Département de chimie moléculaire

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 tumor blood vessel "homing" motif and the other a programmed cell-death-inducing peptide sequence. RGD peptides were selected to direct the mol. conjugate to $\alpha$v$\beta$3 integrin-contg. tumor 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 (i.e., scaffold, RGD units and pro-apoptotic peptide) through chemoselective ligations. We show that one compd. displays significant biol. effect in $\alpha$v$\beta$3 integrin-contg. tumor cells. [on SciFinder(R)]