Antibodies with infinite affinity

Here we report an approach to the design and production of antibody/ligand pairs, to achieve functional affinity far greater than avidin/biotin. Using fundamental chemical principles, we have developed antibody/ligand pairs t hat retain the binding specificity of the antibody, but do not dissociate. Choosing a structurally characterized antibody/ligand pair as an example, w e engineered complementary reactive groups in the antibody binding pocket a nd the ligand, so that they would be in close proximity in the antibody/lig and complex. Cross-reactions with other molecules in the medium are averted because of the low reactivity of these groups; however, in the antibody/li gand complex the effective local concentrations of the complementary reacti ve groups are very large, allowing a covalent reaction to link the two toge ther. By eliminating the dissociation of the ligand from the antibody, we h ave made the affinity functionally infinite. This chemical manipulation of affinity is applicable to other biological binding pairs.