Antibacterial hydrogels of aromatic tripeptides

Self-assembled peptide hydrogels have emerged as alternatives to the conventional approaches employed in controlled drug release, wound-healing, and drug delivery, and as anti-infective agents. However, peptide hydrogels possessing antibacterial properties are less explored. In this work, we have designed three ultrashort antibacterial peptide hydrogels: Fmoc-FFH-CONH₂, Fmoc-FHF-CONH₂, and Fmoc-HFF-CONH₂. The rheological study showed the higher storage modulus of Fmoc-FFH-CONH₂ (30.43 kPa) compared to Fmoc-FHF-CONH₂ and Fmoc-HFF-CONH₂, which may be attributed to the enhanced aromatic interaction in Fmoc-FFH-CONH₂ compared to the other two variants, resulting in more mechanical rigidity. Further, the prepared hydrogels were evaluated for their inherent antibacterial potency against Gram-positive (Staphylococcus aureus, strain MTCC 96) and Gram-negative (Pseudomonas aeruginosa, strain PA01) bacteria. Antibacterial experiments demonstrated the potency of the hydrogels in the order of Fmoc-FFH-CONH₂ > Fmoc-FHF-CONH₂ > Fmoc-HFF-CONH₂. The antibacterial effect of the hydrogels was predominantly due to the osmotic stress and membrane disruption, which was verified by reactive oxygen species (ROS) generation and outer membrane permeabilization assays. Our findings point to the scope of using the synthesized peptide hydrogels as agents for topical applications.