title: Galactosyldiacylglycerol, a mammalian DNA polymerase alpha-specific inhibitor from a sea alga, Petalonia bingbamiae.
abstract: 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 alpha (pol. alpha). GDG, however, had no effect on pol. alpha from a fish or a higher plant. The inhibition of pol. alpha by GDG was dose-dependent with an IC50 value of 54 microM. The compound did not influence the activities of other replicative DNA polymerases such as mammalian pol. delta, or repair-related enzymes such as mammalian pol. beta. 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 1. Kinetic analysis of the compound showed that pol. alpha 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. alpha by the glycolipid group.
authors.affiliation: Department of Nutritional Science, and High Technology Research Center, Kobe-Gakuin University, Hyogo, Japan. mizushin@nutr.kobegakuin.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Mizushina
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Hanashima
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: S
authors.initials: S
authors.lastname: Kamisuki
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Takemura
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: A
authors.initials: A
authors.lastname: Matsukage
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Saneyoshi
authors.forename: F
authors.initials: F
authors.lastname: Sugawara
authors.forename: K
authors.initials: K
authors.lastname: Sakagauchi
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D006017:Glycolipids / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D000459:Phaeophyceae / Q000737:chemistry*; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance
chemical_list: D004791:Enzyme Inhibitors; D005227:Fatty Acids; D006017:Glycolipids; D007527:Isoenzymes; D004256:DNA Polymerase I