Structure-based design of ligands of the m6A-RNA reader YTHDC1
نویسندگان
چکیده
We report new chemical entities for disrupting the interactions between N6-methyladenosine (m6A) mRNA and its reader YT521-B homology-domain-containing protein 1 (YTHDC1). High-throughput docking was used to screen commercially available databases of small molecules, molecular dynamics simulations were employed evaluate binding stability m6A nucleotide analogues. The poses 25 fragment-like binders confirmed by X-ray crystallography. structure-based merging two weak fragments resulted in a ligand-efficient binder (compound 6) which shows an equilibrium dissociation constant 1.7 μM isothermal titration calorimetry measurements ligand efficiency value 0.66 kcal mol−1 nHA−1.
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ژورنال
عنوان ژورنال: European journal of medicinal chemistry reports
سال: 2022
ISSN: ['2772-4174']
DOI: https://doi.org/10.1016/j.ejmcr.2022.100057