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Pascale DELANGLE

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INAC / CEA-Grenoble
17, rue des Martyrs
38 054 Grenoble cedex 9

Position

Principal Investigator

CV

October 2005. Habilitation à Diriger des Recherches, Université Joseph Fourier, Grenoble

Since  1st december 1997. Researcher in CEA laboratoire de Chimie Inorganique et Biologique, INAC, CEA-Grenoble

1997.  post-doc., laboratoire de Chimie Inorganique et Biologique, DRFMC, CEA-Grenoble "Lanthanide ion complexation: high resolution NMR studies in solution haute"

december 1996.  phD thesis at the Ecole Normale Supérieure de Lyon, title"Conception et étude de nouveaux récepteurs de cations : hémisphérands et cavitands phosphorés", in the laboratoire de Stéréochimie et des Interactions Moléculaires (ENS de Lyon, André Collet, Jean-Pierre Dutasta)

July 1992. Agrégation de Sciences Physiques option Chimie

1989-1993. Studies at the Ecole Normale Supérieure de Lyon

1987-1989. Classes préparatoires

 

Research interest: Peptide design for selective metal ion chelation

Cu(I) selective chelators were designed from binding sites found in proteins involved in copper homeostasis. Particularly efficient chelating agents were obtained by mimicking the trigonal planar geometry CuS3 of metallothionein, which are metal detoxification proteins. These chelators were transformed into prodrugs, targeted at the hepatocytes, to treat localized copper accumulation in the liver, the main organ of copper accumulation in the rare Wilson’s disease.

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Book Chapter:

Gateau, C., E. Mintz and P. Delangle, Rational design of Cu and Fe chelators to treat Wilson’s disease and hemochromatosis, in Ligand Design in Medicinal Inorganic Chemistry T. Storr, Editor 2014, WILEY-BLACKWELL.

Selected publications:

Monestier, M., P. Charbonnier, C. Gateau, M. Cuillel, F. Robert, C. Lebrun, E. Mintz, O. Renaudet and P. Delangle, ASGPR-Mediated Uptake of Multivalent Glycoconjugates for Drug Delivery in Hepatocytes. ChemBioChem, 2016, 17, p. 590-594.

Jullien, A.S., C. Gateau, C. Lebrun and P. Delangle, Mercury Complexes with Tripodal Pseudopeptides Derived from D-Penicillamine Favour a HgS3 Coordination. European Journal of Inorganic Chemistry, 2015, p. 3674-3680.

Jullien, A.S., C. Gateau, C. Lebrun and P. Delangle, Pseudo-peptides Based on Methyl Cysteine or Methionine Inspired from Mets Motifs Found in the Copper Transporter Ctr1. Inorganic Chemistry, 2015, 54, p. 2339-2344.

Gateau, C. and P. Delangle, Design of intrahepatocyte copper(I) chelators as drug candidates for Wilson’s disease. Annals of the New York Academy of Sciences, 2014, 1315, p. 30-36.

Jullien, A.-S., C. Gateau, I. Kieffer, D. Testemale and P. Delangle, X-Ray Absorption Spectroscopy Proves the Trigonal Planar Sulfur-Only Coordination of Cu(I) with High Affinity Tripodal Pseudopeptides. . Inorganic Chemistry, 2013, 52, p. 9954-9961.

Pujol, A.M., C. Lebrun, C. Gateau, A. Manceau and P. Delangle, Mercury-sequestering pseudopeptides with a triscysteine environment in water Eur. J. Inorg. Chem., 2012, p. 3835-3843.

Pujol, A.M., M. Cuillel, A.-S. Jullien, C. Lebrun, D. Cassio, E. Mintz, C. Gateau and P. Delangle, A sulfur tripod glycoconjugate releases a high affinity copper chelator in hepatocytes. Angewandte Chemie International Edition, 2012, 51, p. 7445-7448.

Pujol, A.M., C. Gateau, C. Lebrun and P. Delangle, A series of tripodal cysteine derivatives as water-soluble chelators highly selective for Copper (I). Chem. Eur. J., 2011, 17, p. 4418-4428.

