Terminally Symmetric β‑Turn Peptides for 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.