Targeting of nucleic acid junctions: addressing to a branch point an oligodeoxynucleotide conjugated with an intercalator.
It is possible to enhance targeting of a DNA stem flank domain with a complementary DNA when it is conjugated with diphenyl ether at the branch point. The nucleoside 2'-deoxy-5-methyl- N 4-(4-phenoxyphenyl)cytidine (5) was synthesized from thymidineby tritylation, acetylation, amination via 2,4, 6-trimethylbenzenesulfonyl activation and subsequent de-protection. When a three-way junction is formed with a bulged nucleoside 5 at the branch point, the thermal melting temperature was increased by 9 degreesC when compared with wild-type DNA. When hybridizing to one of the flanks at a stem allowing coaxial stacking to the stem, modification at the branch point resulted in DeltaTm= 5.8 degreesC. For targeting to RNA the results were more ambiguous. RNase H activity was observed in some cases when an intercalating aromatic ring was addressed at the branch point. RNase H activity was observed even for a short 7mer ODN.
Department of Chemistry and Department of Molecular Biology, Odense University, Campusvej 55,DK-5230 Odense M, Denmark.
O M
OM
Ali
T
T
Franch
K
K
Gerdes
E B
EB
Pedersen
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D016914:Ribonuclease H / Q000378:metabolism; D013816:Thermodynamics
D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D004247:DNA; D016914:Ribonuclease H