The axis focuses on the design, synthesis and characterization of peptides and/or proteins modulating biological interactions. New chemical ligation methodologies are being developed for protein synthesis incorporating non-canonical amino acids or post-translational modifications.

Constrained peptide mimes (head-to-tail cyclization, staple peptides, etc.) with pharmacological properties that are more favorable to the development of therapeutic agents than their linear analogues are developed, for the design of protein-protein interaction inhibitors (PPIs) in oncology and virology, glycosaminoglycan ligands for cell targeting or biocondensates modulators. Our skills in protein production and purification allow us to produce the targets of interest. In addition to rational design, new approaches allowing the screening and selection of constrained peptides capable of interacting with these biological targets, based on dynamic combinatorial chemistry, are developed. The combinatorial aspect of these syntheses implies important analytical developments for the characterization of libraries and molecules selected by biological targets by liquid chromatography (HPLC), and mass spectrometry (MS). In particular, we are working to better understand the fragmentation of peptides in the gas phase by tandem mass spectrometry, using cyclic or linear peptide sequences and different activation techniques, involving collisions with inert gas (CID: collision induced dissociation) or electrons (ETD: electron transfer dissociation or ECD: electron capture dissociation). We develop sequence-fragmentation studies by MS in tandem and study the thermodynamic parameters of the unimolecular fragmentation reaction by gas phase kinetics experiments.

**Méthodologies associées : **

• Synthesis of modified amino acids, peptides and proteins on solid and in solution (F. Burlina, R. Moumné, L.
• Native chemical ligation and auxiliary-mediated ligation (F. Burlina)
• Functionalization of peptides by dynamic combinatorial chemistry (R. Moumné, L. Rocard)
• MS and MS/MS of polycationic, cyclic, gas-modified peptide ions (E. Sachon)
• Protein production and purification (D. Ravault)