Fox K R, Brassett C, Waring M J
Biochim Biophys Acta. 1985 Jul 5;840(3):383-92. doi: 10.1016/0304-4165(85)90219-3.
Stopped-flow spectrometry and simple mixing techniques have been employed to investigate the detergent-induced dissociation of anthracycline antibiotics from natural and synthetic DNAs. Both daunomycin and nogalamycin dissociate more slowly from poly(dG-dC) than from poly(dA-dT) but the difference is much more marked for nogalamycin. With an equimolar mixture of poly(dG-dC) and poly(dA-dT), or with poly(dA-dC).poly(dG-dT), dissociation of nogalamycin occurs very slowly. In all cases the release of antibiotic from a synthetic polynucleotide is a one-step process following a single exponential. Dissociation of daunomycin, adriamycin and iremycin from calf thymus DNA is a more complex reaction which requires a two-exponential fit, in contrast to earlier reports, but differences between the behaviour of the three antibiotics are minor. Dissociation of nogalamycin from natural DNA requires a three-exponential fit, is in general far slower, and depends upon the base composition, the level of binding and the time allowed for the complex to equilibrate. It is concluded that sequence selectivity is minimal or lacking for daunomycin, whereas nogalamycin binding is sequence dependent and probably involves migration of the antibiotic between DNA binding sites. There is an inverse correlation between dissociation rate constants and antibacterial potency in simple tests.
采用停流光谱法和简单混合技术研究了去污剂诱导蒽环类抗生素从天然和合成DNA上解离的情况。柔红霉素和诺加霉素从聚（dG-dC）上解离的速度比从聚（dA-dT）上解离的速度慢，但诺加霉素的这种差异更为明显。对于聚（dG-dC）和聚（dA-dT）的等摩尔混合物，或聚（dA-dC）·聚（dG-dT），诺加霉素的解离非常缓慢。在所有情况下，抗生素从合成多核苷酸上的释放是一个遵循单指数的一步过程。与早期报道相反，柔红霉素、阿霉素和伊瑞霉素从小牛胸腺DNA上的解离是一个更复杂的反应，需要双指数拟合，但这三种抗生素行为之间的差异较小。诺加霉素从天然DNA上的解离需要三指数拟合，通常要慢得多，并且取决于碱基组成、结合水平以及复合物达到平衡所需的时间。得出的结论是，柔红霉素的序列选择性最小或不存在，而诺加霉素的结合是序列依赖性的，可能涉及抗生素在DNA结合位点之间的迁移。在简单测试中，解离速率常数与抗菌效力之间存在负相关。
