Structure–activity relationship study of amphipathic antimicrobial peptides using helix-destabilizing sarcosine,Journal of Peptide Science

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Structure–activity relationship study of amphipathic antimicrobial peptides using helix-destabilizing sarcosine
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2021-06-23 , DOI: 10.1002/psc.3360
Hidetomo Yokoo ₁ , Motoharu Hirano _{1,

2} , Nobumichi Ohoka ₃ , Takashi Misawa ₁ , Yosuke Demizu _{1,

2}

Affiliation

Antimicrobial peptides (AMPs) are potential therapeutic agents against bacteria. We recently showed that a rationally designed AMP, termed Stripe, with an amphipathic distribution of native cationic and hydrophobic amino acids on its helical structure exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria with negligible hemolytic activity and cytotoxicity. In this study, the structure–activity relationship of Stripe was elucidated by designing a series of antimicrobial peptides whereby amino acid residues of Stripe were exchanged with helix-destabilizing sarcosine residues. Stripe 1–5 peptides with hydrophobic amino acids substituted with sarcosine were predominantly unstructured and showed no antimicrobial activity, except against Escherichia coli (E. coli) (DH5α) cells. The activity against E. coli (DH5α) cells and the helicity of Stripe 1–5 peptides decreased concomitantly as the number of sarcosine residue substitutions increased. Stripe 1–5 peptides showed no hemolytic activity or cytotoxicity. The results indicate that sarcosine substitutions provide an approach to study the structure–activity relationship of helical AMPs, and the helicity of Stripe is an important feature defining its activity.

中文翻译：

使用螺旋去稳定肌氨酸研究两亲性抗菌肽的构效关系

抗菌肽 (AMP) 是针对细菌的潜在治疗剂。我们最近展示了一种合理设计的 AMP，称为Stripe，其螺旋结构上具有天然阳离子和疏水氨基酸的两亲分布，对革兰氏阳性和革兰氏阴性细菌表现出有效的抗菌活性，溶血活性和细胞毒性可忽略不计。在这项研究中，通过设计一系列抗菌肽来阐明Stripe的构效关系，从而将Stripe 的氨基酸残基与螺旋不稳定的肌氨酸残基进行交换。条纹 1–5具有被肌氨酸取代的疏水性氨基酸的肽主要是非结构化的并且没有显示出抗微生物活性，除了针对大肠杆菌（E.coli）（DH5α ）细胞。随着肌氨酸残基取代数量的增加，对大肠杆菌（DH5α ）细胞的活性和Stripe 1-5肽的螺旋度随之降低。条纹 1-5肽没有显示溶血活性或细胞毒性。结果表明，肌氨酸取代为研究螺旋 AMP 的构效关系提供了一种方法，而Stripe的螺旋性是定义其活性的重要特征。

更新日期：2021-06-23

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