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 understand the transfection mechanisms. Conformations of poly(dG-dC).poly(dG-dC), as a model of DNA, were studied in two different cationic liposome complexes prepared from N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) and N,N-I,N-II,N-III-tetramethyl-N,N-I,N-II,N-III-tetrapalmithyl spermine (TM-TPS) with a helper lipid, dioleoyl phosphotidylethanolamine (DOPE) by Raman microscopy. Characteristic spectral changes in guanine peaks and cytosine peaks of the poly(dG-dC).poly(dG-dC) distinguished between the right-handed B-form and left-handed Z-form inside the cationic liposome complexes. The poly(dG-dC).poly(dG-dC) in the TM-TPS/DOPE liposome undergoes the B-Z transition while no conformation change was observed in the poly(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 DOTMA molecule with less cationic nitrogens does not have enough negative charges in the headgroup to cause the B-Z transition. This model was also confirmed by the B-Z transition of the poly(dG-dC).poly(dG-dC) in another cationic polyamine liposome complex, 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA) and the DOPE, whose multi-charged amine chains are more flexible than the amine chains of the TM-TPS. Intermolecular interaction between cationic nitrogen atoms of the 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 transition. Systematic studies of DNA conformations in various cationic liposome complexes may help developing improved gene delivery system.