鸭抗菌肽Cathelicidin的衍生物设计及抑菌机制研究

发布时间：2018-11-17 19:21

【摘要】：鸭抗菌肽Cathelicidin分子[Cath(1-20)]富含疏水性氨基酸及正电荷,通过人工方法设计合成Cath(1-20)的截短肽衍生物,筛选新型安全Cath(1-20)衍生肽,探讨其作用机制。结果表明,与母肽Cath(1-20)相似,三种衍生肽Cath(5-20)、Cath(4-20)、Cath(3-20)均具有明显广谱抑菌活性,MIC值在1~8μmol·L~(-1)范围内,但仅Cath(5-20)溶血及细胞毒性明显降低,治疗指数达19.5,显著高于Cath(1-20)、Cath(4-20)及Cath(3-20)。Cath(1-20)及其衍生肽可破坏E.coli UB1005的内膜完整性,产生去极化作用,并存在时间和剂量依赖效应;透射电镜结果显示Cath(1-20)及Cath(5-20)可破坏细菌细胞膜。研究证实氨基端的色氨酸对鸭抗菌肽Cath(1-20)溶血及细胞毒性起关键作用,其作用靶点主要为细菌细胞膜。
[Abstract]:Duck antimicrobial peptide Cathelicidin molecule [Cath (1-20)] is rich in hydrophobic amino acids and positive charges. The truncated peptide derivatives of Cath (1-20) were designed and synthesized by artificial method. The results showed that the three derivative peptides Cath (5-20), Cath (4-20), Cath (3-20) had broad spectrum antibacterial activity similar to the parent peptide Cath (1-20), and the MIC value was in the range of 1 渭 mol L ~ (-1). However, the hemolysis and cytotoxicity of Cath (5-20) were significantly decreased, and the therapeutic index was 19.5, which was significantly higher than that of Cath (1-20). Cath (4-20) and Cath (3-20). Cath (1-20) and their derived peptides could destroy the intimal integrity and depolarization of E.coli UB1005 in a time-and dose-dependent manner. Transmission electron microscopy showed that Cath (1-20) and Cath (5-20) could destroy bacterial cell membrane. It was confirmed that tryptophan at amino terminal plays a key role in hemolysis and cytotoxicity of duck antimicrobial peptide Cath _ (1-20), and its main target is bacterial cell membrane.
【作者单位】： 东北农业大学动物科学技术学院;
【基金】：黑龙江省自然科学基金(C2016022) 东北农业大学“学术骨干”项目(15XG15)
【分类号】：S852.2
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