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Related Experiment Video

Updated: Jun 9, 2026

In Vitro Chemical Mapping of G-Quadruplex DNA Structures by Bis-3-Chloropiperidines
05:32

In Vitro Chemical Mapping of G-Quadruplex DNA Structures by Bis-3-Chloropiperidines

Published on: May 12, 2023

Unveiling the Structural Modifications of Cyanines to Target G‑Quadruplex DNA through Biophysical, Computational, and

Cristina Galiana-Roselló1,2, Andrea Lázaro-Gómez1, Ariadna Gil-Martínez1

  • 1Department of Inorganic Chemistry, Institute of Molecular Science (ICMol), University of Valencia, Catedrático José Beltrán 2, Paterna 46980, Spain.

ACS Omega
|June 8, 2026
PubMed
Summary

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Cyanine ligands with longer polymethine linkers show enhanced binding to G-quadruplex (G4) DNA structures. The strongest ligand, C3, influences global gene expression in cells, revealing insights into cyanine cellular activity.

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Biophysics

Background:

  • Cyanine dyes are versatile molecules with applications in various biological studies.
  • G-quadruplex (G4) DNA structures are involved in crucial cellular processes and are targets for therapeutic intervention.
  • Understanding the interaction between small molecules and G4 DNA is key to developing novel therapeutics.

Purpose of the Study:

  • To develop and investigate cyanine ligands as potential binders for G-quadruplex DNA.
  • To determine the effect of linker length and substituent modifications on cyanine-G4 DNA binding affinity and selectivity.
  • To elucidate the cellular effects of the most potent cyanine G4 ligand.

Main Methods:

  • Synthesis and characterization of six cyanine ligands with varying polymethine linkers and substituents.

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Last Updated: Jun 9, 2026

In Vitro Chemical Mapping of G-Quadruplex DNA Structures by Bis-3-Chloropiperidines
05:32

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Published on: May 12, 2023

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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

Published on: April 4, 2025

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  • Assessment of DNA binding using fluorescence resonance energy transfer (FRET) melting, UV-vis spectroscopy, and fluorimetric assays.
  • Computational modeling to understand binding modes and interactions.
  • Whole-transcriptome RNA-sequencing (RNA-seq) to analyze gene expression changes in cells treated with the lead compound.

    • Main Results:

    • Ligand interaction with DNA increased with polymethine linker length, with optimal binding observed for ligands with five-carbon linkers.
    • The electronic nature of substituents on the cyanine ring had minimal impact on G4 binding.
    • Binding analysis indicated a preference for the cis conformation of cyanines, facilitating π-π interactions with G-quartets.
    • RNA-seq analysis of cells treated with the lead compound C3 revealed significant global gene expression changes, suggesting a complex cellular response.

    Conclusions:

    • Cyanine ligands with appropriate linker lengths are effective binders of G-quadruplex DNA.
    • The binding affinity is primarily modulated by linker length, with cis conformation and π-π stacking being crucial for interaction.
    • The lead compound C3 exhibits significant cellular activity, impacting global gene expression and offering a potential tool for studying G4-mediated cellular mechanisms.