Probing Secondary Carbohydrate-Protein Interactions with Highly Dense Cyclodextrin-Centered Heteroglycoclusters:The Heterocluster Effect

摘要

Multivalent interactions between carbohydrate ligands and carbohydrate-binding proteins (lectins) play a crucial role in a large variety of basic cellular recognition processes,which include development,differentiation,morphogenesis,fertilization,the immune response,implantation,cell migration,and cancer metastasis.Synthetic multivalent glycoconjugates with well-defined structures have then considerable potential for the elucidation of the mechanisms involved and as possible inhibitors or effectors.A variety of multivalent oligosaccharide and glycoconjugate mimetics have been synthesized.Typically,these systems incorporate several copies of a single type of sugar on an appropriate scaffold (molecular,dendritic,polymeric).However,in nature,a number of different sugar ligands may be essential for a recognition process.Variations in the expression levels of the sugar epitopes in a heterogeneous environment may also affect the individual binding affinities with a given protein receptor by virtue of secondary interactions.However,only a few procedures that allow the construction of well-defined glycoclusters from different sugar moieties have still been described.Trivalent mixed-type oligosaccharide mimetics have been prepared by using orthogonally protected scaffolds.The generation and deconvolution of dynamic combinatorial libraries of di- and trivalent heteroglycoclusters has also been reported.