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Updated: Aug 12, 2026
05:37
Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
Introduction of a Double-Headed Nucleotide Into G-Quadruplex DNA: Position-Dependent Stabilization and Structural
Krista Urup1, Peter Reinholdt1, Kasper Munch Beck1
1Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|August 11, 2026
Summary
A novel double-headed guanine nucleotide (GG) can stabilize G-quadruplex structures. Its effectiveness depends on sequence and topology, offering a new tool for G-quadruplex engineering and aptamer development.
Area of Science:
- Biochemistry
- Molecular Biology
- Biotechnology
Background:
- G-quadruplexes are crucial nucleic acid structures with diverse biological roles.
- Their unique architecture presents opportunities for therapeutic and biotechnological applications.
Purpose of the Study:
- To investigate the incorporation and effects of a double-headed guanine nucleotide (GG) in G-quadruplex structures.
- To understand how sequence context and topology influence GG's impact on G-quadruplex stability and formation.
Main Methods:
- Circular dichroism (CD) spectroscopy
- Thermal denaturation analysis
- UV thermal differential spectroscopy (TDS)
- Fluorescence light-up assays
- Polyacrylamide gel electrophoresis (PAGE)
- Molecular dynamics (MD) simulations
Main Results:
- GG can replace two consecutive guanines in G-quadruplexes and participate in G-tetrad formation.
- GG incorporation is favored in parallel G-quadruplexes with lower native torsional twist.
- GG significantly stabilizes G-quadruplexes, with notable increases in thermal stability observed in both tetramolecular and aptamer systems.
- Altered topological signatures were observed in some GG-modified structures.
Conclusions:
- GG is a potent, context-dependent stabilizer for G-quadruplex structures.
- This study provides design principles for utilizing GG in engineered G-quadruplexes and aptamer development.
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