Fragment Ligands of the m 6 A-RNA Reader YTHDF2.
Nai, F., Nachawati, R., Zalesak, F., Wang, X., Li, Y., Caflisch, A.(2022) ACS Med Chem Lett 13: 1500-1509
- PubMed: 36110386 
- DOI: https://doi.org/10.1021/acsmedchemlett.2c00303
- Primary Citation of Related Structures:  
7R5F, 7R5L, 7R5W, 7YWB, 7YX6, 7YXE, 7Z26, 7Z4U, 7Z54, 7Z5M, 7Z7B, 7Z7F, 7Z8P, 7Z8W, 7Z8X, 7Z92, 7Z93, 7ZG4 - PubMed Abstract: 
We report 17 small-molecule ligands that compete with N6 -methyladenosine (m 6 A) for binding to the m 6 A-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.
Organizational Affiliation: 
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.