Conformation change of Poly(dG-dC)center dot Poly(dG-dC) in cationic polyamine liposome complexes: Effect of charge density and flexibility of amine chains in headgroups

Identification of DNA conformations in delivery cargoes is important to und erstand the transfection mechanisms. Conformations of poly(dG-dC).poly(dG-d C), as a model of DNA, were studied in two different cationic liposome comp lexes prepared from N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium ch loride (DOTMA) and N,N-I,N-II,N-III-tetramethyl-N,N-I,N-II,N-III-tetrapalmi thyl spermine (TM-TPS) with a helper lipid, dioleoyl phosphotidylethanolami ne (DOPE) by Raman microscopy. Characteristic spectral changes in guanine p eaks and cytosine peaks of the poly(dG-dC).poly(dG-dC) distinguished betwee n the right-handed B-form and left-handed Z-form inside the cationic liposo me complexes. The poly(dG-dC).poly(dG-dC) in the TM-TPS/DOPE liposome under goes the B-Z transition while no conformation change was observed in the po ly(dG-dC).poly(dG-dC) inside the DOTMA/DOPE liposome. Each multi-charged TM -TPS molecule contains four cationic nitrogen atoms in the headgroup. The D OTMA molecule with less cationic nitrogens does not have enough negative ch arges in the headgroup to cause the B-Z transition. This model was also con firmed by the B-Z transition of the poly(dG-dC).poly(dG-dC) in another cati onic polyamine liposome complex, 2,3-dioleyloxy-N-[2(sperminecarboxamido)et hyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA) and the DOPE, wh ose multi-charged amine chains are more flexible than the amine chains of t he TM-TPS. Intermolecular interaction between cationic nitrogen atoms of th e DOSPA and oxygen/nitrogen atoms of the guanine sites in poly(dG-dC).poly( dG-dC) is considered to be one of major driving forces for the B-Z transiti on. Systematic studies of DNA conformations in various cationic liposome co mplexes may help developing improved gene delivery system.