TARGETING OF NUCLEIC-ACID JUNCTIONS - ADDRESSING TO A BRANCH POINT ANOLIGODEOXYNUCLEOTIDE 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 bra nch point, The nucleoside 2'-deoxy-5-methyl-N-4-(4-phenoxyphenyl)cytid ine (5) was synthesized from thymidine by tritylation, acetylation, am ination via 2,4,6-trimethylbenzenesulfonyl activation and subsequent d e-protection. When a three-way junction is formed with a bulged nucleo side 5 at the branch point, the thermal melting temperature was increa sed by 9 degrees C 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 Delta T-m = 5,8 degrees C , For targeting to RNA the results were more ambiguous. RNase H activi ty 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.