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. 1988 Jun 10;16(11):5107–5113. doi: 10.1093/nar/16.11.5107

Inhibition of DNA polymerase alpha by aphidicolin derivatives.

L Arabshahi 1, N Brown 1, N Khan 1, G Wright 1
PMCID: PMC336720  PMID: 3133639

Abstract

17-Acetylaphidicolin was 10-fold weaker and two derivatives lacking hydroxyl groups at the 16 and 17 positions were 100-fold weaker than aphidicolin as inhibitors of DNA polymerase alpha from HeLa and Chinese hamster ovary cells. 17,18-Diacetyl, 3,17,18-triacetyl and 3-epi derivatives of aphidicolin were inactive. Active compounds were, like aphidicolin, competitive with dCTP and did not inhibit aphidicolin-resistant DNA polymerases.

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Selected References

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  1. Clements J. E., D'Ambrosio J., Brown N. C. Inhibition of Bacillus subtilis deoxyribonucleic acid polymerase III by phenylhydrazinopyrimidines. Demonstration of a drug-induced deoxyribonucleic acid-enzyme complex. J Biol Chem. 1975 Jan 25;250(2):522–526. [PubMed] [Google Scholar]
  2. Goscin L. P., Byrnes J. J. DNA polymerase delta: one polypeptide, two activities. Biochemistry. 1982 May 11;21(10):2513–2518. doi: 10.1021/bi00539a034. [DOI] [PubMed] [Google Scholar]
  3. Habara A., Kano K., Nagano H., Mano Y., Ikegami S., Yamashita T. Inhibition of DNA synthesis in the adenovirus DNA replication complex by aphidicolin and 2',3'-dideoxythymidine triphosphate. Biochem Biophys Res Commun. 1980 Jan 15;92(1):8–12. doi: 10.1016/0006-291x(80)91511-9. [DOI] [PubMed] [Google Scholar]
  4. Hammond R. A., Byrnes J. J., Miller M. R. Identification of DNA polymerase delta in CV-1 cells: studies implicating both DNA polymerase delta and DNA polymerase alpha in DNA replication. Biochemistry. 1987 Oct 20;26(21):6817–6824. doi: 10.1021/bi00395a035. [DOI] [PubMed] [Google Scholar]
  5. Haraguchi T., Oguro M., Nagano H., Ichihara A., Sakamura S. Specific inhibitors of eukaryotic DNA synthesis and DNA polymerase alpha, 3-deoxyaphidicolin and aphidicolin-17-monoacetate. Nucleic Acids Res. 1983 Feb 25;11(4):1197–1209. doi: 10.1093/nar/11.4.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hiranuma S., Shimizu T., Yoshioka H., Ono K., Nakane H., Takahashi T. Chemical modification of aphidicolin and the inhibitory effects of its derivatives on DNA polymerase alpha in vitro. Chem Pharm Bull (Tokyo) 1987 Apr;35(4):1641–1644. doi: 10.1248/cpb.35.1641. [DOI] [PubMed] [Google Scholar]
  7. Khan N. N., Brown N. C. Purification and characterization of DNA polymerase alpha of Chinese hamster ovary cells. Mol Cell Biochem. 1985 Oct;68(2):169–179. doi: 10.1007/BF00219381. [DOI] [PubMed] [Google Scholar]
  8. Lamothe P., Baril B., Chi A., Lee L., Baril E. Accessory proteins for DNA polymerase alpha activity with single-strand DNA templates. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4723–4727. doi: 10.1073/pnas.78.8.4723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lee M. Y., Tan C. K., Downey K. M., So A. G. Further studies on calf thymus DNA polymerase delta purified to homogeneity by a new procedure. Biochemistry. 1984 Apr 24;23(9):1906–1913. doi: 10.1021/bi00304a003. [DOI] [PubMed] [Google Scholar]
  10. Lee M. Y., Toomey N. L., Wright G. E. Differential inhibition of human placental DNA polymerases delta and alpha by BuPdGTP and BuAdATP. Nucleic Acids Res. 1985 Dec 9;13(23):8623–8630. doi: 10.1093/nar/13.23.8623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Longiaru M., Ikeda J. E., Jarkovsky Z., Horwitz S. B., Horwitz M. S. The effect of aphidicolin on adenovirus DNA synthesis. Nucleic Acids Res. 1979 Jul 25;6(10):3369–3386. doi: 10.1093/nar/6.10.3369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Oguro M., Shioda M., Nagano H., Mano Y., Hanaoka F., Yamada M. The mode of action of aphidicolin on DNA synthesis in isolated nuclei. Biochem Biophys Res Commun. 1980 Jan 15;92(1):13–19. doi: 10.1016/0006-291x(80)91512-0. [DOI] [PubMed] [Google Scholar]
  13. Oguro M., Suzuki-Hori C., Nagano H., Mano Y., Ikegami S. The mode of inhibitory action by aphidicolin on eukaryotic DNA polymerase alpha. Eur J Biochem. 1979 Jul;97(2):603–607. doi: 10.1111/j.1432-1033.1979.tb13149.x. [DOI] [PubMed] [Google Scholar]
  14. Ohashi M., Taguchi T., Ikegami S. Aphidicolin: a specific inhibitor of DNA polymerases in the cytosol of rat liver. Biochem Biophys Res Commun. 1978 Jun 29;82(4):1084–1090. doi: 10.1016/0006-291x(78)90298-x. [DOI] [PubMed] [Google Scholar]
  15. Pedrali-Noy G., Spadari S. Mechanism of inhibition of herpes simplex virus and vaccinia virus DNA polymerases by aphidicolin, a highly specific inhibitor of DNA replication in eucaryotes. J Virol. 1980 Nov;36(2):457–464. doi: 10.1128/jvi.36.2.457-464.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Plevani P., Badaracco G., Ginelli E., Sora S. Effect and mechanism of action of aphidicolin on yeast deoxyribonucleic acid polymerases. Antimicrob Agents Chemother. 1980 Jul;18(1):50–57. doi: 10.1128/aac.18.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sala F., Parisi B., Burroni D., Amileni A. R., Pedrali-Noy G., Spadari S. Specific and reversible inhibition by aphidicolin in the alpha-like DNA polymerase of plant cells. FEBS Lett. 1980 Aug 11;117(1):93–98. doi: 10.1016/0014-5793(80)80920-3. [DOI] [PubMed] [Google Scholar]
  18. Wist E., Prydz H. The effect of aphidicolin on DNA synthesis in isolated HeLa cell nuclei. Nucleic Acids Res. 1979 Apr;6(4):1583–1590. doi: 10.1093/nar/6.4.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wright G. E., Brown N. C. Inhibition of RNA-directed DNA polymerase from avian myeloblastosis virus by a 5-benzyl-6-aminouracil. Biochem Biophys Res Commun. 1985 Jan 16;126(1):109–116. doi: 10.1016/0006-291x(85)90578-9. [DOI] [PubMed] [Google Scholar]

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