7-Deaza-2,8-diazaadenine containing oligonucleotides: synthesis, ring opening and base pairing of 7-halogenated nucleosides

Oligonucleotides containing 7-bromo-7-deaza-2,8-diaza-2′-deoxyadenosine () and 5-amino-3-bromo-4-carbamoyl-1-(2′-deoxy-β-d-erythro-pentofuranosyl)pyrazole () were synthesized. Compound was prepared from 7-bromo-8-aza-7-deaza-2′-deoxyadenosine () via the 1,N6-etheno derivative and was converted into the phosphoramidite . The 7-bromo substituent of increases oligonucleotide duplex stability compared to the non-halogenated nucleoside. Oligonucleotides incorporating are transformed to those containing during long time deprotection at elevated temperature (25% aq ammonia, 60 °C, 30 h). Compound forms a strong base pair with dG. The base pair stability decreases in the order dG>dT>dA>dC. Similar recognition selectivity is observed for the pyrazole nucleoside , however, due to decreased stacking and higher flexibility of the pyrazole moiety, duplexes are less stable than those containing .