title: Multimerization of an apoptogenic TRAIL-mimicking peptide by using adamantane-based dendrons.
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.
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg, France. lamanna@unistra.fr
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lamanna
authors.forename: Cristian R
authors.initials: CR
authors.lastname: Smulski
authors.forename: Neila
authors.initials: N
authors.lastname: Chekkat
authors.forename: Karine
authors.initials: K
authors.lastname: Estieu-Gionnet
authors.forename: Gilles
authors.initials: G
authors.lastname: Guichard
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fournel
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
mesh_terms: D000218:Adamantane / Q000737:chemistry*; D017209:Apoptosis; D045744:Cell Line, Tumor; D057930:Click Chemistry; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000378:metabolism
chemical_list: D050091:Dendrimers; D010455:Peptides; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D000218:Adamantane