Investigating the Transbilayer Distribution of Cholesterol in Asymmetric Unilamellar Vesicles using Small-Angle Scattering

Abstract

A DNA G-quadruplex structure is one of the higher-order DNA structures found in a telomere region of chromosomes and suppresses enzymatic telomere-elongation reactions which frequently occur in cancer cells. Therefore, ligand compounds stabilizing such a DNA G-quadruplex structure is expected as a new-type of anti-cancer agents. To evaluate the interaction of the ligand with DNA G-quadruplexes in an aqueous solution, the examined ligands must be highly water-soluble. Such ligands have been usually substituted with hydrophilic substituents in a molecule. Here we report synthesis of several chlorophyll-a derivatives, in which their inner nitrogen is methylated, to enable their complexation and stabilization with a DNA G-quadruplex in an aqueous solution. Their binding constants with the DNA G-quadruplex structure were determined by optical spectroscopic techniques. The values using cationic N-methylated chlorophyll-a derivatives were larger than those using neutral unmethylated analogs. In addition, the thermodynamic stabilities of several G-quadruplexes with the synthetic ligands were analyzed by CD spectroscopy and will be discussed.