Synthesis of photocaged 6- O -(2-nitrobenzyl)guanosine and 4- O -(2-nitrobenzyl) uridine triphosphates for photocontrol of the RNA transcription reaction

Ohno, Kentaro; Sugiyama, Daiki; Takeshita, Leo; Kanamori, Takashi; Yoshio, Masaki; Sekine, Mitsuo; Seio, Kohji

doi:10.1016/j.bmc.2017.09.032

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…When MeOH was used as a CDI quenching agent instead of water, formation of a methyl carbamate at C4 of the cytosine nucleobase was observed. Triphosphate 18 exhibits good retention on C18 silica, a feature we attribute to the lipophilic TBDMS protecting group . This enabled rapid and scalable purification of the triphosphate by reverse-phase flash chromatography using an aqueous Bu 3 N-AcOH and MeOH ion-pairing eluent system, whereas oligophosphates usually require purification by strong ion-exchange chromatography .…”

Section: Resultsmentioning

confidence: 99%

“…Triphosphate 18 exhibits good retention on C18 silica, a feature we attribute to the lipophilic TBDMS protecting group. 19 This enabled rapid and scalable purification of the triphosphate by reverse-phase flash chromatography using an aqueous Bu 3 N-AcOH and MeOH ion-pairing eluent system, whereas oligophosphates usually require purification by strong ion-exchange chromatography. 20 Traceless TBDMS cleavage was effected by treatment with Dowex resin in water, affording ddhCTP (2) in excellent yield.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP

et al. 2021

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3′-Deoxy-3′,4′-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin as part of the innate immune response. ddhCTP has been shown to act as an obligate chain terminator of flavivirus and SARS-CoV-2 RNA-dependent RNA polymerases; however, further biophysical studies have been precluded by limited access to this promising antiviral. Herein, we report a robust and scalable synthesis of ddhCTP as well as the mono- and diphosphates ddhCMP and ddhCDP, respectively. Identification of a 2′-silyl ether protection strategy enabled selective synthesis and facile purification of the 5′-triphosphate, culminating in the preparation of ddhCTP on a gram scale.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP

et al. 2021

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“…As before, irradiation of the strand with UV light triggers the cleavage of the protecting group to release the deprotected base (strand 22) and the nitrosoketone (23) as a side product (Scheme 2B). Synthetic methodologies to prepare ONBprotected cytidine, 167 thymidine 212 and guanosine 213 bases are also reported.…”

Section: Synthesis and Deprotection Of Onb-modified Nucleic Acidsmentioning

confidence: 99%

Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications

et al. 2023

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This review article introduces mechanistic aspects and applications of photochemically deprotected ortho-nitrobenzyl (ONB)-functionalized nucleic acids and their impact on diverse research fields including DNA nanotechnology and materials chemistry, biological chemistry, and systems chemistry. Specific topics addressed include the synthesis of the ONB-modified nucleic acids, the mechanisms involved in the photochemical deprotection of the ONB units, and the photophysical and chemical means to tune the irradiation wavelength required for the photodeprotection process. Principles to activate ONB-caged nanostructures, ONB-protected DNAzymes and aptamer frameworks are introduced. Specifically, the use of ONB-protected nucleic acids for the phototriggered spatiotemporal amplified sensing and imaging of intracellular mRNAs at the single-cell level are addressed, and control over transcription machineries, protein translation and spatiotemporal silencing of gene expression by ONB-deprotected nucleic acids are demonstrated. In addition, photodeprotection of ONB-modified nucleic acids finds important applications in controlling material properties and functions. These are introduced by the phototriggered fusion of ONB nucleic acid functionalized liposomes as models for cell–cell fusion, the light-stimulated fusion of ONB nucleic acid functionalized drug-loaded liposomes with cells for therapeutic applications, and the photolithographic patterning of ONB nucleic acid-modified interfaces. Particularly, the photolithographic control of the stiffness of membrane-like interfaces for the guided patterned growth of cells is realized. Moreover, ONB-functionalized microcapsules act as light-responsive carriers for the controlled release of drugs, and ONB-modified DNA origami frameworks act as mechanical devices or stimuli-responsive containments for the operation of DNA machineries such as the CRISPR-Cas9 system. The future challenges and potential applications of photoprotected DNA structures are discussed.

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“…In a similar manner, synthetic cells have been activated with 2-nitrobenzyl-caged ATP [ 28 ]. Alternatively, uracil and guanine triphosphates, photocaged on the nucleobase with a 2-nitrobenzyl, prevented Watson–Crick base pairing prior to uncaging [ 29 ].…”

Section: Light-controlled Gene Expression Using Small Moleculesmentioning

confidence: 99%

Controlling gene expression with light: a multidisciplinary endeavour

Hartmann

Smith

Mazzotti

et al. 2020

Biochemical Society Transactions

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The expression of a gene to a protein is one of the most vital biological processes. The use of light to control biology offers unparalleled spatiotemporal resolution from an external, orthogonal signal. A variety of methods have been developed that use light to control the steps of transcription and translation of specific genes into proteins, for cell-free to in vivo biotechnology applications. These methods employ techniques ranging from the modification of small molecules, nucleic acids and proteins with photocages, to the engineering of proteins involved in gene expression using naturally light-sensitive proteins. Although the majority of currently available technologies employ ultraviolet light, there has been a recent increase in the use of functionalities that work at longer wavelengths of light, to minimise cellular damage and increase tissue penetration. Here, we discuss the different chemical and biological methods employed to control gene expression, while also highlighting the central themes and the most exciting applications within this diverse field.

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Synthesis of photocaged 6- O -(2-nitrobenzyl)guanosine and 4- O -(2-nitrobenzyl) uridine triphosphates for photocontrol of the RNA transcription reaction

Cited by 11 publications

References 36 publications

Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP

Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP

Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications

Controlling gene expression with light: a multidisciplinary endeavour

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