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Multimerization of an Apoptogenic TRAIL‐Mimicking Peptide by Using Adamantane‐Based Dendrons
Author(s) -
Lamanna Giuseppe,
Smulski Cristian R.,
Chekkat Neila,
EstieuGionnet Karine,
Guichard Gilles,
Fournel Sylvie,
Bianco Alberto
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201202415
Subject(s) - adamantane , peptide , surface plasmon resonance , chemistry , ligand (biochemistry) , in vitro , receptor , biophysics , monomer , apoptosis , stereochemistry , microbiology and biotechnology , combinatorial chemistry , biochemistry , nanotechnology , biology , nanoparticle , materials science , organic chemistry , polymer
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.