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为了进一步阐明抗癌药与DNA结合的序列选择性和结合本质,用电喷雾质谱方法研究了抗癌药与DNA的相互作用,这些药物包括小沟结合剂(偏端霉素A,DM和纺锤霉素,NP)和嵌入剂(米托蒽醌,MT)。DM与AT富有的DNA主要形成2∶1的特异性复合物,NP只形成1∶1的特异性复合物;MT倾向与GC富有的DNA特异性结合。另外,DM与带5个A/T碱基小沟长度的DNA几乎以2∶1结合,而与带3个A/T碱基的DNA未见结合,而NP与带4个A/T碱基的DNA结合能力最强。MT还与6-mer DNA形成了1∶1特异性复合物。竞争结合实验证明,DM和NP与AT富有的DNA的键合顺序为NP>DM。这些结果为深入研究抗癌药物的作用机制和改进目标药物结构提供了依据。
To further elucidate the sequence selectivity and binding nature of the anticancer drug binding to DNA, the interaction of anticancer drugs with DNA was studied by electrospray mass spectrometry. These drugs include minor groove binders (distamycin A, DM, and spindle ADM, NP) and intercalators (mitoxantrone, MT). DM and AT rich DNA mainly form a 2: 1 specific complex, NP only forms a 1: 1 specific complex; MT tends to specifically bind to GC-rich DNA. In addition, DM binds to DNA with a 5 A / T base minor groove length almost in 2: 1 but not to DNA with 3 A / T bases while NP binds with 4 A / T bases Basis of the DNA binding capacity of the strongest. MT also forms a 1: 1 specific complex with 6-mer DNA. The combination of competition and experiment proved that the order of the binding of DM and NP to AT-rich DNA was NP> DM. These results provide a basis for further study of the mechanism of action of anticancer drugs and improvement of the target drug structure.