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cc by (c) Perdices Seguí, Quim et al, 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/213560

Formation of left-handed helices by C2′-fluorinated nucleic acids under physiological salt conditions

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Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2'F-araC and 2'F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1. The effect of the two nucleotides is so dramatic that Z-form duplexes are the only species observed in 10 mM sodium phosphate buffer and neutral pH, and no B-form is observed at any temperature. Hence, in contrast to other studies reporting formation of Z/B-form equilibria by a preference for purine glycosidic angles in syn, our NMR and computational work revealed that sequential 2'F…H2N and intramolecular 3'H…N3' interactions stabilize the left-handed helix. The equilibrium between B- and Z- forms is slow in the 19F NMR time scale (≥ms), and each conformation exhibited unprecedented chemical shift differences in the 19F signals. This observation led to a reliable estimation of the relative population of B and Z species and enabled us to monitor B-Z transitions under different conditions. The unique features of 2'F-modified DNA should thus be a valuable addition to existing techniques for specific detection of new Z-binding proteins and ligands.

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PERDICES SEGUÍ, Quim, EL-KHOURY, R., CABRERO, Carlos, MOVILLA NÚÑEZ, Santiago, KAUR, H., FRIEDLAND, D., DOMÍNGUEZ, À., THORPE, J. d., ROMAN, Morgane, OROZCO LÓPEZ, Modesto, GONZÁLEZ, C., DAMHA, M. j.. Formation of left-handed helices by C2′-fluorinated nucleic acids under physiological salt conditions. _Nucleic Acids Research_. 2024. Vol. 52, núm. 13, pàgs. 7414–7428. [consulta: 20 de gener de 2026]. ISSN: 1362-4962. [Disponible a: https://hdl.handle.net/2445/213560]

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