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}
}
Dehuyser L, Schaeffer E, Chaloin O, Mueller C G, Baati R, Wagner A
Synthesis of Novel Mannoside Glycolipid Conjugates for Inhibition of HIV-1 Trans-Infection Journal Article
In: Bioconjug.Chem., no. 1520-4812 (Electronic), 2012.
Abstract | BibTeX | Tags: Dendritic Cells, HIV-1, Human, immunodeficiency, infection, inhibition, LECTIN, Lectins, lipid, Mannose-Binding Lectins, prevention, Solubility, Surface Plasmon Resonance, synthesis, Team-Mueller, virus
@article{dehuyser_synthesis_2012,
title = {Synthesis of Novel Mannoside Glycolipid Conjugates for Inhibition of HIV-1 Trans-Infection},
author = {L Dehuyser and E Schaeffer and O Chaloin and C G Mueller and R Baati and A Wagner},
year = {2012},
date = {2012-01-01},
journal = {Bioconjug.Chem.},
number = {1520-4812 (Electronic)},
abstract = {Mannose-binding lectins, such as dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), are expressed at the surface of human dendritic cells (DCs) that capture and transmit human immunodeficiency virus type-1 (HIV-1) to CD4(+) cells. With the goal of reducing viral trans-infection by targeting DC-SIGN, we have designed a new class of mannoside glycolipid conjugates. We report the synthesis of amphiphiles composed of a mannose head, a hydrophilic linker essential for solubility in aqueous media, and a lipid chain of variable length. These conjugates presented unusual properties based on a cooperation between the mannoside head and the lipid chain, which enhanced the affinity and decreased the need for multivalency. With an optimal lipid length, they exhibited strong binding affinity for DC-SIGN (K(d) in the micromolar range) as assessed by surface plasmon resonance. The most active molecules were branched trimannoside conjugates, able to inhibit the interaction of the HIV-1 envelope with DCs, and to drastically reduce trans-infection of HIV-1 mediated by DCs (IC(50s) in the low micromolar range). This new class of compounds may be of potential use for prevention of HIV-1 dissemination, and also of infection by other DC-SIGN-binding human pathogens},
keywords = {Dendritic Cells, HIV-1, Human, immunodeficiency, infection, inhibition, LECTIN, Lectins, lipid, Mannose-Binding Lectins, prevention, Solubility, Surface Plasmon Resonance, synthesis, Team-Mueller, virus},
pubstate = {published},
tppubtype = {article}
}
Singh Ravi, Pantarotto Davide, McCarthy David, Chaloin Olivier, Hoebeke Johan, Partidos Charalambos D, Briand Jean-Paul, Prato Maurizio, Bianco Alberto, Kostarelos Kostas
Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors Journal Article
In: Journal of the American Chemical Society, vol. 127, no. 12, pp. 4388–4396, 2005, ISSN: 0002-7863.
Abstract | Links | BibTeX | Tags: carbon, Cations, DNA, Electron, Gene Transfer Techniques, Genetic Vectors, I2CT, Lysine, Microscopy, Nanotubes, Plasmids, Quaternary Ammonium Compounds, scanning, Surface Plasmon Resonance, Team-Bianco
@article{singh_binding_2005,
title = {Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors},
author = {Ravi Singh and Davide Pantarotto and David McCarthy and Olivier Chaloin and Johan Hoebeke and Charalambos D Partidos and Jean-Paul Briand and Maurizio Prato and Alberto Bianco and Kostas Kostarelos},
doi = {10.1021/ja0441561},
issn = {0002-7863},
year = {2005},
date = {2005-03-01},
journal = {Journal of the American Chemical Society},
volume = {127},
number = {12},
pages = {4388--4396},
abstract = {Carbon nanotubes (CNTs) constitute a class of nanomaterials that possess characteristics suitable for a variety of possible applications. Their compatibility with aqueous environments has been made possible by the chemical functionalization of their surface, allowing for exploration of their interactions with biological components including mammalian cells. Functionalized CNTs (f-CNTs) are being intensively explored in advanced biotechnological applications ranging from molecular biosensors to cellular growth substrates. We have been exploring the potential of f-CNTs as delivery vehicles of biologically active molecules in view of possible biomedical applications, including vaccination and gene delivery. Recently we reported the capability of ammonium-functionalized single-walled CNTs to penetrate human and murine cells and facilitate the delivery of plasmid DNA leading to expression of marker genes. To optimize f-CNTs as gene delivery vehicles, it is essential to characterize their interactions with DNA. In the present report, we study the interactions of three types of f-CNTs, ammonium-functionalized single-walled and multiwalled carbon nanotubes (SWNT-NH3+; MWNT-NH3+), and lysine-functionalized single-walled carbon nanotubes (SWNT-Lys-NH3+), with plasmid DNA. Nanotube-DNA complexes were analyzed by scanning electron microscopy, surface plasmon resonance, PicoGreen dye exclusion, and agarose gel shift assay. The results indicate that all three types of cationic carbon nanotubes are able to condense DNA to varying degrees, indicating that both nanotube surface area and charge density are critical parameters that determine the interaction and electrostatic complex formation between f-CNTs with DNA. All three different f-CNT types in this study exhibited upregulation of marker gene expression over naked DNA using a mammalian (human) cell line. Differences in the levels of gene expression were correlated with the structural and biophysical data obtained for the f-CNT:DNA complexes to suggest that large surface area leading to very efficient DNA condensation is not necessary for effective gene transfer. However, it will require further investigation to determine whether the degree of binding and tight association between DNA and nanotubes is a desirable trait to increase gene expression efficiency in vitro or in vivo. This study constitutes the first thorough investigation into the physicochemical interactions between cationic functionalized carbon nanotubes and DNA toward construction of carbon nanotube-based gene transfer vector systems.},
keywords = {carbon, Cations, DNA, Electron, Gene Transfer Techniques, Genetic Vectors, I2CT, Lysine, Microscopy, Nanotubes, Plasmids, Quaternary Ammonium Compounds, scanning, Surface Plasmon Resonance, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Bianco Alberto, Hoebeke Johan, Godefroy Sylvie, Chaloin Olivier, Pantarotto Davide, Briand Jean-Paul, Muller Sylviane, Prato Maurizio, Partidos Charalambos D
Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties Journal Article
In: Journal of the American Chemical Society, vol. 127, no. 1, pp. 58–59, 2005, ISSN: 0002-7863.
Abstract | Links | BibTeX | Tags: Adjuvants, Animals, carbon, Cations, CpG Islands, I2CT, Immunologic, Interferon-gamma, Interleukin-6, Kinetics, Lymphocytes, Mice, Nanotubes, oligonucleotides, Surface Plasmon Resonance, Team-Bianco
@article{bianco_cationic_2005,
title = {Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties},
author = {Alberto Bianco and Johan Hoebeke and Sylvie Godefroy and Olivier Chaloin and Davide Pantarotto and Jean-Paul Briand and Sylviane Muller and Maurizio Prato and Charalambos D Partidos},
doi = {10.1021/ja044293y},
issn = {0002-7863},
year = {2005},
date = {2005-01-01},
journal = {Journal of the American Chemical Society},
volume = {127},
number = {1},
pages = {58--59},
abstract = {Functionalized cationic carbon nanotubes are able to form a stable complex with CpG ODN based on charge interaction and to increase the immunostimulatory activity of CpG motifs.},
keywords = {Adjuvants, Animals, carbon, Cations, CpG Islands, I2CT, Immunologic, Interferon-gamma, Interleukin-6, Kinetics, Lymphocytes, Mice, Nanotubes, oligonucleotides, Surface Plasmon Resonance, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}