Polyvalent Glycan-Quantum Dots as Multifunctional Structural Probes for Multivalent Lectin-Carbohydrate Interactions

Carbohydrate-binding proteins, also known as lectins, play a key role in pathogen infection, cell-cell communication, and immune regulation. They recognize pathogen surface–specific glycan patterns via their multiple glycan-binding domains and exploit multivalency to enhance binding affinity and impose specificity. As a result, designing glycoconjugates to specifically block pathogen binding to target lectins is an attractive strategy for preventing infection. However, the crystal structures of some key lectins remain unavailable, making it difficult to design glycoconjugates that can match the target lectin binding site arrangement in order to differentiate between lectins with overlapping glycan specificity. This differentiation would be necessary in order to provide potent and highly specific targeting. A good example of this is observed for a pair of closely related and functionally different tetrameric lectins: DC-SIGN and DC-SIGNR. These lectins play a key role in HIV and Ebola virus infection, yet their detailed structural information remains unknown. Herein we show that fluorescent quantum dots displaying a dense layer of polyvalent glycans are powerful multifunctional probes for multivalent lectin-glycan interactions. They can not only provide important structural information on a lectin’s binding site orientation and binding mode, but they also act as potent inhibitors against lectin-mediated virus infection.