A5039537177- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Biochemical and Structural Characterization
- Advanced NMR Techniques and Applications
- Peptidase Inhibition and Analysis
- Carbohydrate Chemistry and Synthesis
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Metabolomics and Mass Spectrometry Studies
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Advanced MRI Techniques and Applications
- Malaria Research and Control
- Protein Hydrolysis and Bioactive Peptides
- Lipid Membrane Structure and Behavior
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Cellular transport and secretion
- Molecular spectroscopy and chirality
- Protein Structure and Dynamics
- Atomic and Subatomic Physics Research
- Electrocatalysts for Energy Conversion
- Fuel Cells and Related Materials
- Bioactive Compounds and Antitumor Agents
- Protease and Inhibitor Mechanisms
Institut Pasteur de Lille
2014-2025
Inserm
2021-2025
Université de Lille
2013-2025
Centre National de la Recherche Scientifique
2012-2025
Centre Hospitalier Universitaire de Lille
2021-2025
Human Factors (Norway)
2025
Integra (United States)
2024
Unité de Glycobiologie Structurale et Fonctionnelle
2018-2023
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2023
Institut de Biologie Structurale
2020-2022
SeEA latent selenoester: go fast by switching to selenium.
Abstract The main protease (3CLp) of the SARS‐CoV‐2, causative agent for COVID‐19 pandemic, is one targets drug development. To be active, 3CLp relies on a complex interplay between dimerization, active site flexibility, and allosteric regulation. deciphering these mechanisms crucial step to enable search inhibitors. In this context, using NMR spectroscopy, we studied conformation dimeric from SARS‐CoV‐2 monitored ligand binding, based signal assignments. We performed fragment‐based...
Abstract Tau proteins as neurofibrillary tangles are one of the molecular hallmarks Alzheimer’s disease (AD) and play a central role in tauopathies, group age-related neurodegenerative disorders. The filament cores from diverse tauopathies share common region tau consisting R3-R4 microtubule-binding repeats part C-terminal domain, but present structural polymorphism. Unlike fibril structure, PTM signature found neuronal inclusions, more particularly hyperphosphorylation, is variable between...
Protein tyrosine kinase 2 (Pyk2), also known as focal adhesion 2, and 1 (Fak1) are two related nonreceptor kinases (hereafter referred to FAKs). Here, we focused on characterizing a linker region of the FAK proteins KFL for Kinase FAT Linker), which in case Pyk2 has previously been shown play functional role calcium sensing through its interaction with calmodulin. Using structural nuclear magnetic resonance spectroscopy, provide chemical shift assignments KFLs, defining their conformational...
The use of the N-acetoacetyl protecting group for N-terminal cysteine residue enabled creation an efficient and mild one-pot native chemical ligation/SEA ligation sequence giving access to large cyclic peptides.
Bridging integrator-1 (BIN1) gene is associated with an increased risk to develop Alzheimer's disease, a tauopathy characterized by intra-neuronal accumulation of phosphorylated Tau protein as paired helical filaments. Direct interaction BIN1 and proteins was demonstrated be mediated through SH3 C-terminal domain (210-240) peptide within proline-rich domain. We previously showed that decreased phosphorylation domain, at least T231. In addition, the BIN1/Tau dynamic equilibrium between closed...
Bis(2-sulfanylethyl)amino PEG resin gives access to large peptide thioester segments and functional SUMO-1 conjugates.
SUMOylation constitutes a major post-translational modification (PTM) used by the eukaryote cellular machinery to modulate protein interactions of targeted proteins. The small ubiquitin-like modifier-1 (SUMO-1) features central and conserved cysteine residue (Cys52) that is located in hydrophobic core tight contact with Phe65, suggesting occurrence an S/π interaction. To investigate importance Cys52 on SUMO-1 thermal stability biochemical properties, we produced total chemical synthesis or...
Chemical protein synthesis gives access to well-defined native or modified proteins that are useful for studying structure and function. The majority of synthesized up now have been produced using chemical ligation (NCL) in solution. Although there significant advantages assembling large peptides by solid phase ligation, reports such approaches rare. We report a novel method which relies on the chemistry acetoacetyl group ketoxime attachment peptide support, tandem...
Inspired by natural sideromycins, the conjugation of antibiotics to siderophores is an attractive strategy facilitate "Trojan horse" delivery into bacteria. Genome analysis a soil bacterium, Dactylosporangium fulvum, found "hybrid" biosynthetic gene cluster responsible for production both antibiotic, pyridomycin, and novel chlorocatechol-containing siderophore named chlorodactyloferrin. While these products were synthesized independently, culture supernatant also identified conjugate...
