Anomeric 5-Aza-7-deaza-2 `-deoxyguanosines in Silver-Ion-Mediated Homo and Hybrid Base Pairs: Impact of Mismatch Structure, Helical Environment, and Nucleobase Substituents on DNA Stability

Abstract

Nucleoside configuration (alpha-d vs. beta-d), nucleobase substituents, and the helical DNA environment of silver-mediated 5-aza-7-deazaguanine-cytosine base pairs have a strong impact on DNA stability. This has been demonstrated by investigations on oligonucleotide duplexes with silver-mediated base pairs of alpha-d and beta-d anomeric 5-aza-7-deaza-2 `-deoxyguanosines and anomeric 2 `-deoxycytidines incorporated in 12-mer duplexes. To this end, a new synthetic protocol has been developed to access the pure anomers of 5-aza-7-deaza-2 `-deoxyguanosine by glycosylation of either the protected nucleobase or its salt followed by separation of the glycosylation products by crystallization and chromatography. Thermal stability measurements were performed on duplexes with alpha-d/alpha-d and beta-d/beta-d homo base pairs or alpha-d/beta-d and beta-d/alpha-d hybrid pairs within two sequence environments, positions 6 or 7, of oligonucleotide duplexes. The respective T-m stability increases observed after silver ion addition differ significantly. Homo base pairs with beta-d/beta-d or alpha-d/alpha-d nucleoside combinations are more stable than alpha-d/beta-d hybrid base pairs. The positional switch of silver-ion-mediated base pairs has a significant impact on stability. Nucleobase substituents introduced at the 5-position of the dC site of silver-mediated base pairs affect base pair stability to a minor extent. Our investigation might lead to applications in the construction of bioinspired nanodevices, in DNA diagnostics, or metal-DNA hybrid materials.