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

几十年来，抗体是各种应用的宝贵工具，主要用于诊断和治疗。它们具有针对性，有效，稳定，可大量生产。所有抗体都由两个功能区组成，即Fab和Fc区。Fab区是抗原识别所需的，而Fc区将抗体偶联至次级免疫效应子功能。在拟议的项目中，全长抗体以及抗体Fc区将用作展示生物活性分子的支架。主要目的是应用生物正交化学和酶介导的连接策略，其允许选择性赋予具有不同配体的抗体以位点特异性地引入细胞识别模块、毒性有效载荷或介导生物活性分子释放到靶细胞的胞质溶胶中的化合物。抗体和抗体片段的多功能化继承了细胞生物学、生物技术和医学中大量潜在的未来应用。

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.