Chemical synthesis of dimer ribonucleotides containing internucleotidic phosphorodithioate linkages

Petersen, Kenneth H.; Nielsen, John

doi:10.1016/s0040-4039(00)94661-6

Cited by 22 publications

(31 citation statements)

References 23 publications

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“…Except at position 183, this oligo was synthesized with standard RNA phosphoramidites. At position 183, an adenosine phosphorothioamidite was coupled that had been synthesized based on methods described previously (Petersen and Nielsen 1990). Following a 30-min coupling or double coupling step, the initial dichlorobenzyl phosphorothioate linkage was converted to a phosphorodithioate linkage by a 400-sec oxidation with 5% sulfur in 1:1 (v/v) pyridine/carbon disulfide or with 0.05 M solution of sulfurizing reagent II in 2:3 (v/v) pyridine/acetonitrile.…”

Section: Rna Preparationmentioning

confidence: 99%

Metal-ion rescue revisited: Biochemical detection of site-bound metal ions important for RNA folding

Frederiksen¹,

Li²,

Das³

et al. 2012

RNA

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Within the three-dimensional architectures of RNA molecules, divalent metal ions populate specific locations, shedding their water molecules to form chelates. These interactions help the RNA adopt and maintain specific conformations and frequently make essential contributions to function. Defining the locations of these site-bound metal ions remains challenging despite the growing database of RNA structures. Metal-ion rescue experiments have provided a powerful approach to identify and distinguish catalytic metal ions within RNA active sites, but the ability of such experiments to identify metal ions that contribute to tertiary structure acquisition and structural stability is less developed and has been challenged. Herein, we use the well-defined P4-P6 RNA domain of the Tetrahymena group I intron to reevaluate prior evidence against the discriminatory power of metal-ion rescue experiments and to advance thermodynamic descriptions necessary for interpreting these experiments. The approach successfully identifies ligands within the RNA that occupy the inner coordination sphere of divalent metal ions and distinguishes them from ligands that occupy the outer coordination sphere. Our results underscore the importance of obtaining complete folding isotherms and establishing and evaluating thermodynamic models in order to draw conclusions from metal-ion rescue experiments. These results establish metal-ion rescue as a rigorous tool for identifying and dissecting energetically important metal-ion interactions in RNAs that are noncatalytic but critical for RNA tertiary structure.

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Section: Rna Preparationmentioning

confidence: 99%

Metal-ion rescue revisited: Biochemical detection of site-bound metal ions important for RNA folding

Frederiksen¹,

Li²,

Das³

et al. 2012

RNA

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“…Currently only the solid-phase synthesis of dithioate DNA is known (21), the only reported RNA-related phosphorodithioate chemistry is the phosphorothioamidite solution-phase synthesis of dimer ribonucleotides containing intemucleotidic phosphorodithioate linkages (22). We used a solid-phase synthetic method for the synthesis of 3 based on the 3'-phosphorothioamidite 2 (Matulic-Adamic, J., Haeberli, P., Karpeisky, A., Beigelman, L., Usman, N. unpublished observations).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological activities of a phosphorodithioate analog of 2′, 5′-oligoadenylate

Beigelman¹,

Matulić‐Adamić²,

Haeberli³

et al. 1995

Nucl Acids Res

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“…21 Moreover, PS2-dimers have shown great resistance to alkaline degradation when compared to natural RNA derivatives. 20 Further, we have demonstrated that the greatly improved gene silencing activities in vitro and in vivo 19, 22 as a result of introducing two PS2 modifications at the 3¢-end of sense strand siRNAs were a consequence of the higher affinity of PS2-RNA for Ago2 protein, presumably caused by a hydrophobic effect. 23 Recent studies have shown that combined 2′-OMe-PS2 or 2′-F-PS2 substitution experiments with in vitro selected RNA aptamers 24, 25 led to either a reduction or increase in binding affinity.…”

mentioning

confidence: 90%

“…It has been shown that dinucleoside phosphorodithioates (PS2-dimers) have high nuclease resistance. 20 In addition, a hammerhead ribozyme with a single PS2 substitution at the cleavage site maintained activity and cleavage resulted in the expected product. 21 Moreover, PS2-dimers have shown great resistance to alkaline degradation when compared to natural RNA derivatives.…”

mentioning

confidence: 97%

Origins of the enhanced affinity of RNA–protein interactions triggered by RNA phosphorodithioate backbone modification

et al. 2017

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Chemical synthesis of dimer ribonucleotides containing internucleotidic phosphorodithioate linkages

Cited by 22 publications

References 23 publications

Metal-ion rescue revisited: Biochemical detection of site-bound metal ions important for RNA folding

Metal-ion rescue revisited: Biochemical detection of site-bound metal ions important for RNA folding

Synthesis and biological activities of a phosphorodithioate analog of 2′, 5′-oligoadenylate

Origins of the enhanced affinity of RNA–protein interactions triggered by RNA phosphorodithioate backbone modification

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