TY  - JOUR
A1  - Binas, Oliver
A1  - Jesus, Vanessa de
A1  - Landgraf, Tom
A1  - Völklein, Albrecht Eduard
A1  - Martins, Jason
A1  - Hymon, Daniel
A1  - Bains, Jasleen Kaur
A1  - Berg, Hannes
A1  - Biedenbänder, Thomas
A1  - Fürtig, Boris
A1  - Gande, Santosh Lakshmi
A1  - Niesteruk, Anna
A1  - Oxenfarth, Andreas
A1  - Qureshi, Nusrat
A1  - Schamber, Tatjana
A1  - Schnieders, Robbin
A1  - Tröster, Alix Friederike
A1  - Wacker, Anna
A1  - Wirmer-Bartoschek, Julia
A1  - Wirtz Martin, Maria Alexandra
A1  - Stirnal, Elke
A1  - Azzaoui, Kamal
A1  - Richter, Christian
A1  - Sreeramulu, Sridhar
A1  - Blommers, Marcel Jules José
A1  - Schwalbe, Harald
T1  - 19F NMR-based fragment screening for 14 different biologically active RNAs and 10 DNA and protein counter-screens
T2  - ChemBioChem
N2  - We report here the nuclear magnetic resonance 19F screening of 14 RNA targets with different secondary and tertiary structure to systematically assess the 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.
KW  - DNA-PAINT
KW  - 19F
KW  - FBS
KW  - fluorine
KW  - fragment-based screening
KW  - proteins
KW  - RNA
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63851
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-638516
SN  - 1439-7633
N1  - The work was supported by funds from DFG in collaborative research center 902: “Molecular principles of RNA-based regulation”, by EU-funded project iNEXT-discovery. Work at BMRZ is supported by the state of Hesse. V.D.J. was supported by Boehringer Ingelheim Fonds. R.S. was supported by Fonds der Chemischen Industrie. Open access funding enabled and organized by Projekt DEAL.
VL  - 22
IS  - 2
SP  - 423
EP  - 433
PB  - Wiley-VCH
CY  - Weinheim
ER  -