[{"type":"journal_article","volume":2,"status":"public","publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"citation":{"ieee":"R. C. A. Dubini, E. Korytiaková, T. Schinkel, P. Heinrichs, T. Carell, and P. Rovo, “1H NMR chemical exchange techniques reveal local and global effects of oxidized cytosine derivatives,” ACS Physical Chemistry Au, vol. 2, no. 3. American Chemical Society, pp. 237–246, 2022.","apa":"Dubini, R. C. A., Korytiaková, E., Schinkel, T., Heinrichs, P., Carell, T., & Rovo, P. (2022). 1H NMR chemical exchange techniques reveal local and global effects of oxidized cytosine derivatives. ACS Physical Chemistry Au. American Chemical Society. https://doi.org/10.1021/acsphyschemau.1c00050","short":"R.C.A. Dubini, E. Korytiaková, T. Schinkel, P. Heinrichs, T. Carell, P. Rovo, ACS Physical Chemistry Au 2 (2022) 237–246.","ista":"Dubini RCA, Korytiaková E, Schinkel T, Heinrichs P, Carell T, Rovo P. 2022. 1H NMR chemical exchange techniques reveal local and global effects of oxidized cytosine derivatives. ACS Physical Chemistry Au. 2(3), 237–246.","ama":"Dubini RCA, Korytiaková E, Schinkel T, Heinrichs P, Carell T, Rovo P. 1H NMR chemical exchange techniques reveal local and global effects of oxidized cytosine derivatives. ACS Physical Chemistry Au. 2022;2(3):237-246. doi:10.1021/acsphyschemau.1c00050","chicago":"Dubini, Romeo C. A., Eva Korytiaková, Thea Schinkel, Pia Heinrichs, Thomas Carell, and Petra Rovo. “1H NMR Chemical Exchange Techniques Reveal Local and Global Effects of Oxidized Cytosine Derivatives.” ACS Physical Chemistry Au. American Chemical Society, 2022. https://doi.org/10.1021/acsphyschemau.1c00050.","mla":"Dubini, Romeo C. A., et al. “1H NMR Chemical Exchange Techniques Reveal Local and Global Effects of Oxidized Cytosine Derivatives.” ACS Physical Chemistry Au, vol. 2, no. 3, American Chemical Society, 2022, pp. 237–46, doi:10.1021/acsphyschemau.1c00050."},"file_date_updated":"2022-07-29T07:53:20Z","author":[{"full_name":"Dubini, Romeo C. A.","last_name":"Dubini","first_name":"Romeo C. A."},{"first_name":"Eva","last_name":"Korytiaková","full_name":"Korytiaková, Eva"},{"full_name":"Schinkel, Thea","first_name":"Thea","last_name":"Schinkel"},{"first_name":"Pia","last_name":"Heinrichs","full_name":"Heinrichs, Pia"},{"full_name":"Carell, Thomas","last_name":"Carell","first_name":"Thomas"},{"first_name":"Petra","id":"c316e53f-b965-11eb-b128-bb26acc59c00","last_name":"Rovo","full_name":"Rovo, Petra","orcid":"0000-0001-8729-7326"}],"publication":"ACS Physical Chemistry Au","acknowledgement":"We thank Markus Müller for valued discussions and Felix Xu for assistance in the measurement of UV/vis melting profiles. This work was supported in part by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – SFB 1309-325871075, EU-ITN LightDyNAmics (ID: 765266), the ERC-AG EpiR (ID: 741912), the Center for NanoScience, the Excellence Clusters CIPSM, and the Fonds der Chemischen Industrie. Open access funding provided by Institute of Science and Technology Austria (ISTA).\r\n\r\n","doi":"10.1021/acsphyschemau.1c00050","intvolume":" 2","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2694-2445"]},"day":"11","related_material":{"link":[{"relation":"earlier_version","url":"https://www.biorxiv.org/content/10.1101/2021.12.14.472563"}]},"year":"2022","date_updated":"2023-01-31T07:33:07Z","date_published":"2022-02-11T00:00:00Z","month":"02","department":[{"_id":"NMR"}],"_id":"10758","title":"1H NMR chemical exchange techniques reveal local and global effects of oxidized cytosine derivatives","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"American Chemical Society","oa_version":"Published Version","quality_controlled":"1","issue":"3","date_created":"2022-02-16T11:18:21Z","ddc":["540"],"article_type":"original","oa":1,"scopus_import":"1","license":"https://creativecommons.org/licenses/by/4.0/","pmid":1,"external_id":{"pmid":["35637781"]},"abstract":[{"lang":"eng","text":"5-Carboxycytosine (5caC) is a rare epigenetic modification found in nucleic acids of all domains of life. Despite its sparse genomic abundance, 5caC is presumed to play essential regulatory roles in transcription, maintenance and base-excision processes in DNA. In this work, we utilize nuclear magnetic resonance (NMR) spectroscopy to address the effects of 5caC incorporation into canonical DNA strands at multiple pH and temperature conditions. Our results demonstrate that 5caC has a pH-dependent global destabilizing and a base-pair mobility enhancing local impact on dsDNA, albeit without any detectable influence on the ground-state B-DNA structure. Measurement of hybridization thermodynamics and kinetics of 5caC-bearing DNA duplexes highlighted how acidic environment (pH 5.8 and 4.7) destabilizes the double-stranded structure by ∼10–20 kJ mol–1 at 37 °C when compared to the same sample at neutral pH. Protonation of 5caC results in a lower activation energy for the dissociation process and a higher barrier for annealing. Studies on conformational exchange on the microsecond time scale regime revealed a sharply localized base-pair motion involving exclusively the modified site and its immediate surroundings. By direct comparison with canonical and 5-formylcytosine (5fC)-edited strands, we were able to address the impact of the two most oxidized naturally occurring cytosine derivatives in the genome. These insights on 5caC’s subtle sensitivity to acidic pH contribute to the long-standing questions of its capacity as a substrate in base excision repair processes and its purpose as an independent, stable epigenetic mark."}],"page":"237-246","has_accepted_license":"1","file":[{"creator":"dernst","checksum":"5ce3f907848f5c7caf77f1adfe5826c6","date_updated":"2022-07-29T07:53:20Z","relation":"main_file","access_level":"open_access","file_size":2351220,"success":1,"file_id":"11692","content_type":"application/pdf","date_created":"2022-07-29T07:53:20Z","file_name":"2022_ACSPhysChemAU_Dubini.pdf"}],"article_processing_charge":"Yes (via OA deal)","project":[{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}]},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"citation":{"ieee":"F. Xu et al., “Isoxazole nucleosides as building blocks for a plausible proto‐RNA,” Angewandte Chemie International Edition, vol. 61, no. 45. Wiley, 2022.","short":"F. Xu, A. Crisp, T. Schinkel, R.C.A. Dubini, S. Hübner, S. Becker, F. Schelter, P. Rovo, T. Carell, Angewandte Chemie International Edition 61 (2022).","apa":"Xu, F., Crisp, A., Schinkel, T., Dubini, R. C. A., Hübner, S., Becker, S., … Carell, T. (2022). Isoxazole nucleosides as building blocks for a plausible proto‐RNA. Angewandte Chemie International Edition. Wiley. https://doi.org/10.1002/anie.202211945","ama":"Xu F, Crisp A, Schinkel T, et al. Isoxazole nucleosides as building blocks for a plausible proto‐RNA. Angewandte Chemie International Edition. 2022;61(45). doi:10.1002/anie.202211945","ista":"Xu F, Crisp A, Schinkel T, Dubini RCA, Hübner S, Becker S, Schelter F, Rovo P, Carell T. 2022. Isoxazole nucleosides as building blocks for a plausible proto‐RNA. Angewandte Chemie International Edition. 61(45), e202211945.","chicago":"Xu, Felix, Antony Crisp, Thea Schinkel, Romeo C. A. Dubini, Sarah Hübner, Sidney Becker, Florian Schelter, Petra Rovo, and Thomas Carell. “Isoxazole Nucleosides as Building Blocks for a Plausible Proto‐RNA.” Angewandte Chemie International Edition. Wiley, 2022. https://doi.org/10.1002/anie.202211945.","mla":"Xu, Felix, et al. “Isoxazole Nucleosides as Building Blocks for a Plausible Proto‐RNA.” Angewandte Chemie International Edition, vol. 61, no. 45, e202211945, Wiley, 2022, doi:10.1002/anie.202211945."