阿非科林通过抑制DNA聚合酶α来抑制DNA合成，并且通过类似机制抑制分离的细胞核（的相关活动）。
Aphidicolin inhibits DNA synthesis by DNA polymerase alpha and isolated nuclei by a similar mechanism.
作者信息
Krokan H, Wist E, Krokan R H
出版信息
Nucleic Acids Res. 1981 Sep 25;9(18):4709-19. doi: 10.1093/nar/9.18.4709.
Abstract
Aphidicolin is a selective inhibitor of DNA polymerase alpha. In contrast to earlier reports, the drug was found to inhibit DNA synthesis catalyzed by DNA polymerase alpha and isolated HeLa cell nuclei by a similar mechanism. For both systems aphidicolin primarily competed with dCTP incorporation. However, the apparent Vmax for dCTP incorporation was reduced by 50-60% at relatively low concentrations of aphidicolin, thus the mechanism of inhibition is complex. Furthermore, a 2-5 fold increase in apparent Km for dTTP was observed in the presence of aphidicolin, but the apparent Km values for dATP and dGTP were essentially unaltered. This, together with additional evidence, suggested that the mechanism of action of aphidicolin involves a strong competition with dCMP incorporation, a weaker competition with dTMP incorporation and very little, if any, competition with dGMP and dAMP incorporation.
摘要
阿非迪霉素是DNA聚合酶α的选择性抑制剂。与早期报告不同的是，发现该药物通过类似机制抑制DNA聚合酶α催化的DNA合成以及分离的海拉细胞核中的DNA合成。对于这两种系统，阿非迪霉素主要与dCTP掺入竞争。然而，在相对较低浓度的阿非迪霉素下，dCTP掺入的表观Vmax降低了50 - 60%，因此抑制机制较为复杂。此外，在阿非迪霉素存在的情况下，观察到dTTP的表观Km增加了2 - 5倍，但dATP和dGTP的表观Km值基本未改变。这一点，连同其他证据表明，阿非迪霉素的作用机制涉及与dCMP掺入的强烈竞争、与dTMP掺入的较弱竞争以及与dGMP和dAMP掺入的极少竞争（如果有竞争的话）。
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