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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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Rationally Designed G-Quadruplex Selective "Turn-On" NIR Fluorescent Probe with Large Stokes Shift for Nucleic Acid

Sajiya Parveen1,2, Nirupa Chaurasia3,2, Suchitra Gupta1

  • 1Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.

ACS Applied Bio Materials
|October 28, 2024
PubMed
Summary
This summary is machine-generated.

Researchers developed a new near-infrared fluorescent probe, 4a, that selectively binds to G-quadruplexes in live cells. This probe offers improved cellular visualization for studying G-quadruplex structures and their biological functions.

Keywords:
G-quadruplexG4-interacting ligandThiazole orangecellular imagingfluorescence

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Chemical Biology

Background:

  • Guanine-rich sequences form G-quadruplexes, crucial in cellular processes.
  • Existing fluorescent probes lack selectivity, optimal spectral properties, or near-infrared (NIR) emission for cellular imaging.
  • Developing selective NIR fluorescent probes is vital for G-quadruplex research.

Purpose of the Study:

  • To design and synthesize novel NIR fluorescent probes for selective G-quadruplex detection.
  • To evaluate the photophysical properties, selectivity, and cellular imaging capabilities of the designed probes.
  • To investigate the binding mechanism of the lead compound with G-quadruplex structures.

Main Methods:

  • Rational design and synthesis of quinolinium-based NIR fluorescent probes.
  • Spectroscopic analysis (fluorescence emission, Stokes shift) and binding studies with various nucleic acid structures.
  • Molecular docking simulations to elucidate binding modes.
  • Live-cell fluorescence imaging in HeLa cells.

Main Results:

  • Compound 4a exhibits far-red fluorescence (λmax = 680 nm) with a large Stokes shift (∼182 nm).
  • 4a selectively binds to human telomeric G-quadruplexes, showing minimal interaction with single- and double-stranded DNA/RNA.
  • Molecular docking reveals groove binding via π-π stacking and anion-π interactions.
  • 4a demonstrates cell permeability, biocompatibility, and effective imaging of nuclear DNA and cytoplasmic RNA G-quadruplexes in live cells.

Conclusions:

  • The designed NIR probe 4a possesses excellent photophysical properties and high selectivity for G-quadruplexes.
  • 4a enables effective cellular imaging of G-quadruplexes without disturbing their structure or stability.
  • This probe holds significant potential for advancing G-quadruplex biology research and cellular imaging applications.