2′‐SCF₃ Uridine—A Powerful Label for Probing Structure and Function of RNA by ¹⁹F NMR Spectroscopy

Abstract

Fluorishing: The Togni reagent allows efficient synthetic access to fluorine‐labeled RNA molecules (see picture). These are in turn highly useful for NMR spectroscopic analyses of secondary and tertiary structures, RNA–protein interactions, and functionality of riboswitch modules.

19F-Site-Specific-Labeled Nucleotides for Nucleic Acid Structural Analysis by NMR

“…2 0 -Deoxy-2 0 -fluorinated nucleosides are effectively locked in the C3 0 -endo sugar pucker normally associated with A-form RNA geometry (Barchi, Jeong, Siddiqui, & Marquez, 1997;Deleavey & Damha, 2012;Kreutz, Kahlig, Konrat, & Micura, 2005;Reif et al, 1997;Thibaudeau, Plavec, & Chattopadhyaya, 1998). While attractive due to the increased sensitivity associated with three magnetically equivalent 19 F reporters (Fauster, Kreutz, & Micura, 2012), the 2 0 -trifluoromethylthio (2 0 -SCF 3 ) modification proposed by Micura and coworkers decreases the stability of regular A-form helices (Kosutic et al, 2014).…”

19F-labeling of the adenine H2-site to study large RNAs by NMR spectroscopy

“…The modification on the ribosyl moiety of nucleotides allows the use of one similar labeling schema for all nucleobases. Using the 2 0 -deoxy-2 0 -trifluoromethylthio (SCF3) unit or other highly fluorinated substitutions can even enhance the sensitivity of 19 F-NMR spectroscopy (Fauster et al 2012;Kiviniemi and Virta 2010;Kosutic et al 2014), in particular for large RNAs. However, uniform labeling of the RNA with 2 0 F-substituted nucleotides can disrupt tertiary interactions that involve the 2 0 OH group and shift the conformational preferences of the ribofuranosyl sugar unit to preferentially adopt the 3 0 -endo conformation and therefore influences the structural behavior (Reif et al 1997).…”

Electrophilic trifluoromethylthiolation of thiols with trifluoromethanesulfenamide

“…White solid (160 mg, 69%), mp 113.9-116. 1-Methyl-2-nitro-4-((triuoromethyl)sulnothioyl)benzene (14). Yellow solid (114 mg, 71%) …”