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Updated: Aug 7, 2025
08:28
Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
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Polymorphism and Ligand Binding Modulate Fast Dynamics of Human Telomeric G-Quadruplexes
Luca Bertini1, Valeria Libera1,2, Francesca Ripanti1
1Department of Physics and Geology, University of Perugia, Via Alessandro Pascoli, 06123 Perugia, Italy.
International Journal of Molecular Sciences
|March 11, 2023
Summary
Telomeric G-quadruplexes (G4s) exhibit structural polymorphism influenced by ions. Their dynamics are linked to conformation and hydration, impacting anticancer drug development.
Area of Science:
- Biochemistry
- Structural Biology
- Drug Discovery
Background:
- Telomeric G-quadruplexes (G4s) are crucial in cancer research as drug targets.
- G4 structure exhibits polymorphism, influencing their function and interactions.
Purpose of the Study:
- Investigate the impact of conformation and ion presence on telomeric G-quadruplex (Tel22) dynamics.
- Examine the effect of BRACO19 ligand complexation on Tel22 dynamics.
Main Methods:
- Fourier transform Infrared spectroscopy to determine G4 topology.
- Elastic incoherent neutron scattering to probe sub-nanosecond dynamics.
- Studied Tel22 in hydrated powder state with K+ and Na+ ions.
Main Results:
- Tel22 adopts parallel (K+) and mixed antiparallel/parallel (Na+) topologies.
- Na+ ions reduce Tel22 mobility, suggesting more stable antiparallel conformations.
- Complexation with BRACO19 enhances Tel22 dynamics, attributed to water binding.
Conclusions:
- G4 polymorphism and ligand complexation effects on dynamics are mediated by hydration water.
- Understanding G4 dynamics is key for developing targeted anticancer therapies.
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