Selective multifunctionalization of antibody fragments and antibodies by enzyme-mediated orthogonal ligations

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Since decades antibodies are invaluable tools for various applications mainly for use in diagnostics and therapy. They are target-specific and effective, stable and can be produced in large amounts. All antibodies are composed of two functional regions, namely the Fab and the Fc region. The Fab region is required for antigen recognition, while the Fc region couples the antibody to secondary immune effector functions. In the proposed project, the full length antibody as well as the antibody Fc region will be used as a scaffold for the display of bioactive molecules. The main objective is to apply bioorthogonal chemical and enzyme-mediated ligation strategies that allow for selective endowment of antibodies with different ligands to site-specifically introduce cell recognition modules, toxic payloads, or compounds that mediate the release of bioactive molecules into the cytosol of a target cell. Multiple functionalization of antibodies and antibody fragments inherits a plethora of potential future applications in cell biology, biotechnology, and medicine.