Crafting precise multivalent architectures

Multivalency is a powerful strategy in molecular pharmacology that can establish high-affinity binding between multiple conjoined ligands and corresponding biomolecular targets. Recent advances in chemical synthesis techniques have enabled the development of elaborate two-dimensional multivalent displays appended on natural or synthetic molecular scaffolds. These constructs have the potential to address disease targets that otherwise may be classified as ‘undruggable.’ In this review, synthetic strategies to generate and functionalize different classes of scaffolds are evaluated. Particular focus is placed on crafting multivalent assemblies that occupy a ‘middle space’ of molecular weight, along with a consideration of their potential applications in pharmacology.