Fragment Ligands of the m⁶A-RNA Reader YTHDF2.

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.

SUBMITTER: Nai F 

PROVIDER: S-EPMC9466600 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature