Department of Chemistry, Faculty and Graduate School of Science, Kyushu University, Fukuoka 819-0395, Japan.
Faculty of Arts and Science, Kyushu University, Fukuoka 819-0395, Japan.
Biochemistry. 2023 Sep 5;62(17):2559-2570. doi: 10.1021/acs.biochem.3c00146. Epub 2023 Aug 4.
Synthetic elastin-like peptides (ELPs) that possess characteristic tropoelastin-derived hydrophobic repetitive sequences, such as (VPGVG), exhibit thermoresponsive reversible self-assembly. Although their thermoresponsive properties have been well-studied, the sequence-dependent and structural requirements for self-assembly remain ambiguous. In particular, it is still unclear whether the amino acid sequences derived from tropoelastin are necessary for self-assembly. In this study, 11 sequence-shuffled ELP analogues based on (FPGVG), which is a previously developed short ELP (sELP), were designed to elucidate the sequence-dependent and structural requirements for their self-assembly. Among them, eight shuffled peptides exhibited self-assembling properties, whereas the other three peptides were difficult to dissolve in water. Structural analyses revealed that the structural characteristics of the three insoluble peptides were different from those of their thermoresponsive analogues. Furthermore, the secondary structures of the peptide analogues possessing the self-assembly abilities were different from each other. These results suggest that the potential for self-assembly and water solubility of sELPs depend on the primary structure in each repeated unit. Moreover, several shuffled analogues exhibited more potent self-assembling properties than the original (FPGVG), indicating that shorter ELPs can be obtained using their novel motifs as repetitive units. We also observed that the presence of Pro-Gly sequence in the repeating units was advantageous in terms of peptide solubility. Although further analysis will be necessary to elucidate the molecular mechanism underlying the self-assembly of these sELPs, this study provides insights into the relationship between the amino acid sequence and the self-assembling ability of the peptides for developing new sELPs for various applications.
合成弹性蛋白样肽（ELPs）具有特征性的原弹性蛋白衍生的疏水性重复序列，如（VPGVG），表现出热响应性可逆自组装。尽管它们的热响应特性已经得到了很好的研究，但自组装的序列依赖性和结构要求仍然不清楚。特别是，原弹性蛋白衍生的氨基酸序列是否对自组装是必要的，这仍然不清楚。在这项研究中，设计了 11 种基于（FPGVG）的序列改组 ELP 类似物，这是一种以前开发的短 ELP（sELP），以阐明其自组装的序列依赖性和结构要求。其中，八个改组肽表现出自组装性质，而另外三个肽很难溶解在水中。结构分析表明，三种不溶性肽的结构特征与其热响应类似物不同。此外，具有自组装能力的肽类似物的二级结构彼此不同。这些结果表明，sELP 的自组装潜力和水溶性取决于每个重复单元的一级结构。此外，几个改组类似物表现出比原始（FPGVG）更强的自组装性质，表明可以使用其新颖的基序作为重复单元获得更短的 ELPs。我们还观察到，重复单元中脯氨酸-甘氨酸序列的存在有利于肽的溶解性。尽管需要进一步分析来阐明这些 sELP 自组装的分子机制，但这项研究为开发用于各种应用的新型 sELP 提供了关于肽的氨基酸序列与其自组装能力之间关系的见解。
