Nebularine (9-2′-deoxy-β-d-ribofuranosylpurine) has the template characteristics of adenine in vivo and in vitro

Rahman, M. Sayeedur; Humayun, M. Zafri

doi:10.1016/s0027-5107(97)00084-5

“…The residue was purified by chromatography (acetone/heptane + 2% Et 3 N) to obtain the product as a mixture of two isomers (0.29 g, 44%). 31 6-Chloro-9-(3,5-di-O-acetyl-2-deoxy-β-D-ribofuranosyl)-purine (42). Acetyl protected deoxyadenosine 41 (5.0 g, 14.9 mmol) was dissolved in anhydrous CH 2 Cl 2 (100 mL) at 0 °C.…”

Section: The Journal Of Organic Chemistrymentioning

confidence: 99%

“…As it was previously presented by Eritja and co-workers, 12 melting points of duplexes containing 2′-deoxynebularine are quite low compared to the fully matched canonical duplexes, except for the nebularine−thymine pair. Also, Rahman and Humayun showed 42 that T was preferably inserted both in vitro and in vivo opposite 2′-deoxynebularines. We observed that T is also the preferred partner for the methylated purine base (X4 > X5 > X3) (Tables 3 and 4).…”

Section: ■ Introductionmentioning

confidence: 99%

N⁸-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties

Leonczak

¹

,

Srivastava

²

,

Bande

³

et al. 2019

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In this report, we present the synthesis of N 8glycosylated 8-aza-2-methylhypoxanthine and 8-aza-6-thiohypoxanthine 2′-deoxynucleosides as well as methylated 2′-deoxynebularine derivatives. In vitro base pairing properties between each modified and canonical nucleobase were studied. As demonstrated by T m , incorporation of the modified bases in DNA resulted, with few exceptions, in low stability of duplexes. Modified bases studied in this report are preferentially recognized by T (for N 8 -glycosylated 8aza-2-methylhypoxanthine and methylated purines) and G (N 8glycosylated 8-aza-2-methylhypoxanthine). The base pair formed between N 8 -glycosylated 8-aza-6-thiohypoxanthine and N 9 -glycosylated 2-methyl-6-thiohypoxanthine (X2:X6) showed, to some extent, an orthogonal interaction. Based on T m studies, the only potential self-pairing system is formed by the N 8 -glycosylated 8-aza-6-thiohypoxanthine nucleoside (X2) but only in the absence of canonical G and T. This study indicated that the canonical thymine base is the preferential base partner of methylated purine bases.

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“…It has been reported that 2'-deoxynebularine acts as an analogue of adenosine in DNA and predominantly forms base pairs with thymidine. [24] Nebularine has also been used during nucleotide analogue interference mapping (NAIM) of RNA, which requires its incorporation during in vitro transcription. [25] Thus, when ATP was replaced by NeTP (Figure 4a) during in vitro transcription of the 19-nt RNA Tr1, T7 RNA polymerase was able to generate a full-length product, which contained a single Ne nucleoside, as shown by HR-ESI-MS analysis and by LC-MS after digestion (Figure S7).…”

mentioning

confidence: 99%

Ribozyme‐Catalyzed Late‐Stage Functionalization and Fluorogenic Labeling of RNA

Scheitl

¹

,

Okuda

²

,

Adelmann

³

et al. 2023

Angewandte Chemie

0

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Site‐specific introduction of bioorthogonal handles into RNAs is in high demand for decorating RNAs with fluorophores, affinity labels or other modifications. Aldehydes represent attractive functional groups for post‐synthetic bioconjugation reactions. Here, we report a ribozyme‐based method for the synthesis of aldehyde‐functionalized RNA by directly converting a purine nucleobase. Using the methyltransferase ribozyme MTR1 as an alkyltransferase, the reaction is initiated by site‐specific N1 benzylation of purine, followed by nucleophilic ring opening and spontaneous hydrolysis under mild conditions to yield a 5‐amino‐4‐formylimidazole residue in good yields. The modified nucleotide is accessible to aldehyde‐reactive probes, as demonstrated by the conjugation of biotin or fluorescent dyes to short synthetic RNAs and tRNA transcripts. Upon fluorogenic condensation with a 2,3,3‐trimethylindole, a novel hemicyanine chromophore was generated directly on the RNA. This work expands the MTR1 ribozyme's area of application from a methyltransferase to a tool for site‐specific late‐stage functionalization of RNA.

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Ribozyme‐Catalyzed Late‐Stage Functionalization and Fluorogenic Labeling of RNA

Scheitl

¹

,

Okuda

²

,

Adelmann

³

et al. 2023

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Site‐specific introduction of bioorthogonal handles into RNAs is in high demand for decorating RNAs with fluorophores, affinity labels or other modifications. Aldehydes represent attractive functional groups for post‐synthetic bioconjugation reactions. Here, we report a ribozyme‐based method for the synthesis of aldehyde‐functionalized RNA by directly converting a purine nucleobase. Using the methyltransferase ribozyme MTR1 as an alkyltransferase, the reaction is initiated by site‐specific N1 benzylation of purine, followed by nucleophilic ring opening and spontaneous hydrolysis under mild conditions to yield a 5‐amino‐4‐formylimidazole residue in good yields. The modified nucleotide is accessible to aldehyde‐reactive probes, as demonstrated by the conjugation of biotin or fluorescent dyes to short synthetic RNAs and tRNA transcripts. Upon fluorogenic condensation with a 2,3,3‐trimethylindole, a novel hemicyanine chromophore was generated directly on the RNA. This work expands the MTR1 ribozyme's area of application from a methyltransferase to a tool for site‐specific late‐stage functionalization of RNA.

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Nebularine (9-2′-deoxy-β-d-ribofuranosylpurine) has the template characteristics of adenine in vivo and in vitro

Cited by 7 publications

References 23 publications

N⁸-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties

N⁸-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties

Ribozyme‐Catalyzed Late‐Stage Functionalization and Fluorogenic Labeling of RNA

Ribozyme‐Catalyzed Late‐Stage Functionalization and Fluorogenic Labeling of RNA

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Nebularine (9-2′-deoxy-β-d-ribofuranosylpurine) has the template characteristics of adenine in vivo and in vitro

Cited by 7 publications

References 23 publications

N8-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties

N8-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties

Ribozyme‐Catalyzed Late‐Stage Functionalization and Fluorogenic Labeling of RNA

Ribozyme‐Catalyzed Late‐Stage Functionalization and Fluorogenic Labeling of RNA

Contact Info

Product

Resources

About

N⁸-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties

N⁸-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties