Solid-phase synthesis of 89 polyamine-based cationic lipids for DNA delivery to mammalian cells

Chemistry. 2004 Jan 23;10(2):463-73. doi: 10.1002/chem.200305232.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cations / chemical synthesis
  • Cations / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • DNA / drug effects
  • DNA / metabolism*
  • Genetic Vectors / chemical synthesis*
  • Genetic Vectors / pharmacology
  • Genetic Vectors / toxicity
  • Guanidine / chemistry
  • Humans
  • Lipids / chemical synthesis*
  • Lipids / toxicity
  • Molecular Structure
  • Plasmids / drug effects
  • Plasmids / metabolism
  • Polyamines / chemical synthesis
  • Polyamines / chemistry*
  • Structure-Activity Relationship
  • Transfection / methods*


  • Cations
  • Lipids
  • Polyamines
  • DNA
  • Guanidine