title: Synthesis and gene transfer activities of novel serum compatible reducible tocopherol-based cationic lipids.
abstract: The molecular structure of the cationic lipids greatly influences their transfection efficiency. High transfection efficiencies of tocopherol-based simple monocationic transfection lipids with hydroxylethyl headgroups were recently reported by us (Kedika, B., et al. J. Med. Chem.2011, 54 (2), 548-561). Toward enhancing the transfection efficiency of tocopherol-based lipids, we have synthesized two tocopherol-based dicationic lipids (1 and 2) using simple cystine in the headgroup region. The efficiency of tocopherol-based lipids (1 and 2) were compared with nontocopherol-based lipids (3 and 4) with cystine in the headgroup region. We report also a comprehensive structure-activity relationship study that identified tocopherol-based gemini cationic lipid 1 is a better transfecting agent than its monomeric lipid counterpart 2 and two other nontocopherol-based gemini cationic lipids (3 and 4). The transfection efficiency of lipid 1 was also greater than that of commercial formulation in HepG2 cell lines. A major characteristic feature of this investigation is that serum does not inhibit the transfection activity of tocopherol-based lipids (1 and 2) in general and in particular lipid 1 which is found to be highly serum-compatible even at higher concentrations of serum when compared to its monomeric counterpart lipid 2 and the other two control lipid analogues 3 and 4.
authors.affiliation: Department of Chemistry, National Institute of Technology, Warangal 506004, Andhra Pradesh, India.
authors.forename: Bhavani
authors.initials: B
authors.lastname: Kedika
authors.forename: Srilakshmi V
authors.initials: SV
authors.lastname: Patri
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis* / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids; D008081:Liposomes / Q000737:chemistry; D008856:Microscopy, Fluorescence; D024505:Tocopherols / Q000737:chemistry*; D014162:Transfection / Q000379:methods
chemical_list: D008055:Lipids; D008081:Liposomes; D024505:Tocopherols