Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury101, 02-089 Warsaw, Poland.
Faculty of Biology, Institute of Microbiology, Department of Bacterial Genetics, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
Langmuir. 2020 Nov 3;36(43):12900-12910. doi: 10.1021/acs.langmuir.0c02135. Epub 2020 Oct 21.
We have designed and synthesized new short lipopeptides composed of tetrapeptide conjugated to fatty acids with different chain lengths. The amino acid sequence of the peptide moiety included d-phenylalanine, two residues of l-2,4-diaminobutyric acid and l-leucine. To explore the possible mechanism of lipopeptide action, we have provided a physicochemical characterization of their interactions with artificial lipid membranes. For this purpose, we have used monolayers and bilayers composed of lipids representative of Gram-negative and Gram-positive bacterial membranes. Using surface pressure measurements and atomic force microscopy, we were able to monitor the changes occurring within the films upon exposure to lipopeptides. Our experiments revealed that all lipopeptides can penetrate the lipid membranes and affect their molecular ordering. The latter results in membrane thinning and fluidization. However, the effect is stronger in the lipid films mimicking Gram-positive bacterial membranes. The results of the physicochemical characterization were compared with the biological activity of lipopeptides. The effect of lipopeptides on bacterial growth was tested on several strains of bacteria. It was revealed that lipopeptides show stronger antimicrobial activity against Gram-positive bacteria. At the same time, all tested compounds display relatively low hemolytic activity.
我们设计并合成了新的短肽脂类化合物，由不同链长的脂肪酸连接的四肽组成。肽部分的氨基酸序列包括 d-苯丙氨酸、两个 l-2,4-二氨基丁酸残基和 l-亮氨酸。为了探索脂肽作用的可能机制，我们对它们与人工脂质膜的相互作用进行了物理化学特性分析。为此，我们使用了由革兰氏阴性和革兰氏阳性细菌膜代表性脂质组成的单层膜和双层膜。通过表面压力测量和原子力显微镜，我们能够监测到脂肽暴露后膜内发生的变化。我们的实验表明，所有脂肽都可以穿透脂质膜并影响其分子排列。这导致膜变薄和流化。然而，这种影响在模拟革兰氏阳性细菌膜的脂质膜中更强。物理化学特性分析的结果与脂肽的生物学活性进行了比较。我们在几种细菌菌株上测试了脂肽对细菌生长的影响。结果表明，脂肽对革兰氏阳性菌表现出更强的抗菌活性。同时，所有测试的化合物显示出相对较低的溶血活性。
