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Related Concept Videos

Labeling DNA Probes03:31

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DNA probes are fragments of DNA labeled with a reporter tag to enable their detection or purification. The resulting labeled DNA probes can then hybridize to target nucleic acid sequences through complementary base-pairing, and may be used to recover or identify these regions.
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
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Berberrubine Phosphate: A Selective Fluorescent Probe for Quadruplex DNA.

Peter Jonas Wickhorst1, Heiko Ihmels1

  • 1Department of Chemistry-Biology, University of Siegen, Center of Micro- and Nanochemistry and Engineering (Cµ), Adolf-Reichwein-Str. 2, 57068 Siegen, Germany.

Molecules (Basel, Switzerland)
|April 30, 2021
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Summary

A novel phosphate-substituted berberine derivative selectively binds to G4-DNA and duplex DNA. This compound

Keywords:
DNA ligandG4-DNAalkaloidslight-up probequadruplex DNAzwitterion

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Area of Science:

  • Medicinal Chemistry
  • Biochemistry
  • Molecular Biology

Background:

  • Berberine derivatives are explored for DNA binding.
  • Phosphate substitution can alter DNA interaction properties.
  • G-quadruplex (G4) DNA structures are targets for therapeutic intervention.

Purpose of the Study:

  • Synthesize a phosphate-substituted, zwitterionic berberine derivative.
  • Investigate its binding affinity and modes with duplex DNA and G4-DNA.
  • Evaluate its potential for selective G4-DNA detection.

Main Methods:

  • Photometric, fluorimetric, and polarimetric titrations.
  • Thermal DNA denaturation experiments.
  • Synthesis of a novel phosphate-substituted berberine derivative.

Main Results:

  • High affinity binding to both duplex DNA (K_b = 2-7 × 10^5 M^-1) and G4-DNA.
  • Slight stabilization of G4-DNA, particularly the telomeric 22AG quadruplex.
  • Distinct fluorescence "light-up" upon G4-DNA binding, unlike duplex DNA binding.

Conclusions:

  • The compound exhibits unique binding modes: aggregation/intercalation with duplex DNA and terminal stacking with G4-DNA.
  • Represents a rare example of a phosphate-substituted DNA binder.
  • Differential fluorescence response enables selective fluorimetric detection of G4-DNA.