Photoinduced Hydrogel-Forming Caged Peptides with Improved Solubility

Self-assembling peptides are attractive alternatives in the field of biomaterial science due to their variability and biocompatibility. Unfortunately, such peptides have poor solubility, and their purification, synthesis, and overall handling are challenging. Our main objective was to develop a cage peptide design with full control over self-assembly. Theoretically, aggregation can be suppressed by temporally masking the amino acid side chains at critical positions. Taking into account several biological and synthetic requirements, a photosensitive protecting group, p-hydroxy-phenacyl (pHP), was chosen as the "masking" moiety. To test our theory, EAK16-II was chosen as a model self-assembling peptide, and a caged derivative containing photosensitive pHP groups was synthesized. Both spectroscopic and in vitro experiments on A2058 melanoma cells confirmed our hypothesis that the caged-EAK16-II peptide has good solubility and that the hydrogel formed after photolysis results in similar viability and cell aggregate formation of melanoma cells as the native EAK16-II-based hydrogel.