Cation-π Interactions Involving Aromatic Amino Acids

The cation-π interaction is a general, strong, noncovalent binding force that is used throughout nature. The side chains of the aromatic amino acids [phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp)] provide a surface of negative electrostatic potential than can bind to a wide range of cations through a predominantly electrostatic interaction. In this brief overview, the fundamental nature of the cation-π interaction will be described, relying on fundamental, gas phase studies of the effect. Then, several examples of cation-π interactions involving aromatic amino acids will be described. These include contributions to protein secondary structure, in which Phe/Tyr/Trp···lysine (Lys)/arginine interactions are common. We will also describe several examples of protein-ligand interactions that make use of cation-π interactions. We will place special emphasis on the binding of quaternary ammonium ions, such as trimethylated Lys and the neurotransmitter acetylcholine.