Perdices Seguí, QuimEl-Khoury, R.Cabrero, CarlosMovilla Núñez, SantiagoKaur, H.Friedland, D.Domínguez, À.Thorpe, J. D.Roman, MorganeOrozco López, ModestoGonzález, C.Damha, M. J.2024-06-252024-06-252024-06-141362-4962https://hdl.handle.net/2445/213560Recent 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.15 p.application/pdfengcc by (c) Perdices Seguí, Quim et al, 2024http://creativecommons.org/licenses/by/3.0/es/NucleòsidsCitologiaNucleosidesCytologyinfo:eu-repo/semantics/article2024-06-21info:eu-repo/semantics/openAccess661842538874502