Effect of number of lysine motifs on the bactericidal and hemolytic activity of short cationic antimicrobial peptides

Antimicrobial peptides (AMPs) are vital components of the nonspecific immune system that represent a promising broad-spectrum alternative to conventional antibiotics. Several short cationic antimicrobial peptides show highly effective antibacterial activity and low hemolytic activity, which are based on the action of a few critical amino acids, such as phenylalanine (F) and lysine (K). Previous studies have re-ported that Fmoc-based phenylalanine peptides possess appreciable antibacterial potency against Gram-positive bacteria, but their ability to kill Gram-negative bacteria was suboptimal. In this study, we designed and prepared a series of Fmoc-KnF peptide (n 1/4 1-3) series by adding lysine motifs to strengthen their broad-spectrum antibacterial activity. The effect was investigated that the amount of lysine in Fmoc-F peptides on their antibacterial properties and hemolytic activities. Our results showed that the Fmoc-KKF peptide holds the strongest antimicrobial activity against both Gram-positive and negative bacteria among all designed peptides, as well as low hemolytic activity. These results provide support for the general strategy of enhancing the broad-spectrum antibacterial activity of AMPs through increased lysine content.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Antimicrobial peptides (AMPs) are potential alternatives to antibiotics and show effective antibacterial activity through the action of critical amino acids. Previous studies have shown that Fmoc-based phenylalanine peptides have good antibacterial potency against Gram-positive bacteria but are suboptimal against Gram-negative bacteria. In this study, a series of Fmoc-KnF peptides were designed to enhance their broad-spectrum antibacterial activity by adding lysine motifs. The Fmoc-KKF peptide showed the strongest antimicrobial activity against both types of bacteria, as well as low hemolytic activity.