These authors contributed equally to this work.
Multimerization of an Apoptogenic TRAIL-Mimicking Peptide by Using Adamantane-Based Dendrons†
Article first published online: 13 DEC 2012
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chemistry - A European Journal
Volume 19, Issue 5, pages 1762–1768, January 28, 2013
How to Cite
Lamanna, G., Smulski, C. R., Chekkat, N., Estieu-Gionnet, K., Guichard, G., Fournel, S. and Bianco, A. (2013), Multimerization of an Apoptogenic TRAIL-Mimicking Peptide by Using Adamantane-Based Dendrons . Chem. Eur. J., 19: 1762–1768. doi: 10.1002/chem.201202415
TRAIL=tumor necrosis factor-related apoptosis-inducing ligand.
- Issue published online: 17 JAN 2013
- Article first published online: 13 DEC 2012
- Manuscript Revised: 3 OCT 2012
- Manuscript Received: 6 JUL 2012
- Centre National de la Recherche Scientifique (CNRS)
- Agence Nationale de la Recherche. Grant Numbers: ANR-07-PCVI-0031–01, ANR-08-PCVI-0034–01
- Ligue Nationale Contre le Cancer, Comité de la Dordogne
- Strasbourg University
- NANOTHER. Grant Number: 2010 NANO 008 01
- French “Ministère de la Recherche”
- click chemistry;
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.