Detection of CAG repeat DNA sequences by pyrene-functionalized pyrrole-imidazole polyamides

Bioorg Med Chem. 2007 Nov 15;15(22):6937-42. doi: 10.1016/j.bmc.2007.07.055. Epub 2007 Aug 24.

Abstract

Five N-methylpyrrole-N-methylimidazole (Py-Im) polyamides possessing a fluorescent pyrene were synthesized by Fmoc solid-phase synthesis using Py/Im monomers and pyrenylbutyl-pyrrole monomer compound 9. The steady state fluorescence of conjugates 1-5 was examined in the presence and absence of (CAG)(12)-containing oligodeoxynucleotides (ODNs) 1 and 2. Of the conjugates, conjugate 1 showed no background emission around 470 nm in the absence of ODNs, and a clear increase of emission at 475 nm was observed upon addition of ODNs 1 and 2. The emission of conjugate 1 at 475 nm increased linearly with the concentration of ODN and the number of CAG repeats. The results indicate that conjugate 1 efficiently forms a pyrene excimer upon binding in the minor groove of DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / analysis*
  • Fluorescence
  • Imidazoles / chemistry*
  • Nylons / chemical synthesis
  • Nylons / chemistry*
  • Oligodeoxyribonucleotides / chemistry
  • Pyrenes / chemistry*
  • Pyrroles / chemistry*
  • Sequence Analysis, DNA / methods
  • Spectrometry, Fluorescence / methods
  • Trinucleotide Repeats*

Substances

  • Imidazoles
  • Nylons
  • Oligodeoxyribonucleotides
  • Pyrenes
  • Pyrroles
  • imidazole
  • DNA
  • pyrene