title: Anchor dependency for non-glycerol based cationic lipofectins: mixed bag of regular and anomalous transfection profiles.
abstract: Although detailed structure-activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure-activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1-15) of recently reported non-glycerol based monocationic transfection lipids. The C(14) analogues in both series 1 (lipids 1-6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C(12) analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C(10) and C(14) analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure-activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane reorganizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1-15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37 degrees C).
authors.affiliation: Division of Lipid Science and Technology Indian Institute of Chemical Technology Hyderabad 500 007, India.
authors.forename: Rajkumar Sunil
authors.initials: RS
authors.lastname: Singh
authors.forename: Koushik
authors.initials: K
authors.lastname: Mukherjee
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Banerjee
authors.forename: Arabinda
authors.initials: A
authors.lastname: Chaudhuri
authors.forename: Samik Kumar
authors.initials: SK
authors.lastname: Hait
authors.forename: Satya Priya
authors.initials: SP
authors.lastname: Moulik
authors.forename: Yerramsetti
authors.initials: Y
authors.lastname: Ramadas
authors.forename: Amash
authors.initials: A
authors.lastname: Vijayalakshmi
authors.forename: Nalam Madhusudhana
authors.initials: NM
authors.lastname: Rao
mesh_terms: D000818:Animals; D019556:COS Cells; D002412:Cations / Q000737:chemistry; D004247:DNA / Q000378:metabolism / Q000493:pharmacokinetics; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D008081:Liposomes / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D010316:Particle Size; D010714:Phosphatidylethanolamines; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D013696:Temperature; D014162:Transfection / Q000379:methods / Q000592:standards*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D002412:Cations; D005456:Fluorescent Dyes; D008081:Liposomes; D010714:Phosphatidylethanolamines; D013501:Surface-Active Agents; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D001616:beta-Galactosidase