title: Synthesis and biological characterisation of targeted pro-apoptotic peptide.
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 alpha(V)beta(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 alpha(V)beta(3) integrin-containing tumour cells.
authors: Département de Chimie Moléculaire, UMR CNRS-UJF 5250, ICMG FR 2607, 301, rue de la chimie, BP 53, FR 38041 Grenoble Cedex 9, France.
authors: Stéphanie
authors: S
authors: Foillard
authors: Zhao-hui
authors: ZH
authors: Jin
authors: Elisabeth
authors: E
authors: Garanger
authors: Didier
authors: D
authors: Boturyn
authors: Marie-Christine
authors: MC
authors: Favrot
authors: Jean-Luc
authors: JL
authors: Coll
authors: Pascal
authors: P
authors: Dumy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002477:Cells / Q000166:cytology / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid