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Related Experiment Video

Updated: Feb 7, 2026

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

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Published on: April 4, 2025

Small molecule regulated dynamic structural changes of human G-quadruplexes.

Manish Debnath¹, Shirsendu Ghosh², Deepanjan Panda¹

¹Department of Organic Chemistry , Indian Association for the Cultivation of Science , Jadavpur , Kolkata-700032 , India .

Chemical Science

|July 13, 2018

Summary

This summary is machine-generated.

A novel carbazole derivative (BTC) promotes the folding of G-rich DNA sequences like c-MYC and h-TELO into G-quadruplex structures. This binding influences DNA dynamics and conformational equilibria, aiding in the formation of folded structures.

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Area of Science:

Molecular Biology
Biochemistry
Structural Biology

Background:

G-rich DNA sequences, including oncogenic (c-MYC) and telomeric (h-TELO) sequences, can form G-quadruplex structures.
Ligand binding to pre-folded G-quadruplexes is a known phenomenon, but its effect on the conformational dynamics of unfolded sequences is less understood.
Understanding these interactions is crucial for developing novel therapeutic strategies targeting DNA structures.

Purpose of the Study:

To elucidate the structural and dynamic changes in c-MYC and h-TELO G-rich DNA upon binding of a novel carbazole derivative (BTC).
To investigate how ligand binding influences the conformational equilibria of both unstructured and K+-folded G-quadruplexes.
To characterize the specific conformations recognized by BTC in c-MYC and h-TELO quadruplexes.

Main Methods:

Single-molecule Förster resonance energy transfer (sm-FRET) spectroscopy to monitor structural changes and dynamics.
Fluorescence correlation spectroscopy (FCS) to analyze diffusion coefficients and molecular interactions.
NMR spectroscopy to provide detailed structural insights into DNA-ligand complexes.

Main Results:

In the absence of K+, c-MYC and h-TELO exist as unfolded or partially folded conformations.
BTC binding shifts the conformational equilibrium towards folded G-quadruplex structures for both DNA sequences.
BTC binding increases diffusion coefficients and accelerates end-to-end contact formation, indicating enhanced folding dynamics.
BTC specifically recognizes a minor conformation of the c-MYC quadruplex and two-tetrad basket conformations of the h-TELO quadruplex.

Conclusions:

The carbazole derivative BTC effectively induces G-quadruplex folding in unstructured G-rich DNA sequences.
BTC binding modulates the conformational landscape of both unfolded and pre-folded G-quadruplexes, impacting their dynamics.
The specific recognition of distinct quadruplex conformations by BTC highlights its potential as a targeted therapeutic agent.