A5017059477- Nicotinic Acetylcholine Receptors Study
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Venomous Animal Envenomation and Studies
- Marine Toxins and Detection Methods
- Insect and Pesticide Research
- Toxin Mechanisms and Immunotoxins
- Healthcare and Venom Research
- Neurobiology and Insect Physiology Research
- Cholinesterase and Neurodegenerative Diseases
- Chemical Synthesis and Analysis
- Neuroscience and Neuropharmacology Research
- Antimicrobial Peptides and Activities
- Photoreceptor and optogenetics research
- Nitric Oxide and Endothelin Effects
- Biochemical and Structural Characterization
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and Biological Evaluation
- Neuropeptides and Animal Physiology
- Chemical Reactions and Isotopes
- Insect-Plant Interactions and Control
- Transgenic Plants and Applications
- Pain Mechanisms and Treatments
- Redox biology and oxidative stress
- Computational Drug Discovery Methods
Technologies pour la Santé
2018-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2016-2025
CEA Paris-Saclay
2016-2025
Université Paris-Saclay
2017-2025
Centre National de la Recherche Scientifique
1989-2024
Frédéric Joliot Institute for Life Sciences
2017-2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2020-2023
Institut de Biologie et Technologies
2013-2022
Université Paris-Sud
2020
University of California, Santa Barbara
2020
Boiga dendrophila (mangrove catsnake) is a colubrid snake that lives in Southeast Asian lowland rainforests and mangrove swamps preys primarily on birds. We have isolated, purified, sequenced novel toxin from its venom, which we named denmotoxin. It monomeric polypeptide of 77 amino acid residues with five disulfide bridges. In organ bath experiments, it displayed potent postsynaptic neuromuscular activity irreversibly inhibited indirectly stimulated twitches chick biventer cervicis...
Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal epilepsy (ADNFLE). In several ADNFLE families, mutations were identified the nAChR α4 or β2 subunit, which together compose main cerebral nAChR. Electrophysiological assessment using vitro expression systems indicated gain function mutant receptors. However precise mechanisms by they contribute to pathogenesis focal remain obscure, especially since α4β2 nAChRs...
Spirolide and gymnodimine macrocyclic imine phycotoxins belong to an emerging class of chemical agents associated with marine algal blooms shellfish toxicity. Analysis 13-desmethyl spirolide C A by binding voltage-clamp recordings on muscle-type α1 2 βγδ neuronal α3β2 α4β2 nicotinic acetylcholine receptors reveals subnanomolar affinities, potent antagonism, limited subtype selectivity. Their acetylcholine-binding proteins (AChBP), as soluble receptor surrogates, exhibits picomolar affinities...
Pinnatoxins belong to an emerging class of potent marine toxins the cyclic imine group. Detailed studies their biological effects have been impeded by unavailability complex natural product from sources. This work describes development a robust, scalable synthetic sequence relying on convergent strategy that delivered sufficient amount toxin for detailed and its commercialization use other research groups regulatory agencies. A central transformation in synthesis is highly diastereoselective...
Long chain and short curaremimetic toxins from snakes possess 66–74 residues with five disulfide bonds 60–62 four bonds, respectively. Despite their structural differences all of these bind high affinity to the peripheral nicotinic acetylcholine receptors (AChR). Binding experiments have now revealed that long only, like neuronal κ-bungarotoxin, a for chimeric form α7 receptor, <i>K</i> <sub>d</sub> values ranging about 1 12 nm. In contrast, other receptor low affinity, with<i>K</i> between...
Abstract Gymnodimines (GYMs) are phycotoxins exhibiting unusual structural features including a spirocyclic imine ring system and trisubstituted tetrahydrofuran embedded within 16‐membered macrocycle. The toxic potential the mechanism of action GYM‐A, highly purified from contaminated clams, have been assessed. GYM‐A in isolated mouse phrenic hemidiaphragm preparations produced concentration‐ time‐dependent block twitch responses evoked by nerve stimulation, without affecting directly...
Transcripts for α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits are found in diverse tissues. The function of α9α10 nAChRs is best known mechanosensory cochlear hair cells, but elsewhere their roles less well understood. have been implicated as analgesic targets α-conotoxins that block produce analgesia. However, some these peptides show large potency differences between species. Additionally several studies indicated conotoxins may also activate GABAB receptors (GABABRs). To...
