Multimerization of an apoptogenic TRAIL-mimicking peptide by using adamantane-based dendrons
| Autor: | Cristian R. Smulski, Neila Chekkat, Sylvie Fournel, Gilles Guichard, Giuseppe Lamanna, Alberto Bianco, Karine Estieu-Gionnet |
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| Přispěvatelé: | Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Systèmes Fonctionnels, Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2012 |
| Předmět: |
Dendrimers
Stereochemistry Adamantane TRAIL Peptide Apoptosis [CHIM.THER]Chemical Sciences/Medicinal Chemistry 01 natural sciences Catalysis TNF-Related Apoptosis-Inducing Ligand 03 medical and health sciences chemistry.chemical_compound Dendrimer Cell Line Tumor Humans Surface plasmon resonance Receptor 030304 developmental biology chemistry.chemical_classification 0303 health sciences 010405 organic chemistry Organic Chemistry General Chemistry multivalency Ligand (biochemistry) In vitro 0104 chemical sciences Receptors TNF-Related Apoptosis-Inducing Ligand chemistry Biophysics Click Chemistry Chimie/Chimie thérapeutique Signal transduction Peptides Signal Transduction |
| Zdroj: | Chemistry-A European Journal Chemistry-A European Journal, Wiley-VCH Verlag, 2012, 19 (5), pp.1762-1768. ⟨10.1002/chem.201202415⟩ |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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