A simple and rapid synthesis of nucleotide analogues containing a phosphorothioate moiety at the terminal position of the phosphate chain

Kowalska, Joanna; Lewdorowicz, Magdalena; Darżynkiewicz, Edward; Jemielity, Jacek

doi:10.1016/j.tetlet.2007.05.170

Cited by 38 publications

(29 citation statements)

References 31 publications

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“…We assigned the product as the β-thiophosphate product based on 31 P NMR, which showed a downfield shift (~44 ppm) of the phosphorous atom due to its bonding to the sulfur atom, whereas the shift for the α-phosphorus atom was unchanged. 13–14 …”

Section: Resultsmentioning

confidence: 99%

Enzymatic synthesis and properties of uridine-5′-O-(2-thiodiphospho)-N-acetylglucosamine

Cai

Ban

Guan

et al. 2011

Carbohydrate Research

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Section: Resultsmentioning

confidence: 99%

Enzymatic synthesis and properties of uridine-5′-O-(2-thiodiphospho)-N-acetylglucosamine

Cai

Ban

Guan

et al. 2011

Carbohydrate Research

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“…Tributylammonium pyrophosphate was prepared according to Ludwig and Eckstein 30. Thiophosphate TEA salt was obtained from its trisodium salt as described earlier 25. Guanosine 5'-monophosphate disodium salt was purchased from Fluka and before use converted into its triethylammonium (TEA) salt by passing through Dowex 50 W × 8 (100–200 mesh), evaporating collected fractions to dryness and drying in vacuum over P 2 O 5 .…”

Section: Methodsmentioning

confidence: 99%

Towards mRNA with superior translational activity: synthesis and properties of ARCA tetraphosphates with single phosphorothioate modifications

et al. 2010

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We describe the chemical synthesis and preliminary biophysical and biochemical characterization of a series of mRNA 5' end (cap) analogs designed as reagents for obtaining mRNA molecules with augmented translation efficiency and stability in vivo and as useful tools to study mRNA metabolism. The analogs share three structural features: (i) 5',5'-bridge elongated to tetraphosphate to increase their affinity to translation initiation factor eIF4E (ii) a single phosphorothioate modification at either the α, β, γ or δ-position of the tetraphosphate to decrease their susceptibility to enzymatic degradation and/or to modulate their interaction with specific proteins and (iii) a 2'-O-methyl group in the ribose of 7-methylguanosine, characteristic to AntiReverse Cap Analogs (ARCAs), which are incorporated into mRNA during in vitro transcription exclusively in the correct orientation. The dinucleotides bearing modified tetraphosphate bridge were synthesized by ZnCl 2 mediated coupling between two mononucleotide subunits with isolated yields of 30-65%. The preliminary biochemical results show that mRNAs capped with new analogs are 2.5-4.5 more efficiently translated in a cell free system than m 7 GpppG-capped mRNAs, which makes them promising candidates for RNA-based therapeutic applications such as gene therapy and anti-cancer vaccines.

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“…Such an approach provides a relatively simple way to obtain a wide scope of chemically modified oligophosphate mono-and diesters (Fig. 7), including phosphorothioates [79][80][81], seleno- [82], borano- [83], and fluorophosphates [84], as well as phosphoramidates [85], C-phosphonates [86], and bisphosphonates [87]. P-imidazolides were shown to react readily with other inorganic nucleophiles such as fluorides [84] and sulfates [88] to yield fluorophosphates and phosphosulfates, respectively.…”

Section: Synthesis Of Rna Caps: P-imidazolides and MCL 2 -Mediated Comentioning

confidence: 99%

Applications of Phosphate Modification and Labeling to Study (m)RNA Caps

Warmiński

Sikorski

Kowalska

et al. 2017

Phosphate Labeling and Sensing in Chemical Biology

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The cap is a natural modification present at the 5 0 ends of eukaryotic messenger RNA (mRNA), which because of its unique structural features, mediates essential biological functions during the process of gene expression. The core structural feature of the mRNA cap is an N7-methylguanosine moiety linked by a 5 0 -5 0 triphosphate chain to the first transcribed nucleotide. Interestingly, other RNA 5 0 end modifications structurally and functionally resembling the m 7 G cap have been discovered in different RNA types and in different organisms. All these structures contain the 'inverted' 5 0 -5 0 oligophosphate bridge, which is necessary for interaction with specific proteins and also serves as a cleavage site for phosphohydrolases regulating RNA turnover. Therefore, cap analogs containing oligophosphate chain modifications or carrying spectroscopic labels attached to phosphate moieties serve as attractive molecular tools for studies on RNA metabolism and modification of natural RNA properties. Here, we review chemical, enzymatic, and chemoenzymatic approaches that enable preparation of modified cap structures and RNAs carrying such structures, with emphasis on phosphate-modified mRNA cap analogs and their potential applications.M. Warminski and P. J. Sikorski have contributed equally to this work.

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A simple and rapid synthesis of nucleotide analogues containing a phosphorothioate moiety at the terminal position of the phosphate chain

Cited by 38 publications

References 31 publications

Enzymatic synthesis and properties of uridine-5′-O-(2-thiodiphospho)-N-acetylglucosamine

Enzymatic synthesis and properties of uridine-5′-O-(2-thiodiphospho)-N-acetylglucosamine

Towards mRNA with superior translational activity: synthesis and properties of ARCA tetraphosphates with single phosphorothioate modifications

Applications of Phosphate Modification and Labeling to Study (m)RNA Caps

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