Steric and Stereoelectronic Effects of 7-Deazapurine Bases on the Sugar Conformation of 2′-Deoxynucleosides

Sirivolu

et al. 2005

Acta Crystallogr C

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Section: Commentmentioning

confidence: 99%

3-Bromo-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine: a nucleoside which strongly enhances DNA duplex stability

Sirivolu

et al. 2005

Acta Crystallogr C

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“…Unfortunately, we were not able to determine the synlanti ratio of 7-deaza-2'-deoxyguanosine (2a) due to an overlap of the signals of H-C(7) and H-C(1'). We also examined the sugar puckering on the basis of vicinal 'H,'H-coupling constants using the PSEUROT program (version 6.2) [18]. From these data, the N/S ratio was found to be 28 : 72 for compound 2b, which was the same as found for 2a.…”

mentioning

confidence: 97%

Methylated DNA: The influence of 7‐deaza‐7‐methylguanine on the structure and stability of oligonucleotides

Chen

1997

Helvetica Chimica Acta

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The 7-deaza-2'-deoxy-7-methylguanosine (Zb) [9], which is the glycosylic-bond-stable, noncharged analogue of 2'-deoxy-7-methylguanosine (lb), was incorporated in DNA by solid-phase synthesis. As building blocks, the protected phosphonate 3a and the phosphoramidite 3b were prepared. The 7-methyl group of 2b stabilizes the B-DNA dnplex compared to 7-deaza-2'-deoxyguanosine but does not induce a B-Z transition as it is known from compound lb. The stabilization by the 7-deaza-7-methylguanine moiety is sequence-dependent, and the nearestneighbor influence is different from that of 7-deazaguanine. Homooligonucleotides of 2b show sigmoidal melting indicating a highly ordered single-stranded structure. In general, oligonucleotides containing 2b are very stable against hydrolysis with calf-spleen phosphodiesterase (CS-PDE, 5' + 3' exonuclease), while phosphodiester hydrolysis with snake-venom phosphodiesterase (SV-PDE, 3' + 5' exonuclease) is only slightly reduced.

“…These data demonstrate that the higher the electron-withdrawing effect of the 7-substituent is, the more the N > S equilibrium of the sugar moiety is biased towards the N-conformation [23] [24]. Table 3 compares the data with a series of other 7-halogenated 7-deazapurine nucleosides 1a ± c related to dA, dG, and dI [6 ± 9] [25] [26], i.e., 6a ± c, 7a ± c, and 8a ± c, which show the same phenomenon. The conformation in the solid state was already reported for compound 1a [27].…”

mentioning

confidence: 99%

7‐Halogenated 7‐Deaza‐2′‐deoxyxanthine 2′‐Deoxyribonucleosides

Shaikh

2004

Helvetica Chimica Acta

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The synthesis of the 7-halogenated derivatives 1b (7-bromo) and 1c (7-iodo) of 7-deaza-2'-deoxyxanthosine (1a) is described. A partial Br 3 I exchange was observed when the demethylation of 6-methoxy precursor compound 4b was performed with Me 3 SiCl/NaI. This reaction is circumvented by the nucleophilic displacement of the MeO group under strong alkaline conditions. The halogenated 7-deaza-2'-deoxyxanthosine derivatives 1b,c show a decreased S-conformer population of the sugar moiety compared to the nonhalogenated 1a. They are expected to form stronger triplexes when they replace 1a in the 1 ¥ dA ¥ dT base triplet.Introduction. ± The synthesis of 7-deaza-2'-deoxyxanthosine (1a) via the glycosylation of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine was already reported from our laboratory in 1985 [1]. Later the nucleoside was prepared by a deamination/ demethylation route from 4-methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine 2'-deoxyribonucleoside 2a [2]. Compound 1a was incorporated into oligonucleotides without base protection by solid-phase synthesis by using phosphonate chemistry [2]. Triplexes containing 7-deazaxanthine in place of thymine showed a high third-strand-binding affinity under neutral conditions [2]. Contrary to the extremely labile 2'-deoxyxanthosine (3), in which the glycosylic bond hydrolyzes spontaneously under physiological conditions [3 ± 5], the glycosylic bond of the 7-deazapurine nucleoside 1a is resistant to −depurination× [1] [2].