Department of Chemical and Biological Engineering/Physical Chemistry, Chalmers University of Technology, Kemivägen 10, S-412 96 Gothenburg, Sweden.
Biochem Biophys Res Commun. 2012 Oct 19;427(2):261-5. doi: 10.1016/j.bbrc.2012.09.030. Epub 2012 Sep 16.
Cell-penetrating peptides and antimicrobial peptides are two classes of positively charged membrane active peptides with several properties in common. The challenge is to combine knowledge about the membrane interaction mechanisms and structural properties of the two classes to design peptides with membrane-specific actions, useful either as transporters of cargo or as antibacterial substances. Membrane active peptides are commonly rich in arginine and tryptophan. We have previously designed a series of arg/trp peptides and investigated how the position and number of tryptophans affect cellular uptake. Here we explore the antimicrobial properties and the interaction with lipid model membranes of these peptides, using minimal inhibitory concentrations assay (MIC), circular dichroism (CD) and linear dichroism (LD). The results show that the arg/trp peptides inhibit the growth of the two gram positive strains Staphylococcus aureus and Staphylococcus pyogenes, with some individual variations depending on the position of the tryptophans. No inhibition of the gram negative strains Proteus mirabilis or Pseudomonas aeruginosa was noticed. CD indicated that when bound to lipid vesicles one of the peptides forms an α-helical like structure, whereas the other five exhibited rather random coiled structures. LD indicated that all six peptides were somehow aligned parallel with the membrane surface. Our results do not reveal any obvious connection between membrane interaction and antimicrobial effect for the studied peptides. By contrast cell-penetrating properties can be coupled to both the secondary structure and the degree of order of the peptides.
细胞穿透肽和抗菌肽是两类带正电荷的膜活性肽，具有许多共同的特性。挑战在于将这两类肽的膜相互作用机制和结构特性的知识结合起来，设计具有膜特异性作用的肽，既可用作货物的载体，也可用作抗菌物质。膜活性肽通常富含精氨酸和色氨酸。我们之前设计了一系列精氨酸/色氨酸肽，并研究了色氨酸的位置和数量如何影响细胞摄取。在这里，我们使用最小抑菌浓度测定法 (MIC)、圆二色性 (CD) 和线二色性 (LD) 来研究这些肽的抗菌特性和与脂质模型膜的相互作用。结果表明，精氨酸/色氨酸肽抑制了两种革兰氏阳性菌株金黄色葡萄球菌和酿脓链球菌的生长，个别色氨酸位置的变化会导致不同的抑制效果。革兰氏阴性菌奇异变形杆菌和铜绿假单胞菌则不受抑制。CD 表明，当与脂质囊泡结合时，其中一种肽形成类似α-螺旋的结构，而其他五种则呈现出相当随机的卷曲结构。LD 表明，所有六种肽都以某种方式与膜表面平行排列。我们的研究结果并未揭示所研究的肽的膜相互作用与抗菌效果之间的明显联系。相比之下，细胞穿透特性可以与肽的二级结构和有序程度相关联。
