title: Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.
abstract: 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.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Science Park (PCB), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Martin
authors.forename: Christian
authors.initials: C
authors.lastname: Dohmen
authors.forename: Carlos
authors.initials: C
authors.lastname: Mas-Moruno
authors.forename: Christina
authors.initials: C
authors.lastname: Troiber
authors.forename: Petra
authors.initials: P
authors.lastname: Kos
authors.forename: David
authors.initials: D
authors.lastname: Schaffert
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lächelt
authors.forename: Meritxell
authors.initials: M
authors.lastname: Teixidó
authors.forename: Michael
authors.initials: M
authors.lastname: Günther
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage*; D004980:Ethane / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods; D014162:Transfection
chemical_list: D000577:Amides; D010455:Peptides; D011092:Polyethylene Glycols; D004247:DNA; D004980:Ethane