Article
Biochemistry & Molecular Biology
Stephan Werner, Aurellia Galliot, Florian Pichot, Thomas Kemmer, Virginie Marchand, Maksim Sednev, Tina Lence, Jean-Yves Roignant, Julian Koenig, Claudia Hoebartner, Yuri Motorin, Andreas Hildebrandt, Mark Helm
Summary: NOseq is a novel method for detecting m(6)A residues using chemical deamination with nitrous acid. It utilizes a mapping algorithm adapted to sequence degeneration caused by deamination, enabling detection of m(6)A sites with a modification level of around 50% in defined amplicons.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Goran Kokic, Hauke S. Hillen, Dimitry Tegunov, Christian Dienemann, Florian Seitz, Jana Schmitzova, Lucas Farnung, Aaron Siewert, Claudia Hoebartner, Patrick Cramer
Summary: Remdesivir is the only FDA-approved drug for treating COVID-19 patients, working by inhibiting the RNA-dependent RNA polymerase (RdRp) of coronaviruses. It hinders RNA synthesis and impairs proofreading by the viral 3'-exonuclease, leading to a stalled replication process.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Anam Liaqat, Maksim V. Sednev, Carina Stiller, Claudia Hoebartner
Summary: Deoxyribozymes have been identified as modification-specific endonucleases that selectively respond to different natural methylated cytidines, accelerating the cleavage of modified RNA. These deoxyribozymes can be programmed to interrogate natural RNAs of interest, demonstrating the potential of synthetic functional DNA in shaping highly selective active sites.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Florian Kabinger, Carina Stiller, Jana Schmitzoval, Christian Dienemann, Goran Kokic, Hauke S. Hillen, Claudia Hoebartner, Patrick Cramer
Summary: Molnupiravir is an oral antiviral drug candidate that increases viral RNA mutations frequency and inhibits replication of SARS-CoV-2 by altering the substrate preference of RdRp. This two-step mutagenesis mechanism can explain the broad-spectrum antiviral activity of molnupiravir, making it a promising COVID-19 treatment option.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Bin Liu, Yvonne Vonhausen, Alexander Schulz, Claudia Hoebartner, Frank Wuerthner
Summary: The study demonstrated the suitability of the N-(2-aminoethyl)-glycine oligomers backbone for the formation of structurally defined dye stacks, but the peptide backbone cannot direct the formation of a defined duplex architecture upon further extension of the oligomer.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Julia Dietzsch, David Bialas, Johannes Bandorf, Frank Wuerthner, Claudia Hoebartner
Summary: This study reports the tuning of exciton coupling by changing the double helix conformation. Different arrangements of dyes were achieved by changing the backbone constitution and geometry of nucleic acids, resulting in distinct optical characteristics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Maksim Sednev, Anam Liaqat, Claudia Hoebartner
Summary: DZ-seq is a new high-throughput sequencing method that allows for the direct measurement and localization of activity and cleavage sites of thousands of deoxyribozymes. It provides an effective tool for the discovery of novel catalytic motifs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Nicole Kleiber, Nicolas Lemus-Diaz, Carina Stiller, Marleen Heinrichs, Mandy Mong-Quyen Mai, Philipp Hackert, Ricarda Richter-Dennerlein, Claudia Hoebartner, Katherine E. Bohnsack, Markus T. Bohnsack
Summary: RNA modifications, specifically the enzyme METTL8, play a crucial role in regulating RNA functions and have significant impacts on tRNA structure and mitochondrial translation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Carolin P. M. Scheitl, Mateusz Mieczkowski, Hermann Schindelin, Claudia Hoebartner
Summary: RNA-catalyzed RNA methylation has been found to be part of the catalytic repertoire of ribozymes. The crystal structure of methyltransferase ribozyme MTR1 has been determined, revealing a guanine-binding site similar to natural guanine riboswitches. The structure also suggests the involvement of a protonated cytidine in the methyl transfer reaction. The synergistic effect of 2'-O-methylated ribose residues in the active site accelerates methyl group transfer. These findings suggest that modified nucleotides may have played a role in early RNA catalysis and that metabolite-binding riboswitches resemble inactivated ribozymes.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Hermann Neitz, Irene Bessi, Valentin Kachler, Manuela Michel, Claudia Hoebartner
