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Updated: Mar 20, 2026

Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
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Distance measurements between paramagnetic ligands bound to parallel stranded guanine quadruplexes.

M P Donohue1, V A Szalai2

  • 1Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. matthew.donohue@nist.gov and Maryland NanoCenter, University of Maryland, College Park, MD 20742, USA.

Physical Chemistry Chemical Physics : PCCP
|May 25, 2016
PubMed
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Cationic porphyrins bind to guanine quadruplexes, with binding stoichiometry of 2:1. Ligand end-stacking distance decreases as quadruplex length increases, indicating structural changes in DNA secondary structure.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Deoxyribonucleic acid (DNA) can form non-canonical structures beyond the double helix.
  • Guanine quadruplexes are one such structure, with potential roles in cellular processes.
  • Cationic porphyrins are known to interact with guanine quadruplexes.

Purpose of the Study:

  • To investigate the structural effects of cationic porphyrin binding on guanine quadruplexes with varying numbers of guanine quartets.
  • To elucidate the binding stoichiometry and distances between ligands.
  • To understand how ligand binding influences the secondary structure of longer guanine quadruplexes.

Main Methods:

  • Utilized Double Electron-Electron Resonance (DEER) spectroscopy at X-band (9.5 GHz).

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  • Employed broadband, shaped inversion pulses for precise distance measurements.
  • Studied model parallel-stranded guanine quadruplexes with increasing guanine quartet numbers.

    • Main Results:

    • A 2:1 binding stoichiometry between porphyrins and each quadruplex was determined.
    • Measured copper-copper distances showed a linear relationship with the number of guanines.
    • Ligand end-stacking distance unexpectedly decreased as quadruplex length increased.

    Conclusions:

    • Cationic porphyrin binding to guanine quadruplexes is stoichiometric and distance-dependent.
    • Increased quadruplex length induces conformational changes in secondary structure upon ligand binding.
    • Further research is needed to fully understand these structural dynamics.