Synthesis of damaged DNA containing the oxidative lesion 3′-oxothymidine

Abstract

Oxidative events that take place during regular oxygen metabolism can lead to the formation of organic or inorganic radicals. The interaction of these radicals with macromolecules in the organism and with DNA in particular is suspected to lead to apoptosis, DNA lesions and cell damage. Independent generation of DNA lesions resulting from oxidative damage is used to promote the study of their effects on biological systems. An efficient synthesis of oligodeoxyribonucleotides (ODNs) containing the oxidative damage lesion 3′-oxothymidine has been accomplished via incorporation of C3′-hydroxymethyl thymidine as its corresponding 5′-phosphoramidite. Through oxidative cleavage using sodium periodate in aqueous solution, the lesion of interest is easily generated. Due to its inherent instability it cannot be directly isolated, but must be generated in situ. 3′-Oxothymidine is a demonstrated damage product formed upon generation of the C3′-thymidinyl radical in ODN.