Delivery of DNA and siRNA by novel gemini-like amphiphilic peptides.
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.
Damen
Mark
M
Department of Organic Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, The Netherlands.
Aarbiou
Jamil
J
van Dongen
Stijn F M
SF
Buijs-Offerman
Ruvalic M
RM
Spijkers
Patricia P
PP
van den Heuvel
Maaike
M
Kvashnina
Kristina
K
Nolte
Roeland J M
RJ
Scholte
Bob J
BJ
Feiters
Martin C
MC
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
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