Targeting histone lysine demethylases by truncating the histone 3 tail to obtain selective substrate-based inhibitors

TY - JOUR

T1 - Targeting histone lysine demethylases by truncating the histone 3 tail to obtain selective substrate-based inhibitors

AU - Lohse, Brian

AU - Nielsen, Anders L

AU - Kristensen, Jan B L

AU - Helgstrand, Charlotte

AU - Cloos, Paul Andreas Compare

AU - Olsen, Lars

AU - Gajhede, Michael

AU - Clausen, Rasmus Prætorius

AU - Kristensen, Jesper Langgaard

N1 - Keywords: cancer, enzymes, epigenetics, inhibitors, medicinal chemistry

PY - 2011/9/19

Y1 - 2011/9/19

N2 - 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.

AB - 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.

KW - Former Faculty of Pharmaceutical Sciences

KW - BRIC

U2 - 10.1002/anie.201101849

DO - 10.1002/anie.201101849

M3 - Journal article

C2 - 21919140

SN - 1433-7851

VL - 50

SP - 9100

EP - 9103

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 39

ER -