Galactosyldiacylglycerol, a Mammalian DNA Polymerase .ALPHA.-Specific Inhibitor from a Sea Alga, Petalonia bingbamiae.

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  • MIZUSHINA Yoshiyuki
    Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, and High Technology Research Center, Kobe-Gakuin University
  • SUGIYAMA Yuichi
    Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
  • YOSHIDA Hiromi
    Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, and High Technology Research Center, Kobe-Gakuin University
  • HANASHIMA Shinya
    Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
  • YAMAZAKI Takayuki
    Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
  • KAMISUKI Shinji
    Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
  • OHTA Keisuke
    Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
  • TAKEMURA Masaharu
    Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine
  • YAMAGUCHI Toyofumi
    Department of Biological Science, Teikyo University of Science and Technology
  • MATSUKAGE Akio
    Department of Chemical and Biological Sciences, Japan Women’s University
  • YOSHIDA Shonen
    Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine
  • SANEYOSHI Mineo
    Department of Biological Science, Teikyo University of Science and Technology
  • SUGAWARA Fumio
    Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
  • SAKAGAUCHI Kengo
    Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo

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  • Galactosyldiacylglycerol, a Mammalian DNA Polymerase α-Specific Inhibitor from a Sea Alga, Petalonia bingbamiae
  • Galactosyldiacylglycerol a Mammalian DNA Polymerase アルファ Specific Inhibitor from a Sea Alga Petalonia bingbamiae

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The glycolipid galactosyldiacylglycerol (GDG), containing C16 : 0 and C18 : 1 fatty acids, was isolated from the sea alga Petalonia bingbamiae as a potent inhibitor of the activities of mammalian DNA polymerase α (pol. α). GDG, however, had no effect on pol. α from a fish or a higher plant. The inhibition of pol. α by GDG was dose-dependent with an IC50 value of 54 μM. The compound did not influence the activities of other replicative DNA polymerases such as mammalian pol. δ, or repair-related enzymes such as mammalian pol. β. GDG also did not influence the activities of prokaryotic DNA polymerases such as the Klenow fragment of DNA polymerase I, T4 DNA polymerase, Taq DNA polymerase, DNA polymerases from the higher plant, cauliflower, or DNA metabolic enzymes such as calf thymus terminal deoxynucleotidyl transferase, human immunodeficiency virus type 1 reverse transcriptase and deoxyribonuclease I. Kinetic analysis of the compound showed that pol. α was non-competitively inhibited with respect to both the DNA template and the nucleotide substrate. In this study, we demonstrated the structure-function relationship in the selective inhibition of pol. α by the glycolipid group.

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