摘要：We found and previously reported a new mammalian DNA polymerase inhibitor from a sea alga, Gigartina tenella, (Ohta K., et al., Chem. Pham. Bull., 46, 684-686, 1998). It was a new sulfolipid compound that belonged in the class of sulfoquinovosyldiacylglycerol. The biochemical properties have been investigated here. The compound, temporarily designated KM043, potently inhibited the activities of mammalian DNA polymerase α(pol. α) and DNA polymerase β(pol. β) and terminal deoxynucleotidyl transferase (TdT), and moderately, human immunodeficiency virus reverse transcriptase (HIV-RT). KM043 dose-dependently inhibited their activities, and each of their IC50 values was 0.25 μM for pol. a, 0.38 μM for TdT, 3.6 μM for pol. β, or 11.2 μM for HIV-RT, and almost complete inhibition of each was achieved at 1.0 to 2.0 μM for pol. αand TdT, 7.5 μM for pol. β and about 30 μM for HIV-RT. However, the compound did not influence the activities of prokaryotic DNA polymerases such as E. coli DNA polymerase I, and DNA metabolic enzymes like DNase 1. Inhibition of pol. α or β by KM043 was non-competitive with both the DNA template and the substrate deoxythymidine 5'-triphosphate (dTTP). KM043 was weakly cytotoxic to cultured HeLa-S3 cells, and the IC50 value was 80 μM. KM043 could synergistically enhance the cytocidal effect of an anti-cancer chemotherapy agent, bleomuycin. In the presence of 50 μM KM043, the effect ratio of (bleomycin plus KM043) /(bleomysin only) decreased from 0.76 to 0.22.
