Peptides and peptidomimetics: extending the natural amino acid repertoire to probe and interfere with biomolecular interactions

Our team has strong expertise in the characterization of natural or chemically modified peptides in concert with the design of peptidic and peptidomimetic ligands. These molecules can contain chemical modifications that expand the chemical repertoire of proteinogenic amino acids, such as fluorinated amino acids, aza-amino acids, cyclic motifs (diketopiperazines, modified prolines…). One advantage of these molecules lies in their ability to adopt stable conformations in aqueous solution such as alpha-helices, polyproline-II helices, beta-turns and beta-hairpins. The studied molecules are designed to interact with different biological targets linked to human pathologies: antimicrobial infection, cancer, inflammation, amyloid diseases…Solution state NMR spectroscopy is at the heart of our strategy to probe the conformational space and the interactions of molecules, based on 1H, 13C, 15N and 19F NMR. We also use circular dichroism and fluorescence spectroscopy together with molecular dynamics simulations.

Recent projects:

• Design of human ACE2 peptide mimics blocking SARS-CoV-2 infection (collaboration with P. Karoyan’s team)
• FluFOLD ANR project (collaboration with S. Ongeri’s and G. Chaume’s groups): design of fluorinated foldamers interacting with amyloid proteins and biomembranes
• Fluorinated Collagen Mimetic Peptides
• Fluorinated ligands of Pin1 rotamase