Unique inhibitory effect of 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-methyluracil 5'-triphosphate on Epstein-Barr virus and human DNA polymerases.
Unique inhibitory effect of 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-methyluracil 5'-triphosphate on Epstein-Barr virus and human DNA polymerases.
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1-(2-脱氧-2-氟-β-L-阿拉伯呋喃糖基)-5-甲基尿嘧啶 5-三磷酸对 Epstein-Barr 病毒和人类 DNA 聚合酶具有独特的抑制作用。
DOI:
10.1016/s0006-2952(97)00598-4
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发表时间:
1998
影响因子:
5.8
通讯作者:
Cheng,YC
中科院分区:
文献类型:
--
作者:
Kukhanova,M;Lin,ZY;Yas'co,M;Cheng,YC
1-(2′-Deoxy-2′-fluoro-β-l-arabinofuranosyl)-5-methyluracil (l-FMAU) was shown to have potent antiviral activity against Epstein-Barr virus (EBV) without any cellular toxicity at concentrations up to 200 μM (Yao et al., Biochem Pharmacol51: 941–947, 1996). The 5′-triphosphate of l-FMAU was not a substrate for EBV or cellular DNA polymerases, but could inhibit the elongation reaction, 3′-to-5′ exonuclease activity, and nucleotide turnover catalyzed by EBV DNA polymerase. DNA synthesis catalyzed by human DNA polymerases was inhibited to a lesser extent. The inhibition pattern of EBV DNA polymerase by l-FMAU-5′-triphosphate (l-FMAU-TP) was consistent with an uncompetitive mechanism when dNTP or template-primer were used as the variable substrates. The Kivalues were 38 ± 10 μM for the elongation reaction, and about 50 ± 10 μM for both nucleotide exchange and 3′-to-5′ exonuclease reactions, values that were 10–20 times less than that for GMP. l-FMAU-TP is the first nucleoside 5′-triphosphate shown to have such unique behavior toward DNA polymerases. EBV DNA polymerase could be one of the targets for the inhibitory effect of l-FMAU-TP on EBV replication.
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影响因子:
4.8
作者:
D. Derse;K. Bastow;Y. Cheng
通讯作者:
Y. Cheng
影响因子:
3.7
作者:
T. Tsurumi
通讯作者:
T. Tsurumi
影响因子:
14.9
作者:
FOCHER, F;MAGA, G;SPADARI, S
通讯作者:
SPADARI, S
影响因子:
3.7
作者:
T. Tsurumi
通讯作者:
T. Tsurumi
DOI:
10.1016/s0021-9258(19)73999-4
发表时间:
1992
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
N. Van Draanen;S. C. Tucker;F. L. Boyd;B. Trotter;J. Reardon
通讯作者:
J. Reardon