SAPPHYRIN-OLIGONUCLEOTIDE CONJUGATES - NOVEL SEQUENCE-SPECIFIC DNA PHOTOMODIFYING AGENTS WITH INCREASED BINDING-AFFINITY

The synthesis of a novel sapphyrin-oligonucleotide conjugate is descri bed along with its DNA photocleavage and nucleic acid binding properti es. The sapphyrin-oligonucleotide conjugate produces photodamage on a complementary oligonucleotide target when irradiated at wavelengths ab ove 620 mm. Upon piperidine treatment, guanine residues on the target strand in the vicinity of the sapphyrin macrocycle are found to be cle aved more effectively than guanines remote from the sapphyrin subunit. No sequence-specific photomodification was observed when noncomplemen tary oligonucleotides were used as st target. The duplexes formed betw een the sapphyrin conjugate and complementary nucleic acids were found to have higher melting temperatures than analogous control systems co nsisting of unmodified oligonucleotides of the same sequence. Melting temperature studies using variable salt concentrations and oligonucleo tide targets indicate that the binding enhancement is due to hydrophob ic interactions. The sapphyrin unit attached to an oligonucleotide can thus serve a dual role; it can act as a sequence-specific photomodifi cation agent at irradiation wavelengths >620 nn, and it can increase t he affinity of a sapphyrin-bearing oligonucleotide to a complementary sequence.