Assessing The Key Photophysical Properties of Triangulenium Dyes for DNA Binding by Alteration of the Fluorescent Core.
Assessing The Key Photophysical Properties of Triangulenium Dyes for DNA Binding by Alteration of the Fluorescent Core.
复制标题
通过改变荧光核心来评估 Triangulenium 染料用于 DNA 结合的关键光物理特性。
DOI：
10.1002/chem.202003875
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Lewis BW
中科院分区：
文献类型：
--
作者：
Lewis BW
四链G-四链体（G4）DNA是一种非典型的DNA拓扑结构，已被提出在细胞中形成，并在基因组如何被细胞机器读取和使用中发挥关键作用。以前，荧光triangulenium探针（DAOTA-M2）被用于可视化G4在细胞中，这要归功于其与不同DNA拓扑结构结合时的不同荧光寿命。在本文中，可用的triangulenium探针库被扩展以探索对分子的荧光核心的修饰如何影响其生物物理特性、与DNA的相互作用和细胞定位。合成并表征了具有乙基吗啉取代基的苯并桥连和异丙基桥连的二氮杂三角铀鎓染料BDATA-M2和CDATA-M2。这些分子与不同的DNA拓扑结构的相互作用进行了研究，以确定其结合亲和力，荧光增强和荧光寿命响应。最后，这些光学探针的细胞摄取和定位进行了研究。虽然对triangulenium核心的结构修饰仅轻微改变与DNA的结合亲和力，但BDATA-M2和CDATA-M2无法通过其荧光寿命区分DNA拓扑结构。理论和实验表明，这是由于光诱导电子转移（PET）淬灭的有效性降低。这项工作提供了有价值的新证据，证明当使用triangulenium染料的荧光寿命来区分G4 DNA和双链DNA时，PET淬灭的关键作用，突出了在开发新的基于triangulenium的G4探针时微调氧化还原和光谱特性的重要性。
Four‐stranded G‐quadruplex (G4) DNA is a non‐canonical DNA topology that has been proposed to form in cells and play key roles in how the genome is read and used by the cellular machinery. Previously, a fluorescent triangulenium probe (DAOTA‐M2) was used to visualise G4sin cellulo, thanks to its distinct fluorescence lifetimes when bound to different DNA topologies. Herein, the library of available triangulenium probes is expanded to explore how modifications to the fluorescent core of the molecule affect its photophysical characteristics, interaction with DNA and cellular localisation. The benzo‐bridged and isopropyl‐bridged diazatriangulenium dyes,BDATA‐M2andCDATA‐M2respectively, featuring ethyl‐morpholino substituents, were synthesised and characterised. The interactions of these molecules with different DNA topologies were studied to determine their binding affinity, fluorescence enhancement and fluorescence lifetime response. Finally, the cellular uptake and localisation of these optical probes were investigated. Whilst structural modifications to the triangulenium core only slightly alter the binding affinity to DNA,BDATA‐M2andCDATA‐M2cannot distinguish between DNA topologies through their fluorescence lifetime. It is argued theoretically and experimentally that this is due to reduced effectiveness of photoinduced electron transfer (PET) quenching. This work presents valuable new evidence into the critical role of PET quenching when using the fluorescence lifetime of triangulenium dyes to discriminate G4 DNA from duplex DNA, highlighting the importance of fine tuning redox and spectral properties when developing new triangulenium‐based G4 probes.