The interaction between methyl-lysine binding proteins and methylated histones plays a crucial role in the regulation of gene expression. Herein we describe the development of structure-activity relationships (SAR) surrounding UNC669, the first reported small molecule ligand for a methyl-lysine binding domain, using multiple assay formats. These studies revealed the key features required for successful inhibition of the L3MBTL1-methylated histone protein-protein interaction, while the selectivity of designed compounds against a panel of related methyl-lysine readers was also evaluated. Additionally, an optimized compound was demonstrated to successfully inhibit the recognition of H4K20me1 by L3MBTL1 in the context of an affinity pull down assay. © The Royal Society of Chemistry.
CITATION STYLE
Herold, J. M., James, L. I., Korboukh, V. K., Gao, C., Coil, K. E., Bua, D. J., … Frye, S. V. (2012). Structure-activity relationships of methyl-lysine reader antagonists. In MedChemComm (Vol. 3, pp. 45–51). Royal Society of Chemistry. https://doi.org/10.1039/c1md00195g
Mendeley helps you to discover research relevant for your work.