Fiche publication
Date publication
janvier 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FOURNEL Sylvie
,
Dr BIANCO Alberto
Tous les auteurs :
Lamanna G, Smulski CR, Chekkat N, Estieu-Gionnet K, Guichard G, Fournel S, Bianco A
Lien Pubmed
Résumé
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.
Référence
Chemistry. 2013 Jan 28;19(5):1762-8
