Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes.
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.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.|Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Yasuaki
Y
Kimura
Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Nae
N
Saito
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Kayo
K
Hanada
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Jiaan
J
Liu
Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Takayoshi
T
Okabe
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. skawashima@mol.f.u-tokyo.ac.jp.|Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. skawashima@mol.f.u-tokyo.ac.jp.
Shigehiro A
SA
Kawashima
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. yamatsugu@mol.f.u-tokyo.ac.jp.|Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. yamatsugu@mol.f.u-tokyo.ac.jp.
Kenzo
K
Yamatsugu
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. kanai@mol.f.u-tokyo.ac.jp.|Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. kanai@mol.f.u-tokyo.ac.jp.
Motomu
M
Kanai
D000595:Amino Acid Sequence; D001710:Biotin / Q000737:chemistry; D047250:Calixarenes / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D020349:Surface Plasmon Resonance
D006657:Histones; D008024:Ligands; D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes; D001710:Biotin
gene expression; histone tail; ligand design; post-translational modifications; pull-down; trimethyllysine