Molecular recognition properties of acyclic cucurbiturils toward amino acids, peptides, and a protein

Abstract

ABSTRACTThe binding of 1 and 2 toward 19 amino acid amides by 1H NMR and ITC is reported. Hosts 1 and 2 bind to aromatic or hydrophobic residues by cavity inclusion leaving the cationic residues at the C=O portals. Ka values range from 102 to >106 M−1 with H-Phe-NH2, H-Trp-NH2, and H-Tyr-NH2 displaying sub-micromolar Kd values. Hosts 1 and 2 bind tightly to dicationic H-Lys-NH2 and H-Arg-NH2 which are poor guests for CB[7]. Comparison of the affinity of 1 and 2 toward the amino acid amide, N-acetyl-amino-acid amide, and amino acid forms of Phe revealed that the removal of the NH3+ to O=C and SO3− electrostatic interactions costs 3.8 kcal/mol whereas the introduction of an unfavourable CO2− to O=C and SO3− electrostatic interactions costs 2.1 kcal/mol. Hosts 1 and 2 bind to insulin with low micromolar affinity. Acyclic CB[n] display high affinity toward a wider range of N-terminal amino acids residues than CB[n] which suggests a broad range of applications.