Robinson Jenna, Majid Aatikah, Kuimova Marina K, Vilar Ramon
Department of Chemistry, Imperial College London Molecular Sciences Research Hub, White City Campus, 82 Wood Lane, London, W12 0BZ, UK.
Angew Chem Int Ed Engl. 2025 May 26;64(22):e202424931. doi: 10.1002/anie.202424931. Epub 2025 Apr 21.
The study of G-quadruplex (G4) structures that form in DNA and RNA is a rapidly growing field, which has evolved from in vitro studies of isolated G4 sequences to genome-wide detection of G4s in a cellular context. This work has revealed the tangible and significant effects that G4s may have on biological regulation. This minireview describes recent progress in the design of photoluminescent intensity-independent optical probes for G4s. We discuss the design and use of probes based on fluorescence or phosphorescence lifetime, rather than intensity-based detection; spectral ratiometric probes; and fluorescent probes for single-molecule G4-detection. We argue that each of these modalities improve unbiased G4 detection in cellular experiments, overcoming problems associated with unknown cellular uptake of probes or their organelle concentration. We discuss the improvements offered by these types of probes, as well as limitations and future research directions needed to facilitate more robust research into G4 biology.
对DNA和RNA中形成的G-四链体（G4）结构的研究是一个快速发展的领域，它已从对分离的G4序列的体外研究发展到在细胞环境中对G4进行全基因组检测。这项工作揭示了G4可能对生物调节产生的切实而重大的影响。这篇小型综述描述了用于G4的光致发光强度无关光学探针设计的最新进展。我们讨论了基于荧光或磷光寿命而非基于强度检测的探针的设计和使用；光谱比率探针；以及用于单分子G4检测的荧光探针。我们认为，这些方法中的每一种都能在细胞实验中改善无偏差的G4检测，克服与探针未知的细胞摄取或其细胞器浓度相关的问题。我们讨论了这些类型探针带来的改进，以及促进对G4生物学进行更有力研究所需的局限性和未来研究方向。
