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 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.