Cyclodextrin-based multivalent glycodisplays: covalent and supramolecular conjugates to assess carbohydrateprotein interactionsPart of the multivalent scaffolds in glycosciences themed issue

• Main Authors: Martnez, lvaro, Ortiz Mellet, Carmen, Garca Fernndez, Jos M
• Format: Article
• Language: English
• ISSN: 0306-0012; 1460-4744
• DOI: 10.1039/c2cs35424a

Covalent attachment of biorecognizable sugar ligands in several copies at precise positions of cyclomaltooligosaccharide (cyclodextrin, CD) macrocycles has proven to be an extremely flexible strategy to build multivalent conjugates. The commercial availability of the native CDs in three different sizes, their axial symmetry and the possibility of position- and face-selective functionalization allow a strict control of the valency and spatial orientation of the recognition motifs (glycotopes) in low, medium, high and hyperbranched glycoclusters, including glycodendrimerCD hybrids. Click-type ligation chemistries, including copper( i )-catalyzed azidealkyne cycloaddition (CuAAC), thiolene coupling or thiourea-forming reactions, have been implemented to warrant full homogeneity of the adducts. The incorporation of different glycotopes to investigate multivalent interactions in heterogeneous environments has also been accomplished. Not surprisingly, multivalent CD conjugates have been, and continue to be, major actors in studies directed at deciphering the structural features ruling carbohydrate recognition events. Nanometric glycoassemblies endowed with the capability of adapting the inter-saccharide distances and orientations in the presence of a receptor partner or capable of mimicking the fluidity of biological membranes have been conceived by multitopic inclusion complex formation, rotaxanation or self-assembling. Applications in the fields of sensors, site-specific drug and gene delivery or protein stabilization attest for the maturity of the field. Multivalent cyclodextrin conjugates, from covalent to self-assembled constructs, can be tailored to investigate and control carbohydrate binding to biological receptors.