Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes |
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| Authors: | Dr. Yasuaki Kimura Nae Saito Kayo Hanada Jiaan Liu Prof. Takayoshi Okabe Dr. Shigehiro A. Kawashima Dr. Kenzo Yamatsugu Prof. Motomu Kanai |
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| Affiliation: | 1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan;2. Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Tokyo, Japan;3. Drug Discovery Initiative, The University of Tokyo, Tokyo, Japan |
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| Abstract: | Post‐translational modification of histone tails plays critical roles in gene regulation. Thus, molecules recognizing histone tails and controlling their epigenetic modification are desirable as biochemical tools to elucidate regulatory mechanisms. There are, however, only a few synthetic ligands that bind to histone tails with substantial affinity. We report CA2 and CA3, which exhibited sub‐micromolar affinity to histone tails (especially tails with a trimethylated lysine). Multivalent display of trisulfonated calix[4]arene was important for strong binding. CA2 was applicable not only to synthetic tail peptides but also to endogenous histone proteins, and was successfully used to pull‐down endogenous histones from nuclear extract. These findings indicate the utility of these supramolecular ligands as biochemical tools for studying chromatin regulator protein and as a targeting motif in ligand‐directed catalysis to control epigenetic modifications. |
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| Keywords: | gene expression histone tail ligand design post-translational modifications pull-down trimethyllysine |
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