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Title: | Formation of left-handed helices by C2′-fluorinated nucleic acids under physiological salt conditions |
Author: | PERDICES SEGUI, Quim El-Khoury R Cabrero C MOVILLA NUÑEZ, Santiago Kaur H Friedland D Domínguez À Thorpe JD Roman M Orozco Lopez, Modesto Gonzalez C Damha MJ |
Keywords: | Astronomia / física Biochemistry & molecular biology Biodiversidade Biotecnología Ciência da computação Ciências agrárias i Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Engenharias ii Farmacia Genetics Interdisciplinar Matemática / probabilidade e estatística Medicina i Medicina ii Nutrição Química Saúde coletiva Zootecnia / recursos pesqueiros |
Issue Date: | 14-Jun-2024 |
Abstract: | 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. |
Note: | https://doi.org/10.1093/nar/gkae508 |
It is part of: | Nucleic Acids Research, 2024, |
URI: | http://hdl.handle.net/2445/213560 |
Related resource: | https://doi.org/10.1093/nar/gkae508 |
ISSN: | El-Khoury R; Cabrero C; Movilla S; Kaur H; Friedland D; Domínguez A; Thorpe JD; Roman M; Orozco M; González C; Damha MJ (2024). Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions.. Nucleic Acids Research, (), -. DOI: 10.1093/nar/gkae508 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Files in This Item:
File | Description | Size | Format | |
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SMovilla_MOrozco_NAR_full_2024.pdf | 4.54 MB | Adobe PDF | View/Open |
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