Department of Biotechnology, Research Institute for Biomedical and Health Science, College of Biomedical and Health Science, Konkuk University, Chungju, Chungbuk 380-701, Korea.
Molecules. 2013 Jan 11;18(1):859-76. doi: 10.3390/molecules18010859.
In an effort to develop short antimicrobial peptides with simple amino acid compositions, we generated a series of undecapeptide isomers having the L(5)K(5)W formula. Amino acid sequences were designed to be perfectly amphipathic when folded into a helical conformation by converging leucines onto one side and lysines onto the other side of the helical axis. The single tryptophans, whose positions were varied in the primary structures, were located commonly at the critical amphipathic interface in the helical wheel projection. Helical conformations and the tryptophanyl environments of the 11 L(5)K(5)W peptides were confirmed and characterized by circular dichroism, fluorescence and nuclear magnetic resonance spectroscopy. All of the isomers exhibited a potent, broad-spectrum of antibacterial activity with just a slight variance in individual potency, whereas their hemolytic activities against human erythrocytes were significantly diversified. Interestingly, helical dispositions and fluorescence blue shifts of the peptides in aqueous trifluoroethanol solutions, rather than in detergent micelles, showed a marked linear correlation with their hemolytic potency. These results demonstrate that our de novo design strategy for amphipathic helical model peptides is effective for developing novel antimicrobial peptides and their hemolytic activities can be estimated in correlation with structural parameters.
为了开发具有简单氨基酸组成的短抗菌肽，我们生成了一系列具有 L(5)K(5)W 公式的十一肽异构体。当氨基酸序列折叠成螺旋构象时，它们的设计是完全两亲性的，通过将亮氨酸集中在螺旋轴的一侧，将赖氨酸集中在另一侧。位置在一级结构中变化的单个色氨酸通常位于螺旋轮投影中的关键两亲性界面。通过圆二色性、荧光和核磁共振波谱学证实和表征了 11 种 L(5)K(5)W 肽的螺旋构象和色氨酸环境。所有异构体均表现出强大、广谱的抗菌活性，个体活性略有差异，而它们对人红细胞的溶血活性则有显著差异。有趣的是，肽在三氟乙醇水溶液中的螺旋排列和荧光蓝移，而不是在去污剂胶束中，与它们的溶血活性呈明显的线性相关。这些结果表明，我们用于设计两亲性螺旋模型肽的从头设计策略对于开发新型抗菌肽是有效的，并且可以与结构参数相关联来估计它们的溶血活性。
