Fatty acid chain modification enhances the serum stability of antimicrobial peptide B1 and activities against Staphylococcus aureus and Klebsiella pneumoniae

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2024-11-28 DOI:10.1016/j.bioorg.2024.108015

Zhouyuji Liao , Yong Wu , Meng Liu , Junjie Zhang , Yunfei Cui , Dongting Zhangsun , Sulan Luo

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Abstract

Antimicrobial peptides (AMPs) possess broad-spectrum antibacterial properties and low resistance development, making them promising candidates for new antibacterial drugs. Incorporating fatty acid chains into AMPs can increase their hydrophobicity, strengthen membrane affinity, and improve their antibacterial effectiveness and stability. This study introduces fatty acid chains of varying lengths into the naturally derived antimicrobial peptide B1. These modified peptides were evaluated for their antibacterial activity, stability, and biocompatibility to identify the optimal chain length for analogues. The analogues B1-C6 and B1-C8 exhibited significantly enhanced antimicrobial activities against Staphylococcus aureus (S. aureus) and Klebsiella pneumoniae (K. pneumonia), demonstrating better stability and biocompatibility. Following acute toxicity and skin irritation tests on mice, further in vivo tests using a mouse skin inflammation model showed that these peptides significantly restrain bacterial growth and promote wound healing. The skin healing rate in the high-concentration group reached 95.92%, 97.35% 98.42% and 98.17%, respectively. These findings indicated that optimizing the hydrophobic-hydrophilic balance in AMPs is crucial for maximizing their therapeutic potential. This research offers a promising approach for designing effective AMPs to treat infections caused by S. aureus and K. pneumoniae.

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.