Shunmei He

Amino acid-based hydrogels have received widespread attention because of their wide range of sources, biodegradability, and biocompatibility. Despite considerable progress, the development of such hydrogels has been limited by critical problems such as bacterial infection and complex preparation. Herein, by using the non-toxic gluconolactone (GDL) to adjust the pH of the solution to induce the rapid self-assembly of N-[(benzyloxy)carbonyl]-L-tryptophan (ZW) to form a three-dimensional (3D) gel network, we developed a stable and effective self-assembled small-molecule hydrogel. Characterization assays and molecular dynamics studies indicate that π–π stacking and hydrogen bonding are the main drivers of self-assembly between ZW molecules. In vitro experiments further confirmed this material’s sustained release properties, low cytotoxicity, and excellent antibacterial activity, particularly against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. This study provides a different and innovative perspective for the further development of antibacterial materials based on amino acid derivatives.

Oleanolic acid (OA), a natural product with diverse biological activities, faces clinical limitations due to its poor bioavailability caused by hydrophobic pentacyclic structure. To address this issue, we designed a novel class of oleanolic acid-short peptide derivatives (OA-GFFK) by conjugating OA with a water-soluble short peptide (glycine-phenylalanine-phenylalanine-lysine, GFFK). Molecular dynamics simulation (MD) and density functional theory (DFT) predicted its gelation properties, and OA-GFFK was successfully transformed into supramolecular hydrogels via a simple three-step process (dissolution-ultrasonication-resting). Structural characterization revealed that gelation is driven by π-π stacking and hydrogen bonding, leading to a nanofiber network. And the hydrogels exhibited excellent self-healing, shear response, biocompatibility, and antibacterial activity. This study details a research process for the design and simple preparation of oleanolic acid-short peptide derivative hydrogels, providing design insights and a theoretical basis for developing OA derivatives.