title: Solid-phase synthesis of 89 polyamine-based cationic lipids for DNA delivery to mammalian cells.
abstract: The ability of non-viral gene delivery systems to overcome extracellular and intracellular barriers is a critical issue for future clinical applications of gene therapy. In recent years much effort has been focused on the development of a variety of DNA carriers, and cationic liposomes have become the most common non-viral gene delivery system. Solid-phase synthesis was used to produce three libraries of polyamine-based cationic lipids with diverse hydrophobic tails. These were characterised, and structure-activity relationships were determined for DNA binding and transfection ability of these compounds when formulated as cationic liposomes. Two of the cationic lipids produced high-efficiency transfection of human cells. Surprisingly, these two compounds were from the library with two headgroups and one aliphatic tail, a compound class regarded as detergent-like and little investigated for transfection. These cationic lipids are promising reagents for gene delivery and illustrate the potential of solid-phase synthesis methods for lipoplex discovery.
authors.affiliation: Department of Chemistry, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Boon-Ek
authors.initials: BE
authors.lastname: Yingyongnarongkul
authors.forename: Mark
authors.initials: M
authors.lastname: Howarth
authors.forename: Tim
authors.initials: T
authors.lastname: Elliott
authors.forename: Mark
authors.initials: M
authors.lastname: Bradley
mesh_terms: D001665:Binding Sites; D002412:Cations / Q000138:chemical synthesis / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D005822:Genetic Vectors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis* / Q000633:toxicity; D015394:Molecular Structure; D010957:Plasmids / Q000187:drug effects / Q000378:metabolism; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D008055:Lipids; D011073:Polyamines; D004247:DNA; D019791:Guanidine