6-aza-2'-deoxyisocytidine: synthesis, properties of oligonucleotides, and base-pair stability adjustment of DNA with parallel strand orientation.

6-Aza-5-methyl-2'-deoxyisocytidine (1a) and 6-aza-2'-deoxyisocytidine (1b) have been synthesized, converted into phosphoramidite building blocks, and incorporated into oligodeoxynucleotides. The glycosylic bond stability of 1a,b under acidic conditions increases compared to that of 5-methyl-2'-deoxyisocytidine (2a) and 2'-deoxyisocytidine (2b). Oligonucleotides incorporating 1a or 1b show an enhanced stability against the 3'-exonuclease snake-venom phosphodiesterase. The duplexes containing 6-azapyrimidine nucleosides 1a or 1b have lower T(m) values than duplexes containing 2a or 2b with either antiparallel or parallel chain orientation. This was used to adjust the stability of the tridentate m5iCd-dG base pair to the level of the bidentate reverse Watson-Crick dA-dT pair.