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-alpha-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.