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- W4290667683 abstract "Probing the kinetics of ligand binding to biomolecules is of paramount interest in biology and pharmacology. Measurements of such kinetic processes provide information on the rate-determining steps that control the binding affinity of ligands to biomolecules, thereby predicting the mechanism of the molecular interaction. In this context, ligand binding to G-quadruplex DNA (GqDNA) structures has attracted tremendous attention primarily because of their use in possible anticancer therapy. Although a large number of G-quadruplex-specific ligands have been proposed, probing the kinetics of G-tetrad-selective binding of (multiple) ligands within a G-quadruplex DNA (GqDNA) structure remains challenging. Most of the earlier studies focused on the thermodynamics of ligand binding; however, the kinetics of ligand association and dissociation with GqDNA, particularly binding of multiple ligands within a GqDNA structure, have not been explored. Here, we propose a simple fluorescence correlation spectroscopy-based method that measures the G-tetrad-selective association and dissociation rates of ligands within a GqDNA structure by correlating the fluorescence fluctuations of a site-specific (5' or 3' end-labeled) fluorophore (Cy3) in GqDNA due to quenching of Cy3 fluorescence, induced by the ligand binding to the G-tetrads. We show that well-known GqDNA ligands, BRACO19, TMPyP4, Hoechst 33258, and Hoechst 33342, have G-tetrad-selective association and dissociation rates, which suggest site-dependent variation of free energy barriers for binding/unbinding of the ligands with GqDNA. We also show that the measured kinetic rates depend not only on the G-tetrad site (5' vs 3' end) but also on the ligand and GqDNA structures." @default.
- W4290667683 created "2022-08-08" @default.
- W4290667683 creator A5001998891 @default.
- W4290667683 creator A5003561176 @default.
- W4290667683 date "2022-08-08" @default.
- W4290667683 modified "2023-10-12" @default.
- W4290667683 title "G-Tetrad-Selective Ligand Binding Kinetics in G-Quadruplex DNA Probed with Fluorescence Correlation Spectroscopy" @default.
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- W4290667683 doi "https://doi.org/10.1021/acs.jpcb.2c04181" @default.
- W4290667683 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35939531" @default.
- W4290667683 hasPublicationYear "2022" @default.
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