DC1: RAFAEL JIMÉNEZ RIOBOO (SP)
Partner of attachment: CEA (French Alternative Energies and Atomic Energy Commission) FR
Supervisor : Dr. Grégory PIETERS
University of Attachment : UPSAC (University Paris-Saclay) FR
Director of Thesis : Dr. Grégory PIETERS

Over the past few years, biologics like peptides, proteins, and oligonucleotides have experienced an increase in popularity because they offer greater specificity and lower toxicity compared to traditional small molecules drugs. In order to obtain some information about the biodistribution and pharmacokinetics of these large molecules their radiolabeling is considered as a method of choice. However, due to their complexity and their poor solubility in organic solvents, radiolabeling of biopharmaceuticals poses significant challenges. In this context, our goal is to develop new general methods for deuterium and tritium labelling of biologics using metal nanoparticles as catalysts.
The development of an effective method for tritium labeling remains a significant challenge critical to advancing drug discovery. A major obstacle is the limited solubility of some biologics in organic solvents, such as some amino acids and peptides. In addition, the aqueous environment is incompatible with many efficient catalysts used for deuterium/tritium labeling, resulting in low isotopic incorporation. With the aim to address this issue, we have synthesized new water-soluble catalysts and explore their catalytic activities to mediate hydrogen isotope exchange reactions in water are currently explored.
Alternative methods for biomolecule labeling often involve using a TAG or linker to attach a pre-radiolabeled compound, rather than direct labeling. However, this approach requires careful consideration of two main factors: the stability of the label and the potential alteration of the properties of the molecule due to the chemical modification. In this context, we also started to investigate the design of novel deuterated and tritiated reagents that might allow an effective labelling of proteins and oligonucleotides.
In summary, developing an efficient method for tritium/deuterium labeling is vital for progressing drug discovery, but it encounters obstacles due to the poor solubility of certain biologics in organic solvents. We anticipate that our newly developed water-soluble catalyst will address this issue, though further optimization is needed. Meanwhile, the prevalent TAG/ used for protein labeling today has substantial potential for enhancement. We believe our novel reagent might offer superior performance and eagerly anticipate testing it with biomolecule samples.
