Chemistry and cellular aspects of cationic facial amphiphiles

A series of compounds containing a bile acid core and a polyamine side chain have been synthesized to evaluate their ability to promote the uptake of DNA into cells. These compounds differ from conventional cationic lipids because they contain a positively charged chain attached to a facial amphiphile rather than to a hydrophobic moiety. Formulations of several of the designed compounds were found to dramatically increase the cellular uptake of both plasmid and oligonucleotide DNA. Moreover, initial experiments have shown that some of the compounds promote plasmid gene expression in various tissues after introduction into animals. These results have provided interesting information about structure-activity relationships as well as clues to the mechanism of action that may lead to further improvements in the design.