Galactosyldiacylglycerol, a mammalian DNA polymerase alpha-specific inhibitor from a sea alga, Petalonia bingbamiae

The glycolipid galactosyldiacvlglycerol (GDG), containing C16:0 and C18:1 f atty 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 o f 54 muM. The compound did not influence the activities of other replicativ e DNA polymerases such as mammalian pol. delta, or repair-related enzymes s uch as mammalian pol. beta. GDG also did not influence the activities of pr okaryotic DNA polymerases such as the Klenow fragment of DNA polymerase I, T4 DNA polymerase, Taq DNA polymerase, DNA polymerases from the higher plan t, cauliflower, or DNA metabolic enzymes such as calf thymus terminal deoxy nucleotidyl transferase, human immunodeficiency virus type I reverse transc riptase and deoxyribonuclease 1. Kinetic analysis of the compound showed th at pot. a,was non-competitively inhibited with respect to both the DNA temp late and the nucleotide substrate. In this study, we demonstrated the structure-function relationship in the s elective inhibition of pol. alpha by the glycolipid group.