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Chemical‐Labeling‐Assisted Detection of Nucleobase Modifications by Quantum‐Tunneling‐Based Single‐Molecule Sensing
Author(s) -
Furuhata Takafumi,
Ohshiro Takahito,
Izuhara Yuichi,
Suzuki Tomoaki,
Ueki Ryosuke,
Taniguchi Masateru,
Sando Shinsuke
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900422
Subject(s) - nucleobase , quantum tunnelling , chemistry , molecule , quantum chemical , nucleotide , quantum , conductance , chemical physics , nanotechnology , dna , computational chemistry , combinatorial chemistry , materials science , quantum mechanics , physics , optoelectronics , biochemistry , organic chemistry , gene , condensed matter physics
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.