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bioRxiv · 10.1101/466284

A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) YEATS domain

Heidenreich, D.·Moustakim, M.·Schmidt, J.·Merk, D.·Brennan, P. E.·Fedorov, O.·Chaikuad, A.·Knapp, S.
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Abstract

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 sub-micromolar binder, providing first starting points for the development of chemical probes for this reader domain family.

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Heidenreich, D., Moustakim, M., Schmidt, J., Merk, D., Brennan, P. E., Fedorov, O., Chaikuad, A., Knapp, S.. 2018-11-08. A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) YEATS domain. https://doi.org/10.1101/466284

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