5‐Aza‐7‐deaza‐2′‐deoxyguanosine and 2′‐Deoxycytidine Form Programmable Silver‐Mediated Base Pairs with Metal Ions in the Core of the DNA Double Helix

Abstract

5-Aza-7-deaza-2'-deoxyguanosine (dZ) forms a silver-mediated base pair with dC. The metal ion pair represents a mimic of the H-bonded Watson-Crick dG-dC pair. The modified nucleoside displays a similar shape as the parent 2'-deoxyguanosine from which it can be constructed by transposition of nitrogen-7 to the bridgehead position-5. It lacks the major groove binding site as the positional change moves the dG- acceptor position from nitrogen-7 to nitrogen-1. As a shape mimic of dG, it fits nicely in the DNA double helix. The purine-pyrimidine dZ-dC hetero pair shows a relationship to the pyrimidine-pyrimidine dC-dC homo base pair. The dZ-dC pair forms a mismatch in the absence of silver ions and matches after addition of metal ions. Base-pair formation was verified on self-complementary 6-mer duplexes and 12-mer DNA with random composition by UV-dependent T measurements. Modified silver-mediated and hydrogen-bonded canonical base pairs can coexist. The dZ-Ag -dC base pair is slightly less stable than the dG-dC pair, shows sequence dependence, and consumes one or two silver ions. These properties make the dZ-Ag -dC pair suitable for programmable incorporation of silver ions in DNA which cannot be achieved by canonical base pairs. If the silver ion content is higher than the total number of base pairs the duplexes turn into very stable structures in which all base pairs are considered to be in the silver-mediated pairing mode.

Silver(I)‐Ion‐Mediated Cytosine‐Containing Base Pairs: Metal Ion Specificity for Duplex Stabilization and Susceptibility toward DNA Polymerases

“…The study indicated that the Δ T m values of duplexes containing a C‐C, a C‐A or a C‐T mismatch on addition of Ag I ions are +12, +9, and +3 to +6 °C, respectively. This order of stabilization is fairly consistent with our results, although this is not always the case . The stability changes should depend to some degree on the neighboring sequences…”

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

“…By replacing the bridgehead C5 atom of 7C Gbyanitrogen atom, 5-aza-7-deazaguanine 5N7C Gi sf ormed. 5N7C Gh as ap rotonation pattern different from that of the parent nucleobase guanine.I np articular,t he endocyclicN 1a tom [18] d) 5N7C G-Ag I -C. [19] R, R' = DNA backbone.…”

“…Figure 2d shows the resulting 5N7C G-Ag I -C base pair. [19] Compared to 7C G, 5N7C Gisbetter suited for ap rogrammed Ag I -modification of the G:Cb ase pair, because the 5N7C G:Cp air represents am ispair in the absence of Ag I ,but astrongly stabilizing metal-mediated base pair in its presence.S imilar to 7C G, weak binding of one additional Ag I ion per base pair has been observed for 5N7C G, too.…”

Silver‐Mediated Homochiral and Heterochiral α‐dC/β‐dC Base Pairs: Synthesis of α‐dC through Glycosylation and Impact of Consecutive, Isolated, and Multiple Metal Ion Pairs on DNA Stability

“…Such mismatches are formed by homo base pairs of dT-dT,d C-dC, or dG-dG, as well as by the hetero pair of 5aza-7-deaza-2'-deoxyguanosine with 2'-deoxycytidine. [20] A recent X-ray structure determination of ad odecamer duplex that could be expectedt of orm silver-mediated dA-dT and dG-dC base pairs showed insteadt hat silver-mediated homo pairs of dT-dT,d G-dG, and dC-dC were formed, andt hat the dA residues werel ooped out. [6a] Due to the different stabilities of bidentated A-dT and tridentate dG-dC pairs, one may be preferentially convertedi nto as ilver-mediated pair.N evertheless, as already discussed by Gwinn, [8g] silver-mediated homo pairs of dC-dC or dG-dG are more stable than silver-mediated dA-dT or dG-dC pairs.…”