Synthetic Approaches to Study Multivalent Carbohydrate—Lectin Interactions

The specific recognition of carbohydrate structures in biological systems (Box 5) by carbohydrate-binding proteins (lectins) is the basis of numerous intraand intercellular events ranging from the control of protein folding to cell–cell communication during development, inflammation, and cancer metastasis [1]. Investigation of carbohydrate–lectin interactions can be approached from two directions. One is characterization of the protein part by molecular biology and structure determination (X-ray crystallography, NMR spectroscopy) [2]. In the other approach, which relies on synthetic organic chemistry, the specificity and affinity of modified or artificial lectin ligands and their effect on lectin function is studied [3, 4]. Highaffinity lectin ligands are, furthermore, of considerable medicinal interest in the diagnosis and inhibition of carbohydrate-mediated processes such as inflammation or microbial adhesion [5]. The generation of high-affinity lectin ligands, however, is not trivial because most saccharide ligands bind to their protein receptors only weakly with dissociation constants typically in the millito micromolar range. Because many lectins have several binding sites or occur in oligomeric or clustered form on cell membranes, the creation of multivalent carbohydrate derivatives is a promising means of producing high-affinity ligands [3, 6–8].