title: Structure-delivery relationships of lysine-based gemini surfactants and their lipoplexes.
abstract: The synthesis and properties of gemini surfactants of the type (R(1)(CO)-Lys(H)-NH)2(CH2)n are reported. For a spacer length of n = 6, the hydrophobic acyl tail was varied in length (R(1) = C8, C10, C12, C14, C16, and C18) and, for R(1) = C18, the degree of unsaturation. For R(1)(CO) = oleoyl (C18:1 Z) the spacer length (n = 2-8) and the stereochemistry of the lysine building block were varied; a 'half-gemini' derivative with a single oleoyl tail and head group was also prepared. The potential of the gemini surfactants to transfer polynucleotides across a cell membrane was investigated by transfection of HeLa cells with beta-galactosidase, both in the presence and absence of the helper lipid DOPE. Oleoyl was found to be by far the best hydrophobic tail for this biological activity, whereas the effect of the lysine stereochemistry was less pronounced. The effect of an optimum spacer length (n = 6) was observed only in the absence of helper lipid. The most active surfactant, i.e. the one with oleoyl chains and n = 6, formed liposomes with sizes in the range of 60-350 nm, and its lipoplex underwent a transition from a lamellar to a hexagonal morphology upon lowering the pH from 7 to 3.
authors: Radboud University Nijmegen, Institute for Molecules and Materials, Heijendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. m.feiters@science.ru.nl.
authors: Mark
authors: M
authors: Damen
authors: Edgar
authors: E
authors: Cristóbal-Lecina
authors: Glòria Colom
authors: GC
authors: Sanmartí
authors: Stijn F M
authors: SF
authors: van Dongen
authors: Cristina L
authors: CL
authors: García Rodríguez
authors: Igor P
authors: IP
authors: Dolbnya
authors: Roeland J M
authors: RJ
authors: Nolte
authors: Martin C
authors: MC
authors: Feiters
mesh_terms: D002412:Cations / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry* / Q000648:ultrastructure; D008239:Lysine / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D015394:Molecular Structure; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010957:Plasmids / Q000235:genetics; D053838:Scattering, Small Angle; D021241:Spectrometry, Mass, Electrospray Ionization; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection / Q000379:methods; D014961:X-Ray Diffraction; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D013501:Surface-Active Agents; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase; D008239:Lysine