title: Stabilization of DNA Structures with Poly(ethylene sodium phosphate).
abstract: The structure and stability of biomolecules under molecular crowding conditions are of interest because such information clarifies how biomolecules behave under cell-mimicking conditions. The anionic surfaces of chromatin, which is composed of DNA strands and histone complexes, are concentrated in cell nuclei and thus generate a polyanionic crowding environment. In this study, we designed and synthesized an anionic polymer, poly(ethylene sodium phosphate) (PEP·Na), which has a nucleic acid phosphate backbone and created a cell nucleus-like environment. The effects of molecular crowding with PEP·Na on the thermodynamics of DNA duplexes, triplexes, and G-quadruplexes were systematically studied. Thermodynamic analysis demonstrated that PEP·Na significantly stabilized the DNA structures; e.g., a free energy change at 25 °C for duplex formation decreased from -6.6 to -12.8 kcal/mol with 20 wt % PEP·Na. Thermodynamic parameters further indicated that the factors for the stabilization of the DNA structures were dependent on sodium ion concentration. At lower polymer concentrations, the stabilization was attributed to a shielding of the electrostatic repulsion between DNA strands by the sodium ions of PEP·Na. In contrast, at higher polymer concentrations, the DNA structures were entropically stabilized by volume exclusion, which could be enhanced by electrostatic repulsion between phosphate groups in DNA strands and in PEP·Na. Additionally, increasing PEP·Na concentration resulted in increasing enthalpy of the DNA duplex but decreasing enthalpy of DNA G-quadruplex, indicating that the polymers also promoted dehydration of the DNA strands. Thus, polyanionic crowding affects the thermodynamics of DNA structures via the sodium ions, volume exclusion, and hydration. The stabilization of DNA by the cell nucleus-like polyanionic crowding provides new information regarding DNA structures and allows for modeling reactions in cell nuclei.
authors.affiliation: Organization for Research and Development of Innovative Science and Technology, Kansai University , 3-3-35, Yamate-cho, Suita-shi, Osaka 564-8680, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Moriyama
authors.affiliation: Organization for Research and Development of Innovative Science and Technology, Kansai University , 3-3-35, Yamate-cho, Suita-shi, Osaka 564-8680, Japan.|Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University , 3-3-35, Yamate-cho, Suita-shi, Osaka 564-8680, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Faculty of Frontiers of Innovative Research in Science and Technology, Konan University , 7-1-20, Minatojima-minamimachi, Chuo-ku, Kobe-shi, Hyogo 650-0047, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miyoshi
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D054856:G-Quadruplexes / Q000187:drug effects; D008958:Models, Molecular; D011095:Polyethylenes / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D013696:Temperature
chemical_list: D011095:Polyethylenes; D011108:Polymers; C000608163:poly(ethylene sodium phosphate); D004247:DNA