Habila Nathan, Kulkarni Ketav, Lee Tzong-Hsien, Al-Garawi Zahraa S, Serpell Louise C, Aguilar Marie-Isabel, Del Borgo Mark P
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
School of Life Sciences, University of Sussex, Brighton, United Kingdom.
Front Chem. 2020 Mar 31;8:217. doi: 10.3389/fchem.2020.00217. eCollection 2020.
β-peptides consisting exclusively of β-amino acids adopt a variety of non-natural helical structures and can self-assemble into well-defined hierarchical structures by axial head-to-tail self-assembly resulting in fibrous materials of varying sizes and shapes. To allow control of fiber morphology, a lipid moiety was introduced within a tri-β-peptide sequence at each of the three amino acid positions and the N-terminus to gain finer control over the lateral assembly of fibers. Depending on the position of the lipid, the self-assembled structures formed either twisted ribbon-like fibers or distinctive multilaminar nanobelts. The nanobelt structures were comprised of multiple layers of peptide fibrils as revealed by puncturing the surface of the nanobelts with an AFM probe. This stacking phenomenon was completely inhibited through changes in pH, indicating that the layer stacking was mediated by electrostatic interactions. Thus, the present study is the first to show controlled self-assembly of these fibrous structures, which is governed by the location of the acyl chain in combination with the 3-point H-bonding motif. Overall, the results demonstrate that the nanostructures formed by the β-tripeptide foldamers can be tuned via sequential lipidation of N-acetyl β-tripeptides which control the lateral interactions between peptide fibrils and provide defined structures with a greater homogeneous population.
仅由β-氨基酸组成的β-肽会呈现出多种非天然螺旋结构，并且可以通过轴向头对头自组装形成明确的分级结构，从而产生各种尺寸和形状的纤维材料。为了能够控制纤维形态，在三个氨基酸位置以及N端的三-β-肽序列中的每个位置引入了一个脂质部分，以对纤维的侧向组装进行更精细的控制。根据脂质的位置，自组装结构形成了扭曲的带状纤维或独特的多层纳米带。如用原子力显微镜探针刺穿纳米带表面所显示的，纳米带结构由多层肽原纤维组成。这种堆叠现象通过pH值的变化被完全抑制，这表明层堆叠是由静电相互作用介导的。因此，本研究首次展示了这些纤维结构的可控自组装，其由酰基链的位置与三点氢键基序共同控制。总体而言，结果表明，由β-三肽折叠体形成的纳米结构可以通过N-乙酰基β-三肽的顺序脂化来调节，这控制了肽原纤维之间的侧向相互作用，并提供了具有更大均匀群体的明确结构。
