Fmoc-conjugated dipeptide-based hydrogels and their pH-tuneable behaviour†

Abstract

In this work, we designed three dipeptide-based hydrogelators by attaching different hydrophilic amino acids (aspartic acid, glutamic acid, and glutamine) to Fmoc-conjugated phenylalanine. Self-assembly and gelation of the three dipeptides were studied in 50 mM phosphate buffer solutions. The gelation efficiency and kinetics of glutamine-based hydrogelators (FQ) were better than those of aspartic acid and glutamic acid-based hydrogelators FD and FE respectively at neutral pH. The lower gelation efficiency of FE and FD was due to the pH-responsive side chain (carboxylic acid) compared to FQ, where amide group was present as a side chain. Three hydrogelators exhibited better gelation efficiency at lower pHs as the anionic carboxylate group was protonated to the carboxylic group, facilitating better self-assembly and gelation processes. Thioflavin-T (ThT) binding study of hydrogels indicated the formation of β-sheet-like structure in the hydrogel state. The self-assembly process was inspected using molecular dynamic study, revealing that the newly developed FQ gelator possesses a higher aggregation tendency than FE and FD. Finally, these peptide-based injectable biomaterials were examined using fluorescence and FT-IR spectroscopy, scanning electron microscopy, and rheology.