Description du sujet de thèse

Synthesis of Complex N-Glycan Oligosaccharides
This project proposes the (bio)synthesis of high-value N-glycan oligosaccharides. Present on the cell surface, on proteins, in the nucleus and cytoplasm, N-glycans perform structural and recognition functions. They participate in cell growth, host-pathogen interactions, and immunity. Abnormalities in their structure or biosynthesis can cause diseases, including cancer. N-glycans have a common pentasaccharide core (Man3GlcNAc2) which then contains various oligosaccharide branches attached to this core, with specific modifications such as variations in the number and composition of the branches.

As part of the ANR LabCom SweetLab project, organic (glyco)chemistry developed at ICSN and biotechnology to access the substructures of these oligosaccharides, an expertise of the company Elicityl. The core of the project lies in the possibility of carrying out glycosylation reactions directly from N-acetyl-glucosamine (GlcNAc) as a donor sugar. This project will further improve the methodologies for the synthesis of GlcNAc glycosylation to access large quantities (in the order of grams) of oligosaccharides that are not or are still far too rarely commercially available at the microgram or milligram scale.

Contexte de travail

The Institute of Chemistry of Natural Substances is a CNRS Research Unit whose research focuses are chemistry and biology. It is part of the University of Paris-Saclay, which has brought together, since 2015, the research and teaching establishments of southern Paris. The ICSN is located on the Gif-sur-Yvette campus and has approximately 124 employees, including 71 permanent staff, spread over 3 buildings. Within the Chemobiology Department, the recruited employee will join the "Probes and Modulators for Biological Targets" team. He will be placed under the hierarchical authority of the team leader and the project will be carried out under the co-direction of Dr. Sébastien Vidal and Dr. Stéphanie Norsikian. The laboratory is equipped with all the necessary instruments for the project (HPLC, automatic flash chromatography, microwave synthesis reactor, freeze dryer, rotavap, etc.). Several analytical platforms are present in the institute and provide cutting-edge instruments: NMR (300, 500 MHz), mass spectrometry (LCMS, HRMS) and X-ray diffraction in particular.

Contraintes et risques

The project involves the Health and Safety constraints related to the handling of chemicals. The experiments will be carried out in a laboratory equipped with fume hoods.