Barceló F, Mincher D J, Crampton M R, Brown J R, Shaw G
Department of Biology (School of Sciences), University of the Balearic Islands, Palma de Mallorca, Spain.
Anticancer Drug Des. 1991 Feb;6(1):37-46.
The DNA-binding properties of the 2-substituted-1,4-dihydroxyanthraquinones 5-12 were examined. Compounds 5 and 6 were synthesized in this study, 7-12 were already available. Spectral studies were consistent with intercalation of 5, 6 and 8 into DNA. Affinity constants were in the range of 3 x 10(4)M-1. Compounds 7 and 10-12 showed no DNA binding, presumably being sterically excluded from binding. The kinetics of the DNA interaction of 5, 6 and 8 were studied. There is a biphasic process. This may reflect an initial reaction, with drug from this first mode of binding moving into the second binding mode (a sequential process) or independent binding of drug in two sets of sites (a parallel process). The methods used in this study do not allow us to discriminate between these models. However, if the parallel binding model is correct, the compounds show sequence selectivity of binding, and provide a lead for further development of neutral DNA-binding ligands with sequence selectivity.
对2-取代-1,4-二羟基蒽醌5-12的DNA结合特性进行了研究。化合物5和6是本研究中合成的，7-12已有成品。光谱研究表明5、6和8可嵌入DNA。亲和常数在3×10⁴M⁻¹范围内。化合物7和10-12未显示出DNA结合，推测是由于空间位阻而无法结合。研究了5、6和8与DNA相互作用的动力学。这是一个双相过程。这可能反映了一个初始反应，即来自第一种结合模式的药物进入第二种结合模式（一个连续过程），或者药物在两组位点独立结合（一个平行过程）。本研究中使用的方法无法让我们区分这些模型。然而，如果平行结合模型是正确的，这些化合物显示出结合的序列选择性，并为进一步开发具有序列选择性的中性DNA结合配体提供了线索。
