Selective molecular recognition of methylated lysines and arginines by cucurbit[6]uril and cucurbit[7]uril in aqueous solution

Abstract

Cucurbit[7]uril selectively binds the epigenetic mark N(ε),N(ε),N(ε)-trimethyllysine (LysMe(3), K(CB[7]) = (1.8 ± 0.6)× 10(6) dm(3) mol(-1)) by 3500-fold over lysine ((5.3 ± 0.7) × 10(2) dm(3) mol(-1)) in aqueous solution, using ion-dipole interactions and the hydrophobic effect, rather than cation-π interactions, as in the "aromatic cages" of p-SO(3)-calix[4]arene hosts or chromodomain proteins which recognize LysMe(3). The trend in K(CB[7]) of LysMe(3) > LysMe(2) > LysMe > Lys follows the recognition pattern of the chromodomain HP1 and other LysMe(n) protein readers. With CB[6], protonation of the guest carboxylate group is required for the formation of inclusion complexes with the LysMe(n) series. The CB[7] host also displays modest selectivity between the asymmetric ((2.0 ± 0.3) × 10(3) dm(3) mol(-1)) and symmetric ((6.1 ± 0.6) × 10(3) dm(3) mol(-1)) dimethylarginines, both of which bind more strongly than the parent arginine or monomethylarginine.