Competitive ligands are able to interfere in a concentration-dependent manner, although much higher concentrations are required in the ‘forced proximity’ situation. Both delay the attainment of binding equilibrium (resulting in steep saturation curves) and also increase the target residence time. The present differential equation-based simulations explore the way both situations affect ligand binding. However, rebinding will also take place when the diffusion of freshly dissociated ligands is merely slowed down.

This ‘forced proximity’ favours its binding and rebinding (once dissociated) to that site. This is because binding of one pharmacophore forces the second tethered one to stay close to its corresponding site. avidity) and target residence time when both pharmacophores can bind simultaneously to their target sites. Such ligands exhibit markedly increased affinity (i.e. Although the naturally occurring antibodies are predominant, it is becoming more common to combine different antibody fragments or even low molecular weight compounds to generate heterobivalent ligands.

Bivalent ligands are increasingly important therapeutic agents.

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