Liu Lei, Zhang Wei, Zhong Ming-Qing, Jia Meng-Hao, Jiang Fei, Zhang Yan, Xiao Chao-Da, Xiao Xin, Shen Xiang-Chun
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town Guian New District Guizhou 550025 P. R. China
Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University Guiyang 550025 P. R. China
RSC Adv. 2022 May 16;12(23):14765-14775. doi: 10.1039/d2ra01433e. eCollection 2022 May 12.
G-Quadruplex (G4), as a non-canonical nucleic acid secondary structure, has been proved to be prevalent in genomes and plays important roles in many biological processes. Ligands targeting G4, especially small-molecular fluorescent light-up probes with selectivity for special conformations, are essential for studying the relationship between G4 folding and the cellular response. However, their development still remains challenging but is attracting massive attention. Here, we synthesized a new tetraphenylethene derivative, namely TPE-B, as a parallel G4 probe. Fluorescence experiments showed that TPE-B could give out a strong fluorescence response to the G4 structure. Moreover, it gave a much higher fluorescence intensity response to parallel G4s than anti-parallel ones, which indicated that TPE-B could serve as a special tool for probing parallel G4s. The circular dichroism (CD) spectra and melting curves showed that TPE-B could selectively bind and stabilize parallel G4s without changing their topology. ESI-MS studies showed that TPE-B could bind to parallel G4 with a 1 : 1 stoichiometry. The gel staining results showed that TPE-B was a good candidate for probing parallel G4s. Altogether, the TPE-B molecule may serve as a promising new probe that can discriminate parallel G4s.
G-四链体（G4）作为一种非经典核酸二级结构，已被证明在基因组中普遍存在，并在许多生物学过程中发挥重要作用。靶向G4的配体，尤其是对特殊构象具有选择性的小分子荧光点亮探针，对于研究G4折叠与细胞反应之间的关系至关重要。然而，它们的开发仍然具有挑战性，但正吸引着大量关注。在此，我们合成了一种新的四苯乙烯衍生物，即TPE-B，作为平行G4探针。荧光实验表明，TPE-B对G4结构能给出强烈的荧光响应。此外，它对平行G4的荧光强度响应比对反平行G4的高得多，这表明TPE-B可作为探测平行G4的特殊工具。圆二色性（CD）光谱和熔解曲线表明，TPE-B可以选择性地结合并稳定平行G4，而不改变其拓扑结构。电喷雾电离质谱（ESI-MS）研究表明，TPE-B能以1∶1的化学计量比与平行G4结合。凝胶染色结果表明，TPE-B是探测平行G4的良好候选物。总之，TPE-B分子可能是一种有前景的新型探针，可区分平行G4。
