Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes

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.

Protein Recognition by Functionalized Sulfonatocalix[4]arenes

“…Here, we investigated the impact of mono‐functionalization on protein–calix[4]arene binding. A single sulfonate on the upper rim was substituted with a bromo (Br.sclx) or phenyl (Ph.sclx) group (Scheme ) . The interactions of these ligands with cytochrome c were studied by X‐ray crystallography, NMR spectroscopy and isothermal titration calorimetry.…”

Synthetic Receptors for the Recognition and Discrimination of Post‐Translationally Methylated Lysines

“…Kimura et al. employed trisulfonated calixarenes for the design of multivalent ligands . The conjugation of 6 through short amide linkers delivered mono‐, di‐ and trivalent ( 13 ) receptors (Scheme ).…”

NMR Spectroscopy of supramolecular chemistry on protein surfaces

“…In this review, we focus mostly on ligands that recognize either positively or negatively charged patches on a protein surface, discussing the molecules shown in Figure 1 in greater detail. Ligands designed to recognize positively charged regions, containing lysine (Lys) and arginine (Arg) residues, on a protein include supramolecular tweezers [5][6][7][8][9][10][11][12][13][14][15][16][17][18] as well as sulfonatoand phosphonato-calixarenes [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. These ligands contain negatively charged functionalities interacting with the positively charged head groups of Lys and Arg, often combined with a moiety that cradles the hydrophobic portion of the aliphatic side chain.…”