Synthesis of 4-Thiopseudoisocytidine and 4-Thiopseudouridine as Components of Triplex-forming Oligonucleotides

Okamoto, Isaku; Cao, Shougen; Tanaka, Hiroto; Seio, Kohji; Sekine, Mitsuo

doi:10.1246/cl.2009.174

Cited by 8 publications

(7 citation statements)

References 30 publications

(22 reference statements)

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“…Simulations with the application of the AMBER FF99 parameters for the modified residues in combination with the revised γ torsion parameters and the revised χ torsional parameters developed earlier in our lab generated conformations, which were in better agreement with the available experimental (NMR) data ,− compared to those generated by simulations with the default AMBER parameters for each of the modified nucleosides (Figures – and Tables S6–S8). Overall, the observations were quite similar to those for Ψ.…”

Section: Results and Discussionmentioning

confidence: 55%

“…The results obtained from three independent sets of 16 ns REMD simulations using the FF99 parameters, FF99_bsc0 parameters, , FF99_χ IDRP parameters, , and FF99_χ IDRP _bsc0 parameters, ,, were compared to the available experimental (NMR) data ,− for the m 1 Ψ, m 3 Ψ, Ψm, and m 1 acp 3 Ψ residues.…”

Section: Results and Discussionmentioning

confidence: 99%

“…For each of these modifications, three independent 16ns of REMD simulations were carried out in 16 temperature windows ranging from 300 to 400 K, resulting in 256 ns simulation in total. We compared the simulated conformational preferences with the available experimental data ,− and validated the revised parameter sets for each of these modifications. We found that the AMBER FF99-derived parameters for these nucleosides did not reproduce the observed experimental features.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Dynamics Simulation of the Conformational Preferences of Pseudouridine Derivatives: Improving the Distribution in the Glycosidic Torsion Space

Dutta

Sarzyñska

Lahiri

2020

J. Chem. Inf. Model.

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There are only four derivatives of pseudouridine (Ψ) that are known to occur naturally in RNA as post-transcriptional modifications. We have studied the conformational consequences of pseudouridylation and further modifications using replica exchange molecular dynamics simulations at the nucleoside level, and the simulated conformational preferences were compared with the available experimental (NMR) data. We found that the existing AMBER FF99-derived parameters for these nucleosides did not reproduce the observed experimental features and while the recommended bsc0 correction could be combined with these parameters leading to an improvement in the description of sugar pucker distributions, the χOL3 correction could not be applied to these nucleosides as such because of base isomerization. On the other hand, the revised χ torsion parameters (χIDRP) for Ψ developed earlier by us (DebI. Deb, I. J. Comput. Chem.20163715761588) in combination with the AMBER provided parameters and the revised γ torsion parameters generated conformational distributions, which generally were in better agreement with the experimental data. A significant shift of the distribution of base orientation toward the syn conformation was observed with our revised parameter sets compared to the large excess of anti conformation predicted by the FF99 parameters. Overall, our observations indicated that our revised set of parameters (χIDRP) for Ψ were also able to generate conformational distributions for all of the derivatives of Ψ in better agreement with the experimental data.

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Section: Results and Discussionmentioning

confidence: 55%

Section: Results and Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Molecular Dynamics Simulation of the Conformational Preferences of Pseudouridine Derivatives: Improving the Distribution in the Glycosidic Torsion Space

Dutta

Sarzyñska

Lahiri

2020

J. Chem. Inf. Model.

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“…[104] Prompted by prior studies that indicated that triple-stranded RNAs prefer an A-form conformation, [105][106][107] Sekine and coworkers found that s2U bases in triplex forming oligos (TFOs) could also bind AU sites in dsRNA to form triplexes; [108] they subsequently exploited the enhanced stacking of the thione substitution with 4-thiopseudoisocytidine (s 4 ΨiC) bases in TFOs to target GC base pairs in dsRNAs. [109,110] The Chen lab later demonstrated that both s2U and s 4 ΨiC could also target AU and GC pairs in dsRNA when the thio bases are presented on a PNA backbone, driven only by gains in base stacking and hydrogen-bonding in the absence of a sugar backbone. [15,111,112]…”

Section: Native Cytidine and Uridine Derivatives That Stabilize Trimentioning

confidence: 99%

Unnatural bases for recognition of noncoding nucleic acid interfaces

et al. 2020

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The notion of using synthetic heterocycles instead of the native bases to interface with DNA and RNA has been explored for nearly 60 years. Unnatural bases compatible with the DNA/RNA coding interface have the potential to expand the genetic code and co‐opt the machinery of biology to access new macromolecular function; accordingly, this body of research is core to synthetic biology. While much of the literature on artificial bases focuses on code expansion, there is a significant and growing effort on docking synthetic heterocycles to noncoding nucleic acid interfaces; this approach seeks to illuminate major processes of nucleic acids, including regulation of transcription, translation, transport, and transcript lifetimes. These major avenues of research at the coding and noncoding interfaces have in common fundamental principles in molecular recognition. Herein, we provide an overview of foundational literature in biophysics of base recognition and unnatural bases in coding to provide context for the developing area of targeting noncoding nucleic acid interfaces with synthetic bases, with a focus on systems developed through iterative design and biophysical study.

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“…The MD and REMD results with the FF99, FF99χ_YIL, and FF10 force fields showed almost no difference in the population of NORTH and SOUTH conformations and were very much consistent with NMR results for PSU 73,74 (Table 2, Figure 2A, Figure 2B, Figure 2D and Figure S1A, Figure S1B, Figure S1D, Supporting Information). However, simulations with the FF99TOR force field showed a slight shift toward the SOUTH conformation (Table 2).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Conformational Preferences of Modified Uridines: Comparison of AMBER Derived Force Fields

Deb

Sarzyñska

Nilsson

et al. 2014

J. Chem. Inf. Model.

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The widespread occurrence of modified residues in RNA sequences necessitates development of accurate parameters for these modifications for reliable modeling of RNA structure and dynamics. A comprehensive set of parameters for the 107 naturally occurring RNA modifications was proposed by Aduri et al. (J. Chem. Theory Comput. 2007, 3, 1464-1475) for the AMBER FF99 force field. In this work, we tested these parameters on a set of modified uridine residues, namely, dihydrouridine, 2-thiouridine, 4-thiouridine, pseudouridine, and uridine-5-oxyacetic acid, by performing molecular dynamics and replica exchange molecular dynamics simulations of these nucleosides. Although our simulations using the FF99 force field did not, in general, reproduce the experimentally observed conformational characteristics well, combination of the parameter set with recent revisions of the FF99 force field for RNA showed noticeable improvement for some of the nucleosides.

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Synthesis of 4-Thiopseudoisocytidine and 4-Thiopseudouridine as Components of Triplex-forming Oligonucleotides

Cited by 8 publications

References 30 publications

Molecular Dynamics Simulation of the Conformational Preferences of Pseudouridine Derivatives: Improving the Distribution in the Glycosidic Torsion Space

Molecular Dynamics Simulation of the Conformational Preferences of Pseudouridine Derivatives: Improving the Distribution in the Glycosidic Torsion Space

Unnatural bases for recognition of noncoding nucleic acid interfaces

Conformational Preferences of Modified Uridines: Comparison of AMBER Derived Force Fields

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