Pujol, A.M., M. Cuillel, O. Renaudet, C. Lebrun, P. Charbonnier, D. Cassio, C. Gateau, P. Dumy, E. Mintz and P. Delangle, Hepatocyte targeting and intracellular copper chelation by a thiol-containing glycocyclopeptide. Journal of the American Chemical Society, 2011, 133, p. 286-296.

Pujol, A.M., C. Gateau, C. Lebrun and P. Delangle, A Cysteine-Based Tripodal Chelator with a High Affinity and Selectivity for Copper(I). Journal of the American Chemical Society, 2009, 131, p. 6928-6929.

 

About these Cu(I) chelators and silver nanoparticles...

Veronesi, G., T. Gallon, A. Deniaud, B. Boff, C. Gateau, C. Lebrun, C. Vidaud, F. Rollin-Genetet, M. Carrière, I. Kieffer, E. Mintz, P. Delangle and I. Michaud-Soret, XAS Investigation of Silver(I) Coordination in Copper(I) Biological Binding Sites. Inorganic Chemistry, 2015, 54, p. 11688-11696.

Veronesi, G., C. Aude-Garcia, I. Kieffer, T. Gallon, P. Delangle, N. Herlin-Boime, T. Rabilloud and M. Carriere, Exposure-dependent Ag+ release from silver nanoparticles and its complexation in AgS2 sites in primary murine macrophages. Nanoscale, 2015, 7, p. 7323-7330.

 

Short hexapeptide sequences containing unnatural chelating amino acids have been elaborated to chelate lanthanide ions and to exploit their amazing luminescent and magnetic properties in Ln-based probes. We are currently testing their ability to interact with DNA or RNA and to detect these recognition phenomenon via the metal-centered luminescence of terbium or europium complexes or via the relaxivity of the water protons induced by the gadolinium complexes.

 

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Selected publications:

Ancel, L., A. Niedźwiecka, C. Lebrun, C. Gateau and P. Delangle, Rational design of Lanthanide Binding Peptides. C. R. Chimie, 2013, 16, p. 515-523.

Ancel, L., C. Gateau, C. Lebrun and P. Delangle, DNA Sensing by a Eu-Binding Peptide Containing a Proflavine Unit. Inorganic Chemistry, 2013, 52, p. 552-554.

Niedźwiecka, A., F. Cisnetti, C. Lebrun, C. Gateau and P. Delangle, Lanthanide-binding peptides with two pendant aminodiacetate arms: impact of the sequence on chelation. Dalton Trans., 2012, 41, p. 3239-3247.

Niedźwiecka, A., F. Cisnetti, C. Lebrun and P. Delangle, Femtomolar Ln(III) affinity in peptide-based ligands containing unnatural chelating amino acids. Inorg. Chem., 2012, 51, p. 5458-5464.

Cisnetti, F., C. Lebrun and P. Delangle, A lanthanide binding peptide with short chelating side-chains: structural impact of the backbone coordination. Dalton Transactions, 2010, 39, p. 3560-3562.

Cisnetti, F., C. Gateau, C. Lebrun and P. Delangle, Lanthanide(III) complexes with two hexapeptides incorporating unnatural chelating amino acids: secondary structure and stability. Chemistry-a European Journal, 2009, 15, p. 7456-7469.

 

Peptides are interesting tools to rationalise uranyl - protein interactions, which are relevant to uranium toxicity in vivo. Structured cyclic peptide scaffolds were chosen as promising candidates to coordinate uranyl thanks to four amino acid side-chains pre-oriented towards the dioxo cation equatorial plane. The binding of uranyl by a series of decapeptides has been investigated with complementary analytical and spectroscopic methods to evidence the key parameters for the formation of stable uranyl – peptide complexes.       

       

                       

Selected publications:

Starck, M., N. Sisommay, F.A. Laporte, S. Oros, C. Lebrun and P. Delangle, Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl. Inorganic Chemistry, 2015, 54, p. 11557-11562.

Lebrun, C., M. Starck, V. Gathu, Y. Chenavier and P. Delangle, Engineering Short Peptide Sequences for Uranyl Binding. Chemistry – A European Journal, 2014, 20, p. 16566-16573.

