title: Expanding the Scope of 2'-SCF3 Modified RNA.
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 (19) F 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.
authors.affiliation: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck (Austria).
authors.forename: Lukas
authors.initials: L
authors.lastname: Jud
authors.affiliation: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck (Austria).
authors.forename: Marija
authors.initials: M
authors.lastname: Košutić
authors.affiliation: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck (Austria).
authors.forename: Veronika
authors.initials: V
authors.lastname: Schwarz
authors.affiliation: Institute of Biochemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck (Austria).
authors.forename: Markus
authors.initials: M
authors.lastname: Hartl
authors.affiliation: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck (Austria).
authors.forename: Christoph
authors.initials: C
authors.lastname: Kreutz
authors.affiliation: Institute of Biochemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck (Austria).
authors.forename: Klaus
authors.initials: K
authors.lastname: Bister
authors.affiliation: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck (Austria). ronald.micura@uibk.ac.at.
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
mesh_terms: D018360:Crystallography, X-Ray; D005461:Fluorine / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011687:Purines / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D060327:Solid-Phase Synthesis Techniques; D013816:Thermodynamics
chemical_list: D008024:Ligands; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D011687:Purines; D034741:RNA, Small Interfering; C434331:phosphoramidite; D005461:Fluorine; C030985:purine
keywords: NMR spectroscopy; fluorine; oligonucleotides; phosphoramidites; solid-phase synthesis