Our research group works at the interface of chemistry with biology and a main focus is peptides and their interaction with d-block metal ions like copper and zinc. The aims are either to understand the mechanisms of biological processes or to design peptide-metal, metal-ligands or metal-ligand-peptide edifices with applications in catalysis, biology or medicine.

We have several axis of research:

1) Metal complexes with (amyloidogenic) peptides: Amyloidogenic peptides can form amyloids by a self-assembly process are found in several diseases, in particular in neurodegenerative diseases (Alzheimer, Parkinson, Prion,…). High amounts of copper, zinc and iron are found bound to amyloid-beta in the amyloid plaques in Alzheimer patients. Therefore we are interested in how these metal ions interact with amyloidogenic peptides and in the design of peptides for therapeutic approaches.

2) Protein-like scaffolds via assembly of de novo peptides: We are investigating new possibilities offered by peptide self-assembly to develop biomaterials. Natural silks (from the mulberry silkworm or from spiders) are nothing else than filaments made of aggregated proteins. Noteworthy, they display very interesting mechanical properties. Therefore, being able to synthesize silk-like materials made of de novo peptides holds great potential, since it would open the way to fine-tune the mechanical properties via sequence mutation.

3) Synthesis of peptides or peptide-hybrides for biological or medicinal application. Peptides are used as platforms to conjugate inorganic ligands and their metal complexes, fluorophores /luminophores, and other chemical compounds for several applications, such as antimicrobials, copper(II)-sensors via luminescence or magnetic resonance imaging for biological probes, anticancer, etc.

Main Methods:

Analytical methods: Spectroscopical methods (EPR, NMR, X-ray absorption spectroscopy, circular diochroism, absorbance, fluorescence …), microscopies (AFM, TEM), isothermal titration calorimetry, chromatography, electrophoreses.

Synthesis, Peptides: Solid Phase Peptide Synthesis (SPPS Fmoc/tBu) and Chemical ligation (NCL, SEA ligation) technics.

Synthesis ligands: Synthesis of metal-ion ligands to form bioactive metal-ligand complexes and functionalized ligands for conjugation to peptides.

Key words:

biometals; bioinorganic chemistry; bioorganic chemistry; copper, zinc, iron; peptides; Chemical peptide synthesis; Inorganic ligand synthesis; bioconjugation; metalloproteins, reactive oxygen species, self-assembly; amyloids; metal trafficking; fluorophores; inhibitors; spectroscopies.

Liste du matériel et des appareils

Plate reader to measure fluorescence and absorbance in 96 or 384 wells plate
UV-Vis spectrophotometer
HPLC (analytical and preparative)
Lyophilizer

Références bibliographiques récentes

REVIEWS:

Falcone E, Faller P.
Thermodynamics-based rules of thumb to evaluate the interaction of chelators and kinetically-labile metal ions in blood serum and plasma.
Dalton Trans.52, 2197 (2023)

Falcone, E., Okafor, M. Vitale, N., Raibaut L., Sour, A, Faller P.
Extracellular Cu2+ pools and their detection: from current knowledge to next-generation probes
Coord. Chem. Rev. 433, 213727 (2021)

Nguyen PH, Ramamoorthy A, Sahoo BR, Zheng J, Faller P, Straub JE, Dominguez L, Shea JE, Dokholyan NV, De Simone A, Ma B, Nussinov R, Najafi S, Ngo ST, Loquet A, Chiricotto M, Ganguly P, McCarty J, Li MS, Hall C, Wang Y, Miller Y, Melchionna S, Habenstein B, Timr S, Chen J, Hnath B, Strodel B, Kayed R, Lesné S, Wei G, Sterpone F, Doig AJ, Derreumaux P.
Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes and Amyotrophic Lateral Sclerosis
Chem. Rev. 121, 2545-2647 (2021)

Gonzalez P, Bossak K, Stefaniak E, Hureau C, Raibaut L, Bal W., Faller, P.
N-terminal Cu Binding Motifs Xxx-Zzz-His (ATCUN) and Xxx-His and their derivatives Chemistry, Biology and Medicinal Applications
Chem. Eur. J. 24, 8029-8041(2018)

ORIGINAL ARTICLES: (Recent and Selected)

Falcone E, Nobili G, Okafor M, Proux O, Rossi G, Morante S, Faller P, Stellato F.
Chasing the Elusive "In-Between" State of the Copper-Amyloid β Complex by X-ray Absorption through Partial Thermal Relaxation after Photoreduction.
Angew Chem Int Ed Engl. 62:e202217791 (2023)

Okafor M, Gonzalez P, Ronot P, El Masoudi I, Boos A, Ory S, Chasserot-Golaz S, Gasman S, Raibaut L, Hureau C, Vitale N, Faller P.
Development of a Cu(II)-specific peptide shuttles capable of preventing Cu-Amyloid beta toxicity and importing bioavailable Cu into cells
Chem. Sci., 13, 11829-11840 (2022)

Falcone E, Ritacca AG, Hager S, Schueffl H, Vileno B, El Khoury Y, Hellwig P, Kowol CR, Heffeter P, Sicilia E, Faller P.
Copper-Catalyzed Glutathione Oxidation is Accelerated by the Anticancer Thiosemicarbazone Dp44mT and Further Boosted at Lower pH
J. Am. Chem. Soc.,144,14768 (2022)

Falcone E., Gonzalez P., Lorusso L., Sénèque O., Faller P., Raibaut L.
A Terbium(III) luminescent ATCUN-based peptide sensor for selective and reversible detection of Copper(II) in biological media
Chem Comm, 56, 4797-4800 (2020)

Santoro A, Calvo, J.S., Peris-Díaz MD, Krężel A, Meloni, G., Faller P.
The glutathione/metallothionein system challenges the design of efficient O₂-activating Copper complexes
Angew. Chem., Int. Ed. 59, 7830-7835 (2020)

Galerie photos de l'équipe de recherche

Un petit aperçu de notre équipe de recherche