Engineering the Pentapeptide Gelation in Ethanol by a Tiny Side-Chain Difference

Peptide-based gels hold promise for applications in fields ranging from material development to biomedical engineering. However, challenge remains in controlling the assembly of peptides owing to their structure complexity and formation pathways. Here, we report the gelation of four pentapeptides that are slightly different in the side chains of the molecules in ethanol. Results indicated that ECAFF, ECAYF and ECGFF formed ethanol gels, while a transparent solution was obtained by ECGYF. A high storage modulus of ECAFF hydrogel could be up to ∼104 Pa, and such a gel was composed of tightly entangled fiber bundles with more β-sheet secondary structures. We proposed that removing a hydroxyl group from the tyrosine in the pentapeptides enhanced the π-π stacking interactions between the peptides, thus increased the self-assemble tendency into fibrils. In addition, we suggest that a methyl group on the alanine in the peptide sequence play a positively collaborative role in the gelation of peptides compared with glycine. The findings may shed light on devising the peptide gels with desired properties.