博安霉素与DNA相互作用的分子机理研究

通过光谱分析、粘度测定及~１ＨＮＭＲ研究证实：博安霉素（ＢｌｅｏｍｙｃｉｎＡ_６，ＢＬＭＡ_６）是通过双噻唑基嵌插入碱基对之间与ＤＮＡ结合的。同时测定了ＢＬＭＡ_６与ＤＮＡ的结合常数、结合位点数并与博莱霉素Ａ_２（ＢＬＭＡ_２）、Ａ_５（ＢＬＭＡ_５）进行了比较，证实了末端胺基对ＢＬＭＡ_６与ＤＮＡ结合的贡献，琼脂糖凝胶电泳对ＢＬＭＡ_６及其Ｃｕ（Ⅱ）、Ｆｅ（Ⅱ）络合物断裂ＤＮＡ的研究表明，在ＤＮＡ断裂中某种氧自由基的存在及金属螯合部位与ＤＮＡ嵌插部位之间的相互影响，对于ＢＬＭＡ_６及同系物对小鼠肺毒性的差异与不同尾链结构的关系进行了探讨。

Molecular Machenism of the Interaction between Bleomycin A_6 and DNA

Molecular machenism of interaction between Bleomycin A_6 and DNA was studiedfor the first time. Bleomycin A_6 binding to DNA by intercalation of bithiozol group was proved by spectra analysis, increases of DNA viscosity and ￣1HNMR chemical shifts on titration with DNA. Binding strength was evaluated. The comparion of the binding between DNA and BLM analogues proves that terminal-amine moieties contribute to their binding with DNA.The cleavage of PBR322 DNA induced by BLM A_6 and its complexes with Cu(Ⅱ) and Fe(Ⅱ) studied by agarose gel electrophoresis showed the action of oxygen free radicals in the cleavage of DNA and the interrelation on the metal-chelating site and the DNA intercalation site.The correlation between pulmonary toxicity of BLM analogues and their teminal-amine structures are discussed.