Water-Based Synthesis of ß-Sheet-Like Supramolecular Metallohydrogel Organized by Using a Native Ultrashort Peptide Sequence.

Designing supramolecular hydrogels using short peptides is challenging. To control self-assembly, a certain amount of organic solvent is typically added to the system, or the short peptide is modified with a functional group that is hydrophobic, hydrophilic, or highly coordinative. We discovered that l-His-l-Ile-l-Thr (HIT), a very short unmodified "native" tripeptide, selectively responds to Cu2+ ions in pure water to form a transparent supramolecular metallohydrogel. Circular dichroism analysis revealed that Cu2+ ions, but no other metal species, caused HIT to change from a random-coil-like to a ß-sheet-like structure. Other spectroscopic methods were used to characterize the properties of the supramolecular metallohydrogel. These results are expected to facilitate the development of native short peptides as advanced functional biomaterials.