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Updated: Aug 28, 2025

Highly Efficient Ligation of Small RNA Molecules for MicroRNA Quantitation by High-Throughput Sequencing
Published on: November 18, 2014
Fragment Ligands of the m6A-RNA Reader YTHDF2
Francesco Nai1, Raed Nachawati1, František Zálešák1
1Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Abstract:
We report 17 small-molecule ligands that compete with N6-methyladenosine (m6A) for binding to the m6A-reader domain of YTHDF2 (YT521-B homology domain family 2). We determined their binding mode at high resolution by X-ray crystallography and quantified their affinity by a fluorescence-based binding assay. 6-Cyclopropyluracil and a pyrazolopyrimidine derivative have favorable ligand efficiencies of 0.47 and 0.38 kcal mol-1 per non-hydrogen atom, respectively. They represent useful starting points for hit optimization.
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