Lu-Yu Li , Jia-Xuan Yu , Hao-Wen Cao , Ze-Kai Li , Xu-Bo Fan , Jing Shu , Xiao-Feng Yu , Wen-Jing Yi , Ming-Qi Wang
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引用次数: 0
摘要
供受体型染料是构建g -四重体(G4) DNA荧光探针的常用框架。然而,这类染料往往表现出环境敏感特性,容易因极性和粘度等微环境变化而产生非特异性信号,阻碍了其在复杂生物系统中高保真G4检测中的应用。因此,迫切需要对这些染料进行优化,减轻环境因素的干扰。在此,我们提出了一种合理的策略,通过结合定制的转子部分来构建环境不敏感染料,以增强非辐射衰变,从而在达到G4目标之前在复杂的生理环境中保持“荧光关闭”状态。在这种独特的策略下,合成了三种含有不同转子取代基(N, N-二甲苯胺,三苯胺,N-苯基咔唑)的新型咔唑-吡啶结构。值得注意的是,整合N, N-二甲基苯胺转子(命名为ZXS)的“低势垒旋转”的结构框架在广泛的溶剂极性和粘度范围内表现出理想的初始“荧光关闭”状态。这些特点不仅有助于提高信噪比,而且有效地防止了环境变化引起的假阳性信号的产生。与G4s结合后,染料ZXS可以通过与c-MYC g -四重体DNA的特异性相互作用(约225倍增强)引起荧光。特别是染料ZXS对c-MYC具有较好的选择性,在其他G4和非G4 DNA结构存在时,其荧光响应要弱得多。此外,它还可以作为检测细胞核中G4s的潜在工具。
Donor-acceptor framework appended with rotators as environment-insensitive probes for the detection of G4 DNA
Donor-acceptor type dyes are commonly used frameworks for constructing G-Quadruplex (G4) DNA fluorescent probes. However, such dyes frequently exhibit environment-sensitive characteristics and are prone to generate non-specific signals due to microenvironmental changes like polarity and viscosity, which hinders their application in high-fidelity G4 detection within complex biological systems. Therefore, there is an urgent need to optimize these dyes and mitigate interference from environmental factors. Herein, we present a rational strategy for constructing environment-insensitive dyes through incorporation of tailored rotor moieties to enhance nonradiative decay, thereby sustaining a “fluorescence-off” state throughout complex physiological environments prior to reaching G4 targets. In the unique strategy, three novel carbazole-pyridinium architectures incorporating different rotor substituents (N, N-dimethylaniline, triphenylamine, N-phenylcarbazole) were synthesized. Notably, the architectural framework integrating the “low-barrier rotation” of N, N-dimethylaniline rotor (named ZXS) exhibited desirable initial “fluorescence off” state across a wide range of solvent polarities and viscosities. These features not only contribute to an enhanced signal-to-noise ratio but also effectively prevent the generation of false-positive signals caused by environmental variations. Upon binding with G4s, dye ZXS can be fluorescence elicited by its specific interaction with c-MYC G-Quadruplex DNA (∼225-fold enhancement). Especially, dye ZXS shows superior selectivity for c-MYC, exhibiting much weaker fluorescence response in the presence of other G4 and non-G4 DNA structures. Furthermore, it serves as a potential tool for the detection of G4s in the nucleus.
期刊介绍:
Dyes and Pigments covers the scientific and technical aspects of the chemistry and physics of dyes, pigments and their intermediates. Emphasis is placed on the properties of the colouring matters themselves rather than on their applications or the system in which they may be applied.
Thus the journal accepts research and review papers on the synthesis of dyes, pigments and intermediates, their physical or chemical properties, e.g. spectroscopic, surface, solution or solid state characteristics, the physical aspects of their preparation, e.g. precipitation, nucleation and growth, crystal formation, liquid crystalline characteristics, their photochemical, ecological or biological properties and the relationship between colour and chemical constitution. However, papers are considered which deal with the more fundamental aspects of colourant application and of the interactions of colourants with substrates or media.
The journal will interest a wide variety of workers in a range of disciplines whose work involves dyes, pigments and their intermediates, and provides a platform for investigators with common interests but diverse fields of activity such as cosmetics, reprographics, dye and pigment synthesis, medical research, polymers, etc.