Detection of triplet repeat sequences in the double-stranded DNA using pyrene-functionalized pyrrole-imidazole polyamides with rigid linkers.
Methods for sequence-specific detection in double-stranded DNA (dsDNA) are becoming increasingly useful and important as diagnostic and imaging tools. Recently, we designed and synthesized pyrrole (Py)-imidazole (Im) polyamides possessing two pyrene moieties, 1, which showed an increased excimer emission in the presence of (CAG)(12)-containing oligodeoxynucleotides (ODN) 1 and 2. In this study, we synthesized bis-pyrenyl Py-Im polyamides with rigid linkers 2, 3, and 4 to improve their fluorescence properties. Among the conjugates, 2 showed a marked increase in excimer emission, which was dependent on the concentration of the target ODN and the number of CAG repeats in the dsDNA. Unlike conjugate 1, which has flexible linkers, the excimer emission intensity of 2 was retained at over 85%, even after 4h. Py-Im polyamides have the potential to be important diagnostic molecules for detecting genetic differences between individuals.
Fujimoto
Jun
J
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto 606-8502, Japan.
Bando
Toshikazu
T
Minoshima
Masafumi
M
Uchida
Shinsuke
S
Iwasaki
Makoto
M
Shinohara
Ken-ichi
K
Sugiyama
Hiroshi
H
D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism; D009757:Nylons / Q000737:chemistry* / Q000378:metabolism; D011721:Pyrenes / Q000737:chemistry* / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D020349:Surface Plasmon Resonance; D018911:Trinucleotide Repeats
D007093:Imidazoles; D009757:Nylons; D011721:Pyrenes; D011758:Pyrroles; D004247:DNA