title: Structural characterization of an etheno-2'-deoxyguanosine adduct modified by tetrahydrofuran.
abstract: The reaction of 2'-deoxyguanosine with the alpha,beta-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-beta-D-erythro-pentafuranosyl)-7-[3-hydroxy-1-(3-(2'-deoxy-beta-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-beta-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-epsilon dGuo) residues linked to a hydroxy-carbon side chain; adducts A8 and A9 are interconvertible 1,N2-epsilon dGuo derivatives bearing a THF moiety. The proposed reaction mechanism involves the electrophilic attack on 1,N2-epsilon dGuo by the carbonyl of 4-hydroxy-butanal, generated via ring opening of alpha-hydroxy-THF (THF-OH), yielding adducts A8 and A9. A further combination of these adducts with another 1,N2-epsilon dGuo produces the double adduct A7. These findings demonstrate that reactions of unsaturated aldehydes in the presence of THF produce novel condensation 1,N2-epsilon dGuo-THF adducts. Further studies would indicate the relevance of these adducts in THF toxicity.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prof. Lineu Prestes 580, Bloco 13 B, CEP 05508-900 São Paulo, Brazil.
authors.forename: Ana Paula M
authors.initials: AP
authors.lastname: Loureiro
authors.forename: Ivan P
authors.initials: IP
authors.lastname: de Arruda Campos
authors.forename: Osmar F
authors.initials: OF
authors.lastname: Gomes
authors.forename: Ediliz P M
authors.initials: EP
authors.lastname: Possari
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.forename: Marisa H G
authors.initials: MH
authors.lastname: Medeiros
mesh_terms: D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure
chemical_list: D005663:Furans; C018674:tetrahydrofuran; D003849:Deoxyguanosine