抑肽素衍生物对DNA聚合酶α抑制作用的构效关系
Structure-activity relationships for the inhibition of DNA polymerase alpha by aphidicolin derivatives.
作者信息
Prasad G, Edelson R A, Gorycki P D, Macdonald T L
机构信息
Department of Chemistry, University of Virginia, Charlottesville 22901.
出版信息
Nucleic Acids Res. 1989 Aug 11;17(15):6339-48. doi: 10.1093/nar/17.15.6339.
Abstract
Aphidicolin and 17 derivatives that have been structurally modified in the A- and D-rings were assessed for their ability to inhibit DNA polymerase alpha. No derivative surpassed the activity of aphidicolin; derivatives with structural alterations in the A-ring exhibited significantly greater loss of activity relative to derivatives with structural alterations in the D-ring. The conclusions of these studies indicate a critical role for the C-18 function in the interaction of aphidicolin with polymerase alpha. Molecular modelling studies could not identify structural features of the aphidicolin-dCTP "overlap" that is unique to dCTP, relative to the remaining dNTPs, and that is consistent with the extant structure-activity data.
摘要
对在A环和D环进行结构修饰的阿非科林及其17种衍生物抑制DNA聚合酶α的能力进行了评估。没有一种衍生物超过阿非科林的活性；与D环结构改变的衍生物相比，A环结构改变的衍生物活性损失显著更大。这些研究的结论表明C-18官能团在阿非科林与聚合酶α相互作用中起关键作用。分子建模研究无法确定阿非科林-dCTP“重叠”相对于其余dNTPs中dCTP特有的结构特征，且该特征与现有构效关系数据一致。
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本文引用的文献
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New views of the biochemistry of eucaryotic DNA replication revealed by aphidicolin, an unusual inhibitor of DNA polymerase alpha.通过一种不同寻常的DNA聚合酶α抑制剂——阿非科林揭示的真核生物DNA复制生物化学新观点。
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