Assessing the differential affinity of small molecules for noncanonical DNA structures

Chembiochem. 2012 Sep 3;13(13):1905-12. doi: 10.1002/cbic.201200396. Epub 2012 Jul 31.

Abstract

The targeting of higher-order DNA structures has been thoroughly developed with G-quadruplex DNA but not with other structures like branched DNA (also known as DNA junctions). Because these alternative higher-order DNA architectures might be of high biological relevance, we implemented a high-throughput version of the FRET melting assay that enabled us to map the interactions of a candidate with four different DNA structures (duplex- and quadruplex DNA, three- and four-way junctions) in a rapid and reliable manner. We also introduce a novel index, the BONDS (branched and other noncanonical DNA selectivity) index, to conveniently quantify this differential affinity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology
  • Base Sequence
  • Caffeine / analogs & derivatives
  • Caffeine / pharmacology*
  • DNA / chemistry*
  • Fluorescence Resonance Energy Transfer
  • G-Quadruplexes / drug effects
  • Models, Molecular
  • Nucleic Acid Conformation / drug effects*
  • Organogold Compounds / chemistry
  • Organogold Compounds / pharmacology*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Thermodynamics

Substances

  • Anticarcinogenic Agents
  • Organogold Compounds
  • Small Molecule Libraries
  • Caffeine
  • DNA