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

A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL). Heidenreich, D., Moustakim, M., Schmidt, J., Merk, D., Brennan, P., E., Fedorov, O., Chaikuad, A., & Knapp, S. Journal of Medicinal Chemistry, 61(23):acs.jmedchem.8b01457, American Chemical Society, 12, 2018.

Paper

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

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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.

@article{
 title = {A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL)},
 type = {article},
 year = {2018},
 pages = {acs.jmedchem.8b01457},
 volume = {61},
 websites = {http://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01457},
 month = {12},
 publisher = {American Chemical Society},
 day = {13},
 id = {1e5625da-7746-30b2-a701-9947d34c6ff1},
 created = {2019-01-07T10:30:37.327Z},
 accessed = {2019-01-07},
 file_attached = {true},
 profile_id = {64f7fb50-d000-335d-a02d-06c5f340a97a},
 last_modified = {2019-01-21T11:55:59.679Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 citation_key = {Heidenreich2018},
 private_publication = {false},
 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.},
 bibtype = {article},
 author = {Heidenreich, David and Moustakim, Moses and Schmidt, Jurema and Merk, Daniel and Brennan, Paul E. and Fedorov, Oleg and Chaikuad, Apirat and Knapp, Stefan},
 doi = {10.1021/acs.jmedchem.8b01457},
 journal = {Journal of Medicinal Chemistry},
 number = {23}
}

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