A5012549346- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Fluorine in Organic Chemistry
- Alzheimer's disease research and treatments
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Protein Structure and Dynamics
- Synthesis and Catalytic Reactions
- Carbohydrate Chemistry and Synthesis
- Supramolecular Self-Assembly in Materials
- Asymmetric Hydrogenation and Catalysis
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- HIV/AIDS drug development and treatment
- Cyclopropane Reaction Mechanisms
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- HIV Research and Treatment
- Crystallography and molecular interactions
- Peptidase Inhibition and Analysis
- Metal complexes synthesis and properties
- Cholinesterase and Neurodegenerative Diseases
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and Biological Evaluation
- Computational Drug Discovery Methods
Université Paris-Saclay
2005-2024
Centre National de la Recherche Scientifique
2015-2024
Laboratoire des Biomolécules
2017-2021
Laboratoire d'Énergétique Moléculaire et Macroscopique, Combustion
2013-2020
Université Paris-Sud
2010-2019
Molécules d'Intérêt Biologique
2019
Pharmac
2014-2017
Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique
2011-2015
Institut Galien Paris-Saclay
2008-2015
Université Paris Cité
1998-2007
This account summarizes our work on the synthesis of fluorinated peptidomimetics integrating N-CF2R triazole functions. Emphasis is placed development foldamers possessing preferential conformations. We have shown that these are potential modulators amyloid protein aggregation. Ce compte rendu résume nos travaux de synthèse peptidomimétiques fluorés intégrant la fonction N-CF2R. L'accent est mis sur le développement foldamères possédant des conformations préférentielles. Nous avons montré...
A perfect fit: The nanomolar affinity of a diketopiperazine-derived cyclic RGD-peptidomimetic for the integrin αvβ3 receptor can be attributed to its high structural pre-organization. trans-diketopiperazine scaffold induces an extended RGD disposition permitting all important interactions with extracellular domain integrin. metal ion in metal-ion-dependent adhesion site region is represented by magenta sphere. Detailed facts importance specialist readers are published as "Supporting...
Alzheimer's disease is a neurodegenerative disorder linked to oligomerization and fibrillization of amyloid β peptides, with Aβ1-42 being the most aggregative neurotoxic one. We report herein synthesis conformational analysis Aβ1-42-amyloid related β-hairpin peptidomimetics, built on piperidine-pyrrolidine semi rigid β-turn inducer bearing two small recognition peptide sequences, designed oligomeric fibril structures Aβ1-42. According these stable or dynamic equilibrium between possible...
How anti-Alzheimer's drug candidates that reduce amyloid 1-42 peptide fibrillization interact with the most neurotoxic species is far from being understood. We report herein capacity of sugar-based peptidomimetics to inhibit both Aβ1-42 early oligomerization and fibrillization. A wide range bio- physicochemical techniques, such as a new capillary electrophoresis method, nuclear magnetic resonance, surface plasmon were used identify how these molecules can delay aggregation Aβ1-42....
A methodology for the asymmetric synthesis of CF 3 ‐β‐proline and ‐six‐membered cyclic amino acids has been developed starting from readily available N ‐ tert ‐butanesulfinyl‐(3,3,3)‐trifluoroacetaldimine. The Zn‐mediated allylation followed by an intramolecular 5‐ endo trig cyclisation afforded ‐β‐proline, whereas were obtained using a ring‐closing‐metathesis protocol ‐aminodienes.
Introduction of CF 3 -oxazolidines in polyproline type II foldamers maintains PPII helicity, non-cytotoxicity and stability towards proteolysis. The groups enhanced hydrophobicity are used as easy-to-handle 19 F NMR probes.
Abstract 1,4‐Diazabicyclo[2.2.2]octane‐catalyzed asymmetric aza‐Baylis–Hillman (ABH) reaction of ( R )‐ N ‐ tert ‐butanesulfinyl‐(3,3,3)‐trifluoroacetaldimine with various Michael acceptors proceeds exceptionally high rates and stereochemical outcome. This ABH approach provides convenient practical access to previously unknown enantiomerically pure α‐methylene β‐CF 3 β‐amino esters/acids, forthright useable for peptide synthesis.
We report an improved CE method to monitor in vitro the self-assembly of monomeric amyloid β-peptide (42 amino acids β-peptide, Aβ1-42 ) and particular crucial early steps involved formation neurotoxic oligomers. In order start kinetics from beginning, sample preparation was optimized provide samples containing exclusively form. The also using a dynamic coating by reducing separation distance. Using this method, disappearance monomer as well progressive four species during process can now be...
