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Targeting G-Rich lncRNA and Its Structural Polymorphism With Selective G-Quadruplex Ligands: An NMR Study.

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|November 13, 2025
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Summary

Researchers investigated how small molecules interact with RNA G-quadruplexes (rGQs), finding that some molecules effective against DNA G-quadruplexes also stabilize rGQs. This work aids in designing targeted therapies by understanding ligand-rGQ interactions.

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G‐quadruplexNMR spectroscopyligandlncrna

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Area of Science:

  • Biochemistry and Molecular Biology
  • RNA Structure and Dynamics
  • Chemical Biology

Background:

  • Long noncoding RNAs (lncRNAs) utilize complex structures like RNA G-quadruplexes (rGQs) for regulation.
  • Ligand interactions with DNA G-quadruplexes (dGQs) are well-studied, but rGQ interactions remain underexplored.

Purpose of the Study:

  • To investigate the binding and stabilizing effects of small molecules, known to interact with dGQs, on an rGQ derived from the REG1CP lncRNA (SL15P).
  • To assess if these ligands can promote rGQ folding over alternative structures.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy to analyze complex formation.
  • Circular Dichroism (CD) melting experiments to quantify thermal stabilization.
  • Testing 12 small molecules previously shown to bind dGQs.

Main Results:

  • Ligands targeting dGQs showed varied interactions with the SL15P rGQ.
  • Compounds 360A, PhenDC3, and PDS effectively bound and stabilized the rGQ.
  • PhenDC3 exhibited evidence of dual binding interactions.

Conclusions:

  • Ligand binding to rGQs is highly variable and structure-dependent.
  • Findings support the rational design of selective small molecules for therapeutic applications targeting rGQs.