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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
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Loop-mediated fluorescent probes for selective discrimination of parallel and antiparallel G-Quadruplexes
Anup Pandith1, Upendra Nagarajachari2, Ravi Kumara Guralamatta Siddappa1
1Department of Chemistry, Jeonbuk National University, Jeonju 54896, Republic of Korea.
Bioorganic & Medicinal Chemistry
|February 25, 2021
Summary
New pyridinium and quinolinium salts selectively recognize parallel G-quadruplexes (G4s). Probe 1 distinguishes parallel G4s from other types via a far-red fluorescent response, aiding in selective G4 detection.
Area of Science:
- Chemical Biology
- Molecular Recognition
- Supramolecular Chemistry
Background:
- G-quadruplexes (G4s) are non-canonical DNA structures implicated in various biological processes.
- Selective recognition of different G4 topologies remains a challenge.
Purpose of the Study:
- To develop novel pyridinium and quinolinium salts for selective G-quadruplex recognition.
- To investigate the mechanism of selective sensing of parallel G4s by probe 1.
Main Methods:
- Synthesis of pyridinium (1-3) and quinolinium (4) salts.
- UV-Vis absorption and fluorescence spectroscopy.
- Molecular Dynamics (MD) simulations and 1H NMR spectroscopy.
Main Results:
- Probe 1 selectively discriminated parallel G4s (c-KIT-1, c-KIT-2, c-MYC) from anti-parallel/hybrid G4s at pH 7.2.
- A switch-on far-red fluorescent response (emission at 620 nm) was observed due to disaggregation-induced monomer emission.
- Enhanced intramolecular charge transfer (ICT) and π-stacking interactions with parallel G4s were confirmed.
Conclusions:
- Pyridinium and quinolinium salts are effective for selective G4 recognition.
- Probe 1 demonstrates high selectivity for parallel G4s, offering a valuable tool for G4 sensing.
- The findings provide insights for designing future selective parallel G4-targeting compounds.
