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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脂肪酸链修饰提高了抗菌肽B1的血清稳定性和抗金黄色葡萄球菌和肺炎克雷伯菌的活性

抗菌肽具有广谱抗菌特性和低耐药性的特点，是新型抗菌药物的理想选择。将脂肪酸链掺入抗菌肽中，可以增加抗菌肽的疏水性，增强抗菌肽的膜亲和性，提高抗菌肽的抗菌效果和稳定性。本研究将不同长度的脂肪酸链引入天然衍生的抗菌肽B1中。对这些修饰肽的抗菌活性、稳定性和生物相容性进行了评估，以确定类似物的最佳链长。类似物B1-C6和B1-C8对金黄色葡萄球菌（S. aureus）和肺炎克雷伯菌（K. pneumoniae）的抑菌活性显著增强，具有较好的稳定性和生物相容性。在对小鼠进行急性毒性和皮肤刺激试验后，使用小鼠皮肤炎症模型进行的进一步体内试验表明，这些肽可显著抑制细菌生长并促进伤口愈合。高浓度组皮肤愈合率分别达到95.92%、97.35%、98.42%和98.17%。这些发现表明，优化amp的亲疏水平衡对于最大限度地发挥其治疗潜力至关重要。本研究为设计有效的抗菌肽治疗金黄色葡萄球菌和肺炎克雷伯菌引起的感染提供了一条有希望的途径。

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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.