N-Succinylated Canonical vs. Dehydropeptides: Contrasting Self-Assembly Pathways and Hydrogel Properties

Area of Science:

• Materials Science
• Biomaterials Engineering
• Supramolecular Chemistry

Background:

• Supramolecular peptide hydrogels face limitations in mechanical robustness and proteolytic degradation, hindering biomedical use.
• Dehydropeptides offer enhanced stability, self-assembly, and tunable properties, making them promising alternatives.

Purpose of the Study:

• To compare the self-assembly, gelation, mechanical performance, and cargo release of dehydropeptide hydrogels versus canonical peptide hydrogels.
• To assess the advantages of dehydropeptides in terms of proteolytic resistance and supramolecular organization.

Main Methods:

• Synthesis of N-succinylated dehydrotripeptides and canonical analogs.
• Characterization using spectroscopy (CD, ATR-FTIR), microscopy (TEM), molecular dynamics (MD) simulations, and rheology.
• Proteolysis assays and drug release studies using methyl orange.

Main Results:

• Dehydropeptide hydrogels exhibited enhanced gelation efficacy, improved mechanical properties, and sustained drug release compared to canonical analogs.
• Dehydropeptides formed more ordered supramolecular fibrils with β-sheet-like packing.
• Dehydropeptide dicarboxylic acids demonstrated complete resistance to proteolysis.

Conclusions:

• Incorporating dehydroamino acids into peptides allows precise control over supramolecular packing, network architecture, rheology, and cargo release.
• Dehydropeptide-based hydrogels represent high-performance biomaterials with significant potential for technological and biomedical applications.