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Responsable de l’équipe de recherche

Peter FALLER
Professeur à l'Unistra

Année de création de l'équipe - 2015

Site de l'équipe de recherche

https://bcb.chimie.unistra.fr/

Localisation

Institut Le Bel, 4^ème étage Nord

Secrétariat et gestion assurés par

Paola SAGER
courriel : paola.sager@unistra.fr
téléphone : 03 68 85 12 41

Personnels permanents

Personnels non permanents

Doctorants

• Alice SANTORO
  Courriel : alice.santoro@unistra.fr
  
  
• Enrico FALCONE
  Courriel : efalcone@unistra.fr

• Maxime NAUDE
  Courriel : mnaude@unistra.fr

• Thibaut GALLER
  Courriel : tgaller@unistra.fr

• Michael OKAFOR
  Courriel : okafor@unistra.fr

Descriptif de l'équipe de recherche

Our research group works at the interface of chemistry with biology. The main topic deals with amyloidogenic peptides and their interaction with d-block metal ions like copper and zinc. Amyloidogenic peptides can form amyloids by a self-assembly process. Amyloids are fibrils of about 10 nm diameter and several 100ds of nm length and they 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, e.g. to decipher how they impact the self-assembly process and what is the reactivity of these complexes between metal and amyloidogenic peptides. In this context, we are particularly interested in the mechanism of production of reactive oxygen species by Cu-amyloid-beta. We study also the interaction with other metalloproteins concerning metal-exchange reactions or with small compounds like fluorophores (for detection) or inhibitors (potential therapeutic agents).

Recently, building on our expertise on peptide aggregation, our group started to investigate 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 that it would open the way to fine-tune the mechanical properties via sequence mutation. 

Main Methods:

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

Key words:

biometals; bioinorganic chemistry; bioorganic chemistry; copper, zinc, iron; peptides; Chemical protein 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:

Ayala S, Genevaux P, Hureau C, Faller P.
(Bio)Chemical strategies to modulate amyloid-β self-assembly
ACS Chem Neurosci. 10, 3366-3374 (2019)

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)

C. Cheignon, M. Tomas, D. Bonnefont-Rousselot, P. Faller, C. Hureau, F. Collin
Oxidative stress and the amyloid beta peptide in Alzheimer’s Disease
Redox Biology, 2017,  14, 450-464

Nasica-Labouze J, Nguyen PH, Sterpone F, Berthoumieu O, Buchete NV, Coté S, De Simone A, Doig AJ, Faller P, Garcia A, Laio A, Li MS, Melchionna S, Mousseau N, Mu Y, Paravastu A, Pasquali S, Rosenman DJ, Strodel B, Tarus B, Viles JH, Zhang T, Wang C, Derreumaux P.
Amyloid β Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies
Chem Rev. 2015, 115, 3518-63

Faller P, Hureau C, La Penna G.
Metal ions and intrinsically disordered proteins and peptides: from Cu/Zn amyloid-β to general principles
Acc Chem Res. 2014, 47,2252-9

Faller P, Hureau C, Berthoumieu O.
Role of metal ions in the self-assembly of the Alzheimer's amyloid-β peptide.
Inorg Chem. 2013,52, 12193-206

ORIGINAL ARTICLES: (Recent and Selected)

Enrico Falcone, Angélique Sour,  Vincent Lebrun,  Gilles Ulrich,  Laurent Raibaut* and  Peter Faller
Reversible turn-on fluorescent Cu(II) sensors: rather dream than reality?
Dalton Trans, 48, 14233-14237 (2019)

Gonzalez P, Bossak-Ahmad K, Vileno B, Wezynfeld NE, El Khoury Y, Hellwig P, Hureau C, Bal W, Faller P
Triggering Cu-coordination change in Cu(II)-Ala-His-His by external ligands
Chem Comm, 55, 8110 - 8113 (2019)

Wezynfeld NE, Vileno B, Faller P.
Cu(II) binding to the N-terminal model peptide of human Ctr2 transporter at lysosomal and extracellular pH"
Inorg. Chem. 58, 7488-7498 (2019)

Santoro A, Vileno B, Palacios Ò, Peris-Díaz MD, Riegel G, Gaiddon C, Krężel A, Faller P.
Reactivity of Cu(II)-, Zn(II)- and Fe(II)-Thiosemicarbazone Complexes with Glutathione and Metallothionein: from Stability over Dissociation to Transmetallation
Metallomics, 11, 994-1004 (2019)

Santoro A, Wezynfeld NE, Stefaniak E, Pomorski A, Płonka D, Krężel A, Bal W, Faller P.
Cu transfer from Amyloid-β4-16 to Metallothionein-3: the role of neurotransmitter Glutamate and Metallothionein-3 Zn(II)-load states
Chem. Comm., 54, 12634 - 12637 (2018)

Clémence Cheignon, Megan Jones, Elena Atrián-Blasco, Isabelle Kieffer, Peter Faller, Fabrice Collin, Christelle Hureau
dentification of key structural features of the elusive Cu-Aβ complex generating ROS in Alzheimer’s Disease
Chemical Science,2017, 8, 5107-5118 

Reybier K, Ayala S, Alies B, Rodrigues JV, Bustos Rodriguez S, La Penna G, Collin F, Gomes CM, Hureau C, Faller P.
Free Superoxide is an Intermediate in the Production of H2 O2 by Copper(I)-Aβ Peptide and O2
Angew Chem Int Ed Engl. 2016, 55, 1085-9

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