Abstract Type 2 diabetes (T2D) and Alzheimer's disease (AD) belong to the 10 deadliest diseases are sorely lacking in effective treatments. Both pathologies part of degenerative disorders named amyloidoses, which involve misfolding aggregation amyloid peptides, hIAPP for T2D Aβ 1‐42 AD. While inhibitors have been essentially designed target β‐sheet‐rich structures composing toxic oligomers fibrils these strategy aiming at trapping non‐toxic monomers their helical native conformation has...
A combinatorial library of 125 chiral Schiff base ligands 5 was synthesized with the use solution-phase parallel synthesis and solid-phase extraction (SPE) techniques to scavenge excess reagents reaction by-products avoid chromatography. The synthetic methodology coupled five N-Boc-protected beta-amino sulfonyl chlorides 1a-e different amines 2f-j give 25 N-Boc sulfonamides 3, which were in turn deprotected salicylaldehydes 4p-t good yields sufficient purity be used ligand-catalyzed...
Recently, human 5-HT4 receptors have been demonstrated to form constitutive dimers in living cells. To evaluate the role of dimerization on receptor function, we investigated conception and synthesis bivalent molecules able influence process. Their is based a model dimer derived from protein/protein docking experiments. These ligands are constituted by two ML10302 units, specific ligand, linked through spacer different sizes natures. synthesized were evaluated binding assays cyclic AMP...
Abstract Novel fluorinated foldamers based on aminomethyl‐1,4‐triazolyl‐difluoroacetic acid (1,4‐Tz−CF 2 ) units were synthesized and their conformational behaviour was studied by NMR molecular dynamics. Their activity the aggregation of human islet amyloid polypeptide (hIAPP) protein evaluated fluorescence spectroscopy mass spectrometry. The fluorine labelling these allowed analysis interaction with target protein. We demonstrated that preferred extended conformation homotriazolamers...
New "molecular tongs" based on naphthalene and quinoline scaffolds linked to two peptidic strands were synthesized. They designed prevent dimerization of HIV-1 protease by targeting the antiparallel β-sheet involving N- C-termini each monomer. Compared previously described (Bouras, A.; Boggetto, N.; Benatalah, Z.; de Rosny, E.; Sicsic, S.; Reboux-Ravaud, M. J. Med. Chem. 1999, 42, 957−962), main different structural features introduced: positively charged as a new scaffold displaying...
We have designed, synthesized, and evaluated the inhibitory activity metabolic stability of new peptidomimetic molecular tongs based on a naphthalene scaffold for inhibiting HIV-1 protease dimerization. Peptidomimetic motifs were inserted into one peptidic strand to make it resistant proteolysis. The character can be decreased without changing way they inhibit Mutated proteases are also vulnerable dimerization inhibitors, multimutated ANAM-11 is twice as sensitive inhibitor compared...
From carboxylic acid trifluoromethyl aziridines, halogeno β-lactams were obtained stereoselectively by ring expansion. Different conditions such as radical, organometallic reactions allowed easy and selective access to CF3-β-lactams substituted at the C-3 position.
The formation of an NCF3 bond or NCF2R still remains scarce. An efficient direct electrophilic amination fluoroalkyl groups was developed. Difluoroenoxysilanes reacted easily on azodicarboxylate derivatives. These results led to a novel family and NCF2 hydrazine
Abstract Misfolding and aggregation of amyloid β1–42 peptide (Aβ1–42) play a central role in the pathogenesis Alzheimer's disease (AD). Targeting highly cytotoxic oligomeric species formed during early stages process represents promising therapeutic strategy to reduce toxicity associated with Aβ1–42. Currently, thioflavin T (ThT) assay is only established spectrofluorometric method screen inhibitors. The success ThT that it can detect Aβ1–42 aggregates high β‐sheet content, such as...
A library of chiral ligands 5, obtained with a modular building block strategy from the coupling sulfonyl chlorides 1a−e, amines 2f−j and aldehydes 4p−t, was screened in enantioselective, copper-catalysed conjugate addition Et2Zn to aromatic heteroaromatic nitroolefins 6a−e. multisubstrate high-throughput screening realised by performing reactions on an equimolar mixture substrates 6c−d. Good for reaction 6a−e (ee’s up 58%) were identified.