Publication

Article Metrics

Citations


Online attention

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

DOI: 10.1021/acs.jmedchem.8b01457 DOI Help

Authors: David Heidenreich (Goethe-University Frankfurt; Structural Genomics Consortium, Goethe-University Frankfurt) , Moses Moustakim (Target Discovery Institute and Structural Genomics Consortium, University of Oxford) , Jurema Schmidt (Goethe-University Frankfurt) , Daniel Merk (Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt) , Paul E. Brennan (Target Discovery Institute and Structural Genomics Consortium, University of Oxford) , Oleg Fedorov (Structural Genomics Consortium, Goethe-University Frankfurt) , Apirat Chaikuad (Goethe-University Frankfurt; Structural Genomics Consortium, Goethe-University Frankfurt) , Stefan Knapp (Goethe-University Frankfurt; Structural Genomics Consortium, Goethe-University Frankfurt)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Medicinal Chemistry

State: Published (Approved)
Published: November 2018
Diamond Proposal Number(s): 105433

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.

Journal Keywords: Amides; Peptides and proteins; Ligands; Monomers; Aromatic compounds

Diamond Keywords: Leukaemia

Subject Areas: Chemistry, Biology and Bio-materials, Medicine


Instruments: I04-Macromolecular Crystallography

Other Facilities: BESSY II; SLS

Added On: 12/11/2018 09:33

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Structural biology Biophysics Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)