Publications
2013
Schaeffer Evelyne, Dehuyser Laure, Sigwalt David, Flacher Vincent, Bernacchi Serena, Chaloin Olivier, Remy Jean-Serge, Mueller Christopher G, Baati Rachid, Wagner Alain
Dynamic micelles of mannoside glycolipids are more efficient than polymers for inhibiting HIV-1 trans-infection Journal Article
In: Bioconjugate Chemistry, vol. 24, no. 11, pp. 1813–1823, 2013, ISSN: 1520-4812.
Abstract | Links | BibTeX | Tags: Anti-HIV Agents, Calcium, Cells, Chemistry, Cultured, Dendritic Cells, Dose-Response Relationship, Drug, Electron, fluorescence, Glycolipids, HIV, HIV Infections, HIV-1, Human, Humans, immunodeficiency, immunopathology, inhibition, LECTIN, Lectins, lipid, Mannosides, Micelles, Microbial Sensitivity Tests, Microscopy, Models, Molecular, Molecular Structure, Polymers, prophylaxis, Spectrometry, Structure-Activity Relationship, Surface Plasmon Resonance, target, Team-Mueller, Thermodynamics, Transmission, virus
@article{schaeffer_dynamic_2013,
title = {Dynamic micelles of mannoside glycolipids are more efficient than polymers for inhibiting HIV-1 trans-infection},
author = {Evelyne Schaeffer and Laure Dehuyser and David Sigwalt and Vincent Flacher and Serena Bernacchi and Olivier Chaloin and Jean-Serge Remy and Christopher G Mueller and Rachid Baati and Alain Wagner},
doi = {10.1021/bc4000806},
issn = {1520-4812},
year = {2013},
date = {2013-11-01},
journal = {Bioconjugate Chemistry},
volume = {24},
number = {11},
pages = {1813--1823},
abstract = {Mannoside glycolipid conjugates are able to inhibit human immunodeficiency virus type 1 (HIV-1) trans-infection mediated by human dendritic cells (DCs). The conjugates are formed by three building blocks: a linear or branched mannose head, a hydrophilic linker, and a 24-carbon lipid chain. We have shown that, even as single molecules, these compounds efficiently target mannose-binding lectins, such as DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) important for HIV-1 transmission. With the goal to optimize their inhibitory activity by supramolecular structure formation, we have compared saturated and unsaturated conjugates, as single molecules, self-assemblies of dynamic micelles, and photopolymerized cross-linked polymers. Surface plasmon resonance showed that, unexpectedly, polymers of trivalent conjugates did not display a higher binding affinity for DC-SIGN than single molecules. Interactions on a chip or in solution were independent of calcium; however, binding to DCs was inhibited by a calcium chelator. Moreover, HIV-1 trans-infection was mostly inhibited by dynamic micelles and not by rigid polymers. The inhibition data revealed a clear correlation between the structure and molecular assembly of a conjugate and its biological antiviral activity. We present an interaction model between DC-SIGN and conjugates-either single molecules, micelles, or polymers-that highlights that the most effective interactions by dynamic micelles involve both mannose heads and lipid chains. Our data reveal that trivalent glycolipid conjugates display the highest microbicide potential for HIV prophylaxis, as dynamic micelles conjugates and not as rigid polymers.},
keywords = {Anti-HIV Agents, Calcium, Cells, Chemistry, Cultured, Dendritic Cells, Dose-Response Relationship, Drug, Electron, fluorescence, Glycolipids, HIV, HIV Infections, HIV-1, Human, Humans, immunodeficiency, immunopathology, inhibition, LECTIN, Lectins, lipid, Mannosides, Micelles, Microbial Sensitivity Tests, Microscopy, Models, Molecular, Molecular Structure, Polymers, prophylaxis, Spectrometry, Structure-Activity Relationship, Surface Plasmon Resonance, target, Team-Mueller, Thermodynamics, Transmission, virus},
pubstate = {published},
tppubtype = {article}
}
1999
Nisole S, Krust B, Callebaut C, Guichard G, Muller S, Briand J P, Hovanessian A G
The anti-HIV pseudopeptide HB-19 forms a complex with the cell-surface-expressed nucleolin independent of heparan sulfate proteoglycans Journal Article
In: The Journal of Biological Chemistry, vol. 274, no. 39, pp. 27875–27884, 1999, ISSN: 0021-9258.
Abstract | Links | BibTeX | Tags: Anti-HIV Agents, Binding Sites, CD4-Positive T-Lymphocytes, Cell Line, Cell Membrane, Confocal, Fibroblast Growth Factor 2, Flow Cytometry, Heparan Sulfate Proteoglycans, HIV-1, Humans, Microscopy, Oligopeptides, Peptides, Phospholipid Ethers, Phosphoproteins, Proteins, RNA-Binding Proteins
@article{nisole_anti-hiv_1999,
title = {The anti-HIV pseudopeptide HB-19 forms a complex with the cell-surface-expressed nucleolin independent of heparan sulfate proteoglycans},
author = {S Nisole and B Krust and C Callebaut and G Guichard and S Muller and J P Briand and A G Hovanessian},
doi = {10.1074/jbc.274.39.27875},
issn = {0021-9258},
year = {1999},
date = {1999-09-01},
journal = {The Journal of Biological Chemistry},
volume = {274},
number = {39},
pages = {27875--27884},
abstract = {The HB-19 pseudopeptide 5[Kpsi(CH(2)N)PR]-TASP, psi(CH(2)N) for reduced peptide bond, is a specific inhibitor of human immunodeficiency virus (HIV) infection in different CD4(+) cell lines and in primary T-lymphocytes and macrophages. Here, by using an experimental CD4(+) cell model to monitor HIV entry and infection, we demonstrate that HB-19 binds the cell surface and inhibits attachment of HIV particles to permissive cells. At concentrations that inhibit HIV attachment, HB-19 binds cells irreversibly, becomes complexed with the cell-surface-expressed nucleolin, and eventually results in its degradation. Accordingly, by confocal immunofluorescence microscopy, we demonstrate the drastic reduction of the cell-surface-expressed nucleolin following treatment of cells with HB-19. HIV particles can prevent the binding of HB-19 to cells and inhibit complex formation with nucleolin. Such a competition between viral particles and HB-19 is consistent with the implication of nucleolin in the process of HIV attachment to target cells. We show that another inhibitor of HIV infection, the fibroblast growth factor-2 (FGF-2) that uses cell-surface-expressed heparan sulfate proteoglycans as low affinity receptors, binds cells and blocks attachment of HIV to permissive cells. FGF-2 does not prevent the binding of HB-19 to cells and to nucleolin, and similarly HB-19 has no apparent effect on the binding of FGF-2 to the cell surface. The lack of competition between these two anti-HIV agents rules out the potential involvement of heparan sulfate proteoglycans in the mechanism of anti-HIV effect of HB-19, thus pointing out that nucleolin is its main target.},
keywords = {Anti-HIV Agents, Binding Sites, CD4-Positive T-Lymphocytes, Cell Line, Cell Membrane, Confocal, Fibroblast Growth Factor 2, Flow Cytometry, Heparan Sulfate Proteoglycans, HIV-1, Humans, Microscopy, Oligopeptides, Peptides, Phospholipid Ethers, Phosphoproteins, Proteins, RNA-Binding Proteins},
pubstate = {published},
tppubtype = {article}
}