},"publication_status":"published","volume":61,"type":"journal_article","status":"public","intvolume":" 61","language":[{"iso":"eng"}],"publication_identifier":{"issn":["1433-7851"],"eissn":["1521-3773"]},"publication":"Angewandte Chemie International Edition","acknowledgement":"We thank Stefan Wiedemann for the synthesis of reference compounds and Pia Heinrichs for assistance in the NMR measurements of the oligonucleotides. We also thank Dr. Luis Escobar and Jonas Feldmann for valued discussions. This work was supported by the German Research Foundation (DFG) for financial support via CRC1309 (Project ID 325871075, A04), CRC1361 (Project ID 893547839, P02) and CRC1032 (Project ID 201269156, A5). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program under grant agreement No 741912 (EpiR). We are grateful for additional funding from the Volkswagen Foundation (EvoRib). Open Access funding enabled and organized by Projekt DEAL.","doi":"10.1002/anie.202211945","file_date_updated":"2023-01-27T10:28:45Z","author":[{"last_name":"Xu","first_name":"Felix","full_name":"Xu, Felix"},{"first_name":"Antony","last_name":"Crisp","full_name":"Crisp, Antony"},{"full_name":"Schinkel, Thea","first_name":"Thea","last_name":"Schinkel"},{"last_name":"Dubini","first_name":"Romeo C. A.","full_name":"Dubini, Romeo C. A."},{"first_name":"Sarah","last_name":"Hübner","full_name":"Hübner, Sarah"},{"first_name":"Sidney","last_name":"Becker","full_name":"Becker, Sidney"},{"full_name":"Schelter, Florian","last_name":"Schelter","first_name":"Florian"},{"full_name":"Rovo, Petra","orcid":"0000-0001-8729-7326","first_name":"Petra","id":"c316e53f-b965-11eb-b128-bb26acc59c00","last_name":"Rovo"},{"full_name":"Carell, Thomas","last_name":"Carell","first_name":"Thomas"}],"keyword":["General Chemistry","Catalysis"],"date_updated":"2023-08-04T09:32:42Z","year":"2022","day":"07","department":[{"_id":"NMR"}],"isi":1,"_id":"12228","article_number":"e202211945","date_published":"2022-11-07T00:00:00Z","month":"11","issue":"45","quality_controlled":"1","oa_version":"Published Version","title":"Isoxazole nucleosides as building blocks for a plausible proto‐RNA","publisher":"Wiley","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["540"],"article_type":"original","oa":1,"date_created":"2023-01-16T09:49:05Z","external_id":{"isi":["000866428500001"]},"scopus_import":"1","article_processing_charge":"No","abstract":[{"text":"The question of how RNA, as the principal carrier of genetic information evolved is fundamentally important for our understanding of the origin of life. The RNA molecule is far too complex to have formed in one evolutionary step, suggesting that ancestral proto-RNAs (first ancestor of RNA) may have existed, which evolved over time into the RNA of today. Here we show that isoxazole nucleosides, which are quickly formed from hydroxylamine, cyanoacetylene, urea and ribose, are plausible precursors for RNA. The isoxazole nucleoside can rearrange within an RNA-strand to give cytidine, which leads to an increase of pairing stability. If the proto-RNA contains a canonical seed-nucleoside with defined stereochemistry, the seed-nucleoside can control the configuration of the anomeric center that forms during the in-RNA transformation. The results demonstrate that RNA could have emerged from evolutionarily primitive precursor isoxazole ribosides after strand formation.","lang":"eng"}],"has_accepted_license":"1","file":[{"date_updated":"2023-01-27T10:28:45Z","creator":"dernst","checksum":"4e8152454d12025d13f6e6e9ca06b5d0","file_size":1076715,"relation":"main_file","access_level":"open_access","success":1,"file_id":"12422","content_type":"application/pdf","date_created":"2023-01-27T10:28:45Z","file_name":"2022_AngewandteChemieInternat_Xu.pdf"}]}]