Carbohydrate–carbohydrate interaction: from hypothesis to confirmation

Carbohydrates play important roles in a wide range of biological processes. Since the first hypothesis about carbohydrate–carbohydrate interaction (CCI) was proposed by Hakomori et al., an increasing interest has been placed on CCI, using a variety of techniques. Based on all these studies, Lewis^x–Lewis^x interaction (a typical CCI) has been now confirmed to be specific, homotypic, and mediated by the presence of divalent cations such as Ca²⁺. In this review, a detailed overview of the process from hypothesis to confirmation of carbohydrate–carbohydrate interaction is summarized.