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Tau fibrils are with A-beta fibrils the main actors responsible for the destruction of neurons in Alzheimer's disease. Amyloid fibril formation is also involved in other neurodegenerative diseases such as Parkinson’s and Huntington's disease. In this context, we aim to synthesize:
- Aromatic and peptide compounds capable of inhibiting and labeling amyloid fibers for therapeutic and diagnostic purposes. In particular, we developed clickable 2,5-diketopiperazines which are of interest as scaffolds for preparing multivalent inhibitors (Org. Biomol Chem. 2014), and for brain delivering of peptides (J. Label Compd. Radiopharm. 2016).
- Tau fibrils models based on the R3 repeat region of tau protein. These models easier to produce than the full-length protein are practical tools for preliminary screening of inhibitors or markers of tau fibrils. A small library of aurones have been studied for their propensity as beta-sheet binding motifs (ACS Chem. Neurosci. 2016). The tau R3 model of 24 amino acids length adopts a beta-sheet structure in circular dichroism and forms fibrils very similar in AFM to those obtained from the native tau protein (AFM experiments in collaboration with H. Bonnet). This model has been used to prepare anti-tau nanobodies (WO/2018/078140).

Collaborations:
M. Moulin Sallanon and C. Ghezzi (Laboratoire des Radiopharmaceutiques Biocliniques, Grenoble)
A. Boumendjel and M. Peuchmaur (Département de Pharmacochimie Moléculaire, Grenoble)
M. Demeunynck (Département de Pharmacochimie Moléculaire, Grenoble)
B. Furdui and R. Dinica (Faculté des sciences, Galati, Romania)