Project description
Light-activated functionalisation of proteins
The development of new tools for application in fundamental research and clinical medicine involves the functionalisation of biologically active proteins with a range of different cargo molecules. The goal of the EU-funded PhotoPHARMA project is to functionalise proteins by new photochemical reagents that are activated by the light as an alternative to currently available thermally-mediated coupling chemistries. Light-induced activation has the potential to solve many complications encountered in the synthesis of radiolabelled antibodies and other protein-conjugates using thermal coupling. The ultimate project goals are to enable the synthesis and clinical translation of protein-drug conjugates by introducing a radical new technology based on the fast, reliable and automated approach of using light-induced chemistry.
Objective
The ability to functionalise a biologically active protein with a range of different cargo molecules is crucial to accessing new tools for use in fundamental science and clinical medicine. For instance, antibody-conjugates that graft reporter molecules including fluorescent tags or radioactive metal ion chelates play vital roles in diagnostic imaging with optical and nuclear medicine techniques like positron emission tomography (PET). State-of-the-art advances in chemotherapy also take advantage of the biophysical properties of antibodies in the design of highly potent antibody-drug conjugates (ADCs) that facilitate specific delivery and uptake of cytotoxic or radiotoxic payloads to disease lesions. Surprisingly, almost all existing methods to produce protein-conjugates rely on thermally-mediated coupling chemistries. In PhotoPHARMA, the goal is to break away from the convention of using heat to drive protein functionalisation by designing new photochemical reagents that are activated by the absorption of light. Light-induced activation has the potential to solve many of the practical issues encountered in the synthesis of radiolabelled antibodies and other protein-conjugates. The work encompasses 4 main Objectives: Objective 1. Explore the biochemical scope of light-induced reactions for bimolecular protein-ligation Objective 2. Synthesis, characterisation and biological studies of photo(radio)labelled antibodies for use in diagnostic imaging and therapy Objective 3. Develop automated technologies for photoradiochemical synthesis of 89Zr-antibodies Objective 4. Establish the GLP-synthesis and Chemistry, Manufacturing and Controls (CMC) for future translation of photoradiolabelled 89Zr-antibodies to the clinic The long-term goals are to facilitate the synthesis and clinical translation of protein-drug conjugates by introducing a radical new technology based on the fast, reliable and automated approach of using light-induced chemistry.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
8006 Zurich
Switzerland