Flexible customization of the self‐assembling abilities of short elastin‐like peptide Fn analogs by substituting N‐terminal amino acids
Flexible customization of the self‐assembling abilities of short elastin‐like peptide Fn analogs by substituting N‐terminal amino acids
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DOI：
10.1002/bip.23521
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发表时间：
2022-07
期刊：
影响因子：
2.9
通讯作者：
K. Suyama;M. Shimizu;I. Maeda;T. Nose
中科院分区：
文献类型：
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作者：
K. Suyama;M. Shimizu;I. Maeda;T. Nose
弹性蛋白样肽(ELP)是一种受天然弹性蛋白特有的重复序列启发而产生的热敏生物聚合物。由于ELP具有依赖于温度的可逆自组装，因此有望成为生物相容的药物传递载体的热响应材料。在这一领域研究最广泛的ELP之一是重复的五肽(VPGXG)n。我们以前报道过含有苯丙氨酸的ELP(FN)类似物，其中重复序列(VPGVG)n的原来的Val残基被Phe取代，表现出短链凝聚(n=5)。Fn类似物序列短，易于通过简单的化学合成修饰氨基酸序列，可用于研究多肽序列与温度响应性的关系。在这项研究中，我们通过用其他氨基酸取代Phe残基(S)或在N末端引入另一个氨基酸来开发FN类似物。随着单个Phe残基的取代，FN类似物的温度响应性发生了很大的变化，这表明芳香氨基酸在其自组装中起着重要的作用。此外，随着N-端氨基酸体积的增大，FN的自组装能力增强。因此，在凝聚过程中，N端残基在疏水性诱导的多肽分子间相互作用中起重要作用。
Elastin‐like peptides (ELPs) are thermoresponsive biopolymers inspired by the characteristic repetitive sequences of natural elastin. As ELPs exhibit temperature‐dependent reversible self‐assembly, they are expected to be biocompatible thermoresponsive materials for drug delivery carriers. One of the most widely studied ELPs in this field is the repetitive pentapeptide, (VPGXG)n. We previously reported that phenylalanine‐containing ELP (Fn) analogs, in which the former Val residue of the repetitive sequence (VPGVG)n is replaced by Phe, show coacervation with a short chain length (n = 5). Owing to their short sequences, Fn analogs are easily modified in amino acid sequences via simple chemical synthesis, and are useful for investigating the relationship between peptide sequences and temperature responsiveness. In this study, we developed Fn analogs by replacing Phe residue(s) with other amino acids or introducing another amino acid at the N‐terminus. The temperature responsiveness of the Fn analogs changed drastically with the substitution of a single Phe residue, suggesting that aromatic amino acids play an important role in their self‐assembly. In addition, the self‐assembling ability of Fn was enhanced by increasing the bulkiness of the N‐terminal amino acids. Therefore, the N‐terminal residue was considered to be important for hydrophobicity‐induced intermolecular interactions between the peptides during coacervation.