Synthesis of protected D-altritol nucleosides as building blocks for oligonucleotide synthesis

D-Altritol Nucleic Acids (ANA): Hybridisation Properties, Stability, and Initial Structural Analysis

“…[14] The dimethylformamidine group was selected for protection of the 2-NH 2 function of the guanine base instead of the more (basic) stable isobutyryl group, which proved difficult to introduce selectively. The obtained phosphoramidites were used to synthesise oligonucleotides on a 1 mmol scale following standard protocol (concentration phosphoramidites 0.12 m), except for a prolonged coupling time of 10 min to ensure adequate coupling yields (comparable with standard RNA synthesis) and a prolonged acid treatment (2 min) to fully deprotect the monomethoxytrityl group.…”

“…General scheme for the synthesis of the modified nucleosides, exemplified by the synthesis of the building block with the adenine base moiety. [14] [a] Determined at 1m NaCl as otherwise no dsDNA could be detected.…”

“…[14] Analytical details for the phosphoramidite building blocks are as follows. Oligonucleotide synthesis was carried out on an automated DNA synthesiser with the phosphoramidite approach, model ABI 381 A (Applied Biosystems).…”

Nonenzymatic Template-Directed Reactions on Altritol Oligomers, Preorganized Analogues of Oligonucleotides

“…[29] The altritol and hexitol nucleic acid templates and nucleosides were synthesized and purified as described. [20,22,23] The monophosphates of the altritol and hexitol nucleic acid nucleosides were synthesized according to the method of Yoshikawa et al [30] pAG: Reaction conditions for the oligomerization of 2-MeImpG (or its mixture with equal amount of 2-MeImpC, 2-MeImpA, 2-MeImpU) on HNA or ANA C 4 XC 4 templates were chosen to permit comparison with earlier published work. [28,29] One set of reactions was run for 14 days at 0 8C in 0.2 m 2,6-lutidine-HCl buffer (pH 7.9 at 25 8C) containing 1.2 m NaCl, 0.2 m MgCl 2 , 0.5 mm of a template and 0.1m 2-MeImpG.…”

“…[15±17] Altritol nucleic acids (ANAs) are novel RNA analogues with a phosphorylated d-altritol backbone and a nucleobase at the 2-(S)-position of the carbohydrate residue (Figure 1b). [22] They can be considered as HNA analogues that have an additional hydroxy group introduced into the sixmembered hexitol ring. In a duplex, this group is directed into the minor groove and contributes to stability of the duplex by increasing the hydration of the groove.…”