biostudies-literaturePallan PSNCRR NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSNIH HHS2854-2867https://www.ebi.ac.uk/biostudies/studies/S-EPMC11062489biostudies-literatureUnknown62(19)Several efforts are currently directed at the creation and cellular implementation of alternative genetic systems composed of pairing components that are orthogonal to the natural dA/dT and dG/dC base pairs. In an alternative approach, Watson-Crick-type pairing is conserved, but one or all of the four letters of the A, C, G, and T alphabet are substituted by modified components. Thus, all four nucleobases were altered to create halogenated deazanucleic acid (DZA): dA was replaced by 7-deaza-2'-deoxyadenosine (dzA), dG by 7-deaza-2'-deoxyguanosine (dzG), dC by 5-fluoro-2'-deoxycytidine (FdC), and dT by 5-chloro-2'-deoxyuridine (CldU). This base-pairing system was previously shown to retain function in <i>Escherichia coli</i>. Here, we analyze the stability, hydration, structure, and dynamicBiochemistryConformational Morphing by a DNA Analogue Featuring 7-Deazapurines and 5-Halogenpyrimidines and the Origins of Adenine-Tract Geometry.PMC11062489R35 GM130207S10 OD020154GM130207S10 RR031634Egli MLybrand TPSchepers GAbramov MHerdewijn PEremeeva ERozners EPallan PSfalseConformational Morphing by a DNA Analogue Featuring 7-Deazapurines and 5-Halogenpyrimidines and the Origins of Adenine-Tract Geometry.Several efforts are currently directed at the creation and cellular implementation of alternative genetic systems composed of pairing components that are orthogonal to the natural dA/dT and dG/dC base pairs. In an alternative approach, Watson-Crick-type pairing is conserved, but one or all of the four letters of the A, C, G, and T alphabet are substituted by modified components. Thus, all four nucleobases were altered to create halogenated deazanucleic acid (DZA): dA was replaced by 7-deaza-2'-deoxyadenosine (dzA), dG by 7-deaza-2'-deoxyguanosine (dzG), dC by 5-fluoro-2'-deoxycytidine (FdC), and dT by 5-chloro-2'-deoxyuridine (CldU). This base-pairing system was previously shown to retain function in <i>Escherichia coli</i>. Here, we analyze the stability, hydration, structure, and dynamic2023-01-01T00:00:00Z2023 Oct2026-06-01T09:08:10.716Z2025-04-06T16:08:30.186ZS-EPMC110624893769472210.1021/acs.biochem.3c00327