The reaction of 3, 4-epoxy-1-butene with deoxyguanosine and DNA in vitro: synthesis and characterization of the main adducts

The reaction of guanosine with 3,4-epoxy-1-butene in acetic acid gives two main products of N-7 alkylation. After acidic hydrolysis the two aglycones have been isolated by h.p.l.c. and shown to be the regioisomeric 7-(2-hydroxy-3-buten-1-yl) guanine (I) and 7-(1-hydroxy-3-buten-2-yl) guanine (II), arising through nucleophilic attack by N-7 of the purine at the two oxirane carbons of 3,4-epoxy-1-butene. Spectral characteristics of both compounds are presented, including u.v., 1H-n.m.r. and mass spectra. Deoxyguanosine reacts with 3,4-epoxy-1-butene in 50% methanol-water at 37 degrees C to give the N-7 alkylated deoxynucleosides corresponding to I and II in a 59:41 ratio. The reaction rate depends on the nucleoside concentration, with second order rate constants at 37 degrees C of 1.6 X 10(-2) and 1.1 X 10(-2) h-1 M-1 for the formation of the two deoxynucleoside adduct corresponding to I and II, respectively. The same two compounds I and II in a similar (54:46) ratio have been identified after acidic or thermal hydrolysis of DNA which had been reacted with 3,4-epoxy-1-butene under similar conditions. The half life for the spontaneous depurination of I and II in the adducted DNA under physiological conditions (37 degrees C, pH 7.2) is 50 h.