Nanopore single-molecule analysis of DNA-doxorubicin interactions

Analytical Chemistry
Fujun YaoXiaofeng Kang

Abstract

Anticancer activity and toxicity of doxorubicin (Dox) are associated with its DNA intercalation. To understand the role in gene regulation and the drug mechanism, it is a challenge to detect the DNA-Dox interaction at the single-molecule level without the use of laborious, time-consuming labeling assays and an error-prone amplification method. Here, we utilized the simplest and cheapest, yet highly sensitive, single-molecule nanopore technology to investigate the DNA-Dox interaction and explore in situ the intercalative reaction kinetics. Distinctive electronic signal patterns between DNA and the DNA-Dox complex allow protein nanopore to readily detect the changes in structure and function of DNA. After Dox insertion, nanopore unzipping time of DNA was elevated 10-fold while the blocking current decreased, demonstrating the higher affinity of the DNA-Dox complex (formation constant K(f) = 3.09 × 10(5) M(-1)). Continuous rapid nanopore detection in real time displayed that Dox intercalation in DNA is a two-state dynamic process: fast binding and slow conformational adaption. The nanopore platform provides a powerful tool for studying small molecule-biomacromolecule interactions and paves the way for novel applications aimed at d...Continue Reading

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Citations

Mar 15, 2016·Journal of Photochemistry and Photobiology. B, Biology·D AgudeloH A Tajmir-Riahi
Jul 5, 2017·Analytical Chemistry·Linlin WangXiao-Feng Kang
Jun 13, 2018·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Stefanos K NomidisEnrico Carlon
Oct 9, 2016·Biopolymers·E F SilvaM S Rocha
May 13, 2020·Analytical Chemistry·Sandra SerresLaurence Salomé

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