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Synthesis and Biological Characterisation of Targeted Pro‐Apoptotic Peptide
Author(s) -
Foillard Stéphanie,
Jin Zhaohui,
Garanger Elisabeth,
Boturyn Didier,
Favrot MarieChristine,
Coll JeanLuc,
Dumy Pascal
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800327
Subject(s) - peptide , in vitro , conjugate , rgd motif , apoptosis , integrin , chemistry , microbiology and biotechnology , peptide library , peptide sequence , biochemistry , cell , biology , mathematical analysis , mathematics , gene
Abstract We report herein the synthesis and in vitro assay of new, multimeric RGD‐peptide conjugates for cell‐targeted drug delivery. We generated a peptide scaffold comprising two functional domains, one a tumour blood vessel “homing” motif and the other a programmed cell‐death‐inducing peptide sequence. RGD peptides were selected to direct the molecular conjugate to α V β 3 integrin‐containing tumour cells. The pro‐apoptotic (Lys‐Leu‐Ala‐Lys‐Leu‐Ala‐Lys) 2 peptide was found to be nontoxic outside cells, but toxic when internalized into targeted cells as it disrupted the mitochondrial membrane. The synthesis of these targeted pro‐apoptotic conjugates was carried out by assembling three different units (that is, scaffold, RGD units and pro‐apoptotic peptide) through chemoselective ligations. We show that one compound displays significant biological effect in α V β 3 integrin‐containing tumour cells.