柔红霉素与DNA作用的序列特异性研究

Studies on the Interaction of Daunomycin and the Specific Sequence of DNA

采用紫外 -可见光谱法和紫外 -可见光谱电化学法研究了柔红霉素 (DNR)与不同寡聚核苷酸之间的相互作用 .结果表明 ,DNR优先作用于寡聚核苷酸的 Cp G位点 ,然后是 Ap G和 Ap C.因为 DNR可与鸟嘌呤之间形成 3个氢键 .与双链寡聚核苷酸作用时 ,DNR最先插入的位点是 (Cp G) 2 碱基对之间 ,其次是 (Tp G)(Cp A)和 (Gp C) (Ap C)碱基对之间 .当 DNR与存在未配对 G碱基的 DNA链作用时 ,因游离的 DNR量增加使其电化学活性增加 ,导致 DNA构象和构型的变化 ,使 DNA生理功能受到损伤 ,DNA碱基增色效应显著上升 .此法可用于 G碱基未配对 DNA链的检测 .

On the ground of UV-spectrophotometry and UV-spectroelectrochemistry, the interaction of daunomycin(DNR) and specific sequence of DNA has been investigated. As the results obtained in this paper, DNR can react with the sequence of oligonucleotide which is CpG, ApG and ApC successively; the sequence of base pairs of double helix of DNA which are intercalated by DNR are (CpG) 2, (TpG)(CpA) and (CpT)(ApG). An important conclusion has been gained in this paper that if G bases were not pairing in the helix of DNA, the spectroelectrochemical characteristic of the adducts containing that kind of DNA and DNR would exhibit a remarkable difference with those adducts consisting of DNR and normal DNA. It indicates that this characteristic can be used to detect and determine the DNA helix which has one base unpaired or mispairing. The results obtained in this paper are of clinical and pharmacal importance.