DNA interstrand cross-link formation initiated by reaction between singlet oxygen and a modified nucleotide.
DNA is the target of many anti-cancer therapies. These agents damage the biopolymer by oxidation or by alkylation. Interstrand DNA cross-links are believed to be the source of cytotoxicity of anti-tumor agents, such as mitomycin C, which alkylate the biopolymer. In contrast, deoxyguanosine oxidation is the result of reaction between DNA and singlet oxygen, which is the damaging species produced in photodynamic therapy. We have shown that, upon oxidation by singlet oxygen, an analogue of thymidine (2) rearranges to a methide, which forms DNA-DNA interstrand cross-links. This novel process suggests that 2 may be a useful adjuvant in photodynamic therapy.
Hong
In Seok
IS
Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Greenberg
Marc M
MM
D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry* / Q000494:pharmacology; D010782:Photolysis; D026082:Singlet Oxygen / Q000737:chemistry* / Q000494:pharmacology
D003432:Cross-Linking Reagents; D009711:Nucleotides; D026082:Singlet Oxygen; D004247:DNA