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 (a-d vs. b-d), nucleobase substituents, and the helicalD NA environment of silvermediated 5-aza-7-deazaguanine-cytosine base pairs have a strong impact on DNA stability. This has been demonstrated by investigations on oligonucleotide duplexes with silvermediated base pairs of a-d and b-d anomeric 5-aza-7-deaza-2'-deoxyguanosines and anomeric 2'-deoxycytidines incorporated in 12-merd uplexes. To this end, anew syntheticprotocol has been developed to access the pure anomerso f5aza-7-deaza-2'-deoxyguanosine by glycosylationo fe ither the protected nucleobase or its salt followed by separation of the glycosylation products by crystallization and chromatography.T hermal stability measurements were performed on duplexes with a-d/a-d and b-d/b-d homo base pairs or a-d/b-d and b-d/a-d hybrid pairs within two sequence environments, positions 6o r7 ,o fo ligonucleotided uplexes. The respective T m stabilityi ncreases observed after silveri on addition differ significantly.H omo base pairs with b-d/b-d or a-d/a-d nucleoside combinations are more stable than a-d/ b-d hybrid base pairs.T he positional switch of silver-ionmediated base pairs has as ignificant impact on stability.N ucleobases ubstituentsi ntroduced at the 5-position of the dC site of silver-mediated base pairs affect base pair stability to am inor extent.O ur investigation might lead to applications in the construction of bioinspired nanodevices,i nD NA diagnostics, or metal-DNA hybrid materials.[a] X.Scheme1.Upper part:S ynthesis of protectednucleobase residues and nucleobase-anion glycosylation protocolf or the synthesis of b-dZ (1)and a-dZ (2). i) (iBu) 2 O, H 3 PO 4 ,reflux;i i) precipitation from the reactionm ixture;iii)recrystallization from aq MeOH; iv) TDA-1, MeCN, K 2 CO 3 ,RT, 1h,v )flashc olumn (FC);vi) recrystallization from aq MeOH; vii)FCo ft he mother liquor; viii)saturated NH 3 /MeOH.Lower part:Protected 5-aza-7-deaza-2'-deoxyguanosine nucleoside derivativesused in this study.

Dynamic Structure and Stability of DNA Duplexes Bearing a Dinuclear Hg(II)-Mediated Base Pair

“…As a result, metal-mediated base pairs are known involving Cu(II), [10][11][12][13] Cu(I), [14] Mn(III) [15], Ni(II) [16], Zn(II) [17], and other metal ions [18,19]. Nevertheless the most prominent metal ions used with artificial nucleobases remain Ag(I) and Hg(II), too [20][21][22][23][24][25][26][27]. Nucleic acids comprising metal-mediated base pairs have been applied in various manners, e.g., in the context of modulating the charge transfer capability of the nucleic acids [28][29][30][31][32], in metal-responsive structural transformations [33][34][35], in the formation of DNA-templated silver nanoclusters [36], and in oligonucleotide recognition [37][38][39].…”

5‐Aza‐7‐deazaguanine–Isoguanine and Guanine–Isoguanine Base Pairs in Watson–Crick DNA: The Impact of Purine Tracts, Clickable Dendritic Side Chains, and Pyrene Adducts

“…The purity of all oligonucleotides was confirmed by means of RP‐18 HPLC (Figure S3 in the Supporting Information) and MALDI‐TOF MS (Table 1). The extinction coefficients, ϵ 260 (H 2 O), of the nucleosides are as follows: dA, 15 400; dG, 11 700; dT, 8800; dC, 7300; z 5 G d , 14 100; [26] i G d , 4300 dm mol −1 cm −1 [27] . The extinction coefficients of the oligonucleotides were calculated from the sum of the extinction coefficients of nucleoside constituents by considering the hypochromic change for particular single strands.…”

Towards polymerase-mediated synthesis of artificial RNA–DNA metal base pairs

“…1,2 Metal base pairs can be constructed using the canonical nucleobases or synthetic nucleoside analogs with nucleobases that are specifically designed to serve as ligands for the specific binding of transition metal cations. 3,4 These metal base pairs have advanced as promising candidates for a number of applications including the development of nanomolecular devices, 5 ion sensors and biosensing devices 6,7 and metal nanowires and nanodevices [8][9][10] as well as for the allosteric control of functional nucleic acids. [11][12][13][14] The formation of metal base pairs mainly occurs by annealing short synthetic oligonucleotides together with specific metal cations.…”