Enzyme-instructed self-assembly (EISA) assists the self-assembly and hydrogelation of hydrophobic peptides.

Enzyme-instructed self-assembly (EISA) has several advantages in the preparation of supramolecular self-assembly materials for biomedical applications. In this study, we demonstrated that the enzyme-instructed self-assembly (EISA) strategy could assist the self-assembly and hydrogelation of two hydrophobic and bioactive peptides, tyroservatide (YSV) and laminin pentapeptide (YIGSR). We first synthesized the peptide derivatives of Nap-GFFYSV (peptide 1) and Nap-GFFYIGSR (peptide 2) and found that both peptides could not self-assemble into hydrogels due to their poor solubility. We therefore designed the phosphorylated precursors of the two hydrophobic peptides, Nap-GFFpYSV (precursor 1) and Nap-GFFpYIGSR (precursor 2), respectively, which had good solubility and can be dephosphorylated by alkaline phosphatase (ALP) to form supramolecular hydrogels. In addition, we found that the EISA could also occur on the surface of cells that overexpress ALP. The EISA strategy was a powerful method to generate hydrogels of hydrophobic compounds. We envision the big promise of the strategy in the preparation of biomaterials and nanomaterials of hydrophobic bioactive molecules.