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Here we report the examination of two convenient strategies, the use of a d-amino acid residue or a glycoside segment, for increasing the proteolytic resistance of supramolecular hydrogelators based on small peptides. Our results show that the introduction of d-amino acid or glycoside to the peptides significantly increases the resistance of the hydrogelators against proteinase K, a powerful endopeptidase. The insertion of d-amino acid in the peptide backbone, however, results relatively low storage moduli of the hydrogels, likely due to the disruption of the superstructures of the molecular assembly. In contrast, the introduction of a glycoside to the C-terminal of peptide enhances the biostability of the hydrogelators without the significant decrease of the storage moduli of the hydrogels. This work suggests that the inclusion of a simple glycogen in hydrogelators is a useful approach to increase their biostability, and the gained understanding from the work may ultimately lead to development of hydrogels of functional peptides for biomedical applications that require long-term biostability.

Introducing d-Amino Acid or Simple Glycoside into Small Peptides to Enable Supramolecular Hydrogelators to Resist Proteolysis