Chemical properties of fatty acid derivatives as inhibitors of DNA polymerases.

Chemical properties of fatty acid derivatives as inhibitors of DNA polymerases. Research Abstract Details 

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Chemical properties of fatty acid derivatives as inhibitors of DNA polymerases. Abstract Text:

Ryoichi Nakamura,Ryo Takeuchi,Kouji Kuramochi,Yoshiyuki Mizushina,Chisato Ishimaru,Yoichi Takakusagi,Masaharu Takemura,Susumu Kobayashi,Hiromi Yoshida,Fumio Sugawara,Kengo Sakaguchi,Ryoichi Nakamura,Ryo Takeuchi,Kouji Kuramochi,Yoshiyuki Mizushina,Chisato Ishimaru,Yoichi Takakusagi,Masaharu Takemura,Susumu Kobayashi,Hiromi Yoshida,Fumio Sugawara,Kengo Sakaguchi,

In this study, the chemical properties of organic acids as DNA polymerase inhibitors were examined. In total, we assayed the inhibitory activities of 23 compounds. We found that the DNA synthesis activity of DNA polymerase was usually reduced to less than 50% in the presence of 100 microM monoprotic acids, which have a Clog P value greater than 7.0 and a pK(a) value less than 5.4. With a minor modification these chemical properties applied to several organic fatty acids previously reported as DNA polymerase inhibitors. Moreover, we also examined the inhibitory activities of perfluorooctadecanoic acid (PFOdA) and perfluorooctanesulfonic acid (PFOS) against DNA polymerase beta in detail. These compounds inhibited the polymerase activity of pol beta competitively with template-primer DNA, and non-competitively with dNTPs. In addition, the 8 kDa domain-defective pol beta was also sensitive to these compounds. Our results suggest that the inhibitory mode of action of PFOdA and PFOS is different from that mediated by the classic fatty acid inhibitors against DNA polymerase beta.

Chemical properties of fatty acid derivatives as inhibitors of DNA polymerases. Publishing Authors By Initials

R Nakamura,R Takeuchi,K Kuramochi,Y Mizushina,C Ishimaru,Y Takakusagi,M Takemura,S Kobayashi,H Yoshida,F Sugawara,K Sakaguchi,R Nakamura,R Takeuchi,K Kuramochi,Y Mizushina,C Ishimaru,Y Takakusagi,M Takemura,S Kobayashi,H Yoshida,F Sugawara,K Sakaguchi,

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Chemical properties of fatty acid derivatives as inhibitors of DNA polymerases. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Organic & biomolecular chemistry

VOLUME: 5

Page Numbers: 3912-21

Journal Abbreviation: Org. Biomol. Chem.

ISSN: 1477-0520

DAY: 5

MONTH: 11

YEAR: 2007

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LANGUAGE: eng

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AFFILIATION: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. sugawara@rs.noda.tus.ac.jp kengo@rs.noda.tus.ac.jp.

Country: England

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MEDLINETA: Org Biomol Chem

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