The regiochemical distribution of positive charges along cholesterol polyamine carbamates plays significant roles in modulating DNA binding affinity and lipofection

We have quantified the effects of the regiochemical distribution of positiv e charges along the polyamine moiety in lipopolyamines for DNA molecular re cognition. High affinity binding leads to charge neutralisation, DNA conden sation and ultimately to lipofection. Binding affinities for calf thymus DN A were determined using an ethidium bromide displacement assay and condensa tion was detected by changes in turbidity using light scattering. The in vi tro transfection competence of cholesterol polyamine carbamates was measure d in CHO cells. In the design of DNA condensing and transfecting agents for non-viral gene therapy, the interrelationship of ammonium ions, not just t heir number, must be considered. (C) 1999 Federation of European Biochemica l Societies.