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Selective molecular probes for G-quadruplex and G-quadruplex-duplex junctions: Cyanine dye interactions and
Aleksey Vasilev1, Diana Cheshmedzhieva2, Hamzah Ahmed3
1Laboratory of Functional and Nanostructured Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Str., Bl. 103A, 1113 Sofia, Bulgaria; Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski", 1 James Bourchier Blvd., 1164 Sofia, Bulgaria.
Two cyanine dyes show distinct DNA binding preferences. Less polar dye 3b aggregates and binds G-quadruplexes, while polar dye R9 selectively binds duplex and G-quadruplex-duplex junctions without aggregation.
Area of Science:
- Biophysical Chemistry
- Molecular Biology
- Medicinal Chemistry
Background:
- Hybrid DNA structures like G-quadruplex-duplex junctions are emerging as potential targets for small molecule ligands.
- Cyanine dyes are widely used as fluorescent probes and therapeutic agents, but their interactions with complex DNA structures require detailed investigation.
Purpose of the Study:
- To investigate the differential interactions of two cyanine dyes, R9 and 3b, with various DNA structures.
- To elucidate the structure-activity relationship governing dye binding to duplex DNA, G-quadruplexes, and G-quadruplex-duplex junctions.
Main Methods:
- Utilized molecular spectroscopic techniques including UV-visible absorption, circular dichroism, and fluorescence spectroscopy.
- Employed nuclear magnetic resonance (NMR) spectroscopy and molecular docking for structural analysis.
- Applied multivariate analysis to interpret complex spectroscopic data.
Main Results:
- Cyanine dye 3b, prone to aggregation, preferentially π-stacks with parallel G-quadruplexes, inducing significant circular dichroism and fluorescence.
- Cyanine dye R9 forms selective, non-aggregating complexes with duplex DNA and G-quadruplex-duplex junctions, exhibiting fluorescence enhancement.
- NMR and docking studies confirmed distinct binding modes: R9 binds selectively, while 3b binds non-specifically, potentially leading to precipitation.
Conclusions:
- The hydrophilicity of cyanine dyes dictates their binding behavior and selectivity towards different DNA structures.
- Dye 3b shows potential for targeting parallel G-quadruplexes, while R9 is suitable for G-quadruplex-duplex junctions.
- Understanding these differential interactions is crucial for designing targeted DNA-binding agents.
