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Synthesis and Characterization of Oligodeoxynucleotides Containing Naphthyridine:Imidazopyridopyrimidine Base Pairs at their Sticky Ends. Application as Thermally Stabilized Decoy Molecules
Author(s) -
Hikishima Sadao,
Minakawa Noriaki,
Kuramoto Kazuyuki,
Ogata Shintaro,
Matsuda Akira
Publication year - 2006
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200600318
Subject(s) - duplex (building) , nucleoside , dna , pyrimidine , chemistry , stereochemistry , molecule , base pair , decoy , biochemistry , organic chemistry , receptor
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.