Oligonucleotides Containing 7-Deaza-2′-deoxyxanthosine: Synthesis, Base Protection, and Base-Pair Stability

Seela, Frank; Shaikh, Khalil I.

doi:10.1002/hlca.200690251

Cited by 10 publications

(21 citation statements)

References 39 publications

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“…Taken together, our data provide the first comprehensive insights into thermodynamic stabilities of xanthosine containing RNA. Thus far, only 2′-deoxyxanthosine was investigated in the context of DNA ( 44 , 45 ); at physiological pH values and typical sodium ion concentrations, xanthine bases caused destabilization when paired to A or C (–9°), and were less destabilizing when paired to G or T (–6° and –5°, respectively) ( 44 ). Hence, the signature of X base pair strength in DNA is distinct to RNA.…”

Section: Resultsmentioning

confidence: 99%

Towards a comprehensive understanding of RNA deamination: synthesis and properties of xanthosine-modified RNA

Mair

Erharter

Renard

et al. 2022

Nucleic Acids Research

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Nucleobase deamination, such as A-to-I editing, represents an important posttranscriptional modification of RNA. When deamination affects guanosines, a xanthosine (X) containing RNA is generated. However, the biological significance and chemical consequences on RNA are poorly understood. We present a comprehensive study on the preparation and biophysical properties of X-modified RNA. Thermodynamic analyses revealed that base pairing strength is reduced to a level similar to that observed for a G•U replacement. Applying NMR spectroscopy and X-ray crystallography, we demonstrate that X can form distinct wobble geometries with uridine depending on the sequence context. In contrast, X pairing with cytidine occurs either through wobble geometry involving protonated C or in Watson–Crick-like arrangement. This indicates that the different pairing modes are of comparable stability separated by low energetic barriers for switching. Furthermore, we demonstrate that the flexible pairing properties directly affect the recognition of X-modified RNA by reverse transcription enzymes. Primer extension assays and PCR-based sequencing analysis reveal that X is preferentially read as G or A and that the ratio depends on the type of reverse transcriptase. Taken together, our results elucidate important properties of X-modified RNA paving the way for future studies on its biological significance.

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Section: Resultsmentioning

confidence: 99%

Towards a comprehensive understanding of RNA deamination: synthesis and properties of xanthosine-modified RNA

Mair

Erharter

Renard

et al. 2022

Nucleic Acids Research

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“…26 Our laboratory developed the 7-deazaxanthine�purine-2,6diamine system. 17 7-Deaza-2′-deoxyxanthosine ( 7 X d , 2a) is stable against depurination 29 and can be functionalized at the 7-position of the base, a site that normally accepts bulky residues in the Watson−Crick double helix. Furthermore, 7deaza-2′-deoxyxanthosine (2a) is more basic than the purine nucleoside 1, and deprotonation is shifted to higher pH.…”

Section: ■ Introductionmentioning

confidence: 99%

Purine DNA Constructs Designed to Expand the Genetic Code: Functionalization, Impact of Ionic Forms, and Molecular Recognition of 7-Deazaxanthine–7-Deazapurine-2,6-diamine Base Pairs and Their Purine Counterparts

Chandankar,

Kondhare,

Leonard

et al. 2023

J. Org. Chem.

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Purine DNA represents an alternative pairing system formed by two purines in the base pair with the recognition elements of Watson–Crick DNA. Base functionalization of 7-deaza-2′-deoxyxanthosine with ethynyl and octadiynyl residues led to clickable side chain derivatives with short and long linker arms. As complementary bases, purine-2,6-diamine or 7-deazapurine-2,6-diamine 2′-deoxyribonucleosides were used. 7-Deaza-7-iodo-2′-deoxyxanthosine served as a starting material for Sonogashira cross-coupling and the p-nitrophenylethyl group for base protection. Phosphoramidite building blocks for DNA synthesis were prepared. Oligonucleotides containing single modifications or runs of three purine base pairs embedded in 12-mer Watson–Crick DNA were synthesized and hybridized with complementary strands with purine- or 7-deazapurine-2,6-diamine located opposite to the xanthine derivatives. The stability of base pairs was evaluated in a comparative study on the basis of DNA melting experiments and T m values. As 7-deazaxanthine and xanthine nucleosides form anionic forms at neutral pH, duplex stability became pK-dependent, and the system with 7-deazapurine displayed a significant higher stability as that containing xanthine. Alkynyl side chains are well accommodated in the purine–purine helix. Click adducts with pyrene showed that short linker arms destabilize duplexes, whereas long linkers increase duplex stability. CD and fluorescence measurements provide further insights into purine–purine base pairing.

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“…Contrary to the guanine–isoguanine base pair, the tautomeric shift for the formation of a tridentate 5‐aza‐7‐deazaguanine–isoguanine pair is not necessary. Later, base pairs of xanthine or 7‐deazaxanthine with 2,6‐diaminopurine or a 2,6‐diaminopurine analogue were described [4b, 10] . Recently, DNA with 5‐aza‐7‐deazaguanine–isoguanine pairs was characterized by X‐ray analysis [6a] .…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Kondhare

Leonard

et al. 2021

Chemistry A European J

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The Watson–Crick coding system depends on the molecular recognition of complementary purine and pyrimidine bases. Now, the construction of hybrid DNAs with Watson–Crick and purine–purine base pairs decorated with dendritic side chains was performed. Oligonucleotides with single and multiple incorporations of 5‐aza‐7‐deaza‐2′‐deoxyguanosine, its tripropargylamine derivative, and 2′‐deoxyisoguanosine were synthesized. Duplex stability decreased if single modified purine–purine base pairs were inserted, but increased if pyrene residues were introduced by click chemistry. A growing number of consecutive 5‐aza‐7‐deazaguanine–isoguanine base pairs led to strong stepwise duplex stabilization, a phenomenon not observed for the guanine–isoguanine base pair. Spacious residues are well accommodated in the large groove of purine–purine DNA tracts. Changes to the global helical structure monitored by circular dichroism spectroscopy show the impact of functionalization to the global double‐helix structure. This study explores new areas of molecular recognition realized by purine base pairs that are complementary in hydrogen bonding, but not in size, relative to canonical pairs.

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Oligonucleotides Containing 7-Deaza-2′-deoxyxanthosine: Synthesis, Base Protection, and Base-Pair Stability

Cited by 10 publications

References 39 publications

Towards a comprehensive understanding of RNA deamination: synthesis and properties of xanthosine-modified RNA

Towards a comprehensive understanding of RNA deamination: synthesis and properties of xanthosine-modified RNA

Purine DNA Constructs Designed to Expand the Genetic Code: Functionalization, Impact of Ionic Forms, and Molecular Recognition of 7-Deazaxanthine–7-Deazapurine-2,6-diamine Base Pairs and Their Purine Counterparts

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

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