A5052630873- Nicotinic Acetylcholine Receptors Study
- HIV Research and Treatment
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- bioluminescence and chemiluminescence research
- Chemical Reactions and Mechanisms
- Oxidative Organic Chemistry Reactions
- Insect and Pesticide Research
- Neuroscience and Neuropharmacology Research
- Venomous Animal Envenomation and Studies
- Chemical Reactions and Isotopes
- Immunotherapy and Immune Responses
- Synthesis and Catalytic Reactions
- RNA Interference and Gene Delivery
- Toxin Mechanisms and Immunotoxins
- Synthesis and Biological Evaluation
- SARS-CoV-2 and COVID-19 Research
- Inflammatory Myopathies and Dermatomyositis
- Healthcare and Venom Research
- Herpesvirus Infections and Treatments
- Chemical Reaction Mechanisms
Inserm
2012-2025
Université de Strasbourg
2024-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2013-2024
CEA Paris-Saclay
2002-2024
Université Paris-Saclay
2017-2024
Technologies pour la Santé
2020-2024
Institut de Biologie et Technologies
2012-2021
National Institute of Allergy and Infectious Diseases
2013
National Institutes of Health
2013
Direction des énergies
2006
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...
A robust, click-chemistry-inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable all carbon isotopes (11 C, 13 14 C), is based on the direct functionalization dioxide: universal building block radiolabeling. The strategy operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, demonstrates superior reactivity as compared to previously reported systems. With this...
Inflammatory myopathies (IM) are a group of severe autoimmune diseases, sharing some similarities, whose cause is unknown and treatment empirical.While C-protein-induced myositis (CIM), the most currently used mouse model IM, has removed roadblocks to understand improve it only been partially characterised its generation limited by poor reproducibility. This study aimed at optimising characterisation CIM. In silico analysis was run identify top three specific immunogenic regions C-protein....
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...
ABSTRACT Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface envelope glycoprotein (gp120) involved in sequential binding to host CD4 and chemokine receptors have been characterized. While these epitopes show low diversity among various isolates, employs many strategies evade humoral immune response toward sensitive sites, including a carbohydrate shield, accessibility buried cavities, conformational masking. Using trimeric gp140, free or bound mimic, as...
In complement to an effective vaccine, development of potent anti-HIV microbicides remains important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic sCD4 presented on 27 amino-acid stable scaffold, inhibits broad range HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report M48U1 efficiently HIV-1Ba-L human mucosal explants cervical and colorectal tissues. vivo efficacy was evaluated nonhuman primate (NHP) model challenge with...
Amphipols (APols) are short amphipathic polymers that stabilize membrane proteins (MPs) in aqueous solutions. In the present study, A8-35, a polyacrylate-based APol, was grafted with hexahistidine tags (His6-tags). The synthesis and characterization of this novel functionalized named HistAPol, described. Its ability to immobilize MPs on nickel ion-bearing surfaces tested using two complementary methods, immobilized metal affinity chromatography (IMAC) surface plasmon resonance (SPR)....
CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by HIV co-receptor CCR5 and CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown elicit CD4i antibody responses in monkeys, which correlated with control virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, Charurat, M., Harris, I., Galmin, L., Pal, (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477–17482). Because inclusion a vaccine formulation should be avoided, due...
The conserved HIV-1 site of coreceptor binding is protected from antibody-directed neutralization by conformational and steric restrictions. While inaccessible to most human antibodies, the has been shown be accessed antibody fragments. In this study, we used X-ray crystallography, surface plasmon resonance, pseudovirus characterize gp120-envelope glycoprotein recognition a heavy chain-only llama antibody, named JM4. We describe full-length IgG2b IgG3 versions JM4 that target...
Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 CD4 cannot fully accessed natural amino acids. To increase gp120 affinity for a family CD4-mimetic miniproteins (miniCD4s), we targeted the Phe43 with 11 non-natural derivatives, introduced into miniCD4 named M48 (1). The best derivative, M48U12 (13), bound YU2 8 pM showed...
Abstract Background Binding of the viral envelope protein (Env), and particularly its gp120 subunit, to cellular CD4 receptor is first essential step HIV-1 entry process. The binding site (CD4bs) gp120, especially a recessed cavity occupied by Phe43 residue, are known be highly conserved among different circulating subtypes therefore constitute interesting targets for vaccine drug design. miniCD4 proteins promising class CD4bs inhibitors. Studying virus evolution under pressure inhibitors...
The identification of HIV-1 envelope glycoprotein (Env) structures that can generate broadly neutralizing antibodies (BNAbs) is pivotal to the development a successful vaccine against aimed at eliciting effective humoral immune responses. To end, production novel Env structure(s) might induce BNAbs by presentation conserved epitopes, which are otherwise occluded, critical. Here, we focus on structure stabilizes in conformation representative its primary (CD4) receptor-bound state, thereby...
Abstract A robust, click‐chemistry‐inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable all carbon isotopes ( 11 C, 13 14 C), is based on the direct functionalization dioxide: universal building block radiolabeling. The strategy operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, demonstrates superior reactivity as compared to previously reported systems. With...
de niveau recherche, publiés ou non, émanant des établissements d'enseignement et recherche français étrangers, laboratoires publics privés.
The renin-angiotensin system (RAS) is one of the main regulatory systems cardiovascular homeostasis. It mainly composed angiotensin-converting enzyme (ACE) and angiotensin II receptors AT1 AT2. ACE are targets choice for treatment hypertension, whereas AT2 receptor still not exploited due to lack knowledge its physiological properties. Peptide toxins from venoms display multiple biological functions associated with varied chemical structural If Brazilian viper have been described inhibit...
Many molecular targets for cancer therapy are located in the cytosol. Therapeutic macromolecules generally not able to spontaneously translocate across membranes reach these cytosolic targets. Therefore a strong need exists tools that enhance delivery. Shiga toxin B-subunit (STxB) is used deliver therapeutic principles disease-relevant cells express its receptor, glycolipid Gb3. Based on naturally existing membrane translocation capacity, STxB delivers antigens cytosol of Gb3-positive...
We determined the distances separating five functionally important residues (Gln(10), Lys(27), Trp(29), Arg(33), and Lys(47)) of a three-fingered snake neurotoxin from reduced disulfide bond alpha(Cys(192)-Cys(193)) located at alphagamma interface Torpedo nicotinic acetylcholine receptor. Each toxin position was substituted individually for cysteine, which then linked to maleimido moiety through three different spacers, varying in length 10 22 A. estimated coupling efficiency between 15...
1-[4-(N-Chlorocarbonyl-N-methylamino)phenyl]-2-(phenylsulfonyl) diazene is the first bifunctional reagent containing a potential photoactivatable arenediazonium function. The synthesis and chemical properties of are described, in particular coupling reactions with series nucleophiles (primary secondary amines phenolate derivative) subsequent deprotection reaction to corresponding diazonium salt.