Synthesis and Characterization of Oligodeoxynucleotides Containing Naphthyridine:Imidazopyridopyrimidine Base Pairs at their Sticky Ends. Application as Thermally Stabilized Decoy Molecules

We describe the synthesis and properties of oligodeoxynucleotides (ODNs) containing 1,8‐naphthyridine C‐nucleoside (Na‐N O ) and imidazo[5′,4′:4,5]pyrido[2,3‐ d ]pyrimidine nucleoside (Im‐O N ) at the termini. The modified ODNs were more resistant (6 to 40 times) than natural DNA to snake venom phosphodiesterase (SVPD). Although incorporation of one pair each of Na‐N O :Im‐O N on the sticky ends of the duplex was insufficient for thermal stabilization (+2.5 °C per pair relative to the G:C pair), the duplex containing two consecutive Na‐N O :Im‐O N pairs at its sticky ends was markedly stabilized thermally. The stabilizing effect of the incorporation of additional Na‐N O :Im‐O N pairs is estimated to be +7.8 °C per pair. Application as thermally stabilized decoy molecules to NF‐κB (p50) was also demonstrated. The DNA duplexes containing the Na‐N O :Im‐O N pairs (ODN I:ODN II and ODN III:ODN IV) acted as competitors to the natural NF‐κB‐binding duplex (ODN V: ODN VI), and the calculated IC 50 values of ODN I:ODN II and ODN III:ODN IV were 20.1±13.3 and 10.9±4.8 n M , respectively, greater than that of ODN V:ODN VI.