Synthesis and biological activity study of pH-responsive amphipathic antimicrobial peptide hydrogels

This study designed and synthesized amphipathic peptides(KF-series peptides) containing lysine K and phenylalanine F to investigate the effects of positive charges on both antibacterial efficacy and gelation performance. Experimental observations via SEM demonstrated that peptides are capable of disrupting the bacterial membrane. Spectroscopic analysis indicates that with the number of positive charges increases, the binding mode of KF-series peptides with DNA transitions from intercalative binding and electrostatic binding to groove binding coupled with electrostatic binding. Antimicrobial experiments demonstrated that the antibacterial efficacy of KF-series peptides progressively enhanced with increasing positive charge quantity, while exhibiting broad-spectrum antimicrobial activity against palmar bacteria. Further structural analysis on KF-1 and KF-2 peptides were demonstrated by inducing their self-assembly into hydrogels in high pH value. TEM results showed distinct microscopic morphologies of the KF-1 peptide under varying pH conditions. Rheological data indicated that KF-1 exhibited superior rheological performance. Although increasing positive charges enhanced the antimicrobial activity of the peptides, this improvement compromised the stability of the gel structure. Therefore, maintaining an appropriate ratio between basic amino acids and nonpolar amino acids is crucial for designing peptides with both antimicrobial capability and gelation capability. This study provides novel insights into the design of innovative dual-functional antimicrobial peptide hydrogels.