Photoinduced hydrogel-forming caged peptides with improved solubility

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