Organogelation to Hydrogelation: Effect of C-Terminal Functionalization of Peptides

Peptide-based self-assembled gels are promising soft materials and have applications in biomedicine and material science. While the effect of the substituents on the N-terminal protecting group on the gelation behavior of peptides is often discussed, the role of the C-terminal substitution is seldom addressed. We report a tetrapeptide, P1 (Boc-Ala-Ala-Val-Phe-OMe) with a methyl ester at the C-terminus that forms organogels in various organic solvents. However, hydrolysis of the ester group in P1 to get a carboxylic acid (P2), or preparing a methyl (P3) or an isopropyl (P4) amide converted the peptide into hydrogelators, whereas the dimethyl amide (P5) derivative resulted in the loss of gelation. FE-SEM and AFM studies showed entangled fibrillar networks, driven by the formation of β-sheets, which was confirmed by spectroscopic studies. Rheological measurements demonstrated predominantly elastic behavior for the hydrogels, with P4 exhibiting the highest mechanical strength. To establish the observed effect and to understand the role of aromatic and hydrophobic sidechains, four other peptides were prepared and their gelation behavior was analyzed. These results show how modifications of the C-terminal carboxyl group of a given peptide sequence can affect its gelation and may provide an easier solution in tuning the properties of peptide-based gels.