8-Aza-7-deaza-2′-deoxyguanosine: Phosphoramidite synthesis and properties of octanucleotides

Base-modified octanucleotides derived from d(G1–G2–A–A–T–T–C–C–) ( 11 ) but containing 8-aza-7-deaza-2′-deoxyguanosine ( 2 ) instead of 2′-deoxyguanosine ( 1 ) have been prepared by solid-phase synthesis employing P(III) chemistry. Isobutyrylation of 2 , followed by 4, 4′-dimethoxytritylation and subsequent phosphitylation yielded the methyl or the cyanoethyl phosphoramidites 6a or 6b , respectively. They were used as building blocks in automated DNA synthesis. The resulting octanucleotides 12–14 containing 2 showed increased T_m values compared to the parent oligomer 11 . The oligomers 11 – 14 were employed as sequence-specific probes in endo-deoxyribonuclease Eco RI oligonucleotide recognition. Whereas displacement of dG-2 (enzymic cleavage site of 11 ) abolished phosphodiester hydrolysis, replacement of dG-1 enhanced the cleavage rate compared to 11 .