Photochemical generation and reaction of 2'-substituted analogues of C4'-oxidized abasic lesion

Abstract

The C4'-oxidized abasic site (1) is one of the oxidatively damaged DNA lesions induced by antitumor bleomycins. The reactivity of 1 with amine under neutral conditions giving lactam 2 and its structural similarity to unmodified DNA suggested the possibility that ODN containing 1 could react with proteins which interact with DNA at lysine residue. In order to provide nucleic acid analogues with useful lysine modifying reactivity, we planned to study reaction of 2'-substituted analogues of 1, such as 3-5, with amine and their corresponding caged precursors 6-8 were synthesized. Uncaging reaction of 16 containing 6 proceeded efficiently. The reaction of obtained 17 containing 3 with Z-Lys-OH did not afford products corresponding to lactam. However, HPLC analysis of the reaction mixture suggested interaction of 3 with Z-Lys-OH.