Semizarov D G, Ias'ko M V, Kukhanova M K, Kraevskiĭ A A
Mol Biol (Mosk). 1995 May-Jun;29(3):689-700.
2'-Deoxythymidine 5'-triphosphate and 2'-deoxyadenosine 5'-triphosphate analogs containing a methylene group between the alpha phosphorus and 5' oxygen were synthesized. The substrate properties of these compounds toward some mammalian DNA polymerases and retroviral reverse transcriptases were evaluated using a system containing phage M13mp10 DNA, a synthetic oligonucleotide, and the enzyme. The compounds containing a hydroxyl at the 3' position were incorporated into the DNA chain by DNA polymerase alpha and terminal deoxynucleotidyl transferase, but were not recognized by retroviral reverse transcriptases and mammalian DNA polymerases epsilon and beta. The selectivity of the compounds synthesized was capitalized on during simultaneous isolation of DNA polymerases alpha and epsilon from human placenta. A methylene group was also introduced into the acyclovir molecule. It was shown that this modification inactivates furanose-related nucleotide analogs, but has a minor effect on the substrate properties of acyclic nucleotide analogs.
合成了在α-磷原子和5'-氧原子之间含有亚甲基的2'-脱氧胸苷5'-三磷酸酯和2'-脱氧腺苷5'-三磷酸酯类似物。使用包含噬菌体M13mp10 DNA、合成寡核苷酸和酶的系统，评估了这些化合物对某些哺乳动物DNA聚合酶和逆转录病毒逆转录酶的底物特性。在3'位含有羟基的化合物可被DNA聚合酶α和末端脱氧核苷酸转移酶掺入DNA链中，但不能被逆转录病毒逆转录酶以及哺乳动物DNA聚合酶ε和β识别。在从人胎盘中同时分离DNA聚合酶α和ε的过程中，利用了所合成化合物的选择性。还将一个亚甲基引入阿昔洛韦分子中。结果表明，这种修饰使呋喃糖相关的核苷酸类似物失活，但对无环核苷酸类似物的底物特性影响较小。
