Synthesis and properties of DNA purine dehydrodimers: 8–8-bideoxyribonucleosides and 8–8-bideoxyribonucleotides

SUMMARY

Purine dimers are formed by oxidation of DNA. There is evidence that these dimers are not repaired by cells from the human disease xeroderma pigmentosum. It has been suggested that unrepaired purine dimers are involved in the etiogenesis of internal cancers and neural degeneration that are observed in this disease. In order to study the properties and biological consequences of such moieties, these compounds were synthesized: 8–8-(2′-deoxyadenosyl)-2′-deoxyadenosine; 8–8-(2′-deoxyadenosyl)-2′-deoxyadenosine-5′-monophosphate; 8–8-(2′-deoxyadenosyl)-2′-deoxyguanosine; 8–8-(2′-deoxyadenosyl)-2′-deoxyguanosine-5′-monophosphate; 8–8-(2′-deoxyguanosyl)-2′-deoxyguanosine; 8–8-(2′-deoxyguanosyl)-2′-deoxyguanosine-5′-monophosphate; 8–8-(2′-deoxyguanosyl)-2′-deoxyadenosine, and 8–8-(2′-deoxyguanosyl)-2′-deoxyadenosine-5′-monophosphate. Following purification, they were characterized by mass spectrometry and nuclear magnetic resonance studies. Ultraviolet, fluorescence, and circular dichroic spectra of these products were established. The behavior of these photoproducts in various chromatographic systems was elucidated. Syntheses of purine dimers and descriptions of their properties can aid the studies of their possible formation in, and excision from, oxidized DNA.