Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery

• Published in: Organic & biomolecular chemistry 2012-01, Vol.10 (16), p.3258-3268
• Main Authors: Martin, Irene, Dohmen, Christian, Mas-Moruno, Carlos, Troiber, Christina, Kos, Petra, Schaffert, David, Lächelt, Ulrich, Teixidó, Meritxell, Günther, Michael, Kessler, Horst, Giralt, Ernest, Wagner, Ernst
• Format: Article
• Language: English
• Subjects: Amides - chemical synthesis; Amides - chemistry; Animals; Cancer cells; Cell Line, Tumor; Cèl·lules canceroses; DNA - administration & dosage; Enginyeria dels materials; Ethane - chemical synthesis; Ethane - chemistry; Humans; Mice; Peptides; Peptides - chemical synthesis; Peptides - chemistry; Plasmids - administration & dosage; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polymers; Polímers; Pèptids; Solid-Phase Synthesis Techniques - methods; Transfection; Àrees temàtiques de la UPC
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c2ob06907e

In the forthcoming era of cancer gene therapy, efforts will be devoted to the development of new efficient and non-toxic gene delivery vectors. In this regard, the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for solid-phase-supported assembly represents a novel promising approach towards fully controlled syntheses of effective gene vectors. Here we report on the synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA) binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with twenty-four oxyethylene units) for shielding; and (iii) specific peptides for targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin receptor and α(v)β(3) integrin, respectively, were chosen because of the high expression of these receptors in many tumoral cells. This study shows the feasibility of designing these kinds of fully controlled vectors and their success for targeted pDNA-based gene transfer.