DNA oligomers having a diazapyrenium dication (DAP2+); synthesis and DNA cleavage activities.
Aiming at the creation of functionalized antisense DNA oligomers possessing site-selective DNA cleaving activity, viologen and a related compound, diazapyrenium dication (DAP2+), were selected and introduced into oligodeoxyribonucleotides as a functionalized molecule. The conjugation of these functionalized molecules with DNA proceeded smoothly by using standard H-phosphonate chemistry. A part of the DAP(2+)-tethered DNA oligomers was synthesized by a combination of solid support method and liquid phase technique. Viologen-tethered DNA oligomers showed no significant activity toward DNA cleavage in spite of their characteristic ESR spectra. On the other hand, it was observed that the DAP(2+)-tethered DNA oligomers formed more stable duplexes with their complementary strands than the corresponding wild type, and these molecules effectively cleaved the complementary strands at the specific site of 2-3 bases away from the modified phosphoramidate linkage. The effect of position and length of the linker arm on the selectivity in the cleavage reaction was also investigated, and it was found that introduction at the 3'- or 5'-end phosphate site is more favorable, probably due to duplex stabilization.
Ikeda
H
H
Institute for Chemical Research, Kyoto University, Japan.
Fuji
K
K
Tanaka
K
K
Iso
Y
Y
Yoneda
F
F
D020650:Combinatorial Chemistry Techniques; D004247:DNA / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000378:metabolism; D010618:Phenanthrolines; D010777:Photochemistry; D010957:Plasmids; D017422:Sequence Analysis, DNA; D013696:Temperature; D014755:Viologens
C401953:2,7-diazapyrenium; D016376:Oligonucleotides, Antisense; D010618:Phenanthrolines; D014755:Viologens; D004247:DNA