Electron-transfer kinetics through nucleic acids untangled by single-molecular fluorescence blinking
Electron-transfer kinetics through nucleic acids untangled by single-molecular fluorescence blinking
复制标题
通过单分子荧光闪烁解开核酸的电子转移动力学
DOI：
10.1016/j.chempr.2022.07.025
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发表时间：
2022
期刊：
影响因子：
23.5
通讯作者：
Kawai Kiyohiko
中科院分区：
文献类型：
--
作者：
Fan Shuya;Xu Jie;Osakada Yasuko;Hashimoto Katsunori;Takayama Kazuya;Natsume Atsushi;Hirano Masaki;Maruyama Atsushi;Fujitsuka Mamoru;Kawai Kumi;Kawai Kiyohiko
系综平均测量揭示了通过生物分子进行电子转移(ET)的物理化学基础，这是开发用于分析和诊断的生物电子器件的基础。然而，这样的测量可能会掩盖与基础科学和实际应用相关的单分子动力学。我们使用DNA通过测量荧光闪烁来研究分子内ET动力学的距离依赖性。对直到∼27的ET速率的距离依赖关系的系统测量清楚地表明了ET动力学的单分子测量，并突出了ET速率的巨大不均一性。每一种核酸都有一个特定的ET速率，因此人们可以通过测量核酸的ET速率来获得序列信息。我们应用单分子ET测量来检测与成人胶质瘤治疗效果相关的异柠檬酸脱氢酶(IDH)mRNA点突变。我们从人脑胶质瘤模型培养细胞制备的病理标本中鉴定了该基因的点突变。
Ensemble-averaged measurements have revealed the physicochemical basis of electron transfer (ET) through biomolecules, which is foundational to the development of bioelectronic devices for analysis and diagnosis. However, such measurements can obscure single-molecule kinetics that are pertinent to the underlying science and practical applications. We used DNA to study the distance dependence of the intramolecular ET kinetics by measuring fluorescence blinking. The systematic measurement of the distance dependence of the ET rate up to ∼27 Å clearly demonstrated the single-molecule measurement of ET kinetics and highlighted the large heterogeneity in the ET rate. Each nucleic acid has a specific ET rate, and thus one can obtain sequence information by measuring the ET rate through nucleic acids. We applied single-molecule ET measurement to detect isocitrate dehydrogenase (IDH) mRNA point mutations, which are correlated with treatment efficacy in adult gliomas. We identified the mRNA point mutation in pathological specimens prepared from human glioma model cultured cells.