Lipopolyamine amides are useful cationic Lipids, synthetic vectors for non-viral gene delivery. Desymmetrisation of readily available symmetrical polyamines is an important first step in the synthesis of such compounds. The application of trifluoroacetyl as a protecting group allows unsymmetrical polyamine amides to be rapidly prepared. A reductive alkylation homologation strategy allows the sequential, regiocontrolled introduction of additional positive charges. Tetraamine spermine and other polyamine derivatives have been N-1-acylated with various single alkyl chains, and their relative binding affinities for DNA determined using an ethidium bromide displacement assay. The important effects on DNA binding affinity of the number of positive charges on the polyamine moiety and also the nature (chain length and degree of unsaturation) of the covalently attached lipid are demonstrated.