Effects of 8-halo-7-deaza-2′-deoxyguanosine triphosphate on DNA synthesis by DNA polymerases and cell proliferation

Yizhen Yin, Shigeki Sasaki, Yosuke Taniguchi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

8-OxodG (8-oxo-2′-deoxyguanosine) is representative of nucleoside damage and shows a genotoxicity. To significantly reveal the contributions of 7-NH and C8-oxygen to the mutagenic effect of 8-oxodG by DNA polymerases, we evaluated the effects of the 8-halo-7-deaza-dG (8-halogenated 7-deaza-2′-deoxyguanosine) derivatives by DNA polymerases. 8-Halo-7-deaza-dGTPs were poorly incorporated by both KF(exo) and human DNA polymerase β opposite dC or dA into the template DNA. Furthermore, it was found that KF(exo) was very sensitive to the introduction of the C8-halogen, while polymerase β can accommodate the C8-halogen resulting in an efficient dCTP insertion opposite the 8-halo-7-deaza-dG in the template DNA. These results indicate that strong hydrogen bonding between 7-NH in the 8-oxo-G nucleobase and 1-N in the adenine at the active site of the DNA polymerase is required for the mutagenic effects. Whereas, I-deaza-dGTP shows an antiproliferative effect for the HeLa cells, suggesting that it could become a candidate as a new antitumor agent.

Original languageEnglish
Pages (from-to)3856-3861
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number16
DOIs
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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