Descripción del proyecto
Funcionalización fotoactivada de proteínas
El desarrollo de herramientas nuevas para su aplicación en investigaciones fundamentales y la medicina clínica implica la funcionalización de proteínas biológicamente activas con una serie de moléculas de carga diferentes. El objetivo del proyecto PhotoPHARMA, financiado con fondos europeos, es funcionalizar las proteínas mediante nuevos reactivos fotoquímicos que se activan con la luz, como alternativa a las químicas de acoplamiento por vía térmica disponibles en la actualidad. La activación fotoinducida tiene el potencial de resolver muchas complicaciones propias de la síntesis de anticuerpos radiomarcados y otros conjugados de proteínas que utilizan el acoplamiento térmico. Los objetivos finales del proyecto son permitir la síntesis y la traducción clínica de los conjugados proteína-fármaco mediante la introducción de una nueva tecnología revolucionaria basada en el método rápido, fiable y automatizado del uso de la química fotoinducida.
Objetivo
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.
Ámbito científico
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Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
8006 Zurich
Suiza