthetic α-methyl-L-phenylalanine as the unnatural amino acid in an aqueous medium. We reveal that one of three newly synthesized cyclic dipeptides can form supramolecular hydrogel and resolve the self-assembled architecture and the folded conformation at atomic scale, where one methyl group introduced at the α-carbon of L-phenylalanine significantly influenced the properties of the hydrogel. Furthermore, we demonstrated 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.