New pyridinium-based fluorescent dyes: A comparison of symmetry and side-group effects on G-quadruplex DNA binding selectivity and application in live cell imaging

Yu-Jing LU, Dong-Ping HU, Kun ZHANG, Wing Leung WONG, Cheuk Fai Stephen CHOW

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19 Citations (Scopus)

Abstract

A series of C₁₋, C₂₋and C₃₋symmetric pyridinium conjugates with different styrene-like side groups were synthesized and were utilized as G-quadruplex selective fluorescent probes. The new compounds were well-characterized. Their selectivity, sensitivity, and stability towards G-quadruplex were studied by fluorescence titration, native PAGE experiments, FRET and circular dichroism (CD) analyses. These new compounds investigated in the fluorescence assays were preferentially bound with G-quadruplex DNA compared with other type of nuclei acids and it is fascinating to realize the effects of molecular symmetry and associated side groups showing unexpectedly great influence on the fluorescent signal enhancement for the discrimination of G-quadruplexes DNA from other nucleic acids. This may correlate with the pocket symmetry and shape of the G-quadruplex DNA inherently. Among the compounds, a C₂₋symmetric dye (2,6-bis-((E)-2-(1H-indol-3-yl)-vinyl)-1-methylpyridin-1-ium iodide) with indolyl-groups substituted was screened out from the series giving the best selectivity and sensitivity towards G-quadruplexes DNA, particularly telo21, due to its high equilibrium binding constant (K=2.17×105 M-1). In addition, the limit of detection (LOD) of the dye to determine telo21 DNA in bioassays was found as low as 33 nM. The results of the study give insight and certain crucial factors, such as molecular symmetry and the associated side groups, on developing of effective fluorescent dyes for G-quadruplex DNA applications including G-quadruplex structure stabilization, biosensing and clinical applications. The compound was also demonstrated as a very selective G-quadruplex fluorescent agent for living cell staining and imaging. Copyright © 2016 Published by Elsevier B.V.
Original languageEnglish
Pages (from-to)373-381
JournalBiosensors and Bioelectronics
Volume81
Early online dateMar 2016
DOIs
Publication statusPublished - Jul 2016

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G-Quadruplexes
Fluorescent Dyes
DNA
Dyes
Imaging techniques
Fluorescence
Styrene
Bioassay
Nucleic acids
Dichroism
Iodides
Titration
Nucleic Acids
Native Polyacrylamide Gel Electrophoresis
Assays
Coloring Agents
Stabilization
Cells
Circular Dichroism
Biological Assay

Bibliographical note

Lu, Y.-J., Hu, D.-P., Zhang, K., Wong, W.-L., & Chow, C.-F. (2016). New pyridinium-based fluorescent dyes: A comparison of symmetry and side-group effects on G-quadruplex DNA binding selectivity and application in live cell imaging. Biosensors and Bioelectronics, 81, 373-381.

Keywords

  • G-quadruplexes DNA
  • Telo21
  • Distyrylpyridinium dye
  • Fluorescence probe
  • Cell