8-Aza-7-deazaadenine N8- and N8-(β-D-2′-Deoxyribofuranosides): Building blocks for automated DNA synthesis and properties of oligodeoxyribonucleotides

TLDR: The palindromic oligomers 18-22 containing 2 or 3 instead of dA outside of the enzymic recognition side reduced the hydrolysis rate, replacement within d(G-A-T-C) abolished phosphodiester Hydrolysis.

Abstract: Oligonucleotides with alternating 8-aza-7-deaza-2′-deoxyadenosine (= c7z8Ad2) and dT residues (see 11, 14 and 16) or 4-aminopyrazolo [3,4-d] pyrimidine N2-(β-D-2′-deoxyribofuranoside) (= c7z8A′d1); (3) and dT residues (see 12) have been prepared by solid-phase synthesis using P(III) chemistry, Additionally, palindromic oligomers derived from d(C-T-G-G-A-T-C-C-A-G) but containing 2 or 3 instead of dA (see 18–22) have been synthesized. Benzoylation of 2 or 3, followed by 4,4′-dimethoxytritylation and subsequent phosphitylation yielded the methyl or the cyanoethyl phosphoramidites 8a,b and 9. They were employed in automated. DNA synthesis. Alternating oligomers containing 2 or 3 showed increase dTm values compared to those with dA, in particular 12 with an unusual N2-glycosylic bond. The palindromic oligomers 18-22 containing 2 or 3 instead of dA outside of the enzymic recognition side reduced the hydrolysis rate, replacement within d(G-A-T-C) abolished phosphodiester hydrolysis.