916735-49-4Relevant academic research and scientific papers
The fate of C5′ radicals of purine nucleosides under oxidative conditions
Boussicault, Fabien,Kaloudis, Panagiotis,Caminal, Clara,Mulazzani, Quinto G.,Chatgilialoglu, Chryssostomos
supporting information; scheme or table, p. 8377 - 8385 (2009/02/02)
The factors that influence the reactivity of C5′ radicals in purine moieties under aerobic conditions are unknown not only in DNA, but also in simple nucleosides. 5′,8-Cyclopurine lesions are the result of a rapid C5′ radical attack to the purine moieties before the reaction with oxygen. These well-known lesions among the DNA modifications were suppressed by the presence of molecular oxygen in solution. Here we elucidate the chemistry of three purine-substituted C5′ radicals (i.e., 2′-deoxyadenosin- 5′-yl, 2′-deoxyinosin-5′-yl, and 2′-deoxyguanosin- 5′-yl) under oxidative conditions using γ-radiolysis coupled with product studies. 2′-Deoxyadenosin-5′-yl and 2′-deoxyinosin- 5′-yl radicals were selectively generated by the reaction of hydrated electrons (eaq-) with 8-bromo-2′-deoxyadenosine and 8-bromo-2′-deoxyinosine followed by a rapid radical translocation from the C8 to the C5′ position. Trapping these two C5′ radicals with Fe(CN)63- gave corresponding hydrated 5′-aldehydes in good yields that were isolated and fully characterized. When an oxygen concentration in the range of 13-266 μM (typical oxygenated tissues) is used, the hydrated 5′-aldehyde is accompanied by the 5′,8-cyclopurine nucleoside. The formation of 5′,8-cyclopurines is relevant in all experiments, and the yields increased with decreasing O2 concentration. The reaction of HO? radicals with 2′-deoxyadenosine and 2′-deoxyguanosine under normoxic conditions was also investigated. The minor path of C5′ radicals formation was found to be ca. 10% by quantifying the hydrated 5′-aldehyde in both experiments. Rate constants for the reactions of the 2′-deoxyadenosin-5′-yl with cysteine and glutathione in water were determined by pulse radiolysis to be (2.1 ± 0.5) × 107 and (4.9 ± 0.6) × 10 7 M-1 s-1 at 22°C, respectively.
