Supramolecular Approaches to the Study of Glycobiology

AbstractEvery mammalian cell is surrounded by carbohydrate conjugates forming a nano‐dimensioned layer termed “glycocalyx,” a name derived from the Greek words “glykos” for “sugar” and “kalyx” for “coat.” A cell's glycocalyx might expand to a width of 100 nanometers and more, with glycoconjugate structures of vast complexity projecting from the cell surface into an aqueous environment. Lectins are able to probe this environment by selectively binding to certain carbohydrate epitopes, and the concert of the corresponding recognition events is essential in cell‐cell communication. Because of the extremely high constitutional complexity of the glycocalyx and the sensitivity of its supramolecular characteristics to, for example, the presence of ions and many other entities, it has been difficult to unravel the secrets of glycobiology, in particular how carbohydrate‐carbohydrate and carbohydrate‐protein interactions are governed and fine‐tuned. Nevertheless, a number of important aspects of carbohydrate recognition have been identified, such as critical factors for carbohydrate complexation in water, the importance of multivalency in carbohydrate‐protein interactions, and the potential of the biosynthetic machinery that makes and delivers complex glycoconjugates. In this chapter, current knowledge about how Nature achieves carbohydrate recognition is summarized. On this basis, different approaches are presented, most of which are firmly rooted in supramolecular chemistry, that aim at elucidating the molecular basis of glycobiology. These approaches comprise the development of low‐molecular weight mimics for lectins, so‐called synthetic carbohydrate receptors, on the one hand and of multivalent and highly complex glycomimetics on the other.