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

• DOI: 10.1002/chem.201202415
• Publication Date: 2012-12-13T20:28:09Z
• Authors: Giuseppe Lamanna; Cristian R. Smulski; Neila Chekkat; Karine Estieu‐Gio...; Gilles Guichard; Sylvie Fournel; Alberto Bianco
• Keywords: Adamantane

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 ligands TRAIL receptor 2 (TR2) was studied surface plasmon resonance, thus demonstrating trimeric and hexameric forms exert increased about 1500‐ 20 000‐fold, respectively, relative monomer. Moreover, only were able induce cell death in TR2 expressing cells (BJAB), confirming form is necessary trigger substantial TR2‐dependent apoptotic response vitro. These results provide interesting insight into multivalency effect on biological ligand/receptor interactions for future therapeutic applications.