Avidity and positive allosteric modulation/cooperativity act hand in hand to increase the residence time of bivalent receptor ligands. doi: 10.1111/fcp.12052

Bivalent ligands bear two target-binding pharmacophores. Their simultaneous binding increases their affinity (avidity) and residence time. They become "bitopic" when the pharmacophores exert allosteric modulation of each other's affinity and/or activity.
Present simulations reveal that positive cooperativity exacerbates these phenomena whereas negative cooperativity curtails them, irrespective of whether the association- or dissociation rate of the individual pharmacophores is affected. Positive cooperativity delays the attainment of equilibrium binding, yielding "hemi-equilibrium" conditions and only apparent affinity constants under usual experimental conditions. Monovalent ligands that bind to one of the target sites decrease the bitopic ligand's residence time concentration-wise; their potency depends on their association rate and thereon acting cooperativity rather than on affinity. This stems from the repetitive, very fast reformation of fully-bound ligand-target complexes by rebinding of freshly dissociated pharmacophores.
These studies deal with kinetic binding properties (of increasing interest in pharmacology) of bitopic ligands (a promising avenue in medicinal chemistry).