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9-β-(2'-叠氮-2'-脱氧-D-阿拉伯呋喃糖基)腺嘌呤5'-三磷酸酯和9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸酯对L1210白血病细胞DNA聚合酶的比较作用。

Comparative effects of the 5'-triphosphates of 9-beta-(2'-azido-2'-deoxy-D-arabinofuranosyl)adenine and 9-beta-D-arabinofuranosyladenine on DNA polymerases from L1210 leukemia cells.

作者信息

Allaudeen H S, Kozarich J W, Sartorelli A C

出版信息

Nucleic Acids Res. 1982 Feb 25;10(4):1379-87. doi: 10.1093/nar/10.4.1379.

DOI:10.1093/nar/10.4.1379
PMID:6175955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC320532/
Abstract

9-beta-(2'-Azido-2'-deoxy-D-arabiofuranosyl)adenine (arazide) causes greater and significantly more persistent inhibition of [3H]-thymidine incorporation into the DNA of neoplastic cells than the related agent 9-beta-D-arabinofuranosyladenine (araA). To elucidate the mechanism(s) responsible, we compared the effects of arazide and araA 5'-triphosphates on DNA polymerases alpha and beta of L1210 leukemia cells. Both nucleoside triphosphate analogs inhibited DNA polymerase alpha activity by competing with dATP; only araATP was inhibitory to DNA polymerase beta. Arazide triphosphate was at least four times more active than araATP as an inhibitor of DNA polymerase alpha. Preincubation of DNA polymerase alpha with either agent did not result in enzyme inactivation. The results suggest that interference with DNA polymerase alpha activity by arazide triphosphate may be in part responsible for the inhibition of DNA synthesis produced by arazide in neoplastic cells.

摘要

9-β-(2'-叠氮基-2'-脱氧-D-阿拉伯呋喃糖基)腺嘌呤（叠氮化物）比相关药物9-β-D-阿拉伯呋喃糖基腺嘌呤（araA）对[3H]-胸苷掺入肿瘤细胞DNA的抑制作用更强且持续时间显著更长。为阐明其作用机制，我们比较了叠氮化物和araA 5'-三磷酸对L1210白血病细胞DNA聚合酶α和β的影响。两种核苷三磷酸类似物均通过与dATP竞争来抑制DNA聚合酶α活性；只有araATP对DNA聚合酶β有抑制作用。作为DNA聚合酶α的抑制剂，叠氮化物三磷酸的活性至少是araATP的四倍。用这两种药物中的任何一种对DNA聚合酶α进行预孵育都不会导致酶失活。结果表明，叠氮化物三磷酸对DNA聚合酶α活性的干扰可能部分导致了叠氮化物对肿瘤细胞DNA合成的抑制。

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Comparative effects of the 5'-triphosphates of 9-beta-(2'-azido-2'-deoxy-D-arabinofuranosyl)adenine and 9-beta-D-arabinofuranosyladenine on DNA polymerases from L1210 leukemia cells.9-β-(2'-叠氮-2'-脱氧-D-阿拉伯呋喃糖基)腺嘌呤5'-三磷酸酯和9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸酯对L1210白血病细胞DNA聚合酶的比较作用。
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本文引用的文献

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CONVERSION OF MONO- AND OLIGODEOXYRIBONUCLEOTIDES TO 5-TRIPHOSPHATES.单脱氧核糖核苷酸和寡脱氧核糖核苷酸向5-三磷酸酯的转化。
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Internucleotide incorporation of arabinosyladenine into herpes simplex virus and mammalian cell DNA.阿拉伯糖腺嘌呤在疱疹 simplex 病毒和哺乳动物细胞 DNA 中的核苷酸间掺入。
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Effects of arabinonucleotides on ribonucleotide reduction by an enzyme system from rat tumor.阿拉伯核苷酸对大鼠肿瘤酶系统还原核糖核苷酸的影响。
J Biol Chem. 1967 May 10;242(9):2116-8.
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A proposed mechanism for the action of 9-beta-D-arabinofuranosyladenine as an inhibitor of the growth of some ascites cells.9-β-D-阿拉伯呋喃糖基腺嘌呤作为某些腹水细胞生长抑制剂的作用机制推测。
Can J Biochem. 1966 Jan;44(1):19-26. doi: 10.1139/o66-003.
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Inhibition of mammalian DNA polymerase by the 5'-triphosphate of 1-beta-d-arabinofuranosylcytosine and the 5'-triphosphate of 9-beta-d-arabinofuranoxyladenine.1-β-D-阿拉伯呋喃糖基胞嘧啶5'-三磷酸酯和9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸酯对哺乳动物DNA聚合酶的抑制作用。
Cancer Res. 1968 Oct;28(10):2061-7.
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Inhibition of mammalian DNA polymerase by the 5'-triphosphate of 9-beta-D-arabinofuranosyladenine.9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸对哺乳动物DNA聚合酶的抑制作用。
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Cytotoxic activity of the adenine arabinoside analogs, 2'-azido- and 2'-amino-2'-deoxy-beta-D-arabinofuranosyladenine.腺嘌呤阿拉伯糖苷类似物2'-叠氮基-和2'-氨基-2'-脱氧-β-D-阿拉伯呋喃糖基腺嘌呤的细胞毒性活性。
Biochem Pharmacol. 1979 Apr 1;28(7):1267-9. doi: 10.1016/0006-2952(79)90342-3.

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