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Issue 1, 2012
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Structure–activity relationships of methyl-lysine reader antagonists

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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.

Graphical abstract: Structure–activity relationships of methyl-lysine reader antagonists

  • This article is part of the themed collection: Epigenetics
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The article was received on 29 Jul 2011, accepted on 13 Sep 2011 and first published on 10 Oct 2011

Article type: Concise Article
DOI: 10.1039/C1MD00195G
Med. Chem. Commun., 2012,3, 45-51

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    Structure–activity relationships of methyl-lysine reader antagonists

    J. M. Herold, L. I. James, V. K. Korboukh, C. Gao, K. E. Coil, D. J. Bua, J. L. Norris, D. B. Kireev, P. J. Brown, J. Jin, W. P. Janzen, O. Gozani and S. V. Frye, Med. Chem. Commun., 2012, 3, 45
    DOI: 10.1039/C1MD00195G

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