TerminallySymmetric β‑Turn Peptidesfor Multidrug-Resistant Bacterial Infections

Antimicrobial peptides (AMPs) are considered promising agents to solve the problem of antibiotic resistance due to their unique membrane-disruption mechanism. In this research, de novo terminally symmetric β-turn AMPs were designed by combining the β-turn sequences derived from Tritrpticin with alternately arranged cationic and hydrophobic amino acid sequences. The structure–activity relationship of the peptides was studied. Among the designed peptides, P-07 (KIKIKPWWWPKIKIK-NH₂) exhibited potent antimicrobial activity against all the tested bacterial strains, showing the highest bacterial selectivity, relatively low cytotoxicity, high bactericidal efficiency, and low potential to induce bacterial resistance. The antimicrobial mechanisms of P-07 involving membrane-disruption and lipopolysaccharide-binding were proven. Moreover, the in vivo studies confirmed the wound-healing ability of P-07 using a mice bacteria-infected full-thickness wound model. Taken together, P-07 showed great promise in the treatment of multidrug-resistant bacterial infections.