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《工程(英文)》 >> 2015年 第1卷 第4期 doi: 10.15302/J-ENG-2015106

吖啶– 核定位序列偶联构建的高活性抗菌肽

1 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
2 Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China

收稿日期: 2015-10-13 修回日期: 2015-11-22 录用日期: 2015-11-26 发布日期: 2015-12-30

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摘要

多重耐药菌的出现迫切需要发现具有新作用机制的抗生素。在本研究中,笔者将疏水的吖啶分子连接到核定位序列 (NLS) 的N末端合成了一种新型的抗菌药物Acr3-NLS。为了进 一步提高该试剂的抗菌活性,笔者将两个单体Acr3-NLS分子通过二硫键连接合成了二聚体(Acr3-NLS)2。结果显示,与NLS相比,Acr3-NLS,特别是(Acr3-NLS)2,对革兰阴性菌和革兰阳性菌表现出显著的抗菌活性。随后,其作用机制的研究表明,Acr3-NLS 和(Acr3-NLS)2 可通过细胞膜破坏方式和DNA 结合方式杀死细菌。作用于细胞膜和细胞内DNA的双靶点抑杀机制可以降低细菌对Acr3-NLS 和(Acr3-NLS)2 产生耐药性的风险。总之, 本研究提供了一种新的策略,可用于设计具有双重作用机制的高效抗菌药物。

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