DNA Analysis by Dynamic Chemistry

Frank R. Bowler, Juan J. Diaz-Mochon, Michael D. Swift, Mark Bradley

Research output: Contribution to journalArticlepeer-review

Abstract

The paper describes a practical application of dynamic chemistry which allows the enzyme free, rapid analysis/identification of nucleic acids, including DNA and microRNAs, with very high specificity. The concept is beautifully simple – a PNA probe with a blank position (a secondary amine group on the PNA backbone) is hybridised to the target DNA and then interrogated with the four bases (each of which carries an aldehyde). Dynamic Schiff’s base formation allows the correct base to be incorporated with quite remarkable selectivity with subsequent mass spectroscopy based analysis. This is the first practical method of enzyme free DNA analysis since Maxim and Gilbert and the only method of DNA analysis that allows the interrogation/analysis of DNA from within the middle of DNA strand. (NB: this approach/chemistry was patented in 2009 (WO2009037473) and led to the University spinout DestiNA in 2010 which has allowed this concept to be expanded to clinical diagnostic testing and screening for prostate cancers and drug toxicology).
Original languageEnglish
Pages (from-to)1809-1812
Number of pages4
JournalAngewandte Chemie International Edition
Volume49
Issue number10
DOIs
Publication statusPublished - Mar 2010

Keywords

  • DNA analysis
  • dynamic chemistry
  • genotyping
  • peptide nucleic acids
  • single-nucleotide polymorphisms
  • TEMPLATE-DIRECTED SYNTHESIS
  • PEPTIDE NUCLEIC-ACIDS
  • RECOGNITION
  • LIGATION
  • REACTIVITY
  • MUTATIONS
  • STACKING
  • ANALOGS
  • ARRAYS
  • RNA

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