Multivalent Glycocluster Design through Directed Evolution

摘要

A vast number of biological processes are mediated by multivalent ligand-receptor interactions, including cell adhesion, host invasion by pathogens, pathogen neutralization by host, and numerous cell regulatory signaling pathways. Multivalency is especially important for carbohydrate-receptor interactions: whereas individual glycans may bind with low affinity to a single binding site, the clustering of glycans creates a high-avidity interaction with clustered binding sites. This "carbohydrate cluster effect" has been demonstrated experimentally with synthetic multivalent carbohydrate ligands which bind well to protein targets. These ligands have included oligo- and polyvalent clusters of glycans on diverse scaffolds, including small molecules, dendrimers, polymers, and even viral capsids.