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Chimie moléculaire Paris Centre
ÉCOLE DOCTORALE 406

Bio-inspired peptide-like ligands to help understanding metal toxicity, regulation and detoxification

Séminaire du Dr Pascale Delangle (CEA Grenoble, France)

Abstract :

Peptides are promising metal-chelating agents, which offer many advantages over synthetic chemical compounds for biological and medical applications. They are made of the same building blocks as proteins and are therefore excellent mimics of biological sites that help predicting high affinity metal binding environments in vivo. They are also very attractive water-soluble ligands to design non-toxic chelating agents for medical applications. Two strategies are developed in our laboratory to obtain peptide-like ligands that efficiently mimic metal binding sites in proteins. These chemical architectures are rationally designed to promote the pre-orientation of several coordinating amino acid side-chains towards the metal center. The first design consists in grafting amino acids on chemical scaffolds such as poly-aminocarboxylates via classical peptide coupling reactions to get pseudo-peptides, whereas the second one exploits cyclodecapeptide sequences that induce β-sheet structures. Synthetic organic chemistry is combined to solid-phase peptide synthesis to obtain high purity bio-inspired peptide-like ligands. These two strategies will be discussed for the design of Cu(I) chelators mimicking copper-binding sites found in copper transporters, metallochaperones or metallothioneins and peptide-like ligands for the hexavalent uranyl cation, UO22+, which is purely toxic and classified as a hard Lewis acid. We will focus on the rational design of the peptide-like ligands, taking into account the metal coordination properties. The structure of the complexes, their stability and selectivity will be discussed in relation to the biological question.

07/06/18

Traductions :

    Contact

    Directrice 

    Anna Proust (anna.proust @ upmc.fr)

     

    Directeur adjoint

    cyril.ollivier @ upmc.fr

     

    Secrétariat

    Irène Rasoarinoro (irene.rasoarinoro @ upmc.fr)

    Tel. : 01 44 27 38 48

     

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