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Targeting Histone Lysine Demethylases by Truncating the Histone 3 Tail to Obtain Selective Substrate‐Based Inhibitors
Author(s) -
Lohse Brian,
Nielsen Anders L.,
Kristensen Jan B. L.,
Helgstrand Charlotte,
Cloos Paul A. C.,
Olsen Lars,
Gajhede Michael,
Clausen Rasmus P.,
Kristensen Jesper L.
Publication year - 2011
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201101849
Subject(s) - lysine , histone , substrate (aquarium) , amino acid , epigenetics , chemistry , peptide , biochemistry , substrate specificity , biology , enzyme , gene , ecology
How low can you go? The natural substrate for the epigenetic regulators PHF8, JmjD2A, and JmjD2C (lysine demethylases), a peptide consisting of 39 amino acid residues, can be truncated to 14, 8, and 4 amino acids, respectively, while maintaining catalytic activity (see picture). Inhibitors were prepared by attaching small molecules to the truncated substrates. Selective inhibition of JmjD2C over JmjD2A and PHF8 was possible.