2′-Deoxyimmunosine: stereoselective synthesis, base pairing and duplex stability of oligonucleotides containing 8-oxo-7-thiaguanine

Abstract

Oligonucleotides containing 7-thia-8-oxoguanine represent a new class of molecules in which sulfur replaces the 7-nitrogen of a purine base. The monomeric 7-thia-8-oxoguanine 2′-deoxyribonucleoside (2′-deoxyimmunosine, 4) was prepared by nucleobase anion glycosylation in a regio- and stereoselective way employing 5-{[(di-n-butylamino)methylidene]amino}thiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione (18) and 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose (6). The nucleoside was converted into the phosphoramidite 22 and oligonucleotides were prepared by solid-phase synthesis. Oligonucleotide duplexes containing the 4–dC base pair show a similar stability as those containing the dG–dC motif. Thus the sterically demanding sulfur and the additional 8-oxo group are well accommodated in the major groove of DNA. As expected, compound 4 does not form a Hoogsteen pair, as reported for 8-oxo-2′-deoxyguanosine. Compared to 2′-deoxyguanosine, 2′-deoxyimmunosine shows a better mismatch discrimination in Watson–Crick base pairs.