Development of a new dumbbell-shaped decoy DNA using a combination of the unnatural base pair ImO(N):NaN(O) and a CuAAC reaction

• Published in: Bioconjugate chemistry Vol. 25; no. 7; pp. 1360 - 1369
• Main Authors: Higuchi, Yosuke, Furukawa, Kazuhiro, Miyazawa, Tadashi, Minakawa, Noriaki
• Format: Journal Article
• Language: English
• Published: United States 16.07.2014
• Subjects: Alkynes - chemistry; Azides - chemistry; Base Pairing; Binding, Competitive; Copper - metabolism; Deoxyribonucleases - metabolism; DNA - chemistry; DNA - metabolism; Humans; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - metabolism
• ISSN: 1520-4812
• DOI: 10.1021/bc500225r

We describe the synthesis and potential application of a new dumbbell-shaped decoy DNA prepared using a combination of the base pair ImO(N):NaN(O) and a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The CuAAC reaction between the azido group on the 5'-end of oligodeoxynucleotide (ODN) and the ethynyl group on the NaN(O) base of the opposite strand did not proceed, whereas that between the azido group and the flexible hexynyl group on the NaN(O) base of the opposite strand proceeded smoothly to give a new dumbbell-shaped double-stranded ODN (dsODN). The resulting dsODN had extremely high thermal stability and exhibited exonuclease resistance. In addition, the terminal modification did not affect its helical structure, and thus, the dumbbell-shaped dsODN displayed promising in vitro activity in a competition assay with the NF-kB p50 transcription factor homodimer.