Beijing National Laboratory for Molecular Sciences (BNLMS), State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
J Am Chem Soc. 2024 Aug 14;146(32):22736-22746. doi: 10.1021/jacs.4c07698. Epub 2024 Jul 30.
G-quadruplex (G4), an unconventional nucleic acid structure, shows polymorphism in its topological morphology. The parallel G4 topology is the most prevalent form in organisms and plays a regulatory role in many biological processes. Designing fluorescent probes with high specificity for parallel G4s is important but challenging. Herein, a supramolecular assembly of the anionic cyanine dye SCY-5 is reported, which selectively identifies parallel G4 topology. SCY-5 can clearly distinguish parallel G4s from other G4s and non-G4s, even including hybrid-type G4s with parallel characteristics. The high specificity mechanism of SCY-5 involves a delicate balance between electrostatic repulsion and π-π interaction between SCY-5 and G4s. Using SCY-5, cellular RNA extracted from peripheral venous blood was quantitatively detected, and a remarkable increase in RNA G4 content in cancer patients compared to healthy volunteers was confirmed for the first time. This study provides new insights for designing specific probes for parallel G4 topology and opens a new path for clinical cancer diagnosis using RNA G4 as a biomarker.
G-四链体（G4）是一种非常规的核酸结构，其拓扑形态表现出多态性。平行 G4 拓扑是生物体内最常见的形式，在许多生物过程中发挥着调节作用。设计对平行 G4 具有高特异性的荧光探针非常重要，但具有挑战性。在此，报道了阴离子花菁染料 SCY-5 的超分子组装体，其可选择性识别平行 G4 拓扑。SCY-5 可以清楚地区分平行 G4 与其他 G4 和非 G4，甚至包括具有平行特征的混合型 G4。SCY-5 的高特异性机制涉及 SCY-5 与 G4 之间静电排斥和 π-π 相互作用之间的微妙平衡。使用 SCY-5，定量检测了来自外周静脉血的细胞 RNA，首次证实癌症患者的 RNA G4 含量明显高于健康志愿者。这项研究为设计平行 G4 拓扑的特异性探针提供了新的思路，并为使用 RNA G4 作为生物标志物进行临床癌症诊断开辟了新途径。
