Abstract
Here, we report a new type of tryptophan-rich short peptides, which act as hydrogelators, form supramolecular assemblies via enzymatic dephosphorylation, and exhibit cell compatibility. The facile synthesis of the peptides starts with the production of phosphotyrosine and then uses solid-phase peptide synthesis to build the phosphopeptides that contain multiple tryptophan residues. Besides exhibiting excellent solubility, these phosphopeptides, unlike the previously reported cytotoxic phenylalanine-rich phosphopeptides, are largely compatible toward mammalian cells. Our preliminary mechanistic study suggests that the tryptophan-rich peptides, instead of forming pericellular assemblies, largely accumulate in lysosomes. Such lysosomal localization may account for their cell compatibility. Moreover, these tryptophan-rich peptides are able to transiently reduce the cytotoxicity of phenylalanine-rich peptide assemblies. This rather unexpected result implies that tryptophan may act as a useful aromatic building block for developing cell compatible supramolecular assemblies for soft materials and find applications for protecting cells from cytotoxic peptide aggregates.