Fiche publication
Date publication
juin 2026
Journal
Chemical science
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ENNIFAR Eric
Tous les auteurs :
Mitteregger C, Bereiter R, Schramm A, Ennifar E, Kreutz C, Micura R
Lien Pubmed
Résumé
Synthetic RNAs bearing deazapurine nucleobases are powerful probes for dissecting RNA-catalyzed reactions by atomic mutagenesis. Here we systematically characterize RNA containing 1-deazainosine (cI) and compare it with inosine (I). We first report the synthesis of a suitably protected cI phosphoramidite and its incorporation into RNA by solid-phase synthesis. We then provide a comprehensive thermodynamic analysis of base-pair stability from UV-melting experiments, showing that cI-C pairs are less stable than the corresponding I-C pairs. Although a two-hydrogen-bond Hoogsteen interaction between cI and protonated C is conceivable, NMR spectroscopy indicates that cI-C predominantly adopts a Watson-Crick-like geometry with a single hydrogen bond. These pairs are accommodated within RNA duplexes without disrupting neighboring base pairing. We also use cI to probe poly(I:C) motifs that mimic viral double-stranded RNA, assessing how strand length governs duplex hairpin formation. Finally, atomic mutagenesis of the twister ribozyme with cI supports the hypothesis that an active-site guanine participates directly in phosphodiester-bond cleavage. Together, these results clarify how deazapurines modulate nucleic-acid properties and provide guidance for their use in atomic mutagenesis to interrogate RNA catalysis.
Référence
Chem Sci. 2026 06 8;:
