Carbohydrate−π Interactions: What Are They Worth?

Protein−carbohydrate interactions play an important role in many biologically important processes. The recognition is mediated by a number of noncovalent interactions, including an interaction between the α-face of the carbohydrate and the aromatic side chain of the protein. To elucidate this interaction, it has been studied in the context of a β-hairpin in aqueous solution, in which the interaction can be investigated in the absence of other cooperative noncovalent interactions. In this β-hairpin system, both the aromatic side chain and the carbohydrate were varied in an effort to gain greater insight into the driving force and magnitude of the carbohydrate−π interaction. The magnitude of the interaction was found to vary from −0.5 to −0.8 kcal/mol, depending on the nature of the aromatic ring and the carbohydrate. Replacement of the aromatic ring with an aliphatic group resulted in a decrease in interaction energy to −0.1 kcal/mol, providing evidence for the contribution of CH−π interactions to the driving force. These findings demonstrate the significance of carbohydrate−π interactions within biological systems and also their utility as a molecular recognition element in designed systems.