DC2: JUSTIN ALICH (DE)
Partner of attachment: CEA (French Alternative Energies and Atomic Energy Commission ) FR
Supervisor : Dr. Davide AUDISIO
University of Attachment: UPSAC (University Paris-Saclay) FR
Director of Thesis : Dr. Davide AUDISIO

In recent years, the importance of biologic drugs in the market has drastically surged, increasing from less than 10% of newly approved drugs in 2007 to over 50% in 2022. These biological drugs offer significant benefits, including high efficacy and good tolerability, but from a chemical perspective, they are much more challenging to modify/functionalize compared to “classical” small- molecule drugs.
To ensure the safe approval and use of these drugs, it is essential to understand their effects and fate in the human body. A key technique for tracking drugs involves the insertion of a small, ideally traceless radioactive label, allowing monitoring their behavior amidst the complex mixture of molecules and cells in the body. However, due to the difficult manipulation of biological drugs, current methods for labeling these compounds are often unsatisfactory.
Therefore, my objective is to develop new methods that allow the selective radioactive labeling of biological drugs, specifically the labeling of peptides, proteins, and antibodies with carbon isotopes.
At first, we focused on investigating unexplored reactive groups for their use in radioactive labeling. This strategy requires establishing entirely new methodologies, but it may allow us to exploit new pathways, overcoming the current limitations in labeling biomolecules.
Upon proof-of-concept and validation of the hypothesized transformation, we were able to optimize the initial reaction conditions and test the methodology's applicability on a range of small molecules. This optimization is crucial for refining the process and ensuring its effectiveness across different contexts.
Radioactive labeling of biomolecules can be achieved either by directly altering the biomolecule or by installing a small handle that carries the label. In exploring the second approach, we investigated the direct labeling of well-known tool molecules used in protein and antibody chemistry. This method offers broad opportunities and remains a promising area of research.
The preliminary results showcase a promising advancement in the field of radioactive labeling. We have successfully applied the new methodology to small molecules and are currently identifying its limitations.
While the direct radioactive labeling of biomolecules remains challenging, it will be further explored in the ongoing project.
Additionally, the initial promising results from labeling tool compounds for biomolecule functionalization present an interesting strategy to circumvent the reactivity limitations of direct biomolecule labeling. This alternative approach could significantly enhance our ability to label and study complex biomolecules effectively.
