Galactosyldiacylglycerol, a mammalian DNA polymerase α-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 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.