title: Investigation of the interactions between methylene blue and intramolecular G-quadruplexes: an explicit distinction in electrochemical behavior.
abstract: G-quadruplex sequences exist in eukaryotic organisms and prokaryotes, and the investigation of the interactions between G-quadruplexes and small molecule ligands is important for gene therapy, biosensor fabrication, fluorescence imaging and so on. Here, we investigated the behaviour of methylene blue (MB), an electroactive molecule, in the presence of different intramolecular G-quadruplexes by an electrochemical method using a miniaturized electrochemical device based on its intrinsic electrochemical properties. Although the effects of MB on different intramolecular G-quadruplex structures are not obvious by circular dichroism spectroscopy, distinct differences in the binding affinities of MB with different intramolecular G-quadruplexes were quickly and easily observed by an electrochemical technique. At the same time, for the human telomerase G-rich sequence (HT), the diffusion current of MB changed sensitively under different ionic conditions due to the formation of different conformations of HT, which indicated that our electrochemical method has the potential to study the influence of metal ions on the conformations of the G-quadruplexes with simplicity, rapid response and low cost. From all these, a new stacking mechanism and rule were obtained, which were also validated by docking studies and isothermal titration calorimetry (ITC).
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, No., 202 Chengfu Road, Haidian District, Beijing 100871, China. zhouyl@pku.edu.cn zxx@pku.edu.cn.
authors.forename: Ting
authors.initials: T
authors.lastname: Cao
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, No., 202 Chengfu Road, Haidian District, Beijing 100871, China. zhouyl@pku.edu.cn zxx@pku.edu.cn.
authors.forename: Fang-Ting
authors.initials: FT
authors.lastname: Zhang
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, No., 202 Chengfu Road, Haidian District, Beijing 100871, China. zhouyl@pku.edu.cn zxx@pku.edu.cn.
authors.forename: Liang-Yuan
authors.initials: LY
authors.lastname: Cai
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, No., 202 Chengfu Road, Haidian District, Beijing 100871, China. zhouyl@pku.edu.cn zxx@pku.edu.cn.
authors.forename: Ying-Lin
authors.initials: YL
authors.lastname: Zhou
authors.affiliation: Physical Organic Chemistry Centre, School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK. buurma@cardiff.ac.uk.
authors.forename: Niklaas J
authors.initials: NJ
authors.lastname: Buurma
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, No., 202 Chengfu Road, Haidian District, Beijing 100871, China. zhouyl@pku.edu.cn zxx@pku.edu.cn.
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Zhang
mesh_terms: D015374:Biosensing Techniques; D002151:Calorimetry; D002942:Circular Dichroism; D055664:Electrochemical Techniques; D054856:G-Quadruplexes; D006801:Humans; D008751:Methylene Blue / Q000737:chemistry*; D062105:Molecular Docking Simulation; D019098:Telomerase / Q000737:chemistry
chemical_list: D019098:Telomerase; D008751:Methylene Blue