Yoshikawa Y, Yoshikawa K, Kanbe T
Graduate School of Human Informatics, Nagoya University, Japan.
Biophys Chem. 1996 Oct 30;61(2-3):93-100. doi: 10.1016/s0301-4622(96)02184-9.
Daunomycin is an antitumor antibiotic known to inhibit DNA replication and transcription. Although the inhibition is assumed to be caused by a direct interaction of the drug with DNA, the exact effect of daunomycin on the higher order DNA structure remains uncertain. We studied the effect of daunomycin on DNA compacted states using fluorescence and electron microscopies. Structural changes in individual DNA molecules were examined under the following conditions. T4 phage DNA (166 kbp) was first compacted by spermidine followed by the addition of daunomycin to the compacted DNA. A direct observation of individual single duplex DNAs by fluorescence microscopy indicated that daunomycin induced unfolding of the compacted DNA. Electron microscopic observation of the morphological changes of the higher order DNA structure supported the results obtained by fluorescence microscopy. We discuss here the mechanisms of the unfolding of the compacted structure following intercalation of daunomycin into DNA particularly in terms of the free energy.
柔红霉素是一种已知可抑制DNA复制和转录的抗肿瘤抗生素。尽管这种抑制作用被认为是由药物与DNA的直接相互作用引起的，但柔红霉素对高阶DNA结构的确切影响仍不确定。我们使用荧光显微镜和电子显微镜研究了柔红霉素对DNA压缩状态的影响。在以下条件下检查单个DNA分子的结构变化。首先用亚精胺压缩T4噬菌体DNA（166 kbp），然后向压缩后的DNA中添加柔红霉素。通过荧光显微镜对单个单链双链DNA的直接观察表明，柔红霉素诱导了压缩DNA的解折叠。对高阶DNA结构形态变化的电子显微镜观察支持了荧光显微镜获得的结果。我们在此讨论柔红霉素插入DNA后压缩结构解折叠的机制，特别是从自由能的角度进行讨论。
