Research Laboratories

Research Unit UMR6014


Rouen Normandie University, CNRS, INSA
Organic and Bioorganic Chemistry, Reactivity, Analysis
COBRA

Head


Pr Xavier Pannecoucke

Contact


CNRS UMR 6014
IRCOF
Rue Tesnière
76130 Mont Saint-Aignan

Phone: +33 235 52 2920
cobra@insa-rouen.fr
pannecoucke@insa-rouen.fr

Research Topics


  • Analysis and modelling
  • Bioorganic chemistry
  • Synthesis of fluorinated molecules
  • Organometallics
  • Heterocycles
  • Supramolecular and supported chemistry

Composition


  • 51 University and INSA researchers, 8 CNRS researchers, 19 engineers and technicians
  • 21 postdoctoral researchers, 47 doctoral students, 6 research master students

Facilities


  • NMR spectrometers (300, 400, 500 and 600 MHz)
  • Mass spectrometers
  • Chromatography (GC-MS, LC-MS)
  • Hyperbar synthesis apparatus
  • Fluorimeter
  • Peptide synthesizer

Activity


The COBRA unit is structured around six general scientific themes (analysis and modelling, bioorganic chemistry, synthesis of fluorinated molecules, organometallics, heterocycles & supramolecular and supported chemistry) and mainly works in the areas of organic, bioorganic, medicinal and analytic chemistryAmong applications, the preparation of compounds with biological interest, in collaboration with biology and pharmacy teams, takes a significant place.
The goal of the bioorganic component is the preparation of biologically active compounds for various domains (cancer, cardiovascular, SNC, antiviral), the vectorization of active substances and the synthesis of probes  and bioconjugates  used in molecular imaging.
The analysis and modelling component provides a support for the chemists to solve structural problems and develops its own research projects at the chemistry-biology interface. These projects are the structural characterization of peptide and protein domains by NMR and molecular modelling as well as the characterization of neuropeptide and GPCR interactions by NMR.
The fact that the COBRA teams benefit from national and international recognition is shown by the numerous invitations, collaborations, and financed projects (ANR, Oséo, FEDER, Interreg, PAI-PHC). The unit has developed strong working relationships with academics and industrial leaders in pharmacy and biotechnology by the Technopôle Chimie-Biologie Santé, the “center for competiveness” Cosmetic valley, and the federal group, PharmaValley. Most of the teams of the unit have developed during this period, strong and durable partnerships with the industry of the pharmaceutical sector (SERVIER, ORIL, SANOFI-AVENTIS, JANSSEN/CILAG, VALDEPHARM, NUFARM, ISOCHEM, EXONIT Therapeutics, ROQUETTE Bros., AAA) and from foundational chemistry (TOTAL, ARKEMA).  ). A compound is in clinical development (a Servier Laboratoires collaboration) and IRIS Biotech has commercialized three compounds originating from research in bioorganic chemistry from the group.  The group also brings important support for the creation of start ups in biotechnology by welcoming the parties involved on its premises.  QUIDD (medical imagery) and POLYINTELL (Innovative polymers for diagnostics) have been hosted for several years in the group. Two start-ups have been created due to the group’s work: TFChem in 2007 (fluorinated sugar for the pharmaceutical industry) and CNS vector in 2011 (vectorization of active principals and radiotracers on the central nervous system).

Main Contributions


  1. Analysis and modelling: solution structure of neuropeptides determined by NMR and molecular modelling. Some of studied neuropeptides have been discovered by U982 Inserm unity (U-II, PACAP, 26RFa). Molecular interaction studies of these neuropeptides with its target (GPCR).  Structural studies of protein domains (v-Myb, Kin17) by NMR and molecular modelling.
  2. Bioorganic chemistry: competences in bioconjugation, screening and total synthesis in order to create flexible, user-friendly and biocompatible chemical tools and in order to explore the living complex mechanisms (fluorescence, proteomics, medical imaging, protein chips, immunodetection, innovative strategies for active biomolecule discovery, fight against neurotoxics).
  3. Synthesis of fluorinated biomolecules: development of new fluorinated molecule synthesis methodologies. Application to syntheses of nucleotides, amino acids, sugar mimetics and peptides for use in pharmaceutical and agrochemical domains.
  4. Heterocycles: development of new synthesis methodologies and heterocycle functionalization. Development in pharmacological domain (cancer, Alzheimer’s disease, pain and inflammation. Preparation of new fluorescent probes used as photosensitizers for the photodynamic diagnostic and therapy.
  5. Supramolecular and supported chemistry: development of new contrast agents for IRM quantification of enzymatic activities. Biomimetic catalysts for neurotoxic agent neutralizing.


 


Main Publications


2013

  • Idriss H, Estour F, Zgani I, Barbot C, Biscotti A, Petit S, Galaup G, Hubert-Roux M, Nicol L, Mulder P, Gouhier G. Effect of the Second Coordination Sphere on New Contrast Agents Based on Cyclodextrin Scaffold for MRI Signal. RSC Adv J 2013, 3: 4531-4534.
  • Pierry C, Couve-Bonnaire S, Guilhaudis L, Neveu C, Marotte A, Lefranc B, Cahard D, Ségalas-Milazzo I, Leprince J and Pannecoucke X. Fluorinated pseudopeptide analogues of the neuropeptide 26RFa: synthesis, biological, and structural studies. Chembiochem 2013, 14: 1620-33.
    23940098

2012

  • Neveu C, Lefranc B, Tasseau O, Do-Rego JC, Bourmaud A, Chan P, Bauchat P, Le Marec O, Chuquet J, Guilhaudis L, Boutin JA, Ségalas-Milazzo I, Costentin J, Vaudry H, Baudy-Floc'h M, Vaudry D and Leprince J. Rational design of a low molecular weight, stable, potent, and long-lasting GPR103 aza-Îß3-pseudopeptide agonist. J Med Chem 2012, 55: 7516-24.
    22800498