Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy.
Institute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Area di Ricerca Site and Headquarters-Via Pietro Castellino 111, 80131 Naples, Italy.
Molecules. 2022 May 7;27(9):2997. doi: 10.3390/molecules27092997.
Trans-polydatin (tPD), the 3-β-D-glucoside of the well-known nutraceutical trans-resveratrol, is a natural polyphenol with documented anti-cancer, anti-inflammatory, cardioprotective, and immunoregulatory effects. Considering the anticancer activity of tPD, in this work, we aimed to explore the binding properties of this natural compound with the G-quadruplex (G4) structure formed by the Pu22 [d(TGAGGGTGGGTAGGGTGGGTAA)] DNA sequence by exploiting CD spectroscopy and molecular docking simulations. Pu22 is a mutated and shorter analog of the G4-forming sequence known as Pu27 located in the promoter of the c-myc oncogene, whose overexpression triggers the metabolic changes responsible for cancer cells transformation. The binding of tPD with the parallel Pu22 G4 was confirmed by CD spectroscopy, which showed significant changes in the CD spectrum of the DNA and a slight thermal stabilization of the G4 structure. To gain a deeper insight into the structural features of the tPD-Pu22 complex, we performed an in silico molecular docking study, which indicated that the interaction of tPD with Pu22 G4 may involve partial end-stacking to the terminal G-quartet and H-bonding interactions between the sugar moiety of the ligand and deoxynucleotides not included in the G-tetrads. Finally, we compared the experimental CD profiles of Pu22 G4 with the corresponding theoretical output obtained using DichroCalc, a web-based server normally used for the prediction of proteins' CD spectra starting from their ".pdb" file. The results indicated a good agreement between the predicted and the experimental CD spectra in terms of the spectral bands' profile even if with a slight bathochromic shift in the positive band, suggesting the utility of this predictive tool for G4 DNA CD investigations.
转白藜芦醇苷（tPD）是众所周知的营养保健品反式白藜芦醇的 3-β-D-葡萄糖苷，是一种具有抗癌、抗炎、心脏保护和免疫调节作用的天然多酚。鉴于 tPD 的抗癌活性，在这项工作中，我们旨在通过 CD 光谱和分子对接模拟探索这种天然化合物与 Pu22 [d(TGAGGGTGGGTAGGGTGGGTAA)] DNA 序列形成的 G-四链体（G4）结构的结合特性。Pu22 是 G4 形成序列 Pu27 的突变和缩短的类似物，位于 c-myc 癌基因的启动子中，该基因的过表达引发了导致癌细胞转化的代谢变化。CD 光谱证实了 tPD 与平行 Pu22 G4 的结合，该光谱显示 DNA 的 CD 光谱发生了显著变化，并且 G4 结构略有热稳定化。为了更深入地了解 tPD-Pu22 复合物的结构特征，我们进行了计算机分子对接研究，该研究表明 tPD 与 Pu22 G4 的相互作用可能涉及与末端 G-四聚体的部分末端堆积和配体的糖部分与不包含在 G-四联体中的脱氧核苷酸之间的氢键相互作用。最后，我们将 Pu22 G4 的实验 CD 图谱与使用 DichroCalc 获得的相应理论输出进行了比较，DichroCalc 是一个基于网络的服务器，通常用于根据其“。pdb”文件预测蛋白质的 CD 光谱。结果表明，在谱带轮廓方面，预测和实验 CD 光谱之间具有良好的一致性，尽管在正带中存在轻微的红移，这表明该预测工具对于 G4 DNA CD 研究的有用性。
