Chemical and Biochemical Properties of Oligonucleotides that Contain (5′S,6S)-Cyclo-5,6-dihydro-2′-deoxyuridine and (5′S,6S)-Cyclo-5,6-dihydrothymidine, Two Main Radiation-Induced Degradation Products of Pyrimidine 2′-Deoxyribonucleosides

The first chemical synthesis of (5′S,6S)-cyclo-5,6-dihydro-2′-deoxyuridine [(5′S,6S)-CyclodHdUrd], a major product of gamma irradiation of oxygen free aqueous solution of 2′-deoxycytidine is reported. Subsequently, the latter cyclonucleoside was incorporated in defined sequence oligodeoxyribonucleotides. The chemical composition of the modified DNA fragments was assessed by enzymatic digestions and mass spectrometry measurements. The latter analyses confirmed the presence and the integrity of the lesion within the synthesised DNA fragments. Replication and repair studies showed that (5′S,6S)-CyclodHdUrd together with (5′S,6S)-CyclodHThd [(5′S,6S)-cyclo-5,6-dihydrothymidine] inserted into DNA oligomers act as blocks for DNA polymerases and are not excised by DNA N-glycosylases.