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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
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Published on: September 19, 2017

G-quadruplex nucleic acids as therapeutic targets.

Shankar Balasubramanian1, Stephen Neidle

  • 1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

Current Opinion in Chemical Biology
|June 12, 2009
PubMed
Summary

Guanine-rich DNA sequences form complex structures called quadruplexes. These structures, found in gene promoters, offer novel therapeutic targets for diseases like cancer by inhibiting gene transcription.

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Area of Science:

  • Biochemistry
  • Genomics
  • Molecular Biology

Background:

  • Nucleic acid sequences with multiple guanine runs form higher-order structures known as quadruplexes.
  • Quadruplexes are notably found at the telomeric ends of eukaryotic chromosomes and within promoter regions of genes, including oncogenes.
  • Bioinformatic surveys reveal over-representation of quadruplexes in gene promoter and 5' untranslated regions (5'UTR).

Purpose of the Study:

  • To explore the potential of quadruplex structures as novel therapeutic targets.
  • To investigate the use of small molecules for stabilizing quadruplexes to inhibit gene transcription, particularly for oncogenes.
  • To discuss the progress and mechanistic challenges in targeting quadruplexes.

Main Methods:

  • Characterization of quadruplex formation at telomeres.
  • Bioinformatic mapping of quadruplex occurrences in the human and other genomes.
  • Design and application of quadruplex-selective small molecules.

Main Results:

  • Quadruplexes are prevalent in specific genomic regions, including gene promoters and telomeres.
  • Small molecules can selectively stabilize quadruplexes, influencing DNA interactions.
  • Quadruplex stabilization offers a potential therapeutic strategy by inhibiting gene transcription.

Conclusions:

  • Quadruplexes represent a promising class of therapeutic targets due to their unique structures and genomic locations.
  • Targeting quadruplexes provides an alternative therapeutic approach to traditional methods like kinase inhibition, potentially circumventing resistance mechanisms.
  • Further research into the mechanistic aspects of quadruplex targeting is crucial for therapeutic development.