Synthesis and Biological Characterisation of Targeted Pro-Apoptotic Peptide. - Archive ouverte HAL Access content directly
Journal Articles ChemBioChem Year : 2008

Synthesis and Biological Characterisation of Targeted Pro-Apoptotic Peptide.

(1) , (2) , (1, 2) , (1) , (3) , (3) , (1)
1
2
3

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.

Dates and versions

inserm-00314521 , version 1 (27-08-2008)

Identifiers

Cite

Stéphanie Foillard, Zhao-Hui Jin, Elisabeth Garanger, Didier Boturyn, Marie-Christine Favrot, et al.. Synthesis and Biological Characterisation of Targeted Pro-Apoptotic Peptide.. ChemBioChem, 2008, epub ahead of print. ⟨10.1002/cbic.200800327⟩. ⟨inserm-00314521⟩
83 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More