Thiocoumarin Caged Nucleotides: Synthetic Access and Their Photophysical Properties

Ma, Jiahui; Ripp, Alexander; Wassy, Daniel; Dürr, Tobias; Qiu, Danye; Häner, Markus; Haas, Thomas; Popp, Christoph; Bezold, Dominik; Richert, Sabine; Esser, Birgit; Jessen, Henning J.

doi:10.3390/molecules25225325

Cited by 10 publications

(13 citation statements)

References 49 publications

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“…We anticipated that a 5′ cap with a coumarin‐based photo‐cleavable group would enrich the scope of light‐activated mRNA translation [12] . The 7‐(diethylamino)‐4‐(hydroxymethyl)coumarin (DEACM) is an established coumarin derivative that can be handled in red light, while still being efficiently cleaved at ≥450 nm [15d, 18] . The redshifted absorption spectrum of coumarin compared to ONB‐derivatives would enable the photolysis reaction by irradiation with longer wavelengths and thus mitigate cell stress, which can cause downregulation of translation [19] .…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, photolysis of coumarin is based on a different mechanism compared to ONB‐derivatives, reducing possible sideproduct formation [20] . The co‐product of photolysis—a coumarin alcohol—is non‐toxic, whereas ONB‐derivatives release nitroso compounds, ketones or aldehydes after irradiation that can be toxic to cells [14a, 15c–e] . Finally, a coumarin‐based FlashCap could potentially be photo‐deprotected in the presence of the previously reported ONB‐derived FlashCaps.…”

Section: Resultsmentioning

confidence: 99%

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Light‐Activated Translation of Different mRNAs in Cells via Wavelength‐Dependent Photouncaging

et al. 2022

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The 5' cap is a hallmark of eukaryotic mRNA involved in the initiation of translation. Its modification with a single photo-cleavable group can bring translation of mRNA under the control of light. However, UV irradiation causes cell stress and downregulation of translation. Furthermore, complex processes often involve timed expression of more than one gene. The approach would thus greatly benefit from the ability to photo-cleave by blue light and to control more than one mRNA at a time. We report the synthesis of a 5' cap modified with a 7-(diethylamino)coumarin (CouCap) and adapted conditions for in vitro transcription. Translation of the resulting CouCap-mRNA is muted in vitro and in mammalian cells, and can be initiated by irradiation with 450 nm. The native cap is restored and no non-natural residues nor sequence alterations remain in the mRNA. Multiplexing for two different mRNAs was achieved by combining cap analogs with coumarinand ortho-nitrobenzyl-based photo-cleavable groups.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Light‐Activated Translation of Different mRNAs in Cells via Wavelength‐Dependent Photouncaging

et al. 2022

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“…7-Diethylamino-4-hydroxymethyl-thiocoumarin (thio-DEACM) caged molecules are recently attracting attention. The thio-DEACM as a caging group has great properties, such as rapid blue-cyan light responsiveness and avoiding UV irradiation of cells in combination with the absence of toxicity of the released photocage [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Thiocoumarins: From the Synthesis to the Biological Applications

et al. 2022

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Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the oxygen atoms are replaced by a sulfur. They are chemically subdivided in three groups: Thiocoumarins, 2-thioxocoumarins, and dithiocoumarins. This review emphasizes the rationale behind the synthesis and biological applications of the most relevant publications related to this family of compounds. Particular attention has been given to their potential as drug candidates, with particular emphasis in the last 5 years. This article is based on the most relevant information collected from multiple electronic databases, including SciFinder, Pubmed, Espacenet, and Mendeley.

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“…We envision LAGOON achieving precise control over NTP availability in dumbbell optical trapping experiments (for example, to achieve a single-turnover regime) and to markedly increase the throughput of optical trapping experiments with surface-tethered substrates. Moreover, coumarin-based 21 and new thiocoumarin-based 47 caged compounds with nanosecond-scale uncaging times and longer uncaging wavelengths that cause less photodamage will likely be useful for force spectroscopy–based LAGOON experiments.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporally controlled generation of NTPs for single-molecule studies

et al. 2022

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Many essential processes in the cell depend on proteins that use nucleoside triphosphates (NTPs). Methods that directly monitor the often-complex dynamics of these proteins at the single-molecule level have helped to uncover their mechanisms of action. However, the measurement throughput is typically limited for NTP-utilizing reactions, and the quantitative dissection of complex dynamics over multiple sequential turnovers remains challenging. Here we present a method for controlling NTP-driven reactions in single-molecule experiments via the local generation of NTPs (LAGOON) that markedly increases the measurement throughput and enables single-turnover observations. We demonstrate the effectiveness of LAGOON in single-molecule fluorescence and force spectroscopy assays by monitoring DNA unwinding, nucleosome sliding and RNA polymerase elongation. LAGOON can be readily integrated with many single-molecule techniques, and we anticipate that it will facilitate studies of a wide range of crucial NTP-driven processes.

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Thiocoumarin Caged Nucleotides: Synthetic Access and Their Photophysical Properties

Cited by 10 publications

References 49 publications

Light‐Activated Translation of Different mRNAs in Cells via Wavelength‐Dependent Photouncaging

Light‐Activated Translation of Different mRNAs in Cells via Wavelength‐Dependent Photouncaging

Thiocoumarins: From the Synthesis to the Biological Applications

Spatiotemporally controlled generation of NTPs for single-molecule studies

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