METHOD OF DESIGNING AN AGENT THAT MIMICS A FUNCTIONAL EPITOPE

摘要

The present invention provides a new use of antibodies (Abs) as the basis for pharmaceutical compound and vaccine development. Antibodies raised against the functional epitope of a biological molecule, when selected using the appropriate criteria, will provide three-dimensional (3D) information of the binding site on the biological molecule. These antibodies will, therefore, act as 3D surrogates of the biological molecules. The surrogate antibody will be used for the rational design of small-molecule agonists, antagonists and vaccine antigens based on the 3D structure of the surrogate antibody combining site that binds the biologically functional epitope. This approach will be applicable to a wide range of biological molecules including, but not limited to, nucleic acids, proteins, lipids, carbohydrates, small molecular weight physiological ligands, pathogenic organisms and tumor cells. The use of the antibody 3D structure as the basis for drug development circumvents technical difficulties associated with biological molecules for which a 3D structure is not available. The present invention also provides an approach for high-specificity, high-throughput binding assay methods for the screening of chemical compounds including, but not limited to, those from combinatorial chemistry methodologies and natural products.