Exploring avidity: understanding the potential gains in functional affinity and target residence time of bivalent and heterobivalent ligands.

ABSTRACT: Bivalent ligands are increasingly important therapeutic agents. 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. Such ligands exhibit markedly increased affinity (i.e. avidity) and target residence time when both pharmacophores can bind simultaneously to their target sites. This is because binding of one pharmacophore forces the second tethered one to stay close to its corresponding site. This 'forced proximity' favours its binding and rebinding (once dissociated) to that site. However, rebinding will also take place when the diffusion of freshly dissociated ligands is merely slowed down. The present differential equation-based simulation

SUBMITTER: Vauquelin G 

PROVIDER: S-EPMC3623049 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature