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Author Spotlight: Characterizing DNA G-Quadruplex by Bis-3-Chloropiperidine Based Chemical Mapping
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Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures.

Anna Aviñó1, Guillem Portella, Ruben Ferreira

  • 1Institute for Advanced Chemistry of Catalonia (IQAC), CSIC, Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.

The FEBS Journal
|December 6, 2013
PubMed
Summary

Guanine-rich DNA sequences form diverse structures like G-quadruplexes. A small modification to the thrombin-binding aptamer (TBA) sequence dramatically altered its G-quadruplex structure, demonstrating high structural plasticity.

Keywords:
DNA polymorphismG-quadruplexnucleic acid structurethermal stabilitythrombin-binding aptamer

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Nucleic Acid Chemistry

Background:

  • Guanine-rich sequences exhibit significant structural polymorphism, forming various DNA structures including duplex, triplex, and quadruplex helices.
  • G-quadruplexes are particularly polymorphic, displaying diverse stoichiometries, strand alignments (parallel and antiparallel), and topological arrangements.

Purpose of the Study:

  • To investigate the equilibrium between intramolecular antiparallel and intermolecular parallel G-quadruplexes in the thrombin-binding aptamer (TBA) sequence.
  • To analyze the impact of a specific loop modification on the structural conformation of TBA G-quadruplexes.

Main Methods:

  • Theoretical modeling of G-quadruplex structures.
  • Experimental validation of predicted structural changes.
  • Nucleotide modification of the TBA sequence.

Main Results:

  • A seemingly minor modification in the TBA loops induced a substantial structural transition.
  • The modified TBA sequence shifted from a monomeric antiparallel G-quadruplex to a parallel G-quadruplex.
  • The resulting parallel G-quadruplex structure incorporated a novel T-tetrad.

Conclusions:

  • G-quadruplex structures are extremely polymorphic and sensitive to nucleotide modifications.
  • Conformation of G-quadruplexes in solution can be readily manipulated through targeted nucleotide alterations.
  • This study highlights the potential for precise control over G-quadruplex folding via sequence engineering.