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Multimerization of an Apoptogenic TRAIL-Mimicking Peptide by Using Adamantane-Based Dendrons

Authors

  • Dr. Giuseppe Lamanna,

    Corresponding author
    1. CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg (France), Fax: (+33) 388610680
    • CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg (France), Fax: (+33) 388610680
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    • These authors contributed equally to this work.

  • Dr. Cristian R. Smulski,

    1. CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg (France), Fax: (+33) 388610680
    2. Current address: University of Lausanne, Department of Biochemistry, Boveresses 155, 1066 Epalinges (Switzerland)
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    • These authors contributed equally to this work.

  • Neila Chekkat,

    1. CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg (France), Fax: (+33) 388610680
    2. Current address: UMR 7199 CNRS-Université de Strasbourg, Laboratoire de Conception et Application de Molécules Bioactives, 74 Route du Rhin, BP 60024- 67401 Illkirch Cédex (France)
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  • Dr. Karine Estieu-Gionnet,

    1. Institut Européen de Chimie et de Biologie CBMN, Université de Bordeaux I - CNRS UMR 5248, 2 Rue Robert Escarpit, 33607 PESSAC (France)
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  • Dr. Gilles Guichard,

    1. Institut Européen de Chimie et de Biologie CBMN, Université de Bordeaux I - CNRS UMR 5248, 2 Rue Robert Escarpit, 33607 PESSAC (France)
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  • Prof. Sylvie Fournel,

    1. CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg (France), Fax: (+33) 388610680
    2. Current address: UMR 7199 CNRS-Université de Strasbourg, Laboratoire de Conception et Application de Molécules Bioactives, 74 Route du Rhin, BP 60024- 67401 Illkirch Cédex (France)
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  • Dr. Alberto Bianco

    Corresponding author
    1. CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg (France), Fax: (+33) 388610680
    • CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg (France), Fax: (+33) 388610680
    Search for more papers by this author

  • TRAIL=tumor necrosis factor-related apoptosis-inducing ligand.

Abstract

We have developed a straightforward strategy to multimerize an apoptogenic peptide that mimics the natural tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by using adamantane-based dendrons as multivalent scaffolds. The selective binding affinity of the ligands to TRAIL receptor 2 (TR2) was studied by surface plasmon resonance, thus demonstrating that the trimeric and hexameric forms of the peptide exert an increased affinity of about 1500- and 20 000-fold, respectively, relative to the monomer. Moreover, only the trimeric and hexameric ligands were able to induce cell death in TR2 expressing cells (BJAB), thus confirming that a multivalent form of the peptide is necessary to trigger a substantial TR2-dependent apoptotic response in vitro. These results provide interesting insight into the multivalency effect on biological ligand/receptor interactions for future therapeutic applications.

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