Fox K R, Waring M J
Biochim Biophys Acta. 1981 Jul 27;654(2):279-86. doi: 10.1016/0005-2787(81)90182-9.
The kinetics of detergent-induced dissociation of triostins A and C and quinomycin C from DNA have been investigated. All three antibiotics dissociate from poly(dA-dT) and poly(dG-dC) in a simple first-order fashion whereas their dissociation from a natural DNA (calf thymus) is complex, requiring three exponential terms for its complete description. This behaviour is attributed to sequence-selectivity on the part of the drugs and seems to represent dissociation from different classes of intercalative binding site. The time constants of dissociation are better resolved for quinomycins than for triostins, consistent with the view that quinomycins are more sequence-specific in their interaction with DNA, but it is not possible to identify any class of binding site with the alternating purine-pyrimidine sequences of the synthetic polydeoxynucleotides. In general, the triostins dissociate an order of magnitude faster than the corresponding quinomycins. This is attributable to a larger entropy of activation, presumably reflecting greater flexibility of the octapeptide ring when the cross-bridge is a disulphide as opposed to the slightly shorter thioacetal found in quinomycins. The longest time constant in the dissociation of each of the four quinoxaline antibiotics from calf thymus DNA correlates well with its antibacterial potency, in agreement with the conclusion that the biological effects result from impairment of the role of DNA as a template for polymerase activity.
研究了去污剂诱导曲菌素A、C以及醌霉素C从DNA上解离的动力学。这三种抗生素从聚（dA-dT）和聚（dG-dC）上以简单的一级方式解离，而它们从小牛胸腺天然DNA上的解离则较为复杂，需要用三个指数项才能完整描述。这种行为归因于药物的序列选择性，似乎代表了从不同类型的嵌入结合位点上的解离。与曲菌素相比，醌霉素解离的时间常数分辨得更好，这与醌霉素在与DNA相互作用中序列特异性更强的观点一致，但无法确定任何与合成聚脱氧核苷酸的嘌呤-嘧啶交替序列相关的结合位点类型。一般来说，曲菌素的解离速度比相应的醌霉素快一个数量级。这归因于更大的活化熵，推测这反映了当交联桥为二硫键时八肽环具有更大的灵活性，而醌霉素中的硫缩醛则稍短。四种喹喔啉抗生素从小牛胸腺DNA上解离的最长时间常数与其抗菌效力密切相关，这与生物效应是由于DNA作为聚合酶活性模板的作用受损所致的结论一致。
