title: Design, synthesis and gene delivery efficiency of novel oligo-arginine-linked PEG-lipids: effect of oligo-arginine length.
abstract: The design, synthesis, and evaluation of in vitro gene delivery efficacy of a novel series of oligo-Arg-lipid conjugates are described. 3,5-Bis(dodecyloxy)benzamide (BDB) was employed as the lipid component, and a poly(ethylene glycol) (PEG) spacer was introduced between the C-terminal of oligo-Arg and the amide group of BDB. Four derivatives with various oligo-Arg lengths (ArgN-PEG-BDB; N = 4, 6, 8, 10: the number of arginine residues) were prepared, and the effect of oligo-Arg length on the gene transfection was investigated in HeLa cells. Transfection efficiency increased as the number of arginine residues increased. Arg10-PEG-BDB showed the highest transfection efficiency, without severe toxicity to cells. These findings well corresponded to the cellular association of the Arg-PEG-BDB/DNA complex determined by flow cytometry. Even in the presence of serum, Arg10-PEG-BDB achieved appreciable cellular association and attained high gene expression. Thus, Arg10-PEG-BDB is potentially a simple and useful gene delivery tool, because one need only to mix it with plasmid DNA and apply the complexes to the cells even in a serum-containing medium.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Furuhata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kawakami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Toma
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D015195:Drug Design; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D008156:Luciferases / Q000235:genetics; D015394:Molecular Structure; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D014162:Transfection
chemical_list: D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D010455:Peptides; D049452:Green Fluorescent Proteins; C015462:polyarginine; D011092:Polyethylene Glycols; D008156:Luciferases