Multivalency

Multivalent interactions, in which multiple ligands on one entity bind simultaneously to multiple receptors on another, are ubiquitous in nature. The use of multivalent agents will undoubtedly transform existing methods that target important disease processes including infection, immune system regulation, cancer, and neurological pathways. The employment of multivalent systems as tools to study biological recognition processes and for therapeutic development is unique in that multivalency can address many problems that traditional monovalent materials cannot. Here, mechanisms of multivalent ligand binding as well as the thermodynamic principals of multivalency including the chelation effect, cooperativity, avidity enhancement, avidity entropy, and effective molarity are described. Experimental techniques that are currently used to study multivalent interactions are briefly compared. Key examples of systems that have been used to study multivalent interactions are highlighted and range from small molecules and carbohydrate-functionalized macromolecules to antibodies and polymers. Overall, this chapter focuses on strategic approaches and enabling technologies that are advancing the development of multivalent therapeutic agents.