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Your search keyword '"Valentina Corvaglia"' showing total 4 results
Start Over Author "Valentina Corvaglia" Topic biology.protein
4 results on '"Valentina Corvaglia"'

1. Crystal structure of a protein-aromatic foldamer composite: macromolecular chiral resolution

Author

Valentina Corvaglia, Ivan Huc, Peter B. Crowley, Jimi Marin Alex, Xiaobo Hu, and Sylvain Engilberge

Subjects
Indoles, Magnetic Resonance Spectroscopy, Saccharomyces cerevisiae Proteins, Polymers, Pyridines, Crystal structure, Saccharomyces cerevisiae, 010402 general chemistry, Crystallography, X-Ray, Ligands, 01 natural sciences, Catalysis, Crystal, Materials Chemistry, Molecule, biology, 010405 organic chemistry, Chemistry, Cytochrome c, Circular Dichroism, Metals and Alloys, Foldamer, Cytochromes c, Stereoisomerism, General Chemistry, Chiral resolution, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Crystallography, Helix, Ceramics and Composites, biology.protein, Crystallization, Macromolecule, Protein Binding
Abstract

Co-crystallization of a 2 kDa tether-free sulfonated foldamer and the 13 kDa lysine-rich cytochrome c yielded a remarkable biohybrid assembly with chiral resolution of the foldamer helix handedness. In the crystal a ∼5 nm foldamer stack was surrounded by eight molecules of protein. NMR and CD experiments suggest interesting differences in the solution state recognition processes.

Published
2019

2. Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: artificial analogues of DNA mimic proteins

Author

Victor Dos Santos, Ivan Huc, Krzysztof Ziach, Valentina Corvaglia, Panchami Prabhakaran, Vincent Parissi, Pradeep K. Mandal, Carole Legeay, Daniel Carbajo, Philippe Pourquier, Rachel Isaksson Vogel, European Research Council, Herrada, Anthony, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians-Universität München (LMU), Sanofi-Aventis R&D, SANOFI Recherche, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), CNRS UMR 5097, Signalisation et Mecanismes Moleculaires de l'Apoptose, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie supramoléculaire biomimétique et bio-organique - Institut Européen de Chimie et Biologie, and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1

Subjects
Stereochemistry, Protein Conformation, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV]Life Sciences [q-bio], [CHIM.THER] Chemical Sciences/Medicinal Chemistry, HIV Integrase, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Crystallography, X-Ray, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Solid-phase synthesis, Chemical Biology and Nucleic Acid Chemistry, Biomimetic Materials, Genetics, Humans, HIV Integrase Inhibitors, ComputingMilieux_MISCELLANEOUS, Solid-Phase Synthesis Techniques, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, Molecular Structure, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Peptide stapling, Topoisomerase, Foldamer, Proteins, Phosphonate, Amides, 3. Good health, Integrase, Monomer, Enzyme, chemistry, DNA Topoisomerases, Type I, biology.protein, Biocatalysis, HIV-1, DNA, B-Form, Peptides, 030217 neurology & neurosurgery, DNA
Abstract

Inspired by DNA mimic proteins, we have introduced aromatic foldamers bearing phosphonate groups as synthetic mimics of the charge surface of B-DNA and competitive inhibitors of some therapeutically relevant DNA-binding enzymes: the human DNA Topoisomerase 1 (Top1) and the human HIV-1 integrase (HIV-1 IN). We now report on variants of these anionic foldamers bearing carboxylates instead of phosphonates. Several new monomers have been synthesized with protecting groups suitable for solid phase synthesis (SPS). Six hexadecaamides have been prepared using SPS. Proof of their resemblance to B-DNA was brought by the first crystal structure of one of these DNA-mimic foldamers in its polyanionic form. While some of the foldamers were found to be as active as, or even more active than, the original phosphonate oligomers, others had no activity at all or could even stimulate enzyme activity in vitro. Some foldamers were found to have differential inhibitory effects on the two enzymes. These results demonstrate a strong dependence of inhibitory activity on foldamer structure and charge distribution. They open broad avenues for the development of new classes of derivatives that could inhibit the interaction of specific proteins with their DNA target thereby influencing the cellular pathways in which they are involved. © The Author(s) 2019., Agence Nationale de la Recherche [ANR-11-BS07-013-01]; European Research Council under the European Union’s Seventh Framework Programme [ERC-2012-AdG-320892 and PEOPLE-2011-IEF-300948]; Ligue Contre Le Cancer (Comité Languedoc-Roussillon); SIRIC Montpellier Cancer [INCa Inserm DGOS 12553]; SIDACTION (AO2016, VIH2016721002). Funding for open access charge: University of Munich fund.

