Multivalency as an action principle in multimodal lectin recognition and glycosidase inhibition: a paradigm shift driven by carbon-based glyconanomaterials

Abstract

The last decade has witnessed a series of discoveries that question the traditional paradigm of multivalency as a “safe” strategy to enhance the binding affinity of a lectin receptor to its cognate carbohydrate ligand. Upon following the initial reports on the supplementary effects operating in the presence of a third carbohydrate species (heteromultivalent effect), the observation of functional promiscuity of glyco(mimetic)ligands elicited by (hetero)multivalency, spreading from lectins to glycoprocessing enzymes (inhibitory multivalent effect), has raised concerns about the potential consequences of glyconanomaterials binding to non-cognate proteins and creating messiness or noise in the processes they participate in. Carbon-based glycomaterials, specifically glyconanodiamonds and glycofullerenes, have been instrumental in increasing our awareness of the frequency of these lectin–enzyme crosstalk behaviours elicited by multivalency, driving a reformulation of the rules and concepts in glycoscience towards a “generalized multivalency” scenario.