Effects of linker amino acids on the potency and selectivity of dimeric antimicrobial peptides
Effects of linker amino acids on the potency and selectivity of dimeric antimicrobial peptides
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连接氨基酸对二聚抗菌肽效力和选择性的影响
DOI：
10.1016/j.cclet.2018.04.011
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发表时间：
2018
影响因子：
9.1
通讯作者：
Wang Rui
中科院分区：
文献类型：
--
作者：
Kai Ming;Zhang Wei;Xie Huan;Liu Liwei;Huang Sujie;Li Xiao;Zhang Zhengzheng;Liu Yuyang;Zhang Bangzhi;Song Jingjing;Wang Rui
二聚化是设计结合不同天然多肽优点的抗菌肽的有效策略。在这项研究中，我们探索了不同的连接氨基酸，包括亮氨酸、脯氨酸和氨基己酸对AM-1、AM-2和AM-3的抗癌、抗菌和溶血活性的影响。脯氨酸和氨基己酸是提高异构体抗菌肽效力和选择性的理想连接物。分子动力学模拟的结果为这一观测结果提供了合理性。AM-2和AM-3在水中均为致密构象，在膜中为弯曲构象。AM-2和AM-3柔性结构的这种变化可能导致这些多肽与两性离子脂双层的结合减少，并增加了对含有酸性磷脂的混合脂双层的损伤。总之，通过评估连接氨基酸的作用而获得的这些发现将有助于设计具有高选择性和高效力的理想的异构体抗菌肽。
Dimerization is an effective strategy for designing antimicrobial peptides that combine the advantages of different native peptides. In this study, we explored the effects of different linker amino acids, including leucine, proline and aminocaproic acid, on the anticancer, antimicrobial and hemolytic activities of the heteromeric antimicrobial peptides AM-1, AM-2, and AM-3. Proline and aminocaproic acid are ideal linkers for increasing the potency and selectivity of heteromeric antimicrobial peptides. The results of MD simulations provided a rationalization for this observation. Both AM-2, which had a proline linker, and AM-3, which had an aminocaproic acid linker, adopted a compact conformation in water and a bent conformation in membranes. This change in the flexible structures of AM-2 and AM-3 could have resulted in decreased binding of these peptides to zwitterionic lipid bilayers and increased damage to mixed lipid bilayers containing acidic phospholipids. In short, these findings obtainedviaassessing the effects of linker amino acids will contribute to the design of ideal heteromeric antimicrobial peptides with high selectivity and potency.