Exploration of Biological Properties and Antibacterial Action against Escherichia coli and Staphylococcus aureus of (LLKK)₃‐Derived Peptides

Abstract In an attempt to develop new antimicrobial peptides (AMPs) with better biological properties, three AMPs of (LLKK) 3 analogues were designed and synthesized. The antibacterial activity, cell toxicity and pepsin stability of the three AMPs were determined, and the antibacterial action of the candidate AMP was analyzed. The results showed that the G(LLKK) 3 L AMP had the stronger antibacterial activity against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) compared to the other AMPs. The hemolytic activity and cytotoxicity of the G(LLKK) 3 L and G(LLKK) 3 AMPs were lower than those of (LLKK) 3 and (LLKK) 3 L AMPs, and the pepsin resistance activity of the G(LLKK) 3 L AMP was higher than that of the other AMPs. Under the treatment of G(LLKK) 3 L AMP, the cell morphology of the E. coli and S. aureus was irregular and wrinkled, their cell membrane was damaged, and the synthesis of their cell wall peptidoglycan was inhibited. Additionally, the G(LLKK) 3 L AMP resulted in a decrease of protein expression and inhibition of DNA synthesis. In summary, the G(LLKK) 3 L AMP exhibited better biological properties, and it can be used as a therapeutic agent against E. coli and S. aureus .