Silver‐Mediated Base Pairs in DNA Incorporating Purines, 7‐Deazapurines, and 8‐Aza‐7‐deazapurines: Impact of Reduced Nucleobase Binding Sites and an Altered Glycosylation Position

Abstract

Formation of silver‐mediated DNA was studied with oligonucleotides incorporating 8‐aza‐7‐deazapurine, 7‐deazapurine, and purine nucleosides. The investigation was performed on non‐self‐complementary duplexes with one or two modifications and self‐complementary duplexes with an alternating dA–dT motif. Homo base pairs as well as base pair mismatches of dA analogues with dC and Watson–Crick pairs with dT were studied by stoichiometric silver ion titration and Tm measurements. N8‐Glycosylated 8‐aza‐7‐deazaadenine forms silver‐ion‐mediated base pairs capturing two silver ions (low silver content) whereas regularly glycosylated 8‐aza‐7‐deazapurine, 7‐deazapurine (c7Ad), and dA do not form comparable structures. Stable silver‐mediated “dA–dC” base pair mismatches were detected for all nucleosides. Two silver ions per base pair are bound by 8‐aza‐7‐deazapurine whereas c7Ad binds only one silver ion. The situation is different when the equivalents of silver ions were increased to the number of total base pairs. Surprisingly, in 12‐mer duplexes as well as in related 25‐mer duplexes every base pair consumed one silver ion.

Functionalized Silver‐Ion‐Mediated α‐dC/β‐dC Hybrid Base Pairs with Exceptional Stability: α‐d‐5‐Iodo‐2′‐Deoxycytidine and Its Octadiynyl Derivative in Metal DNA

“…Earlier,i th as been reported that silver ions can be captured from the silver-mediated base pairb yb romide or iodide ions but not by chloride ions resulting in the originalm eltingp rofiles of the silver-ionf ree duplexes. [32] The same was found for the functionalized hybrid base pairs, when bromide ions were added (Figure 7). The excesso fb romide ions over silver ions was 20-fold.…”

2′‐O,4′‐C‐Methylene‐Bridged Nucleic Acids Stabilize Metal‐Mediated Base Pairing in a DNA Duplex

“…Even for the matched sequences of d m C‐dG ( 21 ) and C L ‐dG ( 22 ), the addition of Ag I improved the duplex‐forming ability (Δ T m 2 =+1 ( 21 ), +3 °C ( 22 )). The T m value improves even in these matched base pairs without a particularly designed Ag I ‐binding site, such as a C−C mismatch, as recently reported . Interestingly, the ΔΔ T m ( 22 − 21 ) value was +2 °C, which suggested that 2′,4′‐BNA/LNA‐ m C stabilized the complex in the presence of Ag I , compared with that in the absence of Ag I .…”

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

“…Biphasic melting is not observeda si nt he absence of silver ions only single strandse xists. [4] [15] - From stoichiometric titration experiments ac onsumption of six silver ions per duplex was confirmed (Figure 3b,c).…”

“…Oligonucleotides M r calcd [a] M r found [b] ODN- [15] -ODN-14 5'-d(AGTATTGACCTA) [15] -ODN-15 5'-d(AGTATTAACCTA) [15] -ODN-16 5'-d(AGTATTTACCTA) [15] -ODN-17 5'-d(TAGGTCAATACT) [15] -…”

“…This makest he dZ-Ag + -dC pair suitable for the programmable incorporation of silver ions in DNA whichc annot be achieved by acanonical base pair. Remarkably,t he unmodified duplex 5'-d(TAG GTC AATA CT) (ODN-17)·3'-d(ATC CAG TTATGA) (ODN-14)a nd its 7-deazapurine counterpart [15] and duplexes such as (ODN-7)·(ODN-9)u sed in this study change their stabilityw hen ah igh content of silver ions is present( equal or excess amounts of silver ions per number of base pairs in the duplex;F igure 8). These new very stable assemblies do not show sigmoidal meltingo rm elting with an extremelyl ow hyperchromicity and do not renature under the measurement conditions.…”