Pandith Anup, Luo Yongyang, Jang Yul, Bae Jeehyeon, Kim Youngmi
Department of Chemistry and Research Institute of Basic Sciences, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea.
Current address, International Ph.D. Program in Biomedical Engineering (IPBME), College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, Taiwan (R.O.C.
Angew Chem Int Ed Engl. 2023 Jan 16;62(3):e202215049. doi: 10.1002/anie.202215049. Epub 2022 Dec 7.
The selective monitoring of G-quadruplex (G4) structures in living cells is important to elucidate their functions and reveal their value as diagnostic or therapeutic targets. Here we report a fluorogenic probe (CV2) able to selectively light-up parallel G4 DNA over antiparallel topologies. CV2 was constructed by conjugating the excimer-forming CV dye with a peptide sequence (l-Arg-l-Gly-glutaric acid) that specifically recognizes G4s. CV2 forms self-assembled, red excimer-emitting nanoaggregates in aqueous media, but specific binding to G4s triggers its disassembly into rigidified monomeric dyes, leading to a dramatic fluorescence enhancement. Moreover, selective permeation of CV2 stains G4s in mitochondria over the nucleus. CV2 was employed for tracking the folding and unfolding of G4s in living cells, and for monitoring mitochondrial DNA (mtDNA) damage. These properties make CV2 appealing to investigate the possible roles of mtDNA G4s in diseases that involve mitochondrial dysfunction.
在活细胞中对G-四链体（G4）结构进行选择性监测，对于阐明其功能以及揭示其作为诊断或治疗靶点的价值至关重要。在此，我们报道了一种荧光探针（CV2），它能够选择性地使平行G4 DNA发出荧光，而不是反平行拓扑结构。CV2是通过将形成激基缔合物的CV染料与一个能特异性识别G4的肽序列（l-精氨酸-l-甘氨酸-谷氨酸）偶联而成。CV2在水性介质中形成自组装的、发出红色激基缔合物荧光的纳米聚集体，但与G4的特异性结合会触发其解聚为刚性化的单体染料，导致荧光显著增强。此外，CV2的选择性渗透使线粒体中的G4比细胞核中的G4染色更明显。CV2被用于追踪活细胞中G4的折叠和解折叠，并监测线粒体DNA（mtDNA）损伤。这些特性使得CV2在研究mtDNA G4在涉及线粒体功能障碍的疾病中可能发挥的作用方面具有吸引力。
