SEQUENCE-SPECIFIC PHOTOMODIFICATION OF DNA BY AN OLIGONUCLEOTIDE-PHENANTHRODIHYDRODIOXIN CONJUGATE

We introduce a new member of a family of photochemically active oligon ucleotide conjugates. A Phenanthrodihydrodioxin (PDHD)-based agent was synthesized and covalently linked to a 5'-end of the 9-mer oligonucle otide via a hexamethylene linker. The conjugate hybridized to a comple mentary 30-nucleotide-long target and efficiently cleaved it in a sequ ence specific manner. Up to 67% of target was specifically damaged (51 % cross-links and 16% direct cleavage). While the photosensitizer alon e nonspecifically damaged only Gs in a single-stranded target, its con jugate cross-linked to and damaged also A, T, and C sites in a target in agreement with duplex and tripler formation.