“…Supramolecular caging compounds, including synthetic receptors, chelating macrocycles, and calixarenes, have been shown to coordinate unmodified and posttranslationally modified amino acids and, therefore, can be applied for studying epigenetic mechanisms (25-31, 45, 46). We have demonstrated previously that calixarenes inhibit binding of the second PHD finger of CHD4 to histone H3 trimethylated at Lys-9, although this binding does not involve the formation of a methyllysine-recognizing aromatic cage (32,33). Here we characterize the mechanisms by which calixarenes interact with the canonical PHDH3K4me3 complexes and examine the effect of the aromatic cage architecture on these interactions.…”