Synthesis and incorporation of tricyclic-imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleosides into oligonucleotides and their thermal stability.
We designed and synthesized four novel tricyclicnucleosides 1-4, which have imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine structures, to construct theramallystable, non-natural, DNA duplexes. Both 1:2 and 3:4 possess four complementary hydrogen-bond pairs and are expected to form more stable base-pairs than the naturally occurring Watson-Crick base-pairs when incorporated into oligodeoxynucleotides (ODNs). NMR studies of these base-pairs at the nucleoside level in CDCl3 identified the expected base-pair formation with four hydrogen bonds. We also synthesized several ODNs containing these nucleosides and measured their thermal stability. We found that if several of the novel base-pairs were incorporated on complementary strands, the resulting DNA duplexes had very high thermal stability.
Kojima
N
N
Faculty of Pharmaceutical Science, Hokkaido University, Sapporo, Japan.
Ueno
Y
Y
Minakawa
N
N
Matsuda
A
A
D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004355:Drug Stability; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D011725:Pyridines; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry*; D013816:Thermodynamics
D007202:Indicators and Reagents; D009705:Nucleosides; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D011725:Pyridines; D011743:Pyrimidines; D004247:DNA