Enzymatically-stable oxetane-based dipeptide hydrogels.

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Peptide Chemistry

Background:

• Enzyme-degradable low molecular weight gelators limit applications.
• Fmoc-protected dipeptides are common gelators but can be susceptible to enzymatic degradation.
• Developing enzyme-resistant gelators is crucial for broader applications.

Purpose of the Study:

• To synthesize and evaluate novel Fmoc-protected dipeptide oxetane analogs as low molecular weight gelators.
• To investigate the self-assembly properties and gelation capabilities of these peptidomimetics.
• To assess the enzymatic stability of the novel gelators compared to parent dipeptides.

Main Methods:

• Synthesis of Fmoc-protected dipeptide oxetane analogs.
• Gelation studies at various concentrations in aqueous solutions.
• Characterization of hydrogel formation and structure (e.g., lack of beta-sheet).
• Proteolysis assays to evaluate enzymatic stability.

Main Results:

• One novel Fmoc-protected dipeptide oxetane analog effectively formed hydrogels at 3 mg mL⁻¹.
• The gelation did not rely on the formation of beta-sheet structures.
• The modified dipeptide exhibited significantly enhanced stability against proteolysis compared to the parent dipeptide.

Conclusions:

• Replacing the amide carbonyl with an oxetane ring yields effective, enzyme-resistant low molecular weight gelators.
• Beta-sheet structure is not essential for gelation in this class of peptidomimetics.
• These oxetane-based peptidomimetics show promise for applications requiring stable hydrogels.