School of Engineering , RMIT University , Melbourne , Victoria 3001 , Australia.
School of Life Sciences , University of Sussex , Falmer , East Sussex BN1 9QG , U.K.
ACS Nano. 2018 Sep 25;12(9):9101-9109. doi: 10.1021/acsnano.8b03131. Epub 2018 Aug 31.
Peptide self-assembly represents a powerful bottom-up approach to the fabrication of nanomaterials. β-Peptides are non-natural peptides composed entirely of β-amino acids, which have an extra methylene in the backbone, and we reported fibers derived from the self-assembly of β-peptides that adopt 14-helical structures. β-Peptide assemblies represent a class of stable nanomaterials that can be used to generate bio- and magneto-responsive materials with proteolytic stability. However, the three-dimensional structure of many of these materials remains unknown. To develop structure-based criteria for the design of β-peptide-based biomaterials with tailored function, we investigated the structure of a tri-β-peptide nanoassembly by molecular dynamics simulations and X-ray fiber diffraction analysis. Diffraction data was collected from aligned fibrils formed by Ac-β[LIA] in water and used to inform and validate the model structure. Models with 3-fold radial symmetry resulted in stable fibers with a triple-helical coiled-coil motif and measurable helical pitch and periodicity. The fiber models revealed a hydrophobic core and twist along the fiber axis arising from a maximization of contacts between hydrophobic groups of adjacent tripeptides on the solvent-exposed fiber surface. These atomic structures of macroscale fibers derived from β-peptide-based materials provide valuable insight into the effects of the geometric placement of the side chains and the influence of solvent on the core fiber structure which is perpetuated in the superstructure morphology.
肽自组装代表了一种从下至上制造纳米材料的强大方法。β-肽是完全由β-氨基酸组成的非天然肽，其主链上有一个额外的亚甲基，我们曾报道过由β-肽自组装形成的纤维，这些纤维采用 14 螺旋结构。β-肽组装体代表了一类稳定的纳米材料，可以用来生成具有蛋白水解稳定性的生物和磁响应材料。然而，这些材料中的许多三维结构仍然未知。为了开发基于结构的标准，以设计具有特定功能的基于β-肽的生物材料，我们通过分子动力学模拟和 X 射线纤维衍射分析研究了三-β-肽纳米组装体的结构。从 Ac-β[LIA]在水中形成的取向纤维中收集衍射数据，并用于为模型结构提供信息和验证。具有 3 重径向对称的模型产生了稳定的纤维，具有三螺旋卷曲螺旋结构，并具有可测量的螺旋间距和周期性。纤维模型揭示了纤维轴上的疏水性核心和扭曲，这是由于相邻三肽疏水区之间的接触最大化，从而产生了溶剂暴露的纤维表面。这些源自基于β-肽的材料的宏观纤维的原子结构为侧链的几何排列对核心纤维结构的影响以及溶剂对超结构形态的影响提供了有价值的见解。
