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-NO) and imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleoside (Im-ON) 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-NO:Im-ON on the sticky ends of the duplex was insufficient for thermal stabilization (+2.5 degrees C per pair relative to the G:C pair), the duplex containing two consecutive Na-NO:Im-ON pairs at its sticky ends was markedly stabilized thermally. The stabilizing effect of the incorporation of additional Na-NO:Im-ON pairs is estimated to be +7.8 degrees C per pair. Application as thermally stabilized decoy molecules to NF-kappaB (p50) was also demonstrated. The DNA duplexes containing the Na-NO:Im-ON pairs (ODN I:ODN II and ODN III:ODN IV) acted as competitors to the natural NF-kappaB-binding duplex (ODN V: ODN VI), and the calculated IC50 values of ODN I:ODN II and ODN III:ODN IV were 20.1+/-13.3 and 10.9+/-4.8 nM, respectively, greater than that of ODN V:ODN VI.
Hikishima
Sadao
S
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Minakawa
Noriaki
N
Kuramoto
Kazuyuki
K
Ogata
Shintaro
S
Matsuda
Akira
A
D020029:Base Pairing; D001483:Base Sequence; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009287:Naphthyridines / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
D007093:Imidazoles; D016328:NF-kappa B; D009287:Naphthyridines; D009841:Oligonucleotides; D011741:Pyrimidine Nucleosides