Effects of N-terminal modifications on the stability of antimicrobial peptide SAMP-A4 analogues against protease degradation,Journal of Peptide Science

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Effects of N-terminal modifications on the stability of antimicrobial peptide SAMP-A4 analogues against protease degradation
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2021-05-24 , DOI: 10.1002/psc.3352
Ruifang Li ₁ , Songlin He ₁ , Kedong Yin ₂ , Beibei Zhang ₁ , Yanjie Yi ₁ , Meng Zhang ₁ , Nanqi Pei ₁ , Liang Huang ₁

Affiliation

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.

中文翻译：

N端修饰对抗菌肽SAMP-A4类似物抗蛋白酶降解稳定性的影响

耐多药 (MDR) 病原体感染越来越引起公众健康的关注。合成抗菌肽 A4 (SAMP-A4) 是一种由我们的研究团队计算设计的肽，是一种潜在的候选药物。然而，抗菌肽 SAMP-A4 在血清中很容易被降解。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，包括脂肪酸结合、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PEG化。随着脂肪酸链长的增加，SAMP-A4类似物在血清和胰蛋白酶溶液中的稳定性显着提高，对MDR细菌和念珠菌的活性也显着提高。显着增强。即使己酸与 SAMP-A4 偶联，溶血作用也没有明显变化，因此得到的类似物 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。

更新日期：2021-05-24

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