title: Polypod-Shaped DNAs: Small-Angle X-ray Scattering and Immunostimulatory Activity.
abstract: We explored in detail the relationship between the structure in aqueous solution and immunostimulatory activity of polypod-shaped DNAs, called polypodnas. The polypodnas were constructed using 3-6 oligodeoxynucleotides (ODNs) to obtain tri-, tetra-, penta-, and hexapodna, each of which had 3, 4, 5, and 6 arms made of double-stranded DNA, respectively. A highly potent immunostimulatory CpG sequence was included into each of the polypodnas. Synchrotron X-ray scattering analysis showed that the double-stranded DNA arms of all of the polypodnas adopted a B-form DNA conformation. The analysis also suggested that some nucleotides in the central parts of pentapodna and hexapodna did not form base pairs, whereas those of tripodna and tetrapodna all formed base pairs. This difference would occur because of an increase in steric hindrance and electrical repulsion with increasing number of arms. The pentapodna and hexapodna induced a large amount of tumor necrosis factor α-release from macrophage-like cells compared with the tripodna and tetrapodna, suggesting that the partly loosened DNA in polypodna with many arms is advantageous for exposing the immunostimulatory sequences of the polypodna.
authors.affiliation: Department of Chemistry and Biochemistry, University of Kitakyushu , 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.|Structural Materials Science Laboratory SPring-8 Center, RIKEN Harima Institute Research 1-1-1 Kouto, Sayo-cho, Sayo, Hyogo 679-5148, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sanada
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Shiomi
authors.affiliation: Department of Chemical Science and Engineering, Ariake National College of Technology , 150 Higashihagio-Machi, Omuta, Fukuoka 836-8585, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okobira
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Department of Chemistry and Biochemistry, University of Kitakyushu , 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.|Structural Materials Science Laboratory SPring-8 Center, RIKEN Harima Institute Research 1-1-1 Kouto, Sayo-cho, Sayo, Hyogo 679-5148, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Akiba
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.affiliation: Department of Chemistry and Biochemistry, University of Kitakyushu , 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.|Structural Materials Science Laboratory SPring-8 Center, RIKEN Harima Institute Research 1-1-1 Kouto, Sayo-cho, Sayo, Hyogo 679-5148, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D018899:CpG Islands; D004247:DNA / Q000737:chemistry* / Q000494:pharmacology; D004705:Endocytosis; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D053838:Scattering, Small Angle; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014965:X-Rays
chemical_list: D007155:Immunologic Factors; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D004247:DNA