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Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL)

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journal contribution
posted on 08.11.2018, 00:00 by David Heidenreich, Moses Moustakim, Jurema Schmidt, Daniel Merk, Paul E. Brennan, Oleg Fedorov, Apirat Chaikuad, Stefan Knapp
Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.