Synthesis and anti-pseudomonal activity of new ß-Ala modified analogues of the antimicrobial peptide anoplin.

In this study, a series of new β-Ala modified-antimicrobial peptide analogues of anoplin were designed and synthesized, and their biological activities were described. Most of the new peptides showed perfect antimicrobial activities against two antibiotic-sensitive Pseudomonas aeruginosa strains and three clinical isolates of multidrug-resistant P. aeruginosa strains without significant hemolysis or cytotoxicity. More significantly, Ano-1β and Ano-8β (substituting positions 1 and 8 of anoplin with β-Ala, respectively) exhibited the best antimicrobial potency. Additionally, the two new peptides were stable under physiological conditions and displayed preferable in vivo antimicrobial activity with less acute toxicity. Notably, Ano-1β and Ano-8β hardly generated resistance in contrast to conventional antibiotics rifampicin and gentamicin, and they exhibited better anti-biofilm activity and synergistic or additive effects in combination with conventional antibiotics. What's more, Ano-1β and Ano-8β had strong membrane disruption as evidenced by outer membrane permeabilization and cytoplasmic membrane depolarization assays. Confocal laser scanning microscopy and scanning electron microscopy further demonstrated that the two new peptides could destroy the bacterial membrane integrity. Collectively, the incorporation of β-Ala was a reasonable approach for new antimicrobial peptides design, and the new peptides Ano-1β and Ano-8β might be promising antimicrobial candidates i...
Source: International Journal of Medical Microbiology - Category: Microbiology Authors: Tags: Int J Med Microbiol Source Type: research