title: Physical and biological properties of cationic triesters of phosphatidylcholine.
abstract: The properties of a new class of phospholipids, alkyl phosphocholine triesters, are described. These compounds were prepared from phosphatidylcholines through substitution of the phosphate oxygen by reaction with alkyl trifluoromethylsulfonates. Their unusual behavior is ascribed to their net positive charge and absence of intermolecular hydrogen bonding. The O-ethyl, unsaturated derivatives hydrated to generate large, unilamellar liposomes. The phase transition temperature of the saturated derivatives is very similar to that of the precursor phosphatidylcholine and quite insensitive to ionic strength. The dissociation of single molecules from bilayers is unusually facile, as revealed by the surface activity of aqueous liposome dispersions. Vesicles of cationic phospholipids fused with vesicles of anionic lipids. Liquid crystalline cationic phospholipids such as 1, 2-dioleoyl-sn-glycero-3-ethylphosphocholine triflate formed normal lipid bilayers in aqueous phases that interacted with short, linear DNA and supercoiled plasmid DNA to form a sandwich-structured complex in which bilayers were separated by strands of DNA. DNA in a 1:1 (mol) complex with cationic lipid was shielded from the aqueous phase, but was released by neutralizing the cationic charge with anionic lipid. DNA-lipid complexes transfected DNA into cells very effectively. Transfection efficiency depended upon the form of the lipid dispersion used to generate DNA-lipid complexes; in the case of the O-ethyl derivative described here, large vesicle preparations in the liquid crystalline phase were most effective.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA. macd@nwu.edu
authors.forename: R C
authors.initials: RC
authors.lastname: MacDonald
authors.forename: G W
authors.initials: GW
authors.lastname: Ashley
authors.forename: M M
authors.initials: MM
authors.lastname: Shida
authors.forename: V A
authors.initials: VA
authors.lastname: Rakhmanova
authors.forename: Y S
authors.initials: YS
authors.lastname: Tarahovsky
authors.forename: D P
authors.initials: DP
authors.lastname: Pantazatos
authors.forename: M T
authors.initials: MT
authors.lastname: Kennedy
authors.forename: E V
authors.initials: EV
authors.lastname: Pozharski
authors.forename: K A
authors.initials: KA
authors.lastname: Baker
authors.forename: R D
authors.initials: RD
authors.lastname: Jones
authors.forename: H S
authors.initials: HS
authors.lastname: Rosenzweig
authors.forename: K L
authors.initials: KL
authors.lastname: Choi
authors.forename: R
authors.initials: R
authors.lastname: Qiu
authors.forename: T J
authors.initials: TJ
authors.lastname: McIntosh
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002459:Cell Fusion; D004247:DNA / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D004952:Esters; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism*; D010767:Phosphorylcholine / Q000737:chemistry / Q000378:metabolism; D055585:Physical Phenomena; D013010:Sonication; D013499:Surface Properties; D014162:Transfection; D044366:Transition Temperature; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D004952:Esters; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D014867:Water; D010767:Phosphorylcholine; D004247:DNA