Expanding the Scope of 2′‐SCF3 Modified RNA
Open Access
- 12 June 2015
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 21 (29) , 10400-10407
Abstract
The 2′‐trifluoromethylthio (2′‐SCF3) modification endows ribonucleic acids with exceptional properties and has attracted considerable interest as a reporter group for NMR spectroscopic applications. However, only modified pyrimidine nucleosides have been generated so far. Here, the syntheses of 2′‐SCF3 adenosine and guanosine phosphoramidites of which the latter was obtained in highly efficient manner by an unconventional Boc‐protecting group strategy, are reported. RNA solid‐phase synthesis provided site‐specifically 2′‐SCF3‐modified oligoribonucleotides that were investigated intensively. Their excellent behavior in 19F NMR spectroscopic probing of RNA ligand binding was exemplified for a noncovalent small molecule–RNA interaction. Moreover, comparably to the 2′‐SCF3 pyrimidine nucleosides, the purine counterparts were also found to cause a significant thermodynamic destabilization when located in double helical regions. This property was considered beneficial for siRNA design under the aspect to minimize off‐target effects and their performance in silencing of the BASP1 gene was demonstrated.Keywords
This publication has 49 references indexed in Scilit:
- 2′‐SCF3 Uridine—A Powerful Label for Probing Structure and Function of RNA by 19F NMR SpectroscopyAngewandte Chemie International Edition, 2012
- 2′-Azido RNA, a Versatile Tool for Chemical Biology: Synthesis, X-ray Structure, siRNA Applications, Click LabelingACS Chemical Biology, 2012
- Novel Modifications in RNAACS Chemical Biology, 2011
- Comparison of a PreQ1 Riboswitch Aptamer in Metabolite-bound and Free States with Implications for Gene RegulationJournal of Biological Chemistry, 2011
- Chemical Synthesis of Site‐Specifically 2′‐Azido‐Modified RNA and Potential Applications for Bioconjugation and RNA InterferenceChemBioChem, 2010
- New strategy for the synthesis of chemically modified RNA constructs exemplified by hairpin and hammerhead ribozymesProceedings of the National Academy of Sciences, 2010
- Stem cell-specific activation of an ancestral myc protooncogene with conserved basic functions in the early metazoan HydraProceedings of the National Academy of Sciences, 2010
- 5-Fluoro pyrimidines: labels to probe DNA and RNA secondary structures by 1D 19 F NMR spectroscopyNucleic Acids Research, 2009
- Inhibition of Myc-induced cell transformation by brain acid-soluble protein 1 (BASP1)Proceedings of the National Academy of Sciences, 2009
- A Nonafluoro Nucleoside as a Sensitive 19F NMR Probe of Nucleic Acid ConformationOrganic Letters, 2008