Synthesis and characterization of oligodeoxynucleotides containing an N1 beta-hydroxyalkyl adduct of 2'-deoxyinosine.

Abstract

Hydroxyethyl adducts arising by the reactions of simple epoxides at the N1 position of adenine nucleosides can deaminate to give the inosine analogues which, if formed in DNA, are suspected of being highly mutagenic. A method has been developed for synthesis of oligonucleotides containing N1-adducted 2'-deoxyinosines. The 2'-deoxyinosine adduct of 3,4-epoxy-1-butene was prepared from (+/-)-4-acetoxy-3-bromo-1-butene and tetraisopropyldisiloxanediyl-protected 2'-deoxyinosine with base. The 2'-deoxyinosine derivative was then incorporated into the oligodeoxynucleotide sequence 5'-d(CGGACXAGAAG)-3' (X = N1-(1-hydroxy-3-buten-2-yl)-2'-deoxyinosine).