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J Med Chem. 2018 Dec 13;61(23):10929-10934. doi: 10.1021/acs.jmedchem.8b01457. Epub 2018 Nov 26.

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

Author information

1
Institute of Pharmaceutical Chemistry , Goethe-University Frankfurt , 60438 Frankfurt , Germany.
2
Structural Genomics Consortium, BMLS , Goethe-University Frankfurt , 60438 Frankfurt , Germany.
3
Target Discovery Institute and Structural Genomics Consortium , University of Oxford , Oxford OX3 7DQ , U.K.
4
Chemistry Research Laboratory, Department of Chemistry , University of Oxford , Oxford OX1 3TA , U.K.

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

PMID:
30407816
DOI:
10.1021/acs.jmedchem.8b01457
[Indexed for MEDLINE]

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