Regioselective 2′‐Silylation of Purine Ribonucleosides for Phosphoramidite RNA Synthesis

Gaffney, Barbara L.; Jones, R. A. C.

doi:10.1002/0471142700.nc0208s06

Cited by 3 publications

(6 citation statements)

References 10 publications

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“…The chemical synthesis consists of eight steps with N ‐benzoyl‐2’‐O‐TBS‐protected adenosine phosphoramidite as initial substrate [21] . The synthesis starts with hydrolysis, removal of the cyanoethyl group, and subsequent detritylation, whereby an H‐phosphonate is obtained.…”

Section: Resultsmentioning

confidence: 99%

“…The chemical 2’3’‐cGAMP synthesis (Figure 1) was calculated based on a detailed synthesis protocol with a yield of 5 % [18,21] . The synthesis contains eight main steps, which in turn can be divided into 20 sub‐steps.…”

Section: Methodsmentioning

confidence: 99%

“…The synthesis routes differ significantly from each other and therefore lead to different process characteristics. The chemical synthesis results in a significantly lower yield, but the reaction mixture is already highly concentrated in the last step and requires only a few purification steps [21] . In contrast, biocatalysis results in a high reaction yield, but in a low titer (310 mg L −1 ), and thus a more complex downstream processing is required to isolate the polar hydrophilic product from the aqueous reaction mixture [17] .…”

Section: Introductionmentioning

confidence: 99%

“…Individual LCAs were created for the substrates ATP, GTP, and yeast extract based on patents. For the chemical synthesis of 2’3’‐cGAMP, a synthesis protocol by Gaffney and Jones on a gram scale served as the basis for the calculation, [21] which was similarly scaled up. For this LCA study, a full life cycle inventory is not available, making a gate‐to‐gate LCA the most appropriate and practical approach for assessing potential environmental impacts.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Life Cycle Assessment of Chemical and Biocatalytic 2’3’‐Cyclic GMP‐AMP Synthesis

et al. 2022

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Life cycle assessments (LCAs) can provide insights into the environmental impact of production processes. In this study, a comparative LCA was performed for the synthesis of 2’3’‐cyclic GMP‐AMP (2’3’‐cGAMP) in an early development stage. The cyclic dinucleotide (CDN) is of interest for pharmaceutical applications such as cancer immunotherapy. CDNs can be synthesized either by enzymes or chemical catalysis. It is not known which of the routes is more sustainable as both routes have their advantages and disadvantages, such as a poor yield for the chemical synthesis and low titers for the biocatalytic synthesis. The synthesis routes were compared for the production of 200 g 2’3’‐cGAMP based on laboratory data to assess the environmental impacts. The biocatalytic synthesis turned out to be superior to the chemical synthesis in all considered categories by at least one magnitude, for example, a global warming potential of 3055.6 kg CO2 equiv. for the enzymatic route and 56454.0 kg CO2 equiv. for the chemical synthesis, which is 18 times higher. This study demonstrates the value of assessment at an early development stage, when the choice between different routes is still possible.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Life Cycle Assessment of Chemical and Biocatalytic 2’3’‐Cyclic GMP‐AMP Synthesis

et al. 2022

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“…Several groups have also developed strategies to obtain 13 C/ 15 N-labeled amidites. Initial efforts were developed by the Pitsch [ 62 ] and Jones [ 63 , 64 , 65 , 66 ] research groups. More recently, the Micura [ 67 , 68 ] and Kreutz [ 17 , 61 , 69 , 70 , 71 ] research groups have dramatically improved the efficiency and scalability of amidite synthesis for NMR analysis.…”

Section: Stable Isotope Labeling Of Rna Building Blocksmentioning

confidence: 99%

Isotope-Labeled RNA Building Blocks for NMR Structure and Dynamics Studies

et al. 2021

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RNA structural research lags behind that of proteins, preventing a robust understanding of RNA functions. NMR spectroscopy is an apt technique for probing the structures and dynamics of RNA molecules in solution at atomic resolution. Still, RNA analysis by NMR suffers from spectral overlap and line broadening, both of which worsen for larger RNAs. Incorporation of stable isotope labels into RNA has provided several solutions to these challenges. In this review, we summarize the benefits and limitations of various methods used to obtain isotope-labeled RNA building blocks and how they are used to prepare isotope-labeled RNA for NMR structure and dynamics studies.

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Solid-Phase Chemical Synthesis of Stable Isotope-Labeled RNA to Aid Structure and Dynamics Studies by NMR Spectroscopy

2019

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RNA structure and dynamic studies by NMR spectroscopy suffer from chemical shift overlap and line broadening, both of which become worse as RNA size increases. Incorporation of stable isotope labels into RNA has provided several solutions to these limitations. Nevertheless, the only method to circumvent the problem of spectral overlap completely is the solid-phase chemical synthesis of RNA with labeled RNA phosphoramidites. In this review, we summarize the practical aspects of this methodology for NMR spectroscopy studies of RNA. These types of investigations lie at the intersection of chemistry and biophysics and highlight the need for collaborative efforts to tackle the integrative structural biology problems that exist in the RNA world. Finally, examples of RNA structure and dynamic studies using labeled phosphoramidites are highlighted.

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Regioselective 2′‐Silylation of Purine Ribonucleosides for Phosphoramidite RNA Synthesis

Cited by 3 publications

References 10 publications

Comparative Life Cycle Assessment of Chemical and Biocatalytic 2’3’‐Cyclic GMP‐AMP Synthesis

Comparative Life Cycle Assessment of Chemical and Biocatalytic 2’3’‐Cyclic GMP‐AMP Synthesis

Isotope-Labeled RNA Building Blocks for NMR Structure and Dynamics Studies

Solid-Phase Chemical Synthesis of Stable Isotope-Labeled RNA to Aid Structure and Dynamics Studies by NMR Spectroscopy

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