Physical and biological properties of cationic triesters of phosphatidylcholine

Robert C. MacDonald*, Gary W. Ashley, Miho M. Shida, Vera A. Rakhmanova, Yury S. Tarahovsky, Dennis P. Pantazatos, Michael T. Kennedy, Edvin V. Pozharski, Kent A. Baker, Ramoun D. Jones, Howard S. Rosenzweig, Kenneth L. Choi, Ruozi Qiu, Thomas J. McIntosh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2612-2629
Number of pages18
JournalBiophysical Journal
Issue number5
StatePublished - Nov 1999

ASJC Scopus subject areas

  • Biophysics


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