Fluorinated Diaminocyclopentanes as Chiral Sensitive NMR Probes of RNA Structure

Abstract

The supramolecular chiral recognition between rac-2a and several structured RNA leads to a distinct (19)F NMR signal splitting. The (19)F NMR analysis of the diastereomeric pairs formed upon binding of this racemic probe delivers a topological footprint of the RNA. This phenomenon can be exploited to investigate dynamic events involving structural equilibria, as demonstrated in a melting experiment. This work provides a proof of concept that small fluorinated moderate binders can act as external probes of RNA structures.

Stereoselective Synthesis of Fluorinated 1,3-cis-Diaminocyclopentanes

“…have been previously described. 5 Compound 8 has been previously described. 11 Compounds 23, 24, 26 have been previously described.…”

Diazanorbornene: A Valuable Synthon towards Carbocycles and Heterocycles

“…The research group of Micouin was also engaged in the fragment-based design of t-RNA ligands. [48] They utilized 1,3-diaminocyclopentenes obtained from diazabicyclic olefins as topological probes for studying RNA structures (Scheme 64). As the introduction of F-atom to RNA makes it possible to gather information on its dynamic structure through 19 F NMR spectroscopy, Micouin et al synthesized fluorinated diaminocyclopentane 170 from hydroxylated diaminocyclopentanes 169 which was initially obtained from the bicyclic species.…”

2′-O-Trifluoromethylated RNA – a powerful modification for RNA chemistry and NMR spectroscopy

“…The attractiveness of uorine labeling of biomolecules for 19 F-NMR spectroscopic applications originates from its unique properties, namely a 100% natural abundance, high NMR sensitivity, and large chemical shi dispersion. [1][2][3][4][5][6][7][8][9] Moreover, uorine is bio-orthogonal, meaning that it is hardly encountered in native biomolecular systems. [10][11][12][13][14][15] Appropriate probes for ribonucleic acids have mainly focused on single uorine atoms attached to the 5-position of pyrimidine nucleobases [16][17][18][19][20] or at the ribose 2 0 -position.…”