Cholesterol and its fatty acid esters in native DNA preparations: lipid analysis,computer simulation of their interaction with DNA and cholesterol binding to immobilized oligodeoxyribonucleotides

Supramolecular DNA complexes were isolated from rat normal cells and murine tumors. The content of DNA-bound lipids (cholesterol and its esters) was determined. The content of cholesterol esters is higher than that of free cholesterol; the lipid content in tumor cells is higher than in normal cells. Using the molecular mechanics approach, it is demonstrated for the first time that cholesterol and its esters with stearic, oleic, linoleic, and linolenic acids bind to the DNA minor groove more strongly than with the major groove. The calculated DNA binding energies of cholesterol and its esters depend on both the number of double bonds in the fatty acid residue and on the DNA nucleotide composition. The formation of stable complexes between cholesterol molecules and d(AT)-rich oligonucleotides was demonstrated using biological microchip containing immobilized octadeoxyribonucleotides. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2138–2144, September, 2005.     

DNA-bound lipids: computer modeling of DNA interaction with stearic acid and unsaturated fatty acids

It was shown for the first time by computer experiments that fatty acids are strongly bound to DNA. This is consistent with the presence of free fatty acids in the specimens of DNA-bound lipids isolated from various cells. Binding of all fatty acids to the DNA minor groove is stronger than to the major groove, which is correlated with the presence of two pools of free fatty acids isolated from DNA specimens by biochemical methods. Since DNA polymerase is also bound to the DNA minor groove, fatty acids can play an important role in the regulation mechanism of DNA replication and signal transmission. The energy of interaction of fatty acids with DNA depends on both the number of double bonds and the geometric configuration of the fatty acid and the nucleotide composition of DNA. Dependence on the bond energy in the DNA—fatty acid complex on the nucleotide composition attests to the possibility of site-specific binding of lipids to DNA. On passing from a saturated fatty acid to unsaturated acids containing one, two, or three double trans-bonds, the bond energy of DNA with the fatty acid gradually decreases. The presence of one or three double cis-bonds results in weakening of the strength of the DNA—fatty acid complexes compared to those with the saturated acid. The strongest binding between DNA and fatty acid was found for the unsaturated acid with two double cis-bonds (linoleic). This can be explained by the fact that the bent (boomerang) shape of the molecule of this acid follows the curve of the DNA helix. The pattern of variation of the energy of DNA complexes with stearic, linoleic, oleic, and linolenic acids correlates with experimental data on the melting points of these complexes: the more stable the DNA—fatty acid complex, the lower the melting point of DNA.