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 language | English |
|---|---|
| Pages (from-to) | 3856-3861 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 24 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Jan 1 2016 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
Effects of 8-halo-7-deaza-2′-deoxyguanosine triphosphate on DNA synthesis by DNA polymerases and cell proliferation. / Yin, Yizhen; Sasaki, Shigeki; Taniguchi, Yosuke.
In: Bioorganic and Medicinal Chemistry, Vol. 24, No. 16, 01.01.2016, p. 3856-3861.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of 8-halo-7-deaza-2′-deoxyguanosine triphosphate on DNA synthesis by DNA polymerases and cell proliferation
AU - Yin, Yizhen
AU - Sasaki, Shigeki
AU - Taniguchi, Yosuke
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84977659728&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2016.06.030
DO - 10.1016/j.bmc.2016.06.030
M3 - Article
C2 - 27372838
AN - SCOPUS:84977659728
VL - 24
SP - 3856
EP - 3861
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 16
ER -