title: Incorporation of oxyethylene units between hydrocarbon chain and pseudoglyceryl backbone in cationic lipid potentiates gene transfection efficiency in the presence of serum.
abstract: Four novel cationic lipids with different numbers of oxyethylene units at the linkage region between the pseudoglyceryl backbone and the hydrocarbon chains have been synthesized and used as mixtures with 1,2-dioleoyl-L-alpha-glycero-3-phosphatidyl ethanolamine (DOPE) for liposome-mediated gene transfection. Incorporation of different numbers of oxyethylene (-CH(2)CH(2)O-) units between long hydrocarbon chain at the C-1 and C-2 positions of the pseudoglyceryl skeleton improved the transfection efficiency considerably compared to the one in which the chains were connected via simple ether links. A pronounced improvement in the gene transfer efficiency was observed with the unsymmetrical cationic lipid 3 in which the long hydrocarbon at the C-1 position of the pseudoglyceryl segment is connected via two (-CH(2)CH(2)O-) units. Notably, the transfection ability of lipid 3 with DOPE in the presence of serum was significantly greater than LIPOFECTAMINE. This suggests that introduction of oxyethylene units between long hydrocarbon chains at the C-1 and C-2 positions of the pseudoglyceryl skeleton provides a novel strategy to achieve efficient gene transfer, especially in conditions where the presence of serum is critical.
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: P V
authors.initials: PV
authors.lastname: Dileep
authors.forename: A
authors.initials: A
authors.lastname: Antony
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D001769:Blood; D002411:Cation Exchange Resins; D002412:Cations / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D020404:Glycerophospholipids; D006838:Hydrocarbons / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D010714:Phosphatidylethanolamines; D010957:Plasmids; D011095:Polyethylenes / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002411:Cation Exchange Resins; D002412:Cations; D005989:Glycerides; D020404:Glycerophospholipids; D006838:Hydrocarbons; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011095:Polyethylenes