19F‐NMR‐based fragment screening for 14 different biologically active RNAs and 10 DNA and protein counter‐screens
| Autor: | Tatjana Schamber, Kamal Azzaoui, Nusrat S. Qureshi, Boris Fürtig, Oliver Binas, Jason N Martins, Marcel J. J. Blommers, Daniel Hymon, Alix Tröster, Jasleen Kaur Bains, Christian Richter, Harald Schwalbe, Elke Stirnal, Andreas Oxenfarth, Julia Wirmer-Bartoschek, Hannes Berg, Anna Wacker, Robbin Schnieders, Tom Landgraf, Vanessa de Jesus, Santosh Lakshmi Gande, Sridhar Sreeramulu, Thomas Biedenbänder, Maria Alexandra Wirtz Martin, Albrecht Eduard Völklein, Anna Niesteruk |
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| Rok vydání: | 2020 |
| Předmět: |
fragment-based screening 19F NMR RNA DNA proteins
Riboswitch Full Paper 010405 organic chemistry Organic Chemistry Druggability RNA 010402 general chemistry 01 natural sciences Biochemistry Protein tertiary structure 3. Good health 0104 chemical sciences chemistry.chemical_compound Terminator (genetics) chemistry Acridine Molecular Medicine Molecular Biology DNA Binding selectivity |
| Zdroj: | ChemBioChem Chembiochem |
| ISSN: | 1439-4227 |
| DOI: | 10.1002/cbic.202000476 |
| Popis: | We report here on the nuclear magnetic resonance (NMR) 19 F screening of 14 RNA targets with different secondary and tertiary structure to systematically assess druggability of RNAs. Our RNA targets include representative bacterial riboswitches that naturally bind with nanomolar affinity and high specificity to cellular metabolites of low molecular weight. Based on counter‐screens against five DNAs and five proteins, we can show that RNA can be specifically targeted. To demonstrate the quality of the initial fragment library that has been designed for easy follow‐up chemistry, we further show how to increase binding affinity from an initial fragment hit by chemistry that links the identified fragment to the intercalator acridine. Thus, we achieve low micromolar binding affinity without losing binding specificity between two different terminator structures. |
| Databáze: | OpenAIRE |
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