Marx A, Amacker M, Stucki M, Hübscher U, Bickle T A, Giese B
Department of Chemistry, University of Basel, St Johanns-Ring 19, CH-4056 Basel, Switzerland.
Nucleic Acids Res. 1998 Sep 1;26(17):4063-7. doi: 10.1093/nar/26.17.4063.
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.
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。
