title: Delivery of DNA and siRNA by novel gemini-like amphiphilic peptides.
abstract: We report the design, synthesis, and characterization of a novel type of cationic lipopeptide, gemini-like amphiphilic peptides or 'geminoids'. As an example, the SPKR peptide, inspired by biological nucleic acid binding motifs, was appended with unsaturated (oleoyl/oleyl) alkyl tails. The compound shows remarkable DNA and siRNA delivery, without lysogenic helper lipid, in a variety of cells, with a moderate cytotoxic effect. It aggregates to nanoparticles that combine with DNA to lipoplexes, which undergo a change from lamellar to the more lysogenic hexagonal packing upon lowering the pH. The versatility of the chemical approach allowed us to study peptides related to SPKR, and to establish that the Pro and at least one of the cationic (Lys, Arg) residues are essential for the biological activity.
authors.affiliation: Department of Organic Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Damen
authors.forename: Jamil
authors.initials: J
authors.lastname: Aarbiou
authors.forename: Stijn F M
authors.initials: SF
authors.lastname: van Dongen
authors.forename: Ruvalic M
authors.initials: RM
authors.lastname: Buijs-Offerman
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Spijkers
authors.forename: Maaike
authors.initials: M
authors.lastname: van den Heuvel
authors.forename: Kristina
authors.initials: K
authors.lastname: Kvashnina
authors.forename: Roeland J M
authors.initials: RJ
authors.lastname: Nolte
authors.forename: Bob J
authors.initials: BJ
authors.lastname: Scholte
authors.forename: Martin C
authors.initials: MC
authors.lastname: Feiters
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002412:Cations; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry; D009829:Oleic Acids / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics; D010316:Particle Size; D010957:Plasmids; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D012474:Salmon; D053838:Scattering, Small Angle; D013501:Surface-Active Agents / Q000737:chemistry*; D014162:Transfection; D014961:X-Ray Diffraction
chemical_list: D000596:Amino Acids; D002412:Cations; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D009829:Oleic Acids; D009842:Oligopeptides; D034741:RNA, Small Interfering; D013501:Surface-Active Agents; D049452:Green Fluorescent Proteins; D004247:DNA