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

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 I showed no background emission around 470 nm in the absence of ODNs, and a clear increase of emission at 475 run was observed upon addition of ODNs I and 2. The emission of conjugate I at 475 nm increased linearly with the concentration of ODN and the number of CAG repeats. The results indicate that conjugate I efficiently forms a pyrene excimer upon binding in the minor groove of DNA. (C) 2007 Elsevier Ltd. All rights reserved.