부산대학교 도서관

• G protein-coupled receptors, ion channels and transporters, are important targets for drug discovery. • Monoclonal antibodies and related molecules may selectively target these integral membrane proteins. • Isolation of antibodies which modulate the function of these targets has proved challenging. • Novel antigen formats and antibody isolation strategies are leading to functional monoclonal antibodies. • Antibody discovery strategies with a focus on membrane protein antigen formats are reviewed. Complex integral membrane proteins, which are embedded in the cell surface lipid bilayer by multiple transmembrane spanning helices, encompass families of proteins which are important target classes for drug discovery. These protein families include G protein-coupled receptors, ion channels and transporters. Although these proteins have typically been targeted by small molecule drugs and peptides, the high specificity of monoclonal antibodies offers a significant opportunity to selectively modulate these target proteins. However, it remains the case that isolation of antibodies with desired pharmacological function(s) has proven difficult due to technical challenges in preparing membrane protein antigens suitable to support antibody drug discovery. In this review recent progress in defining strategies for generation of membrane protein antigens is outlined. We also highlight antibody isolation strategies which have generated antibodies which bind the membrane protein and modulate the protein function. [ABSTRACT FROM AUTHOR]