A 5'-monophosphate form of bredinin selectively inhibits the activities of mammalian DNA polymerases in vitro.

  • Authors:
    • T Horie
    • Y Mizushina
    • M Takemura
    • F Sugawara
    • A Matsukage
    • S Yoshida
    • K Sakaguchi
  • View Affiliations

  • Published online on: January 1, 1998     https://doi.org/10.3892/ijmm.1.1.83
  • Pages: 83-173
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Abstract

Bredinin is an immunosuppressive drug which is used clinically in Japan. In this study, we investigated bredinin's molecular mode of action to clarify its immunosuppressive effects. We focused on the DNA polymerases in the somatic DNA synthesis which may be required in the process of lymphocyte differentiation. We found that bredinin-5'-monophosphate (breMP) could be a potent inhibitor of mammalian DNA polymerase alpha(pol.alpha) and (pol.beta) in vitro, although bredinin itself has no such effects. BreMP inhibited the pol. alpha activity at less than 7 micrograms/ml and the pol. activity at 7 micrograms/ml. Neither breMP nor bredinin influenced the activities of a plant DNA polymerase, prokaryotic DNA polymerases such as E. coli DNA polymerase I and Taq DNA polymerase, or DNA-metabolic enzymes such as DNase I, indicating that breMP selectively suppressed the activities of the mammalian DNA polymerases. For pol., beta breMP acted by competing with both the substrate and template-primer. For pol. alpha, it acted by competing only with the substrate, and non-competitively with the template-primer. The ribose of bredinin is quickly and quantitatively converted to its ribose-5'-phosphate form in vivo as soon as it is incorporated into cells. The action mode of bredinin and its use as an immunosuppressive drug are discussed based on these results.

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Jan 1998
Volume 1 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Horie T, Mizushina Y, Takemura M, Sugawara F, Matsukage A, Yoshida S and Sakaguchi K: A 5'-monophosphate form of bredinin selectively inhibits the activities of mammalian DNA polymerases in vitro.. Int J Mol Med 1: 83-173, 1998
APA
Horie, T., Mizushina, Y., Takemura, M., Sugawara, F., Matsukage, A., Yoshida, S., & Sakaguchi, K. (1998). A 5'-monophosphate form of bredinin selectively inhibits the activities of mammalian DNA polymerases in vitro.. International Journal of Molecular Medicine, 1, 83-173. https://doi.org/10.3892/ijmm.1.1.83
MLA
Horie, T., Mizushina, Y., Takemura, M., Sugawara, F., Matsukage, A., Yoshida, S., Sakaguchi, K."A 5'-monophosphate form of bredinin selectively inhibits the activities of mammalian DNA polymerases in vitro.". International Journal of Molecular Medicine 1.1 (1998): 83-173.
Chicago
Horie, T., Mizushina, Y., Takemura, M., Sugawara, F., Matsukage, A., Yoshida, S., Sakaguchi, K."A 5'-monophosphate form of bredinin selectively inhibits the activities of mammalian DNA polymerases in vitro.". International Journal of Molecular Medicine 1, no. 1 (1998): 83-173. https://doi.org/10.3892/ijmm.1.1.83