Selenopeptides can be transamidated by cysteinyl peptides in water using mild conditions (pH 5.5, 37 °C) the presence of an arylthiol catalyst. Similar also catalyze metathesis selenopeptides. The usefulness selenophosphine derived from TCEP (TCEP═Se) for inhibiting TCEP-induced deselenization selenocysteine residue is reported.
Bis(2-sulfanylethyl)amido (SEA) side-chain derivatives of aspartic and glutamic acids enable the synthesis tail-to-side chain cyclic or branched peptides using standard Fmoc-SPPS followed by SEA native peptide ligation.
Protein total chemical synthesis enables the atom-by-atom control of protein structure and therefore has a great potential for studying function. Native ligation C-terminal peptide thioesters with N-terminal cysteinyl peptides related methodologies are central to field synthesis. Consequently, methods enabling facile using Fmoc-SPPS value. Herein, we provide detailed protocol preparation bis(2-sulfanylethyl)amino polystyrene resin as starting point bis(2-sulfanylethyl)amido derived from...
Reaction of bis(2-sulfanylethyl)amido (SEA) peptides with triisopropylsilylthiol in water at neutral pH yields peptide thiocarboxylates. An alkylthioester derived from β-alanine was used to trap the released bis(2-sulfanylethyl)amine and displace equilibrium toward thiocarboxylate.
SEA ligation proceeds chemoselectively at pH 3, i.e., a where the O-acyl isopeptides are protected by protonation. This property was used for synthesizing unprotected in water, starting from peptide segments which easily accessible Fmoc SPPS.
Peptide alkylthioesters can be prepared at neutral pH by <italic>bis</italic>(2-sulfanylethyl)amide-thiol exchange.
The resistance of gram-negative bacteria to silver ions is mediated by a efflux pump, which mainly relies on tripartite complex SilCBA, metallochaperone SilF and an intrinsically disordered protein SilE. However, the precise mechanism are extruded from cell different roles SilB, SilF, SilE remain poorly understood. To address these questions, we employed nuclear magnetic resonance mass spectrometry investigate interplay between proteins. We first solved solution structures in its free...
Amodiaquine remains one of the most prescribed antimalarial 4-aminoquinoline. To assess importance 4-hydroxyl group and subsequent hydrogen bond in activity amodiaquine (AQ), a series new analogues which this functionality was replaced by various amino groups synthesized. The incorporation 3- pyrrolidinamino instead 3-diethylamino function AQ allowed development parallel amopyroquine derivatives. compounds were screened against both chloroquine (CQ)-sensitive – resistant strains Plasmodium...
Abstract 4′‐Substituted analogues of amodiaquine and amopyroquine were synthesized using Csp 2 –Csp 3 Suzuki–Miyaura cross‐coupling reactions as the key step. The new derivatives found to be active against both chloroquine (CQ)‐sensitive CQ‐resistant strains P. falciparum , with IC 50 values in range 7–200 n M ; one compound showed vivo activity. magnified image prophylactic administration (AQ), a 4‐aminoquinoline antimalarial drug, has been associated side effects such agranulocytosis liver...
A bis(2-sulfanylethyl)amido group reacts significantly faster with cysteinyl peptides when installed on the C-terminal end of a peptide in comparison side-chain Asp and Glu. This property enabled design kinetically controlled chemoselective cyclization reaction, giving straightforward access to cyclic branched one pot.
Feline immunodeficiency virus (FIV) is a veterinary infective agent for which there currently no efficient drug available. Drugs targeting the lentivirus capsid are under development treatment of human 1 (HIV-1). Here we describe lead compound that interacts with FIV capsid. This compound, 696, modulates in vitro assembly and stabilizes assembled protein. To decipher mechanism binding this to protein, performed first nuclear magnetic resonance (NMR) assignment p24 Experimental NMR chemical...
1H-1H coupling constants are one of the primary sources information for NMR structural analysis. Several selective 2DJ experiments have been proposed that allow their individual measurement at pure shift resolution. However, all these fail in not uncommon case when coupled protons very close chemical shifts. Firstly, between with overlapping multiplets is inaccessible due to inability a frequency-selective pulse invert just them. Secondly, strong condition affects accuracy measurements...