Site-specific photomodification of DNA by porphyrin-oligonucleotide conjugates synthesized via a solid phase H-phosphonate approach

Abstract

meso-Tris(4-pyridyl)[[(ω- hydroxyhexamethylene)carbamoyl]phenyl]porphyrin was converted to its H- phosphonate derivative and conjugated using solid phase synthesis with the 5'-hydroxyl group of deoxyribonucleotides d(TCTTCCCA) and d(T)12. These conjugates were transformed into their (N-methylpyridiniumyl)porphyrin analogs in the reaction with methyl iodide. A 532 nm laser beam was utilized to photoactivate both types of the conjugates in the presence of the target 22-mer and 16-mer oligonucleotides. Photoactivation of porphyrin- oligonucleotide conjugates resulted in site-specific DNA modification characterized by a main reaction site size of ~5 bases.