Summary: This study demonstrates the use of tolane-perfluorotolane interaction as a base pair replacement in DNA by modifying the DNA backbone. Thermodynamic analyses show that only THH/TFF heteropairs connected to the BuNA backbone significantly stabilize the DNA duplex, while no such effect is observed with the shorter GNA linker. NMR studies confirm the preference of the BuNA backbone for enhanced polar pi-stacking. This work defines the principles of tailoring orthogonal supramolecular interactions by small structural changes in the DNA backbone and inspires future studies of arene-fluoroarene-programmed assembly of DNA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Carolin P. M. Scheitl, Takumi Okuda, Juliane Adelmann, Claudia Hoebartner
Summary: This article reports a method for synthesizing aldehyde-functionalized RNA by directly converting a purine nucleobase using a ribozyme-based approach. The modified nucleotide can react with aldehyde-reactive probes, allowing for the conjugation of biotin or fluorescent dyes to short synthetic RNAs and tRNA transcripts. The condensation of a 2,3,3-trimethylindole with the modified RNA generates a novel hemicyanine chromophore directly on the RNA. This work expands the application of the MTR1 ribozyme from a methyltransferase to a tool for site-specific late-stage functionalization of RNA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Hermann Neitz, Irene Bessi, Jochen Kuper, Caroline Kisker, Claudia Hoebartner
Summary: Covalent crosslinking of DNA strands using modified nucleoside PhedU enables light-induced interstrand DNA crosslinking reaction. The crosslinking ability is controlled by base pairing and metal ion interaction, allowing efficient formation of PhedU dimer within DNA duplex. The covalent crosslink prevents DNA unwinding, suggesting potential applications in biochemistry or structural biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Julia Dietzsch, Ajay Jayachandran, Stefan Mueller, Claudia Hoebartner, Tobias Brixner
Summary: We synthesized and analyzed the spectroscopy of RNA with barbituric acid merocyanine rBAM2 as a nucleobase surrogate. Incorporating rBAM2 into RNA by solid-phase synthesis resulted in enhanced fluorescence compared to the free chromophore. Linear absorption studies showed the formation of an excitonically coupled H-type dimer in the hybridized duplex. Ultrafast transient absorption spectroscopy of the non-fluorescent dimer suggested immediate exciton transfer and annihilation within sub-200 fs due to the proximity of rBAM2 units.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Mark Helm, Markus T. Bohnsack, Thomas Carell, Alexander Dalpke, Karl-Dieter Entian, Ann Ehrenhofer-Murray, Ralf Ficner, Christian Hammann, Claudia Ho''bartner, Andres Ja''schke, Albert Jeltsch, Stefanie Kaiser, Roland Klassen, Sebastian A. Leidel, Andreas Marx, Mario Mo''rl, Jochen C. Meier, Gunter Meister, Andrea Rentmeister, Marina Rodnina, Jean-Yves Roignant, Raffael Schaffrath, Peter Stadler, Thorsten Stafforst
Summary: This article describes the impact and subsequent effects of the DFG-funded priority program SPP1784 on the field of nucleic acid modifications. The program has facilitated interdisciplinary collaborations and contributed to the development of the nucleic acid chemistry community. The extension of funding during the COVID-19 pandemic has led to increased interest and research in the field of RNA and RNA modifications, particularly in the context of vaccination campaigns against SARS-CoV-2.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Physical
David Fischermeier, Christian Steinmetzger, Claudia Hoebartner, Roland Mitric
Summary: Forster resonant energy transfer (FRET) is used to study tertiary structures of RNA aptamers by binding specific fluorophoric ligands. This study combined classical molecular dynamics with Forster exciton theory to investigate the preferred orientation and exciton transfer efficiency in mutated RNA aptamers. The methodology presented here can reliably evaluate nucleobase analogues in terms of their structural behavior and exciton transfer properties.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)