In the frame of a collaborative project aiming at discovering new binders for neurodegenerative diseases, our group is developing new labelling technologies, combinatorial chemistry and high throughput screening for application in nuclear imaging (see Angew. Chem. Int. Ed. 2018, 57, 9744; Chem. Commun. 2021, DOI: 10.1039/D1CC02665H). The project aims to develop new combinatorial synthetic approaches to prepare libraries of molecules which will be used to accelerate the discovery of new ligands able to selectively bind protein aggregates involved in Alzheimer, Parkinson and Huntington diseases. The strategy is based on Click Chemistry combined with a mass enhancer and radiolabeling, to identify specific ligands for neurodegenerative diseases and map their distribution by imaging. The postdoctoral fellow will be hosted in the SCBM (Service de Chimie Bioorganique et de Marquage) at CEA-Saclay and will work in close collaboration with several teams within the network. All experiments will be conducted with stable isotopes. CEA personnel will perform experiments with radiolabeled compounds.
In the frame of a collaborative project aiming at discovering new scaffolds of interest, our groups are developing new synthesis methodologies, using innovative technologies to accelerate the optimization and scope processes. This project aims at developing catalytic enantioselective cycloadditions of sydnones in order to efficiently access chiral pyrrazolines. The design of the corresponding catalytic process will rely on the concept of dual catalysis in which both the dipolarophile and the sydnone could be activated. We will study cycloaddition reactions with either electron rich or electron-poor dipolarophiles, which may be activated with a chiral catalyst, while the sydnone may be activated by energy transfer via a photocatalyst from visible light. A High Throughput Experimentation (HTE) approach will be deployed to empower and speed-up the discovery and the optimization of suitable catalytic conditions, and exploring a large number of dipolarophiles.
In the frame of a collaborative project aiming at discovering compounds that interfere with the intracellular retrograde trafficking, our group is developing small molecules that have been shown by us and other groups to have a broad "therapeutic" activity (look for Retro-2 references) . Based on the experience we acquired on Retro-2 analogs (see for instance J. Med. Chem. 2013, 56, 8, 3404-3413) and based on in silico design we now aim at developing a completely new chemical series for which we already have encouraging preliminary results. The postdoctoral fellow will be hosted at the SCBM (Service de Chimie Bioorganique et de Marquage/Université Paris-Saclay) at CEA-Saclay under the supervision of Dr Jean-Christophe Cintrat and will work in close collaboration with biology team within the network. All experiments will be dealing with heterocyclic chemistry and may require some basic knowledge of in silico drug design.