Présentation du CNRS Présentation de l′Université Faculté de Pharmacie


Sur ce site

Accueil > Équipes de recherche > Molécules Fluorées et Peptides d’Intérêt Thérapeutique - FLUOPEPIT > Amyloid protein aggregation inhibitors

Amyloid protein aggregation inhibitors

  • Comprehensive understanding of the aggregation process of amyloid proteins : Aβ1-42 involved in Alzheimer’s disease and hIAPP involved in type II Diabetes
  • Inhibition of the aggregation process by the design of small peptides and peptidomimetics
  • Discovery of selective diagnostic tools to detect toxic soluble species of amyloid proteins

 Design and synthesis of peptides and peptidomimetic inhibitors

 Study of amyloid aggregation, peptides and peptidomimetic inhibitors activities and ligand/protein interactions.

The study of the aggregation of the amyloid proteins and the validation of the activity of the compounds synthesized are performed by various biophysical tools, available in our laboratory or in collaboration with other team at Paris Sud University.

  • Kinetics of fibrillization is assayed by Thioflavin-T (ThT) fluorescence spectroscopy and by transmission electron microscopy (TEM).
  • Oligomeric forms of amyloid proteins is detected mainly by Capillary electrophoresis and IMS-MS.
    Capillary electrophoresis (CE) : In collaboration with Prof. Myriam Taverna (Institut Galien, Univ. Paris Sud), we recently developed a method to monitor easily and reproducibly the very early steps of Aβ 1-42 oligomerization kinetics (Electrophoresis, 2014, 35, 3302) and of hIAPP oligomerization kinetics (J. Chromatogr. A. 2018, These techniques are now used routinely to evaluate our compounds.
    IMS-MS is performed on hIAPP, in collaboration with Prof. G. Van Der Rest (LCP, Univ. Paris Sud)
  • The interaction of the synthesized compounds with the amyloid species is performed by :
  1. Liquid-state NMR : Saturation-Transfer Difference (STD), 2D 1H-15N and 2D 1H-13C HSQC spectra of 15N,13C-labelled proteins (see for ex. J. Med Chem. 2016, 59, 2025) are performed in collaboration with Prof. O. Lequin (UPMC).
  2. Surface plasmon resonance (SPR) : we optimized the grafting/regeneration of the chip and characterized the immobilized Aβ1-42. ( J. Med Chem. 2016, 59, 2025)
  • Cells (human neuroblastoma cells) have been exposed to oligomeric forms of Aβ1-42, at the University of Lancaster (Collaboration with Prof. David Allsop, Lancaster Univ., UK). Markers related to membrane integrity, changing calcium ion levels, mitochondrial function, oxidative stress, ER stress, proteostasis, and the cytoskeleton, were also assessed in these cells (J. Med Chem. 2016, 59, 2025 ; Chem. Sci. 2017, 8, 1295).