Published
2019
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3. Unleashing Cancer Cells on Surfaces Exposing Motogenic IGDQ Peptides

Author

Riccardo Marega, Federica De Leo, Valentina Corvaglia, Davide Bonifazi, Carine Michiels, Corvaglia, Valentina, Marega, Riccardo, De Leo, Federica, Michiels, Carine, and Bonifazi, Davide

Subjects
0301 basic medicine, Cell signaling, Cancer cells, cell migration, Surface Properties, 010402 general chemistry, 01 natural sciences, chemical gradient, Conserved sequence, Focal adhesion, Biomaterials, 03 medical and health sciences, Cell Movement, Cell Line, Tumor, Neoplasms, Humans, General Materials Science, Cell migration, Engineering (miscellaneous), cancer cell, cancer cells, chemical gradients, IGD motifs, peptide SAMs, Biotechnology, Microscopy, Confocal, biology, Water, General Chemistry, IGD motif, Biomaterial, Peptide SAMs, peptide SAM, 0104 chemical sciences, Cell biology, Fibronectin, 030104 developmental biology, Cell culture, Cancer cell, biology.protein, Phosphorylation, Chemical gradients, Gold, Peptides
Abstract

Thiolated peptides bearing the Ile-Gly-Asp (IGD) motif, a highly conserved sequence of fibronectin, are used for the preparation of anisotropic self-assembled monolayers (SAM gradients) to study the whole-population migratory behavior of metastatic breast cancer cells (MDA-MB-231 cells). Ile-Gly-Asp-Gln-(IGDQ)-exposing SAMs sustain the adhesion of MDA-MB-231 cells by triggering focal adhesion kinase phosphorylation, similarly to the analogous Gly-Arg-Gly-Asp-(GRGD)-terminating surfaces. However, the biological responses of different cell lines interfaced with the SAM gradients show that only those exposing the IGDQ sequence induce significant migration of MDA-MB-231 cells. In particular, the observed migratory behavior suggests the presence of cell subpopulations associated with a "stationary" or a "migratory" phenotype, the latter determining a considerable cell migration at the sub-cm length scale. These findings are of great importance as they suggest for the first time an active role of biological surfaces exposing the IGD motif in the multicomponent orchestration of cellular signaling involved in the metastatic progression.

Published
2016
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4. Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA

Author

Frédéric Godde, Jean-Marie Schmitter, Vincent Parissi, Valentina Corvaglia, Philippe Pourquier, Stéphane Chaignepain, Mathieu Marchivie, Céline Chollet, Ivan Huc, Panchami Prabhakaran, Krzysztof Ziach, Partha Pratim Bose, Katta Laxmi-Reddy, Toulin, Stéphane, BLANC - Mimes oligoamides aromatiques de l'ADN double brin - - ARYNAMICS2011 - ANR-11-BS07-0013 - BLANC - VALID, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ANR-11-BS07-0013,ARYNAMICS,Mimes oligoamides aromatiques de l'ADN double brin(2011), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Service de Chimie Bio-Organique et de Marquage (SCBM), Médicaments et Technologies pour la Santé (MTS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay, CNRS UMR 5097, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Institut Européen de Chimie et Biologie, Signalisation et Mecanismes Moleculaires de l'Apoptose, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie supramoléculaire biomimétique et bio-organique - Institut Européen de Chimie et Biologie, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1, École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and Microbiologie cellulaire et moléculaire et pathogénicité (MCMP)

Subjects
Surface Properties, [SDV]Life Sciences [q-bio], General Chemical Engineering, 010402 general chemistry, 01 natural sciences, DNA-binding protein, chemistry.chemical_compound, Molecule, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, [CHIM.MATE] Chemical Sciences/Material chemistry, biology, 010405 organic chemistry, Chemistry, Topoisomerase, Chemical tools, DNA-binding proteins, Nucleic acids, [CHIM.MATE]Chemical Sciences/Material chemistry, General Chemistry, Amides, 3. Good health, 0104 chemical sciences, Integrase, Enzyme, biology.protein, Nucleic acid, Biophysics, Nucleic Acid Conformation, DNA, B-Form, Double stranded, DNA
Abstract

This work was supported by the Agence Nationale de la Recherche (project no. ANR-11-BS07-013-01 and project RETROSelect, jcjc2011 program), by the French National Research Agency against AIDS (ANRS, AO2016), by SIDACTION (AO2016, VIH20160721002), by the European Union under the Seventh Framework Programme (grant agreements nos. ERC-2012-AdG-320892 and PEOPLE-2011-IEF-300948) and by the Ligue contre le Cancer (Comité Languedoc Roussillon).; International audience; Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein–DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known. Here, we report the design, synthesis and structural characterization of aromatic oligoamides that fold into single helical conformations and display a double helical array of negatively charged residues in positions that match the phosphate moieties in B-DNA. These molecules were able to inhibit several enzymes possessing non-sequence-selective DNA-binding properties, including topoisomerase 1 and HIV-1 integrase, presumably through specific foldamer–protein interactions, whereas sequence-selective enzymes were not inhibited. Such modular and synthetically accessible DNA mimics provide a versatile platform to design novel inhibitors of protein–DNA interactions.

Published
2018
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