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基于发夹 DNA 修饰金电极的电化学生物传感器用于检测杂交型抗癌药物嵌入引起的 DNA 损伤。

An electrochemical biosensor based on Hairpin-DNA modified gold electrode for detection of DNA damage by a hybrid cancer drug intercalation.

机构信息

Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, Maceió, AL, 57072-970, Brazil; University of Central Florida. NanoBioelectrochemistry Laboratory, Department of Chemistry, University of Central Florida, 4000 Central Florida Blvd., Orlando, FL 32816, United States.

Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, Maceió, AL, 57072-970, Brazil.

出版信息

Biosens Bioelectron. 2019 May 15;133:160-168. doi: 10.1016/j.bios.2019.02.071. Epub 2019 Mar 14.

Abstract

An efficient and new electrochemical biosensor for detection of DNA damage, induced by the interaction of the hybrid anti-cancer compound (7ESTAC01) with DNA, was studied by differential pulse voltammetry (DPV). The biosensor consists of a Stem-Loop DNA (SL-DNA) probe covalently attached to the gold electrode (GE) surface that hybridizes to a complementary DNA strand (cDNA) to form a double-stranded DNA (dsDNA). The interaction and DNA damage induced by 7ESTAC01 was electrochemically studied based on the oxidation signals of the electroactive nucleic acids on the surface of the GE by DPV. As a result, the SL-DNA/GE and dsDNA/GE were tested with the reduced 7ESTAC01, showing the voltammetric signal of guanine and adenine, increase in the presence of 7ESTAC01. Under optimum conditions, the dsDNA/GE biosensor exhibited excellent DPV response in the presence of 7ESTAC01. The bonding interaction between 7ESTAC01 and calf thymus DNA (ctDNA) was confirmed by UV-Vis absorption spectroscopy, dynamic simulations (performed to investigate the DNA structure under physiological conditions), and molecular docking. Theoretical results showed the presence of hydrogen bonding and intercalation in the minor groove of DNA, involving hydrophobic interactions.

摘要

一种用于检测由杂交抗癌化合物(7ESTAC01)与 DNA 相互作用引起的 DNA 损伤的高效新型电化学生物传感器,通过差分脉冲伏安法(DPV)进行了研究。该生物传感器由共价附着在金电极(GE)表面的茎环 DNA(SL-DNA)探针组成,该探针与互补 DNA 链(cDNA)杂交形成双链 DNA(dsDNA)。通过 DPV 研究了 7ESTAC01 的相互作用和 DNA 损伤,基于 GE 表面电活性核酸的氧化信号。结果表明,SL-DNA/GE 和 dsDNA/GE 与还原态 7ESTAC01 进行了测试,在存在 7ESTAC01 的情况下显示出鸟嘌呤和腺嘌呤的伏安信号增加。在最佳条件下,dsDNA/GE 生物传感器在存在 7ESTAC01 的情况下表现出优异的 DPV 响应。通过紫外可见吸收光谱、动态模拟(在生理条件下研究 DNA 结构)和分子对接证实了 7ESTAC01 与小牛胸腺 DNA(ctDNA)之间的键合相互作用。理论结果表明,DNA 小沟中存在氢键和嵌入,涉及疏水相互作用。

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