DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action

Rahul Palchaudhuri, Paul Hergenrother

Research output: Contribution to journalReview article


Small molecules that bind to DNA are extremely useful as biochemical tools for the visualization of DNA both in vitro and inside the cell. Additionally, the clinical significance of DNA-binding compounds can hardly be overstated, as many anticancer regimens include a compound that binds to and/or modifies DNA. Although many of the important DNA-binding anticancer drugs were discovered in phenotypic, cell-based screens, in vitro experiments have been developed that enable a precise determination of how a compound interacts with DNA. This review provides a summary of the assays that should be performed when it is suspected that DNA may be a target for a given small molecule. A battery of in vitro assays readily distinguishes between DNA intercalation, DNA groove binding, and the inhibition of topoisomerases. Further cell-based investigations can implicate a direct effect of a compound on DNA within the cell. Together, these assays are powerful tools to determine the mechanism of previously discovered molecules, and will be crucial to the discovery of the next generation of DNA-binding anticancer drugs.

Original languageEnglish (US)
Pages (from-to)497-503
Number of pages7
JournalCurrent Opinion in Biotechnology
Issue number6
StatePublished - Dec 1 2007


ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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