Delangle, P. and C. Berthomieu, Mimer le vivant pour piéger les radionucléides. Biofutur, 2014, 353, p. 39-42.

Pardoux, R., S. Sauge-Merle, D. Lemaire, P. Delangle, L. Guilloreau, J.-M. Adriano and C. Berthomieu, Modulating Uranium Binding Affinity in Engineered Calmodulin EF-Hand Peptides: Effect of Phosphorylation. PLos ONE, 2012, 7, p. e41922.

Bonnet, C.S., P.H. Fries, S. Crouzy and P. Delangle, Outer-Sphere Investigation of MRI Relaxation Contrast Agents. Example of a Cyclodecapeptide Gadolinium Complex with Second-Sphere Water. Journal of Physical Chemistry B, 2010, 114, p. 8770-8781.

Bonnet, C.S., P.H. Fries, S. Crouzy, O. Sénèque, F. Cisnetti, D. Boturyn, P. Dumy and P. Delangle, A Gadolinium-Binding Cyclodecapeptide with a Large High-Field Relaxivity Involving Second-Sphere Water. Chemistry-a European Journal, 2009, 15, p. 7083-7093.

 

Collaborators

Yves Chenavier (physico-chemical studies of the complexes)
Christelle Gateau (design and organic synthesis of new ligands)
Colette Lebrun (peptide synthesis, purification and mass spectrometry)
Elisabeth Mintz, Peggy Charbonnier, CEA Grenoble, BIG, LCBM: Cellular assays with copper chelators
Olivier Renaudet, UJF, DCM: cyclodecapeptide targeted to hepatocytes
Michel Jaquinod, Virginie Brun, CEA Grenoble, iRTSV, BGE: animal studies and pharmacokinetics
 

Current group members

Alexandra Botz, PhD 2013-2016
"Ln-Binding peptides to probe DNA"
Fanny Laporte, PhD 2014-2017
"Uranyl-binding peptides relevant to binding sites found in proteins"
Edit Mesterhazy, PhD 2014-2017 cotutelle with Pr Attila Jancso, Szeged Universitey, Hungary
"Copper(I)-binding peptides as potential treatments for Wilson disease"

Previous group members

phDs
Marie Monestier, 2 october 2015
"Targeting of copper chelators to the liver: recognition of glycoconjugates by lectins "
Laetitia Ancel, 22 november 2013
"DNA recognition by lanthanide-peptide complexes"
Anne-Solène Jullien, 4 October 2013
"Chelators targeted at the hepatocytes to treat metal overload"
Anaïs Pujol, 24 septembre 2010.
"Selective chelators of copper(I) to treat Wilson's disease"
Célia Bonnet, 6 July 2006.
"Complexation des cations lanthanides trivalents par des ligands d'origine biologique pour l'IRM : Structure, thermodynamique et méthodes"
Florence Bravard, 8 October2004.
"Complexation des cations lanthanides trivalents par des ligands azotés et oxygénés : études physico-chimiques de l'association et de la sélectivité en solution"
David Chapon, 26 October2001.
"Coordination des éléments 4f et 5f par des ligands cyclohexaniques polyfonctionnels : complexes homo- et hétérotrinucléiares en solution"

Post-docs
Bastien Boff (2013-2015)
Matthieu Starck (2012-2014)
Federico Cisnetti (2007-2009)
Pierre Rousselot (2005)
Olivier Sénèque (2003-2004)
Béatrice Maubert (2002)
Samuel Delagrange (2000)
 

Others

Faustine Robert, technician 2015
Céline Rivaux, technician 2012-2013
Vicky Gathu Technician 2010-2012

 

Organization of ICBIC16 in Grenoble

Teaching

since 2003. Master M2 Bioorganic and Bioinorganic chemistry, Université Joseph Fourier, Grenoble (Metals, Environment, Health)

since 2002. Licence L3, Université Joseph Fourier, Grenoble (Metals and chemistry)

1993-1997. Teacher at the Ecole Normale Supérieure de Lyon

 

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