4'-酰化胸苷5'-三磷酸：一种提高对HIV-1逆转录酶选择性的工具。
4'-Acylated thymidine 5'-triphosphates: a tool to increase selectivity towards HIV-1 reverse transcriptase.
作者信息
Marx A, Amacker M, Stucki M, Hübscher U, Bickle T A, Giese B
机构信息
Department of Chemistry, University of Basel, St Johanns-Ring 19, CH-4056 Basel, Switzerland.
出版信息
Nucleic Acids Res. 1998 Sep 1;26(17):4063-7. doi: 10.1093/nar/26.17.4063.
Abstract
4'-Acylated thymidines represent a new class of DNA chain terminators, since they have been shown to act as post-incorporation chain-terminating nucleotides despite the presence of a free 3'-hydroxyl group. Here, we describe the action of the 4'-acetyl- (MeTTP) and 4'-propanoylthymidine 5'-triphosphate (EtTTP) on HIV-1 reverse transcriptase in RNA- and DNA-dependent DNA synthesis and on DNA synthesis catalyzed by the cellular DNA polymerases alpha, beta, delta and epsilon. MeTTP exhibits a high selectivity towards HIV-1 reverse transcriptase. By the use of the bulkier propanoyl group as the 4'-substituent of the nucleoside 5'-triphosphate, selectivity towards HIV-1 reverse transcriptase could be increased without affecting substrate efficiency. Thus, 4'-modifications may serve as a tool to increase selectivity towards HIV-1 reverse transcriptase.
摘要
4'-酰化胸苷代表了一类新的DNA链终止剂，因为尽管存在游离的3'-羟基，但它们已被证明可作为掺入后链终止核苷酸发挥作用。在此，我们描述了4'-乙酰基胸苷三磷酸（MeTTP）和4'-丙酰基胸苷三磷酸（EtTTP）在依赖RNA和DNA的DNA合成中对HIV-1逆转录酶以及对细胞DNA聚合酶α、β、δ和ε催化的DNA合成的作用。MeTTP对HIV-1逆转录酶表现出高选择性。通过使用体积更大的丙酰基作为核苷5'-三磷酸的4'-取代基，可以在不影响底物效率的情况下提高对HIV-1逆转录酶的选择性。因此，4'-修饰可作为提高对HIV-1逆转录酶选择性的一种工具。
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本文引用的文献
1
DNA polymerase delta, an essential enzyme for DNA transactions.DNA聚合酶δ，一种DNA事务中的必需酶。
Biol Chem. 1997 May;378(5):345-62. doi: 10.1515/bchm.1997.378.5.345.
2
3
Regulation of DNA metabolic enzymes upon induction of preB cell development and V(D)J recombination: up-regulation of DNA polymerase delta.前B细胞发育和V(D)J重组诱导过程中DNA代谢酶的调控：DNA聚合酶δ的上调。
Nucleic Acids Res. 1997 Jan 15;25(2):289-96. doi: 10.1093/nar/25.2.289.
4
Lagging strand DNA synthesis by calf thymus DNA polymerases alpha, beta, delta and epsilon in the presence of auxiliary proteins.在辅助蛋白存在的情况下，小牛胸腺DNA聚合酶α、β、δ和ε进行滞后链DNA合成。
Nucleic Acids Res. 1993 Feb 25;21(4):841-6. doi: 10.1093/nar/21.4.841.
5
A mammalian protein complex that repairs double-strand breaks and deletions by recombination.一种通过重组修复双链断裂和缺失的哺乳动物蛋白质复合物。
J Biol Chem. 1993 Jul 15;268(20):15070-9.
6
DNA replication and chemotherapy.DNA复制与化疗
Physiol Rev. 1994 Apr;74(2):259-304. doi: 10.1152/physrev.1994.74.2.259.
7
Selective action of 4'-azidothymidine triphosphate on reverse transcriptase of human immunodeficiency virus type 1 and human DNA polymerases alpha and beta.4'-叠氮胸苷三磷酸对1型人类免疫缺陷病毒逆转录酶以及人类DNA聚合酶α和β的选择性作用。
Biochemistry. 1993 Jun 15;32(23):6002-10. doi: 10.1021/bi00074a011.
8
L- and D-enantiomers of 2',3'-dideoxycytidine 5'-triphosphate analogs as substrates for human DNA polymerases. Implications for the mechanism of toxicity.
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9
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10
Function and structure relationships in DNA polymerases.DNA聚合酶中的功能与结构关系。
Annu Rev Biochem. 1994;63:777-822. doi: 10.1146/annurev.bi.63.070194.004021.
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