Action of a New Mammalian DNA Polymerase Inhibitor, Sulfoquinovosyldiacylglycerol

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概要

• 論文の詳細を見る

• 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 IC_<50> 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 IC_<50> 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.

• 公益社団法人日本薬学会の論文
• 1999-02-15

著者

• HIRATA Noriko

  School of Pharmacy, Kinki University

• SAKAGUCHI Kengo

  Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Sci

• SUGAWARA Fumio

  Department of Applied Biological Science, Tokyo University of Science

• Yoshida S

  Plant Science Center Riken Institute

• Hirata Noriko

  3rd Section Of Research And Development Toyo Suisan Kaisha Ltd.

• Hirata Noriko

  Department Of Pharmaceutical Sciences Kinki University

• Yoshida S

  Cancer Immunotherapy Center Nagoya Kyoritu Hospital

• Yoshida S

  Laboratory Of Cancer Cell Biology Research Institute For Disease Mechanism And Control Nagoya Univer

• Yoshida Shonen

  Laboratory Of Cancer Cell Biology Research Institute For Disease Mechanism And Control Nagoya Univer

• TAKEMURA Masaharu

  Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya Univ

• OHTA Keisuke

  Department of Applied Biological Science, Science University of Tokyo

• MATSUKAGE Akio

  Laboratory of Cell Biology, Aichi Cancer Center Research Institute

• Suzuki Y

  Department Of Applied Biological Chemistry The University Of Tokyo

• Matsukage A

  Department Of Chemical And Biological Sciences Faculty Of Science Japan Women's University

• Matsukage Akio

  Department Of Chemical And Biological Sciences Japan Women's University

• Matsukage Akio

  Laboratory Of Cell Biology

• Hirata N

  3rd Section Of Research And Development Toyo Suisan Kaisha Ltd.

• MIZUSHIMA Yoshiyuki

  Department of Applied Biological Science, Faculty of Science and Technology, Science University of T

• TAKEMURA Masaharu

  Life Science Research Center, Mie University

• Yoshida Shigeki

  Inst. Applied Biochem. Tsukuba Univ.

• Takemura Masaharu

  Life Science Research Center Mie University

• Sakagichi Ken-ichi

  Institute For Protein Research Osaka University

• Yoshida S

  Biological Research Laboratories Sankyo Co. Ltd.

• Sugawara F

  Dep. Of Applied Biological Sci. Tokyo Univ. Of Sci.

• Sugawara Fumio

  Dep. Of Applied Biological Sci. Tokyo Univ. Of Sci.

• Sugawara Fumio

  Department Of Agricultural Chemistry Faculty Of Agriculture Tohoku University

• Ohta Keisuke

  Department Of Anatomy & Histology Kurume University School Of Medicine

• Takemura M

  Life Science Research Center Mie University

• Mizushima Y

  Laboratory Of Food And Nutritional Sciences Department Of Nutritional Science Kobe-gakuin University

• Mizushina Y

  Kobe‐gakuin Univ. Kobe Jpn

• Ohta Keisuke

  Department Of Applied Biological Science Frontier Research Center For Genomic Drug Discovery Tokyo U

• Sakaguchi Kengo

  Department Of Applied Biological Science Tokyo University Of Science

• Sakaguchi Kengo

  Department Of Applied Biological Science Faculty Of Science And Technology Tokyo University Of Scien

• Sakaguchi Kengo

  Department Of Applied Biological Science Faculty Of Science And Technology Science University Of Tok

• Mizushina Yoshiyuki

  Department Of Nutritional Science Kobe Gakuin University

• Sugawara Fumio

  Dep. Of Applied Biological Sci. Fac. Of Sci. And Technol. Tokyo Univ. Of Sci.

• Mizushima Yoshiyuki

  Department Of Applied Biological Science Science University Of Tokyo

• Takemura Masaharu

  Laboratory Of Biology Education Graduate School Of Mathematics And Science Education Tokyo Universit

• Mizushina Yoshiyuki

  Department of Applied Biological Science, Science University of Tokyo

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