Structural characterization of an etheno-2'-deoxyguanosine adduct modified by tetrahydrofuran.

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-edGuo) residues linked to a hydroxy-carbon side chain; adducts A8 and A9 are interconvertible 1,N2-edGuo derivatives bearing a THF moiety. The proposed reaction mechanism involves the electrophilic attack on 1,N2-edGuo by the carbonyl o...