Mackenzie J M, Neville M M, Wright G E, Brown N C
Proc Natl Acad Sci U S A. 1973 Feb;70(2):512-6. doi: 10.1073/pnas.70.2.512.
The active forms of 6-(p-hydroxyphenylazo)-uracil and 6-(p-hydroxyphenylazo)-isocytosine were isolated and identified as their respective hydrazino derivatives. These arylhydrazino pyrimidines selectively inhibited a chromatographically distinct DNA polymerase from Bacillus subtilis. The actions of the reduced drugs on this polymerase were identical to those observed on ATP-dependent DNA synthesis in toluene-treated cells; dGTP competitively antagonized the inhibitory activity of the uracil derivative, and dATP competitively antagonized that of the isocytosine derivative. Analysis of the interactions of the arylhydrazinopyrimidines and nucleic acid bases by nuclear magnetic resonance suggested that hydroxyphenylhydrazino-uracil and hydroxyphenylhydrazino-isocytosine pair in a novel manner with, respectively, cytosine and thymine. A mechanism of inhibitor action, involving binding of the reduced drugs to enzyme and the pyrimidines of DNA template, is proposed.
6 - （对羟基苯偶氮基）尿嘧啶和6 - （对羟基苯偶氮基）异胞嘧啶的活性形式被分离出来，并鉴定为它们各自的肼基衍生物。这些芳基肼基嘧啶选择性地抑制了来自枯草芽孢杆菌的一种色谱上不同的DNA聚合酶。还原药物对这种聚合酶的作用与在甲苯处理的细胞中对ATP依赖的DNA合成所观察到的作用相同；dGTP竞争性拮抗尿嘧啶衍生物的抑制活性，dATP竞争性拮抗异胞嘧啶衍生物的抑制活性。通过核磁共振分析芳基肼基嘧啶与核酸碱基的相互作用表明，羟基苯肼基尿嘧啶和羟基苯肼基异胞嘧啶分别以一种新的方式与胞嘧啶和胸腺嘧啶配对。提出了一种抑制剂作用机制，涉及还原药物与酶以及DNA模板的嘧啶结合。
