Fragment ligands of the m6A-RNA reader YTHDF2
| Title | Fragment ligands of the m6A-RNA reader YTHDF2 |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Nai F., Nachawati R., Zálešák F., Wang X., Li Y., Caflisch A. |
| Journal | ACS Medicinal Chemistry Letters |
| Volume | 13 |
| Start Page | 1500 |
| Issue | 9 |
| Pagination | 1500-1509 |
| Date Published | 2022/08/17 |
| Type of Article | Research Article |
| 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.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. |
| DOI | 10.1021/acsmedchemlett.2c00303 |
| pubindex | 0283 |
| Alternate Journal | ACS Med. Chem. Lett. |
