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Publication Abstract from PubMed

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 Zalpha 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.

Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions.,El-Khoury R, Cabrero C, Movilla S, Kaur H, Friedland D, Dominguez A, Thorpe JD, Roman M, Orozco M, Gonzalez C, Damha MJ Nucleic Acids Res. 2024 Jul 22;52(13):7414-7428. doi: 10.1093/nar/gkae508. PMID:38874502^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.