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Expanding the Scope of 2′‐SCF 3 Modified RNA
Author(s) -
Jud Lukas,
Košutić Marija,
Schwarz Veronika,
Hartl Markus,
Kreutz Christoph,
Bister Klaus,
Micura Ronald
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201500415
Subject(s) - guanosine , rna , chemistry , pyrimidine , purine , combinatorial chemistry , stereochemistry , small molecule , biochemistry , gene , enzyme
The 2′‐trifluoromethylthio (2′‐SCF 3 ) 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′‐SCF 3 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′‐SCF 3 ‐modified oligoribonucleotides that were investigated intensively. Their excellent behavior in 19 F NMR spectroscopic probing of RNA ligand binding was exemplified for a noncovalent small molecule–RNA interaction. Moreover, comparably to the 2′‐SCF 3 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.