New self-assembled supramolecular hydrogels based on dehydropeptides

Area of Science:

• Supramolecular chemistry
• Materials science
• Biotechnology

Background:

• Supramolecular hydrogels self-assemble from small molecules via weak intermolecular forces.
• Peptide-based low molecular weight hydrogelators offer simplicity, versatility, and biocompatibility.
• Naproxen is a widely used non-steroidal anti-inflammatory drug.

Purpose of the Study:

• To design and synthesize novel peptide amphiphiles for self-assembling hydrogel formation.
• To investigate the molecular mechanisms underlying hydrogel self-assembly using computational methods.
• To explore the structure-property relationships of dehydrodipeptide-based hydrogelators.

Main Methods:

• N-conjugation of naproxen with various dehydrodipeptides.
• Molecular dynamics simulations to study self-assembly mechanisms.
• Characterization using transmission electron microscopy (TEM), circular dichroism (CD), fluorescence spectroscopy, and rheological assays.

Main Results:

• Aromatic peptide amphiphiles were successfully synthesized, resisting proteolysis.
• Molecular dynamics simulations provided insights into the self-assembly process, aligning with experimental data.
• Hydrogel formation was observed only with dehydrodipeptides containing at least one aromatic amino acid.

Conclusions:

• Naproxen-conjugated dehydrodipeptides are effective building blocks for supramolecular hydrogels.
• The presence of aromatic amino acids in dehydrodipeptides is crucial for hydrogel formation.
• This study offers a rational design strategy for developing new peptide-based hydrogelators.