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Single or double lipid-modified ultra-short antimicrobial peptides for treating infections caused by resistant bacteria
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DOI：10.1016/j.ejmech.2025.117321.png)
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Abstract
En 中文
Unmodified ultra-short antimicrobial peptides (AMPs) have difficulty attaining high antimicrobial activity and low toxicity concurrently. Our previous studies have shown that single-site lipid modification can enhance the antimicrobial activity of AMPs. However, research on multi-site modification is scarce. This study designed and synthesized a series of single/double-site lipid-modified ultra-short AMPs. Particularly, the new single-site lipidmodified AMP C12 (C12-KKWW-NH2) and double-site lipid-modified AMP DC8 [(C8)2-KKKWW-NH2] showed high bacterial membrane selectivity and presented high stability. It is worth noting that C12 and DC8 exert excellent antibacterial effects on clinically resistant bacteria and have an extremely low resistance tendency. When combined with conventional antibiotics, they show synergistic antibacterial activity against resistant bacteria and curb the resistance of the antibiotics. Additionally, the novel ultra-short AMPs reveal non-receptormediated membrane bactericidal mechanisms and can kill the tested bacteria rapidly. Moreover, both C12 and DC8 have high antibacterial activity and low toxicity in vivo. These results suggest that both single-site and multisite lipid modifications can produce highly efficient AMPs.
Keywords:
Antibiotic resistance
Lipid-modified
Minimalist design
Ultra-short AMPs
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