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 -