A P(V)–N Activation Strategy for the Synthesis of Nucleoside Polyphosphates

Sun, Qi; Gong, Shan‐Shan; Sun, Jian; Liu, Si; Xiao, Qiang; Pu, Shouzhi

doi:10.1021/jo4011156

Cited by 42 publications

(43 citation statements)

References 40 publications

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“…The bond is formed in a reaction of P -nucleophilic and P -electrophilic subunits (usually nucleotides 5′-substituted by an activating group (28–30), which is often mediated by divalent cations in an aprotic polar solvent (31,32). We previously implemented this general method to synthesize cap analogs using P -imidazolides as P -electrophiles, phosphate-modified or unmodified nucleotides as nucleophiles and ZnCl 2 or MgCl 2 as catalysts (33).…”

Section: Resultsmentioning

confidence: 99%

Cap analogs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential

et al. 2016

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Along with a growing interest in mRNA-based gene therapies, efforts are increasingly focused on reaching the full translational potential of mRNA, as a major obstacle for in vivo applications is sufficient expression of exogenously delivered mRNA. One method to overcome this limitation is chemically modifying the 7-methylguanosine cap at the 5′ end of mRNA (m7Gppp-RNA). We report a novel class of cap analogs designed as reagents for mRNA modification. The analogs carry a 1,2-dithiodiphosphate moiety at various positions along a tri- or tetraphosphate bridge, and thus are termed 2S analogs. These 2S analogs have high affinities for translation initiation factor 4E, and some exhibit remarkable resistance against the SpDcp1/2 decapping complex when introduced into RNA. mRNAs capped with 2S analogs combining these two features exhibit high translation efficiency in cultured human immature dendritic cells. These properties demonstrate that 2S analogs are potentially beneficial for mRNA-based therapies such as anti-cancer immunization.

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Section: Resultsmentioning

confidence: 99%

Cap analogs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential

et al. 2016

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“…More recently,a pplication of more-effective catalysts, such as tetrazole and 4,5-dicyanoimidazole (DCI), resulted in symmetricala nd asymmetricald inucleoside polyphosphates and nucleoside 5'-triphosphates 13 (Scheme10), startingf rom nucleotidep iperidates 21 (X = C) in reasonable yields (40-80 %) after 6-30 h. [66][67][68] Phosphoramidates 21 were prepared from protected H-phosphonate precursors and deblocked before furthera pplication. [66] Pu et al [66] studied the roles of an umber of catalysts in the reaction( Scheme 10) and proposedastrategy for P V ÀNb ond activation. [69] Optimized reactionconditions, depending on the cost and solubility of the reactants, were also developed.…”

Section: Phosphoromorpholidatesa Nd Phosphoropiperidatesmentioning

confidence: 99%

ChemInform Abstract: How to Form a Phosphate Anhydride Linkage in Nucleotide Derivatives

Sherstyuk¹,

Абрамова²

2016

ChemInform

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“…More recently, application of more‐effective catalysts, such as tetrazole and 4,5‐dicyanoimidazole (DCI), resulted in symmetrical and asymmetrical dinucleoside polyphosphates and nucleoside 5′‐triphosphates 13 (Scheme ), starting from nucleotide piperidates 21 (X=C) in reasonable yields (40–80 %) after 6–30 h . Phosphoramidates 21 were prepared from protected H ‐phosphonate precursors and deblocked before further application . Pu et al .…”

Section: The Use Of Compounds Containing P−n Bondsmentioning

confidence: 99%

“…Phosphoramidates 21 were prepared from protected H ‐phosphonate precursors and deblocked before further application . Pu et al . studied the roles of a number of catalysts in the reaction (Scheme ) and proposed a strategy for P V −N bond activation .…”

Section: The Use Of Compounds Containing P−n Bondsmentioning

confidence: 99%

How To Form a Phosphate Anhydride Linkage in Nucleotide Derivatives

Sherstyuk

Abramova

2015

ChemBioChem

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The fundamental roles of nucleoside triphosphates and nucleotide cofactors such as NAD(+) in biochemistry are well known. In recent decades, continuing research has revealed the key role of 5'-capped RNA and 5',5'-dinucleoside polyphosphates in the regulation of vitally important physiological processes. Last but not least, the commercial potential of nucleoside triphosphate synthesis can hardly be overestimated. Nevertheless, despite decades of investigation and the obvious topicality of the research on the chemical synthesis of the nucleotide compounds containing phosphate anhydride linkages, none of the existing procedures can be considered an up-to-date "gold standard". However, there are a number of fruitful synthetic approaches to forming phosphate anhydride linkages in satisfactory yield. These are summarized in this concise review, organized by the type of active phosphorous intermediate and reagents used.

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A P(V)–N Activation Strategy for the Synthesis of Nucleoside Polyphosphates

Cited by 42 publications

References 40 publications

Cap analogs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential

Cap analogs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential

ChemInform Abstract: How to Form a Phosphate Anhydride Linkage in Nucleotide Derivatives

How To Form a Phosphate Anhydride Linkage in Nucleotide Derivatives

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