Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047, Japan.
Chembiochem. 2020 Feb 3;21(3):335-339. doi: 10.1002/cbic.201900422. Epub 2019 Oct 22.
Quantum-tunneling-based DNA sensing is a single-molecule technique that promises direct mapping of nucleobase modifications. However, its applicability is seriously limited because of the small difference in conductivity between modified and unmodified nucleobases. Herein, a chemical labeling strategy is presented that facilitates the detection of modified nucleotides by quantum tunneling. We used 5-Formyl-2'-deoxyuridine as a model compound and demonstrated that chemical labeling dramatically alters its molecular conductance compared with that of canonical nucleotides; thus, facilitating statistical discrimination, which is impeded in the unlabeled state. This work introduces a chemical strategy that overcomes the intrinsic difficulty in quantum-tunneling-based modification analysis-the similarity of the molecular conductance of the nucleobases of interest.
基于量子隧穿的 DNA 传感是一种单分子技术，有望直接绘制核苷酸碱基修饰图谱。然而，由于修饰和未修饰核苷酸碱基之间的电导率差异较小，其适用性受到严重限制。在此，提出了一种化学标记策略，通过量子隧穿促进修饰核苷酸的检测。我们使用 5-甲酰基-2'-脱氧尿苷作为模型化合物，证明与典型核苷酸相比，化学标记显著改变了其分子电导率；从而促进了统计区分，而在未标记状态下则受到阻碍。这项工作引入了一种化学策略，克服了基于量子隧穿的修饰分析中固有的困难——即感兴趣的碱基的分子电导率的相似性。
