Small-molecule-mediated G-quadruplex isolation from human cells

Nat Chem. 2010 Dec;2(12):1095-8. doi: 10.1038/nchem.842. Epub 2010 Oct 10.

Abstract

Nucleic acids containing stretches of tandem guanines can fold into four-stranded structures called G-quadruplexes. The existence of such sequences in genomic DNA suggests the occurrence of these motifs in cells, with potential implications in a number of biological processes relevant to cancer. Small molecules have proven to be valuable tools to dissect cell circuitry. Here, we describe a synthetic small molecule derived from an N,N'-bis(2-quinolinyl)pyridine-2,6-dicarboxamide, which is designed to mediate the selective isolation of G-quadruplex nucleic acids. The methodology was successfully applied to a range of DNA and RNA G-quadruplexes in vitro. We demonstrate the general applicability of the method by isolating telomeric DNA-containing G-quadruplex motifs from cells. We show that telomeres are targets for the probe, providing further evidence of the formation of G-quadruplexes in human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Aminoquinolines / chemistry*
  • Biotin / analogs & derivatives*
  • Biotin / chemistry
  • Cell Line, Tumor
  • DNA / isolation & purification
  • G-Quadruplexes*
  • Humans
  • Telomere / chemistry

Substances

  • Amides
  • Aminoquinolines
  • Biotin
  • DNA

Associated data

  • PubChem-Substance/99343620
  • PubChem-Substance/99343621
  • PubChem-Substance/99343622
  • PubChem-Substance/99343623
  • PubChem-Substance/99343624
  • PubChem-Substance/99343625