Wang Taoran, Zou Cunbin, Wen Na, Liu Xingdong, Meng Zhao, Feng Siliang, Zheng Zhibing, Meng Qingbin, Wang Chenhong
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, China.
J Pept Sci. 2021 May;27(5):e3306. doi: 10.1002/psc.3306. Epub 2021 Feb 7.
In this article, a series of modifications were made on an antimicrobial peptide F W, including altering the amino acid sequence, introducing cysteine and other typical amino acids, developing peptide dimers via disulfide bonds, and conjugating with mPEG, in order to enhance the antimicrobial activity, plasma stability, and reduce the hemolytic activity of peptides. The results showed that mPEG conjugation could significantly improve the plasma stability and reduce the hemolytic activity of peptides, while the antimicrobial activity decreased meanwhile. However, altering the sequence of the peptide without changing its amino acid composition had little impact on its antimicrobial activity and plasma stability. The introduction of cysteine enhanced the plasma stability of peptides conspicuously, but at the same time, the increased hydrophobicity of peptides increased their hemolysis. The antimicrobial mechanism and cytotoxicity of the peptides with relatively high antimicrobial activity were also studied. In general, this study provided some ideas for the rational design and structure optimization of antimicrobial peptides.
在本文中，对抗菌肽FW进行了一系列修饰，包括改变氨基酸序列、引入半胱氨酸和其他典型氨基酸、通过二硫键形成肽二聚体以及与甲氧基聚乙二醇（mPEG）偶联，以增强肽的抗菌活性、血浆稳定性并降低其溶血活性。结果表明，mPEG偶联可显著提高肽的血浆稳定性并降低其溶血活性，同时抗菌活性降低。然而，在不改变氨基酸组成的情况下改变肽的序列对其抗菌活性和血浆稳定性影响不大。半胱氨酸的引入显著增强了肽的血浆稳定性，但同时，肽疏水性的增加也增加了它们的溶血作用。还研究了具有较高抗菌活性的肽的抗菌机制和细胞毒性。总体而言，本研究为抗菌肽的合理设计和结构优化提供了一些思路。
