阿霉素及其β异头物与DNA的相互作用。

The interaction of adriamycin and its beta anomer with DNA.

作者信息

Zunino F, Gambetta R, Di Marco A, Velcich A, Zaccara A, Quadrifoglio F, Crescenzi V

出版信息

Biochim Biophys Acta. 1977 May 3;476(1):38-46. doi: 10.1016/0005-2787(77)90283-0.

Abstract

The results of thermal denaturation, fluorescence, calorimetric and viscosimetric studies on the interaction of adriamycin and its beta anomer with DNA are reported. Whereas all equilibrium, hydrodynamic and thermodynamic measurements are consistent with the proposed intercalative binding model for the adriamycin-DNA complex, the binding mechanism for the reaction of the beta anomer with DNA remains uncertaian. All DNA binding properties of this stereoisomer are substantially different from those of the parent compound. The results suggest that the amino sugar residue of the natural antibiotic may interact stero-specifically with the DNA helix, thus dictating the orientation of the tetracvclic chromophore within the intercalation site. The alteration in the DNA binding capacity and the changes in interactions with DNA following in inversion of configuration at C-1', parallel a lack of biological activity observed for the beta anomer.

摘要

报告了对阿霉素及其β异头物与DNA相互作用的热变性、荧光、量热和粘度测定研究结果。虽然所有的平衡、流体动力学和热力学测量结果都与所提出的阿霉素-DNA复合物的嵌入结合模型一致，但β异头物与DNA反应的结合机制仍不确定。这种立体异构体的所有DNA结合特性与母体化合物的特性有很大不同。结果表明，天然抗生素的氨基糖残基可能与DNA螺旋发生立体特异性相互作用，从而决定了四环发色团在嵌入位点内的取向。C-1'构型反转后，DNA结合能力的改变以及与DNA相互作用的变化，与β异头物缺乏生物活性的情况相似。