Analysis of butylphenyl-guanine, butylphenyl-deoxyguanosine, and butylphenyl-deoxyguanosine triphosphate inhibition of DNA replication and ultraviolet-induced DNA repair synthesis using permeable human fibroblasts.
Analysis of butylphenyl-guanine, butylphenyl-deoxyguanosine, and butylphenyl-deoxyguanosine triphosphate inhibition of DNA replication and ultraviolet-induced DNA repair synthesis using permeable human fibroblasts.
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使用可渗透性人成纤维细胞分析丁基苯基鸟嘌呤、丁基苯基脱氧鸟苷和丁基苯基脱氧鸟苷三磷酸对 DNA 复制和紫外线诱导的 DNA 修复合成的抑制作用。
DOI：
10.1016/0006-2952(88)90506-0
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发表时间：
1988
影响因子：
5.8
通讯作者：
Frattini,MG
中科院分区：
文献类型：
--
作者：
Dresler,SL;Frattini,MG
嘌呤碱基和核苷类似物n2 -(对正丁基苯基鸟嘌呤（BuPh-Gua）和n2 -（对正丁基苯基）-2 ' -脱氧鸟嘌呤（BuPh-dGuo）是分离的哺乳动物DNA聚合酶α的强抑制剂，但在完整培养细胞中作为DNA复制抑制剂的作用不如预期的那么有效[G]。李建军，李建军，张建军，等。中华医学杂志，2009,32(1)。这些观察的机制基础是用可渗透的人成纤维细胞来探索的。在100 μM的浓度下，BuPh-Gua和BuPh-dGuo对可渗透细胞的DNA复制只有轻微的抑制作用。紫外线诱导的DNA修复合成也获得了类似的结果，这一过程被认为涉及与复制相同的DNA聚合酶。使用相应的核苷酸类似物N2-（p-n-丁基苯基）-2 ' -脱氧鸟苷-5 ' -三磷酸（BuPh-dGTP）进行了更详细的研究，它比碱基和核苷更具水溶性。在可渗透细胞中，BuPh-dGTP对复制和紫外线诱导的修复合成的抑制作用的明显ki值约为3 μM。这些值比明显的BuPh-dGTP对分离的人DNA聚合酶α的抑制作用（约10 nM）大几百倍。我们得出结论，在完整细胞中，BuPh-Gua和BuPh-dGuo是较差的DNA复制抑制剂，不是因为渗透性障碍，而是因为，与聚合酶α不同，细胞DNA合成对这组抑制剂相对不敏感。这些结果表明，聚合酶α可能不是预测碱基、脱氧核糖核苷和脱氧核糖核苷类似物作为哺乳动物细胞DNA复制抑制剂的效力的良好通用模型。事实上，可渗透细胞系统准确地反映了哺乳动物DNA复制对丁基苯基鸟嘌呤衍生物的相对不敏感，这表明可渗透细胞可能是未来研究碱基和核苷类似物的有用工具。
The purine base and nucleoside analoguesN2-(p-n-butylphenyl-guanine (BuPh-Gua) andN2-(p-n-butylphenyl)-2′-deoxyguanosine (BuPh-dGuo) are strong inhibitors of isolated mammalian DNA polymerase α, but are less potent than expected as inhibitors of DNA replication in intact cultured cells [G. E. Wright, L. W. Dudycz, Z. Kazimierczuk, N. C. Brown and N. N. Khan, J. med. Chem.30, 109 (1987)J. The mechanistic basis for these observations was explored using permeable human fibroblasts. DNA replication in the permeable cells was inhibited only slightly by BuPh-Gua and BuPh-dGuo at 100 μM, the highest concentration which could be attained. Similiar results were obtained for ultraviolet-induced DNA repair synthesis, a process which is though to involve the same DNA polymerase as replication. More detailed studies were performed using the corresponding nucleotide analogue,N2-(p-n-butylphenyl)-2′-deoxyguanosine-5′-triphosphate (BuPh-dGTP), which is much more water-soluble than the base and nucleoside. The apparentKivalues for BuPh-dGTP inhibition of both replication and ultraviolet-induced repair synthesis in permeable cells were approximately 3 μM. These values are several hundred-fold greater than the apparentKifor BuPh-dGTP inhibition of isolated human DNA polymerase α, which is approximately 10 nM. We conclude that BuPh-Gua and BuPh-dGuo are poor inhibitors of DNA replication in intact cells not because of permeability barriers, but because, unlike polymerase α, cellular DNA synthesis is relatively insensitive to this group of inhibitors. These results suggest that polymerase α may not be a good general model for predicting the potency of base, deoxyribonucleoside and deoxyribonucleotide analogues as inhibitors of mammalian cellular DNA replication. The fact that the permeable cell systems accurately reflect the relative insensitivity to butylphenyl-guanine derivatives of mammalian DNA replication suggests that permeable cells may be useful tools in future studies of base and nucleoside analogues.
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人类成纤维细胞中的 DNA 复制和紫外线诱导的 DNA 修复合成对丁基苯基脱氧鸟苷三磷酸的抑制作用远不如 DNA 聚合酶 α 敏感。
影响因子：
14.9
作者：
S. Dresler;M. Frattini
通讯作者：
M. Frattini
1-β-D-阿拉伯呋喃糖基胞嘧啶三磷酸对分离的 HeLa 细胞核 DNA 合成的影响。
影响因子：
2.9
作者：
E. Wist;H. Krokan;H. Prydz
通讯作者：
H. Prydz
Aphidicolin：同步性肥大细胞瘤 P-815 细胞 DNA 合成的特异性抑制剂。
DOI：
10.1254/jjp.30.301
发表时间：
1980
期刊：
Japanese journal of pharmacology
影响因子：
--
作者：
A. Ichikawa;M. Negishi;K. Tomita;S. Ikegami
通讯作者：
S. Ikegami
DOI：
10.1016/s0021-9258(18)50528-7
发表时间：
1979
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Fisher;T. S. Wang;D. Korn
通讯作者：
D. Korn
2,3-二脱氧胸苷-5-三磷酸对 HeLa 细胞体外 DNA 合成的影响：DNA 聚合酶 α 是细胞 DNA 复制所需的唯一聚合酶的证据。
影响因子：
14.9
作者：
M. Waqar;M. J. Evans;J. Huberman
通讯作者：
J. Huberman