Silver(I)-mediated base pairing involving an S-glycosidic GNA nucleoside analogue

The 4S-Ag(I)-C base pair (4S, 3-((2-(methylthio)pyrimidin-4-yl)thio)propane-1,2-diol; C, deoxycytidine) represents the first metal-mediated base pair comprising an S-glycosidic nucleoside analogue. We report here the synthesis of the phosphoramidite suitable for the automated solid-phase synthesis of DNA oligonucleotides containing 4S and its silver(I)-binding ability. The DNA duplexes comprising a 4S:C mispair exhibit a large thermal stabilization upon the addition of one equivalent of silver ions, giving rise to the formation of the above-mentioned silver(I)-mediated base pair. By formally replacing the sulfur atom in the glycosidic bond by an oxygen atom, i.e., by applying 3-((2-(methylthio)pyrimidin-4-yl)oxy)propane-1,2-diol (4 O) as the artificial nucleoside analogue, the participation of this atom as a donor atom in silver(I)-mediated base pairing is shown to be neglectable. Supplemental data for this article is available online at

Automated summary

The study reports the first metal-mediated base pair containing an S-glycosidic nucleoside analogue, and describes the synthesis of the phosphoramidite for solid-phase synthesis of DNA oligonucleotides. The results showed that in DNA duplexes containing a 4S:C mismatch, the addition of silver ions can lead to the formation of a silver(I)-mediated base pair with significant thermal stabilization.