Carbohydrate-protein interactions mediate a wide range of important normal and pathological biological processes. These processes include cellular communication and differentiation, viral and bacterial infection, and the immune response. The ability to influence and interfere with these interactions offers a great opportunity in the study of the biochemistry of these processes with the ultimate goal of preventing and providing cure for certain diseases. However monovalent carbohydrates only show weak affinity to protein targets. This limitation is overcome by the design and implementation of multivalent biomaterials that present multiple copies of the sugar to the protein. The resulting interaction between multivalently presented sugar residues and proteins is generally stronger than the sum of each individual interaction. This phenomenon, referred to as the cluster-glycoside effect, is how nature compensates for the relatively weak interaction between monovalent carbohydrates and proteins. This study reports the use of gold nanoparticles (AuNPs) as effective platforms for the multivalent presentation of carbohydrates. AuNPs of approximately 13-nm diameter encapsulated with galactose, lactose, and Pk antigen were prepared from thiolated carbohydrates and citrate-stabilized AuNPs. These carbohydrate-encapsulated gold nanoparticles (c-AuNPs) were then used as multivalent inhibitors of adsorption of a set of lectins (RCA120, Jacalin, cholera toxin, and PA-I) on carbohydrate-coated gold chips in a Surface Plasmon Resonance (SPR) Inhibition assay. The assay provided inhibition constants (Ki), and other multivalent parameters such as Relative Inhibition Avidity (RIA) and Relative Inhibition Potency (RIP) for the c-AuNPs. The nanoparticles were found to have subnomolar affinities to the lectins and toxin and compare well with reported multivalent inhibitors. The affinities and multivalent enhancement exhibited by the sugars presented on the AuNPs varied from relatively small to large and depended on both the nature of the carbohydrate used and the characteristics of the protein assayed. This study demonstrated that the AuNPs are efficient multivalent platforms for exploring the cluster glycoside effect and that the c-AuNPs are promising inhibitors of the bacterial infection-associated proteins cholera toxin and PA-I, and the ricin surrogate RCA120.

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