Department of Pharmacy, Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II" and DFM Scarl, Via Mezzocannone 16, 80134, Naples, Italy.
Institute of Biostructures and Bioimaging (IBB), CNR, Via Mezzocannone 16, 80134, Naples, Italy.
Chemistry. 2018 May 7;24(26):6804-6817. doi: 10.1002/chem.201800351. Epub 2018 Apr 26.
Phenylalanine-based nanostructures have attracted the attention of the material science community for their functional properties. These properties strongly depend on the hierarchic organization of the nanostructure that in turn can be finely tuned by punctual chemical modifications of the building blocks. Herein, we investigate how the partial or the complete replacement of the Phe residues in PEG -(Phe) (PEG -F6) with tyrosines to generate PEG -(Phe-Tyr) (PEG -(FY)3) or PEG -(Tyr) (PEG -Y6) affects the structural/functional properties of the nanomaterial formed by the parental compound. Moreover, the effect of the PEG derivatization was evaluated through the characterization of the peptides without the PEG moiety (Tyr) (Y6) and (Phe-Tyr) ((FY)3). Both PEG -Y6 and PEG -(FY)3 can self-assemble in water at micromolar concentrations in β-sheet-rich nanostructures. However, WAXS diffraction patterns of these compounds present significant differences. PEG -(FY)3 shows a 2D WAXS oriented fiber diffraction profile characterized by the concomitant presence of a 4.7 Å meridional and a 12.5 Å equatorial reflection that are generally associated with cross-β structure. On the other hand, the pattern of PEG -Y6 is characterized by the presence of circles typically observed in the presence of PEG crystallization. Molecular modeling and dynamics provide an atomic structural model of the peptide spine of these compounds that is in good agreement with WAXS experimental data. Gelation phenomenon was only detected for PEG -(FY)3 above a concentration of 1.0 wt % as confirmed by storage (G'≈100 Pa) and loss (G''≈28 Pa) moduli in rheological studies. The cell viability on CHO cells of this soft hydrogel was certified to be 90 % after 24 hours of incubation.
基于苯丙氨酸的纳米结构因其功能特性引起了材料科学界的关注。这些特性强烈依赖于纳米结构的层次组织，而层次组织又可以通过构建块的精确化学修饰进行精细调整。在这里，我们研究了将 PEG-(Phe)（PEG-F6）中的苯丙氨酸残基部分或全部替换为酪氨酸以生成 PEG-(Phe-Tyr)（PEG-(FY)3）或 PEG-(Tyr)（PEG-Y6）如何影响由母体化合物形成的纳米材料的结构/功能特性。此外，通过对没有 PEG 部分的肽（Tyr）（Y6）和（Phe-Tyr）（（FY）3）的表征来评估 PEG 衍生化的效果。PEG-Y6 和 PEG-(FY)3 均可在微摩尔浓度下在水中自组装成富含β-折叠的纳米结构。然而，这些化合物的 WAXS 衍射图谱存在显著差异。PEG-(FY)3 呈现出具有 2D 取向纤维衍射图案的 WAXS，其特征是同时存在 4.7 Å 的子午线和 12.5 Å 的赤道反射，通常与交叉-β结构相关。另一方面，PEG-Y6 的图案的特征在于存在通常在存在 PEG 结晶时观察到的圆形。分子建模和动力学为这些化合物的肽脊柱提供了原子结构模型，该模型与 WAXS 实验数据非常吻合。通过流变学研究确认仅在 PEG-(FY)3 浓度高于 1.0 wt%时才会出现凝胶现象，表现为存储（G'≈100 Pa）和损耗（G''≈28 Pa）模量。在孵育 24 小时后，CHO 细胞的这种软水凝胶的细胞活力被证明为 90%。
