Zhao Fangyi, Guo Hui, Zhang Zhidong, Ye John, Liu Longlong, Zhao Chun-Xia, Shao Zhengzhong
State Key Laboratory of Molecular Engineering of Polymers, Laboratory of Advanced Materials and Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
J Mater Chem B. 2017 Jul 14;5(26):5189-5195. doi: 10.1039/c7tb00736a. Epub 2017 Jun 15.
Self-assemblies of peptide amphiphiles feature unique structures, high biocompatibility, and potential for various applications, and have attracted increasing interest in supramolecular chemistry, protein science and polymer science. In this paper, isomeric peptide amphiphiles derived from lauric acid and silk fibroin-based peptides with different amino acid sequences (GAGAGAGY, GAGAGYGA, GAGYGAGA and GYGAGAGA) are investigated systematically to figure out the predominant endogenous and exogenous factors for their assembly in aqueous solution. With the position of tyrosine (Y) in the peptide segment gradually moving towards the alkane tails, the assembled peptide amphiphiles substantially change their secondary structures from the β-sheet to the disorder dominant one under neutral pH conditions, because the increase of steric hindrance induced by the position change of Y disturbs the hydrogen bonds relevant to the formation of β-sheets of (GA). Strong alkaline conditions are able to accelerate such a conformational change, due to the synergy of destruction of hydrogen bonds, the steric hindrance effect and electrostatic repulsion. As a consequence, the assembled peptide amphiphiles alter their nanostructures in aqueous solution from well-defined nanofibers to nanospheres with varying sizes. Therefore, it is summarized that the location of Y rather than the other effects such as pH value, etc. plays an essential role in the assembly of our isomeric peptide amphiphiles, which sheds light on the design of various isomeric peptides/peptide amphiphiles for their aggregation as well as potential functionality.
肽两亲分子的自组装具有独特的结构、高生物相容性以及在各种应用中的潜力，在超分子化学、蛋白质科学和聚合物科学领域引起了越来越多的关注。本文系统研究了由月桂酸和具有不同氨基酸序列（GAGAGAGY、GAGAGYGA、GAGYGAGA和GYGAGAGA）的丝素蛋白基肽衍生的同分异构肽两亲分子，以确定其在水溶液中组装的主要内源性和外源性因素。随着肽段中酪氨酸（Y）的位置逐渐向烷烃尾部移动，在中性pH条件下，组装后的肽两亲分子的二级结构从β-折叠显著转变为无序主导结构，这是因为Y位置变化引起的空间位阻增加扰乱了与（GA）β-折叠形成相关的氢键。强碱性条件能够加速这种构象变化，这是由于氢键破坏、空间位阻效应和静电排斥的协同作用。结果，组装后的肽两亲分子在水溶液中的纳米结构从规则的纳米纤维转变为大小各异的纳米球。因此，可以总结出Y的位置而非pH值等其他因素在我们的同分异构肽两亲分子的组装中起着至关重要的作用，这为设计各种同分异构肽/肽两亲分子以实现其聚集及潜在功能提供了启示。
