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

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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Mizushina Y,Watanabe I,Ohta K,Takemura M,Sahara H,Takahashi N,Gasa S,Sugawara F,Matsukage A,Yoshida S,Sakaguchi K

doi

10.1016/s0006-2952(97)00536-4

subject

Has Abstract

pub_date

1998-02-15 00:00:00

pages

537-41

issue

4

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(97)00536-4

journal_volume

55

pub_type

杂志文章

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