Fluorinated Molecules and Peptides of Therapeutic Interest – FLUOPEPIT
Our team’s research focuses on new synthesis methodologies in peptide and organofluorine chemistry, dedicated to medicinal chemistry. Our laboratory has extensive experience in the design, synthesis, and biophysical evaluation of peptides and foldamers as modulators of protein-protein interactions (PPIs) involving β-sheet secondary structures. The team is particularly skilled in the field of PPIs involved in Alzheimer’s disease and type 2 diabetes. The research and development of new therapeutic compounds is supported by the molecular modeling group. The team is also recognized for its novel methods for synthesizing fluorinated amino and sulfur derivatives, non-natural fluorinated amino acids, and fluorinated peptidomimetics. Part of our research is dedicated to developing new environmentally friendly processes through photocatalysis and electrosynthesis, particularly in relation to fluorine chemistry and peptide chemistry.
Team members
Research Topics
- 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
Since long time we devoted to the reactivity of aldimine derivatives derived from fluoral which allowed an easy access to particularly interesting motifs as peptidomimetic units.
Fluoroalkyl alcohols TFE and HFIP possessed particular properties (acidity, polarity, high H-Bond donor, …), and allowed to perform clean and selective reactions without external promotor (Lewis acid, or Brönsted acid).
Our team is interested in the design of new radical precursors via photocatalysis, their application in the development of novel photocatalytic processes, and the study of associated photochemical mechanisms. A significant portion of our research focuses on fluorine chemistry, using fluorinated sulfoximines and their derivatives as sources of perfluoroalkyl radicals, as well as the generation of other fluorinated radicals such as SCF3, SeCF3, and OCF3. Other photochemical developments are also being investigated, notably involving pyridinium salts for the generation of oxygen or nitrogen radicals, and selective remote functionalization processes of α,β-unsaturated carbonyl compounds.
Our research aims to develop innovative and more targeted treatments against serious diseases such as cancer and pulmonary arterial hypertension (PAH).
The BioCIS molecular modeling group develops computational methods for studying biomolecular structures, dynamics, and interactions to support drug discovery and development. Our research involves structural modeling of proteins and protein-ligand interactions, simulations of biomolecular condensates and polymeric nanocarriers, and the design of peptide-derived inhibitors of protein-protein interactions. We also integrate deep-learning approaches with physics-based modeling to characterize biomolecular conformational ensembles, identify interaction interfaces, and support target identification.