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Related Experiment Video

Updated: Sep 9, 2025

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Rapid G4 Ligand Screening Through Spectral Changes Using HT-SRCD with Minimal Material.

Martina Rotondo1, Claudia Honisch2, Pietro Spanu3

  • 1Department of Biology, University of Naples Federico II, 80126 Napoli, Italy.

Molecules (Basel, Switzerland)
|August 28, 2025
PubMed
Summary
This summary is machine-generated.

High-throughput synchrotron radiation circular dichroism (HT-SRCD) spectroscopy effectively analyzes small-molecule interactions with G-quadruplex (G4) DNA structures. This advanced method offers rapid, high-throughput screening for drug discovery targeting G4 sequences.

Keywords:
G-quadruplex (G4)drug discoveryhigh-throughput synchrotron radiation circular dichroism (HT-SRCD)ligand screening

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Area of Science:

  • Biophysical chemistry
  • Structural biology
  • Medicinal chemistry

Background:

  • G-quadruplex (G4) DNA structures are crucial targets for therapeutic intervention.
  • Evaluating small-molecule interactions with G4s is essential for drug development.
  • Conventional methods for G4 interaction analysis have limitations in throughput and sample requirements.

Purpose of the Study:

  • To introduce and validate high-throughput synchrotron radiation circular dichroism (HT-SRCD) spectroscopy for analyzing G4-ligand interactions.
  • To assess the capability of HT-SRCD for discriminating between different ligands and understanding their binding modes.
  • To demonstrate the utility of HT-SRCD in drug discovery efforts targeting G4 structures.

Main Methods:

  • Utilized high-throughput synchrotron radiation circular dichroism (HT-SRCD) spectroscopy.
  • Investigated interactions with three biologically relevant G4 sequences (HTelo1, G3T3, T95-2T).
  • Evaluated interactions with a library of tetrazole-based small molecules and a peptide (Rhau25).

Main Results:

  • HT-SRCD successfully analyzed interactions between G4 sequences and diverse small molecules/peptides.
  • The method effectively discriminated between different ligands based on their G4 interactions.
  • Valuable insights into ligand selectivity and modes of interaction with G4 structures were obtained.

Conclusions:

  • HT-SRCD is a powerful, high-throughput technique for studying G4-ligand interactions.
  • This method overcomes limitations of conventional circular dichroism spectroscopy.
  • HT-SRCD facilitates efficient screening and characterization of potential G4-targeting therapeutics.