SPP 1623 - Subproject: New approaches for the site-selective chemical modification of therapeutic proteins under mild conditions

Basic data for this project

Description

The site-specific chemical modification of protein therapeutics, for example antibodies, protein hormones, and cytokines, is of great importance for applications in cancer and disease treatment, diagnostics, and imaging. Chemical modifications can endow the protein therapeutics with new and tailored properties, for example longer circulation time in the blood-stream, targeted cell-killing (immunoconjugates), and reporting their localization (e.g. by fluorophores or tracers). In the proposed project new methodologies will be developed that overcome several limitations of the currently most widely used classical bioconjugation approaches. The new conjugation strategies are based on protein trans-splicing catalyzed by split inteins and the combination with selected chemo- and regioselective reactions. They will enable site-specific single and double modification of proteins obtained from different expression host organisms. The target proteins will not be exposed to harsh chemical reaction conditions of any kind, but will rather be modified at pH 7 and even in the absence of reducing agents. While the current project will focus on the modification of antibodies, the methodologies developed here will also be applicable to in principle any other protein and thus significantly advance the repertoire of protein chemistry.