De Novo Design of Triblock Amphiphilic Short Antimicrobial Peptides

Antimicrobial peptides (AMPs) exhibit excellent antibacterial capability, and their antibacterial mechanism hardly causes bacterial resistance. Past work on designing AMPs has focused on synthesizing sequences similar to those of natural AMPs. The design and synthesis of highly selective AMPs are important research topics. Triblock amphiphilic peptides (KnFmKn) possess different amino acid sequences and conformations compared with natural AMPs. KnFmKn remain highly active against both Gram-negative and Gram-positive bacteria. The results proved that the newly designed AMPs can focus on the two main elements of the antibacterial mechanism of natural AMPs: the positive charge and hydrophobic amino acids. Suitable aggregates of lysine and long hydrophobic chain length effectively kill bacteria. Minimum inhibitory concentration and hemolysis results showed that these synthetic AMPs exhibit high selectivity against bacteria. The animal infection model experiment showed that these triblock peptides exhibited evident therapeutic effects on bacterial infection. Therefore, the triblock amphiphilic antibacterial peptides exhibit potential applications in the clinical treatment of bacterial infection.