Long chain curarimimetic toxins from snake venom bind with high affinities to both muscular type nicotinic acetylcholine receptors (AChRs) (Kd in the pm range) and neuronal α7-AChRs nmrange). To understand molecular basis of this dual function, we submitted α-cobratoxin (α-Cbtx), a typical long toxin, an extensive mutational analysis. By exploring 36 toxin mutants, found that Trp-25, Asp-27, Phe-29, Arg-33, Arg-36, Phe-65 are involved binding Torpedo(Antil, S., Servent, D., Ménez, A. (1999)...
To understand how snake neurotoxins interact with nicotinic acetylcholine receptors, we have elaborated an experimentally based model of the alpha-cobratoxin-alpha7 receptor complex. This was achieved by using (i) a three-dimensional alpha7 extracellular domain derived from crystallographic structure homologous acetylcholine-binding protein, (ii) previously solved x-ray toxin, and (iii) nine pairs residues identified cycle-mutant experiments to make contacts between alpha-cobratoxin...
α-Cobratoxin, a long chain curaremimetic toxin from Naja kaouthia venom, was produced recombinantly (rα-Cbtx) Escherichia coli. It indistinguishable the snake toxin. Mutations at 8 of 29 explored positions resulted in affinity decreases for Torpedo receptor with ΔΔG higher than 1.1 kcal/mol. These are R33E > K49E D27R K23E F29A ≥ W25A R36A F65A. cover homogeneous surface approximately 880 Å2 and mostly belong to second loop, except Lys-49 Phe-65 which are, respectively, on third loop...
Objectives : Lung cancer is the most common cause of death in world. Cigarette smoking represents major risk factor. Nicotine, an active component cigarettes, can induce cell proliferation, angiogenesis and apoptosis resistance. All these events are mediated through nicotinic acetylcholine receptor (nAChR) expressed on lung cells. We speculate that new insights into pathophysiological roles nAChR may lead to therapeutic avenues reduce non‐small (NSCLC) tumour growth. Materials methods Human...
Disulfide-rich proteins or DRPs are versatile bioactive compounds that encompass a wide variety of pharmacological, therapeutic, and/or biotechnological applications. Still, the production in sufficient quantities is major bottleneck for their complete structural functional characterization. Recombinant expression such small containing multiple disulfide bonds bacteria E. coli considered difficult and general methods protocols, particularly on high throughput scale, limited. Here we report...
We investigated whether protein stability controls antigen presentation using a four disulfide-containing snake toxin and three derivatives carrying one or two mutations (L1A, L1A/H4Y, H4Y). These were anticipated to increase (H4Y) decrease (L1A) the non-covalent stabilizing interactions, H4Y being naturally frequently observed in neurotoxins. The chemically synthesized shared similar three-dimensional structure, biological activity, T epitope pattern. However, they displayed differential...
Abstract Nicotinic acetylcholine receptors (nAChR) are expressed on normal bronchial epithelial and nonsmall cell lung cancer (NSCLC) cells involved in growth regulation. Nicotine induced proliferation. The purpose of this study was to determine if interruption autocrine nicotinic cholinergic signaling might inhibit A549 NSCLC growth. For α‐Cobratoxin (α‐CbT), a high affinity α7‐nAChR antagonist studied. Cell decrease evaluated by Clonogenic MTT assays. Evidence apoptosis identified staining...
Mambalgins are peptides isolated from mamba venom that specifically inhibit a set of acid-sensing ion channels (ASICs) to relieve pain. We show here the first full stepwise solid phase peptide synthesis mambalgin-1 and confirm biological activity synthetic toxin both in vitro vivo. also report determination its three-dimensional crystal structure showing differences with previously described NMR structures. Finally, functional domain by which inhibits ASIC1a was identified loop II more...
Neonicotinoid insecticides act on nicotinic acetylcholine receptor and are particularly effective against sucking pests. They widely used in crops protection to fight aphids, which cause severe damage. In the present study we evaluated susceptibility of pea aphid Acyrthosiphon pisum commonly neonicotinoid imidacloprid (IMI), thiamethoxam (TMX) clothianidin (CLT). Binding studies membrane preparations revealed existence high low-affinity binding sites for [3H]-IMI (Kd 0.16±0.04 nM 41.7±5.9...