Protein Heterodimerization through Ligand-Bridged Multivalent Pre-organization: Enhancing Ligand Binding toward Both Protein Targets.

The design of high-affinity protein ligands is of fundamental interest in biomedical research. Often, one multivalent ligand and one multivalent protein are involved in such studies. Another area of ligand design concerns the so-called chemical inducer of dimerization, where one bifunctional ligand can bind two different proteins simultaneously and affect biological pathways. In such cases, three entities are to be considered in the binding event--one bifunctional ligand and two separate and different target protein molecules. However, these interactions generally involve only a single binding site on each target protein.