SELF-ASSOCIATION OF DAUNOMYCIN
SELF-ASSOCIATION OF DAUNOMYCIN
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DOI：
10.1021/bi00260a004
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发表时间：
1982-01-01
期刊：
影响因子：
2.9
通讯作者：
CROTHERS, DM
中科院分区：
文献类型：
--
作者：
CHAIRES, JB;DATTAGUPTA, N;CROTHERS, DM
道诺霉素，一种有效的蒽环类[抗癌]抗生素，在水溶液中以> 10 μ M的浓度自缔合。可见光吸收，沉降平衡和质子NMR实验，其特征在于这种自关联的报告。与早期报道的该过程是简单的二聚化相反，不确定缔合模型最适合数据，其固有缔合常数Ki = 1500 M-1。从所观察到的NMR谱的温度依赖性，可以得到约8.0计算kcal/mol。NMR数据显示，药物的蒽环部分的芳香族质子受聚集的影响最大，可能是由于蒽环环的堆叠。自缔合过程的适用模型和描述该过程的平衡常数的知识使得能够定量评估药物聚集对药物-DNA结合数据的解释的可能影响。对于这些研究中最常用的离子条件，聚集的柔红霉素量将是轻微的，可以安全地忽略不计。
Daunomycin, a potent anthracycline [anticancer] antibiotic, self-associates in aqueous solution at concentrations > 10 .mu.M. Visible absorbance, sedimentation equilibrium and proton NMR experiments that characterize this self-association are reported. In contrast to earlier reports that the process is a simple dimerization, an indefinite association model best fit the data, with an intrinsic association constant, Ki = 1500 M-1. From the temperature dependence of the observed NMR spectra, an enthalpy of .apprx. 8.0 kcal/mol is calculated. NMR data show that the aromatic protons of the anthracycline portion of the drug are most affected by aggregation, probably due to stacking of the anthracycline rings. Knowledge of the applicable model for the self-association process, and the equilibrium constant that describes the process, enables the quantitative assessment of the possible effects of drug aggregation on the interpretation of drug-DNA binding data. For the ionic conditions most commonly used in such studies, the amount of aggregated daunomycin will be slight and may safely be ignored.