A5043407939- Chemical Synthesis and Analysis
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Neuroendocrine Tumor Research Advances
- Click Chemistry and Applications
- Antimicrobial Resistance in Staphylococcus
- HIV/AIDS drug development and treatment
- Bacterial Genetics and Biotechnology
- Carbohydrate Chemistry and Synthesis
- Lung Cancer Research Studies
- Wnt/β-catenin signaling in development and cancer
- Antimicrobial Peptides and Activities
- Pain Mechanisms and Treatments
- Angiogenesis and VEGF in Cancer
- Cancer-related gene regulation
- X-ray Diffraction in Crystallography
- Protease and Inhibitor Mechanisms
- Asymmetric Synthesis and Catalysis
- Crystallization and Solubility Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Blood Coagulation and Thrombosis Mechanisms
- Antibiotic Resistance in Bacteria
- Signaling Pathways in Disease
École Nationale Supérieure de Chimie de Montpellier
2015-2021
Université de Montpellier
2015-2021
Centre National de la Recherche Scientifique
2012-2021
Institut des Biomolécules Max Mousseron
2015-2021
University of Insubria
2013-2017
Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique
2012-2014
Université Paris-Sud
2012-2014
Pharmac
2014
University of Regensburg
2009
University of Milan
2009
The silylated amino acid (l)-(trimethylsilyl)alanine (TMSAla) was incorporated at the C-terminal end of minimal biologically active neurotensin (NT) fragment, leading to synthesis new hexapeptide NT[8-13] analogues. Here, we assessed ability these NT compounds bind NTS1 and NTS2 receptors, promote regulation multiple signaling pathways, induce inhibition ileal smooth muscle contractions, affect distinct physiological variables, including blood pressure pain sensation. Among modified...
Abstract A dual‐action ligand targeting both integrin α V β 3 and vascular endothelial growth factor receptors (VEGFRs), was synthesized via conjugation of a cyclic peptidomimetic Arg‐Gly‐Asp (RGD) with decapentapeptide. The latter obtained from known VEGFR antagonist by acetylation at the Lys13 side chain. Functionalization precursor ligands carried out in solution solid phase, affording two fragments: an alkyne azide ligand, which were conjugated click chemistry. Circular dichroism studies...
Neurotensin exerts potent analgesia by acting at both NTS1 and NTS2 receptors, whereas activation also results in other physiological effects such as hypotension hypothermia. Here, we used molecular modeling approach to design highly selective ligands investigating the docking of novel NT[8-13] compounds sites. Molecular dynamics simulations revealed an interaction Tyr11 residue with acidic (Glu179) located ECL2 hNTS2 or a basic (Arg212) same position hNTS1. The importance 11 for NTS1/NTS2...
NMR experiments (transferred NOE and Saturation Transfer Difference) were used to shed light on the binding epitope of RGD peptidomimetics 1-3 with integrins αvβ3 α(IIb)β3, expressed membrane ECV304 bladder cancer cells human platelets, respectively. The results supported by docking calculations in active sites α(IIb)β3 integrin receptors compared competitive receptor assays cell adhesion experiments. While cis ligand 1 interacts mainly α subunit through its basic guanidine group, trans...
Cadherins are transmembrane cell adhesion proteins whose aberrant expression often correlates with cancer development and proliferation. We report the crystal structure of an E-cadherin extracellular fragment in complex a peptidomimetic compound that was previously shown to partially inhibit cadherin homophilic adhesion. The reveals unexpected binding mode allows identification druggable interface, thus paving way future structure-guided design inhibitors against cadherin-expressing solid tumors.
Enzymatic regulations are central processes for the adaptation to changing environments. In particular case of metallophore-dependent metal uptake, there is a need quickly adjust production these metallophores level outside cell, avoid shortage or overload, as well waste metallophores. Staphylococcus aureus, CntM catalyzes last biosynthetic step in staphylopine, broad-spectrum metallophore, through reductive condensation pathway intermediate (xNA) with pyruvate. Here, we describe chemical...
In metal-scarce environments, some pathogenic bacteria produce opine-type metallophores mainly to face the host's nutritional immunity. This is case of staphylopine, pseudopaline and yersinopine, identified in Staphylococcus aureus, Pseudomonas aeruginosa Yersinia pestis, respectively. Depending on species, these are synthesized by two (CntLM) or three enzymes (CntKLM), CntM catalyzing last step biosynthesis using diverse substrates (pyruvate α-ketoglutarate), pathway intermediates (xNA yNA)...
