To carry out their activities, Research Teams of the Frédéric Joliot Institute for Life Sciences have developed high-profile technological platforms in many areas : biomedical imaging, structural biology, metabolomics, High-Throughput screening, level 3 microbiological safety laboratory...
All the news of the Institute of life sciences Frédéric Joliot
Scientific result | Green Chemistry
Researchers from the SCBM in collaboration with teams from CEA-IRAMIS, AstraZeneca and the Karolinska Institutet have developed a second marking method based on the dynamic exchange of carbon dioxide, this time without catalysis, by "simple" thermal heating. Ideal for organic molecules of therapeutic interest, the method is described in the journal Angewandte Chemie International Edition.
SCBM chemists continue to explore ways to label organic molecules, to make them faster and less polluting, in order to facilitate their use, for example in pharmacological studies. During the preclinical and clinical testing phases, drugs are "labelled" to track their absorption, distribution, metabolism and excretion in a living organism (animal or human).
A team from SCBM (LMC) are interested in the carbon-14 (14C) labelling of therapeutic molecules. In 2019, in collaboration with NIMBE (CEA-IRAMIS), they discovered a new labelling strategy involving isotopic carbon exchange. This involves, in the same reaction, the breaking of a C-C bond and the formation of a new C-14C bond while keeping the original structure of the drug. They found favourable experimental conditions for the catalysis of an exchange of an unlabelled CO2 molecule against a labelled molecule in molecules of therapeutic interest containing a carboxylic group. This method, which is suitable for aromatic carboxylic acids, was catalysed by copper (JACS 2019, read the news " CO2 and copper to label carbon-based pharmaceuticals " published in January 2019).
In the article published in Angewandte Chemie, researchers from the SCBM and NIMBE, in collaboration with Astra Zeneca and the Karolinska Institutet, describe a new method that allows an exchange of 12CO2 by 14CO2 in the absence of catalysis, simply by thermal heating. This method is particularly suitable for a family of carboxylic acids, phenyl acetic acids, present in non-steroidal anti-inflammatory drugs such as ibuprofen, naproxen, ketoprofen and many others.
Gianluca Destro developed this project as part of his thesis, funded by the European ISOTOPICS project (https://www.isotopics-project.eu/). After finding the optimal conditions, he was able to apply this new method to the labelling of 15 drugs at AstraZenenca. Finally, at the Karolinska Institute (Stockholm, Sweden), he succeeded in adapting the method to carbon-11, the other carbon radioisotope, for the very first time.
G. Destro, K. Horkka, O. Loreau, D.-A. Buisson, Lee Kingston, A. Del Vecchio, M. Schou, C. S. Elmore, F. Taran, T. Cantat, D. Audisio. Transition-Metal-Free Carbon Isotope Exchange of Phenyl Acetic Acids | Angewandte Chemie, 2020
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.