Multimerization of an Apoptogenic TRAIL‐Mimicking Peptide by Using Adamantane‐Based Dendrons |
| |
| Authors: | Dr. Giuseppe Lamanna Dr. Cristian R. Smulski Neila Chekkat Dr. Karine Estieu‐Gionnet Dr. Gilles Guichard Prof. Sylvie Fournel Dr. Alberto Bianco |
| |
| Affiliation: | 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);3. 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);4. Institut Européen de Chimie et de Biologie CBMN, Université de Bordeaux I ‐ CNRS UMR 5248, 2 Rue Robert Escarpit, 33607 PESSAC (France) |
| |
| 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. |
| |
| Keywords: | adamantane click chemistry dendrimers multivalency peptides TRAIL |
|
|
