Li Ruifang, He Songlin, Yin Kedong, Zhang Beibei, Yi Yanjie, Zhang Meng, Pei Nanqi, Huang Liang
College of Biological Engineering, Henan University of Technology, Zhengzhou, China.
College of Information Science and Engineering, Henan University of Technology, Zhengzhou, China.
J Pept Sci. 2021 Oct;27(10):e3352. doi: 10.1002/psc.3352. Epub 2021 May 24.
Infections with multidrug-resistant (MDR) pathogens are increasingly concerning for public health. Synthesized antimicrobial peptide A4 (SAMP-A4), a peptide computationally designed by our research team, is a potential drug candidate. However, the antimicrobial peptide SAMP-A4 is easily degraded in serum. To obtain SAMP-A4 analogues with high biostability, chemical modifications at its N-terminus, including fatty acid conjugation, glycosylation and PEGylation, were carried out. The results showed that the introduction of hydrophobic fatty acids at the N-terminus of SAMP-A4 is better than hydrophilic glycosylation and PEGylation. With increasing fatty acid chain length, the stability of SAMP-A4 analogues in serum and trypsin solutions is significantly improved, and the activities against MDR bacteria and Candida are significantly enhanced. There is no obvious change in haemolysis even when hexanoic acid is coupled with SAMP-A4, so the resulting analogue SAMP-A4-C6, SAMP-A4 conjugated with hexanoic acid, is the most likely of the analogues to become a drug.
耐多药（MDR）病原体感染日益引起公共卫生领域的关注。合成抗菌肽A4（SAMP - A4）是我们研究团队通过计算机设计的一种肽，是一种潜在的药物候选物。然而，抗菌肽SAMP - A4在血清中容易降解。为了获得具有高生物稳定性的SAMP - A4类似物，对其N端进行了化学修饰，包括脂肪酸偶联、糖基化和聚乙二醇化。结果表明，在SAMP - A4的N端引入疏水性脂肪酸优于亲水性糖基化和聚乙二醇化。随着脂肪酸链长度的增加，SAMP - A4类似物在血清和胰蛋白酶溶液中的稳定性显著提高，对耐多药细菌和念珠菌的活性也显著增强。即使己酸与SAMP - A4偶联，溶血现象也没有明显变化，因此所得类似物SAMP - A4 - C6（即与己酸偶联的SAMP - A4）是最有可能成为药物的类似物。
