Molecular recognition plays an important role in living systems.1,2,Representative molecular recognitions in living organisms are saccharide-protein, protein-protein, and antigen-antibody interactions. These biological interactions are possible through molecular interactions, including hydrophobic and electrostatic interactions and hydrogen bonding.3 Though each individual molecular interaction is weak, the accumulation of several interactions makes the overall effect strong, which results in the ability to control complex biological systems. To accumulate these weak interactions, the biological ligands are usually able to bind in a multivalent way. In particular, it is well-known that saccharide interactions are greatly affected by the multivalent effect.4 Though saccharide- protein interactions with monomeric sugars are weak, with a dissociation constant (Kd) in the order of millimolar, interactions that involve multivalent binding are much stronger with Kd values on the order of micromolar.5,6 For glycolipids, Kd values for the saccharide-protein interactions become smaller with increasing glycolipid ratios, which suggests the contribution of a multivalent effect.7 Dense microdomains of lipids or "rafts" mediates multivalent saccharide-protein interactions.8 These lipid raft structures are important in various saccharide-mediated cellular interactions.4 The dendritic saccharide structure of glycoproteins enables a strong interaction with lectins via multivalency. Polysaccharides, such as glycan and glycosaminoglycans, also present saccharides in a multivalent way. The natural saccharides have multivalent structures that enable multivalent binding and, hence, strong interactions.9 Saccharide-protein interactions are found throughout living systems. Cell surfaces are covered by various saccharides. Saccharide interactions are involved in various biological events, including cell-cell adhesion, cell recognition, and cell differentiation. 4 In addition, pathogens, such as viruses and toxin proteins, infect cells though saccharide-protein interactions. Notable examples are the interactions between influenza viruses and sialyl oligosaccharides, the HIV and HIV receptors, cholera toxins and glycolipids, and Shiga toxins and glycolipids. Saccharide interactions are also involved in the folding, transportation, and quality control of proteins (Table 1). Saccharide recognition proteins, known as lectins, usually have multimeric structures. The lectins from both plant and mammalian cells have been studied.10-12 The plant lectin concanavalin A (ConA) has been studied thoroughly since the 1970s. 10 The detailed ConA structure was first analyzed by Xray crystallography, 13-19 and this triggered the intense investigation of saccharide-protein interactions. 20-24 Studies on ConA have provided extensive information on saccharide- protein interactions. ConA has a homo tetramer structure with four sugar binding sites. Previous studies have revealed that the density of mannose (Man) residues and cross-linking via multiple binding play important roles in the amplification of saccharide-protein interactions.
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