Design and characterization of N2-arylaminopurines which selectively inhibit replicative DNA synthesis and replication-specific DNA polymerases: guanine derivatives active on mammalian DNA polymerase alpha and bacterial DNA polymerase III.
Design and characterization of N2-arylaminopurines which selectively inhibit replicative DNA synthesis and replication-specific DNA polymerases: guanine derivatives active on mammalian DNA polymerase alpha and bacterial DNA polymerase III.
复制标题
选择性抑制复制 DNA 合成和复制特异性 DNA 聚合酶的 N2-芳氨基嘌呤的设计和表征：对哺乳动物 DNA 聚合酶 α 和细菌 DNA 聚合酶 III 具有活性的鸟嘌呤衍生物。
DOI：
10.1093/nar/10.14.4431
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发表时间：
1982
影响因子：
14.9
通讯作者：
Brown,NC
中科院分区：
文献类型：
--
作者：
Wright,GE;Baril,EF;Brown,VM;Brown,NC
鸟嘌呤的2-氨基取代衍生物。本文合成了N_2-（对正丁基苯基）鸟嘌呤（BuPG）和N_h-（3 ′，4 ′-三亚甲基苯基）鸟嘌呤（TMPG），发现它们分别对HeLa细胞DNA聚合酶α（pol α）和B.枯草杆菌DNA聚合酶III（pol III）。这两种嘌呤与其相应的尿嘧啶类似物BuAU和TMAU（2.9）一样，在其对靶聚合酶的抑制作用方面与dGTP特异性竞争。Pola α特异性嘌呤BuPG在体内对HeLa细胞也有毒性，选择性抑制DNA合成。与6-取代尿嘧啶不同，这些N_2-取代嘌呤为核苷和核苷酸的合成提供了结构基础，它们具有作为探针分析特异性复制型DNA聚合酶的结构及其在细胞DNA代谢中的功能的潜力。
The 2-amino substituted derivatives of guanine. N2-(p-n-butylphenyl)guanine (BuPG) and Nh(3',4'-trimethylenephenyl) guanine (TMPG); wae synthesized and found to selectively inhibit, respectively, HeLa cell DNA polymerase alpha (pol α) andB. subtilisDNA polymerase III ( pol III). Both purines, like their corresponding uracil analogs, BuAU and TMAU (2.9), were specifically competitive with dGTP in their inhibitory action on their target polymerases. BuPG, the pola α-specific purine, was also toxic for HeLa cellsin vivo, selectively inhibiting DNA synthesis. These N2-substituted purines, in contrast to the 6-substituted uracils, provide astructural basis for the synthesis of nucleosides and nucleotides with considerable potential as probes for the analysis of the structure of specific replicative DNA polyrnerases and their function incellular DNA metabolism.