Development of Amphipathic Antimicrobial Peptide Foldamers Based on Magainin 2 Sequence
Development of Amphipathic Antimicrobial Peptide Foldamers Based on Magainin 2 Sequence
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DOI：
10.1002/cmdc.201900460
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发表时间：
2019-11-06
期刊：
影响因子：
3.4
通讯作者：
Demizu, Yosuke
中科院分区：
文献类型：
--
作者：
Goto, Chihiro;Hirano, Motoharu;Demizu, Yosuke
Magainin 2 (Mag 2) 是从青蛙皮肤中分离出来的，是一种代表性的抗菌肽 (AMP)，通过破坏微生物膜发挥其抗菌活性。据报道，Mag 2的两亲性和螺旋结构在其抗菌活性中发挥着重要作用。在这项研究中，我们揭示了 Mag 2（肽 7）中 17 个氨基酸残基的序列是发挥足够活性所必需的。我们还设计了一组 Mag 2 衍生物，基于通过将 α,α-二取代氨基酸残基掺入 Mag 2 片段来增强螺旋性和/或两亲性，并评估了它们的首选二级结构及其对革兰氏阳性和革兰氏阴性细菌的抗菌活性。结果，肽11在溶液中形成稳定的螺旋结构，对革兰氏阳性菌和革兰氏阴性菌均具有有效的抗菌活性，且没有明显的细胞毒性。
Magainin 2 (Mag 2), which is isolated from the skin of frogs, is a representative antimicrobial peptide (AMP), exerts its antimicrobial activity via microbial membrane disruption. It has been reported that both the amphipathicity and helical structure of Mag 2 play an important role in its antimicrobial activity. In this study, we revealed that the sequence of 17 amino acid residues in Mag 2 (peptide 7) is required to exert sufficient activity. We also designed a set of Mag 2 derivatives, based on enhancement of helicity and/or amphipathicity, by incorporation of alpha,alpha-disubstituted amino acid residues into the Mag 2 fragment, and evaluated their preferred secondary structures and their antimicrobial activities against both Gram-positive and Gram-negative bacteria. As a result, peptide 11 formed a stable helical structure in solution, and possessed potent antimicrobial activities against both Gram-positive and Gram-negative bacteria without significant cytotoxicity.