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Structural Characterization of an Etheno-2‘-deoxyguanosine Adduct Modified by Tetrahydrofuran

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journal contribution
posted on 21.02.2005, 00:00 by Ana Paula M. Loureiro, Ivan P. de Arruda Campos, Osmar F. Gomes, Ediliz P. M. Possari, Paolo Di Mascio, Marisa H. G. Medeiros
The reaction of 2‘-deoxyguanosine with the α,β-unsaturated aldehydes trans-2-octenal, trans-2-nonenal, trans-2-decenal, trans,trans-2,4-nonadienal, and trans,trans-2,4-decadienal in THF gives rise to three novel adducts:  3-(2‘-deoxy-β-d-erythro-pentafuranosyl)-7-[3-hydroxy-1-(3-(2‘-deoxy-β-d-erythro-pentafuranosyl)-3,5-dihydro-imidazo[1,2-a]purin-9-one-7-yl)-propyl]-3,5-dihydro-imidazo[1,2-a]purin-9-one (A7) and 3-(2‘-deoxy-β-d-erythro-pentafuranosyl)-7-(tetrahydrofuran-2-yl)-3,5-dihydro-imidazo[1,2-a]purin-9-one (A8 and A9), which are not observed in the absence of THF. These adducts were isolated from in vitro reactions by reversed-phase HPLC and fully characterized on the basis of spectroscopic measurements. Adduct A7 consists of two 1,N2-etheno-2‘-deoxyguanosine (1,N2-εdGuo) residues linked to a hydroxy-carbon side chain; adducts A8 and A9 are interconvertible 1,N2-εdGuo derivatives bearing a THF moiety. The proposed reaction mechanism involves the electrophilic attack on 1,N2-εdGuo by the carbonyl of 4-hydroxy-butanal, generated via ring opening of α-hydroxy-THF (THF−OH), yielding adducts A8 and A9. A further combination of these adducts with another 1,N2-εdGuo produces the double adduct A7. These findings demonstrate that reactions of unsaturated aldehydes in the presence of THF produce novel condensation 1,N2-εdGuo-THF adducts. Further studies would indicate the relevance of these adducts in THF toxicity.