Cationic oxyethylene lipids. Synthesis, aggregation, and transfection properties.
Four cationic lipids (1-4) with oligo-oxyethylene units at the linkage region between the pseudoglyceryl backbone and the hydrocarbon chains have been synthesized. Two of these lipids (1 and 2) have an equal number of (CH(2)CH(2)O)(n)() units attached to both C-1 and C-2 positions of the pseudoglyceryl backbone, making their linkage regions similar, while the other two (3 and 4) are unsymmetrical in terms of the number of oxyethylene units in the linkage. Synthesis of lipids 1 and 2 involved the coupling of benzyl glycerol with the corresponding tosylates as a key step. Each of these lipids formed membranous aggregates when dispersed in water and exhibited clear thermotropic phase transitions typical of vesicular assemblies. The lipids 1-4 exhibited enhanced biological activities as gene transfer agents compared to their non-oxyethylene diether analogue, DHTMA. Transfection experiments using aqueous suspensions of these lipids and also their mixtures with cholesterol or dioleoyl phosphatidyl ethanolamine (DOPE) were performed on HeLa cells. The best transfection activity was demonstrated by unsymmetrical lipid 3, which had two oxyethylene units only at the C-1 position of the pseudoglycerylbackbone.
Bhattacharya
Santanu
S
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India. sb@orgchem.iisc.ernet.in
Dileep
Padinjarae Vangasseri
PV
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002412:Cations / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D005030:Ethylenes / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008854:Microscopy, Electron / Q000379:methods; D015394:Molecular Structure; D014162:Transfection / Q000379:methods*
D002412:Cations; D005030:Ethylenes; D008055:Lipids; D004247:DNA