Binding Properties of DNA and Antimicrobial Peptide Chensinin-1b Containing Lipophilic Alkyl Tails
Binding Properties of DNA and Antimicrobial Peptide Chensinin-1b Containing Lipophilic Alkyl Tails
复制标题
DNA 与含亲脂烷基尾抗菌肽 Chensinin-1b 的结合特性
DOI：
10.1007/s10895-019-02478-x
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发表时间：
2020-01-01
影响因子：
2.7
通讯作者：
Shang, Dejing
中科院分区：
文献类型：
--
作者：
Dong, Weibing;Luo, Xueyue;Shang, Dejing
多重耐药细菌对人类健康构成了重大威胁。针对chensinin-1b对多药耐药菌（multidrug resistant，MDR）抗菌活性较弱的特点，设计了3种脂溶性chensinin-1b短肽OA-C1 b、LA-C1 b和PA-C1 b，并对其抗菌活性进行了研究。OA-C1 b和LA-C1 b肽均对选定的多重耐药菌株表现出有效的抗微生物活性。除了抗微生物肽直接破坏细菌膜之外，还提出DNA是抗微生物肽的上级细胞内靶标。ctDNA被用作模型，使用各种生物物理方法研究DNA和脂-chensinin-1b肽的结合特性。紫外-可见光谱和圆二色光谱的动力学结果表明，lipo-chensinin-1b多肽与ctDNA之间的相互作用具有浓度依赖性，并导致多核苷酸螺旋度的增加。粘度测量、Trp荧光和碘化物猝灭实验表明，在与ctDNA相互作用时，肽段主要以非经典的沟结合和静电结合两种方式与ctDNA相互作用。此外，使用动态光散射实验监测肽-ctDNA复合物的形成，在此期间肽表现出中和ctDNA表面负电荷的能力。这些结果促进了设计靶向DNA的基于肽的抗生素的可能性。
Multidrug-resistant bacteria present an important threat to human health. In this study, due to the weak antimicrobial activity of chensinin-1b against multidrug-resistant (MDR) bacteria, three lipo-chensinin-1b peptides, including OA-C1b, LA-C1b and PA-C1b, were designed and their activities against MDR bacteria were examined. Both the OA-C1b and LA-C1b peptides exhibited potent antimicrobial activity against selected multidrug-resistant bacterial strains. In addition to the direct disruption of bacterial membranes by antimicrobial peptides, it has also been proposed that DNA is a superior intracellular target for antimicrobial peptides. ctDNA was used as a model to investigate the binding properties of DNA and lipo-chensinin-1b peptides using a variety of biophysical methods. The kinetics results of both UV-Vis and CD spectroscopy suggested that the interaction between lipo-chensinin-1b peptides and ctDNA was concentration-dependent and resulted in an increase in polynucleotide helicity. Viscosity measurements, Trp fluorescence and iodide quenching experiments indicated that nonclassical groove binding and electrostatic binding interaction modes were utilized when the peptides interacted with the ctDNA. In addition, the formation of peptide-ctDNA complexes was monitored using dynamic light scattering experiments, during which the peptide exhibited the ability to neutralize the negative charges on the surface of the ctDNA. These results promote the possibility of designing peptide-based antibiotics targeted to DNA.