Several independent studies have demonstrated the overexpression of NTS1 in various malignancies, which make this receptor interest for imaging and therapy. To date, radiolabeled neurotensin analogues suffer from low plasmatic stability thus insufficient availability high uptake tumors. We report development 68Ga-radiolabeled with improved radiopharmaceutical properties through introduction silicon-containing amino acid trimethylsilylalanine (TMSAla). Among series novel analogues,...
Cyclic RGD peptidomimetics containing a bifunctional diketopiperazine scaffold are novel class of high-affinity ligands for the integrins αVβ3 and αVβ5. Since promising target modulation normal pathological angiogenesis, present study aimed at characterizing ability peptidomimetic cyclo[DKP-RGD] 1 proliferation, migration network formation in human umbilical vein endothelial cells (HUVEC).
We report a first set of peptidomimetic ligands mimicking the adhesive interface identified by recent crystallographic structures E- and N-cadherin. Compounds 2 3 inhibit adhesion epithelial ovarian cancer (EOC) cells with improved efficacy compared to ADH-1 peptide, N-cadherin antagonist that is in early clinical trials EOC patients.
We have designed and synthesized new molecular tongs based on a rigid naphthalene scaffold evaluated their antidimer activity HIV-1 protease (PR). inserted carbonylhydrazide oligohydrazide (azatide) fragments into peptidomimetic arms to reduce hydrophobicity increase metabolic stability. These are disrupt the protein-protein interactions by reproducing hydrogen bond pattern found in antiparallel β-sheet formed between N- C-ends of two monomers native PR. Kinetic analyses fluorescent probe...
Abstract A series of new unnatural amino acids bearing a β‐arylthiazole side chain was synthesized by exploiting diastereoselective alkylation starting from glycine tert ‐butyl ester Schiff base with hydroxypinanone as the chiral inducer. This strategy afforded alanines in good chemical yields and 98 % ee . Due to their aromatic properties, these newly generated were used prepare neurotensin (NT)[8–13] analogues serving replacements for native Tyr11 residue. Incorporation ( L...
The probable first hydrolysis product of succinyldicholine, the monocholine ester succinic acid, has been studied and its actions have compared with those dicholine ester. 1. monoester markedly less myoneural blocking action than diester. In adequate doses, however, blockade does take place. This is longer lasting slower both in onset recovery response from succinyldicholine. 2. reduced by No. 49-204, a substance which antagonizes decamethonium, whereas that not. 51-212 as it...
Alzheimer's disease is a neurodegenerative disorder that linked to oligomerization and fibrillization of different amyloid β‐peptide isoforms. Among these peptides, Aβ 1–42 considered the most aggregative neurotoxic species. We report herein synthesis four β‐sheet mimics composed peptidomimetic arm based on 5‐amino‐2‐methoxy benzhydrazide derivative, 2,5‐diketopiperazine scaffold (either cis ‐DKP or trans ‐DKP) tetrapeptide sequence Gly‐Val‐Val‐Ile, GVVI, Lys‐Leu‐Val‐Phe, KLVF). The...
A concise synthetic pathway yielding to hydrophobic α,α-disubstituted disilylated amino acids based on a hydrosilylation reaction is described. As first example of utilization in solid-phase peptide synthesis, TESDpg was introduced replacement Aib an alamethicin sequence, leading analogues with modified physicochemical properties and conserved helical structures. This study highlights the potential these new as tools for modulation.
To evaluate the contribution of triethylsilyl α,α-di-n-propylglycine, namely TESDpg, to induce a defined secondary structure, we have prepared model tripeptides in which TESDpg was inserted three different positions. Studies solid state and solution with adapted techniques showed that able nascent 310 helix both crystal states.
A new β-hairpin mimic foldamer based on the assembly of a reverse turn inducer, peptidomimetic strand, and tetrapeptide sequence was prepared, its conformation in solution assessed by NMR computational investigations.
A concise synthesis of (<i>S</i>)-γ-fluoroleucine is described in five steps from commercially available compounds, with an overall yield 57%. The Markovnikov hydrofluorination reaction the unsaturated amino acid precursor as last step proved to be effective. This fluorination can also performed directly on a short peptide model same efficiency. could principle applicable for preparation radiolabeled acids and peptides.
Neurotensin (NT) is a tridecapeptide displaying interesting antinociceptive properties through its action on receptors, NTS1 and NTS2. Neurotensin-like compounds have been shown to exert better than morphine at equimolar doses. In this article, we characterized the molecular effects of novel neurotensin (8-13) (NT(8-13)) analog containing an unnatural amino acid. This compound, named JMV2009, displays Silaproline in position 10 replacement proline native NT(8-13). We first examined binding...