Solid-phase synthesis of the self-complementary hexamer d(c7GpCpc7GpCpc7GpC) via the O-3′-phosphoramidite of 7-deaza-2′-deoxyguanosine

Abstract

The synthesis of the 0–3′-phosphoramidite of a suitably protected 7-deaza-2′-deoxyguanosine (c ⁷ G) which is an isostere of 2′-deoxyguanosine is described. The phosphoramidite of the modified nucleoside was used in the synthesis of the self-complementary hexamer d(c ⁷ GpCpc ⁷ GpCpc ⁷ GpC) on function alized silica gel in a mini-reactor. As expected from the parent hexamer d(GpCpGpCpGpC) the isosteric d(c ⁷ GpCpc ⁷ GpCpc ⁷ GpC) exhibits a rigid secondary structure (22% hypochromicity at 280 nm) and forms a duplex in 1 M aqueous sodium chloride solution. Due to the altered π-electron system of the pyrrolo[2, 3-d]pyrimidine nucleobase, which affects base stacking and hydrogen bonding, the T _m of the modified duplex is decreased by 10°C compared to that of the parent purine hexamer. Moreover, it is expected that the incor poration of c ⁷ G influences the pitch of the helix.