Site-selective strand cleavage at methylated cytosine: regional effect of naphthoquinone chromophore on the one-electron photooxidation of 5-methylcytosine and positive charge transfer in DNA

Abstract

Photoirradiation and subsequent hot piperidine treatment of the duplex consisting of 5-methylcytosine ((m)C)-containing DNA and 2-methyl-1,4-naphthoquinone (NQ)-tethered complementary ODN led to oxidative strand cleavage selectively at the (m)C site, when the NQ was arranged so as to be in close contact with the target (m)C. Well designed incorporation of NQ into an interior of ODN could suppress a competitive strand cleavage at consecutive guanines, which occurred as a result of positive charge transfer. In contrast to the ODNs bearing NQ in an interior of the strand, photoirradiation of the duplex with an NQ tethered to a flexible methylene linker at the strand end resulted in not only strong strand cleavage at (m)C but also small amount of strand cleavage at the G doublet. Thus, optimization of the regional position of photosensitizing NQ could provide exclusive strand cleavage at (m)C without unfavorable cleavage at G.