利用亮氨酸和赖氨酸设计新型α-螺旋抗菌肽-微生物学报.PDFVIP

微生物学通报 Feb. 20, 2014, 41(2): 312−318 Microbiology China © 2014 by Institute of Microbiology, CAS tongbao@ DOI: 10.13344/j.microbiol.china.130153 研究报告 利用亮氨酸和赖氨酸设计新型α-螺旋抗菌肽 * 王良 马清泉 单安山 董娜 吕银凤 ( 150030) 摘 要: 【目的】根据螺旋轮模型设计以亮氨酸(L)为疏水面，赖氨酸(K)为亲水面的新型 α-螺 旋抗菌肽LK ，并对该抗菌肽的生物学活性进行检测。【方法】利用圆二色光谱分析LK 的二级 结构，同时，评价LK 的抑菌活性、稳定性和细胞选择性。【结果】在模拟细胞膜的环境中LK 呈 α-螺旋型结构。LK 对多种革兰氏阳性菌和革兰氏阴性菌有很强的抑菌活性，最小抑菌浓度 (MIC)在2−4 μmol/L 之间。LK 具有很强的酸碱盐稳定性。肽浓度为2−4 μmol/L 时, LK 表现出 较低的溶血活性和细胞毒性。【结论】根据螺旋轮模型结构，以疏水性的L 和正电荷性的K 设 计的新型抗菌肽LK 具有较高的细胞选择性及稳定性，具有替代抗生素的发展潜力。 关键词: 抗菌肽, α-螺旋，溶血活性，细胞毒性 Rational design of α-helical antimicrobial peptide with Leu and Lys residues WANG Liang MA Qing-Quan SHAN An-Shan* DONG Na LÜ Yin-Feng (Institute of Animal Nutrition , Northeast Agricultural University , Harbin , Heilongjiang 150030, China) Abstract: [Objective] We designed a new antibacterial peptide LK. The peptide was composed of Leu residues in the nonpolar face and Lys residues in the polar face based on the helical wheel projection. The activities of LK were tested. [Methods] The secondary structure of LK was studied by Circular Dichroism (CD) spectrometry. Minimal inhibitory concentrations (MICs) of LK against Gram-positive and Gram-negative bacteria were determined. The stability, hemolytic activity and cytotoxicity of LK were also determined. [Results] LK had strong antimicrobial activities against detected bacteria with MICs of 2−4 μmol/L. LK exhibited high pH stability and salt tolerance. The peptide showed very w