Studies on inhibitors of mammalian DNA polymerase alpha and beta: sulfolipids from a pteridophyte, Athyrium niponicum.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Studies on inhibitors of mammalian DNA polymerase alpha and beta: sulfolipids from a pteridophyte, Athyrium niponicum.

Biochem Pharmacol. 1998 Feb 15;55(4):537-41. Unique Identifier : AIDSLINE MED/98173023
Mizushina Y; Watanabe I; Ohta K; Takemura M; Sahara H; Takahashi N; Gasa S; Sugawara F; Matsukage A; Yoshida S; Sakaguchi K; Department of Applied Biological Science, Science University of Tokyo,; Japan.

Abstract: Three sulfolipid compounds, 1, 2, and 3, have been isolated from a higher plant, a pteridophyte, Athyrium niponicum, as potent inhibitors of the activities of calf DNA polymerase alpha and rat DNA polymerase beta. The inhibition by the sulfolipids was concentration dependent, and almost complete inhibition of DNA polymerase alpha and DNA polymerase beta was achieved at 6 and 8 microg/mL, respectively. The compounds did not influence the activities of calf thymus terminal deoxynucleotidyl transferase, prokaryotic DNA polymerases such as the Klenow fragment of DNA polymerase I, T4 DNA polymerase and Taq polymerase, the DNA metabolic enzyme DNase I, and even a DNA polymerase from a higher plant, cauliflower. Similarly, the compounds did not inhibit the activity of the human immunodeficiency virus type 1 reverse transcriptase. The kinetic studies of the compounds showed that DNA polymerase alpha was inhibited non-competitively with respect to the DNA template and substrate, whereas DNA polymerase beta was inhibited competitively with both the DNA template and substrate. The binding to DNA polymerase beta could be stopped with non-ionic detergent, but the binding to DNA polymerase alpha could not.

Keywords: *DNA Polymerase beta/ANTAGONISTS & INHIB *DNA Polymerase I/ANTAGONISTS & INHIB *Enzyme Inhibitors/PHARMACOLOGY *Lipids/PHARMACOLOGY
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