DNA oligomers having a diazapyrenium dication (DAP(2+)); Synthesis and DNAcleavage activities

Aiming at the creation of functionalized antisense DNA oligomers possessing site-selective DNA cleaving activity, viologen and a related compound, dia zapyrenium dication (DAP(2+)), were selected and introduced into oligodeoxy ribonucleotides as a functionalized molecule. The conjugation of these func tionalized molecules with DNA proceeded smoothly by using standard H-phosph onate chemistry. A part of the DAP(2+)-tethered DNA oligomers was synthesiz ed by a combination of solid support method and liquid phase technique. Vio logen-tethered DNA oligomers showed no significant activity toward DNA clea vage in spite of their characteristic ESR spectra. On the other hand, it wa s observed that the DAP(2+)-tethered DNA oligomers formed more stable duple xes with their complementary strands than the corresponding wild type, and these molecules effectively cleaved the complementary strands at the specif ic site of 2-3 bases away from the modified phosphoramidate linkage. The ef fect of position and length of the linker arm on the selectivity in the cle avage reaction was also investigated, and it was found that introduction at the 3'- or 5'-end phosphate site is more favorable, probably due to duplex stabilization.