Nuss M E, James T L, Apple M A, Kollman P A
Biochim Biophys Acta. 1980 Aug 26;609(1):136-47. doi: 10.1016/0005-2787(80)90207-5.
The mode of action of the widely used anticancer drug daunomycin was studied by 360 MHz and 100 MHz proton NMR. Information obtained from scalar coupling constants indicates that the conformation of the A ring of the aglycone moiety of daunomycin is maintained upon binding to dinucleotides but that the conformation of the daunosamine ring moiety is altered upon binding. Ring-current-induced chemical shifts of the drug protons were observed as the drug was titrated with deoxydinucleotides. The chemical shift results that daunomycin forms 1 : 1 complexes with deoxydinucleotides and that the strength of the drug-nucleotide interaction is dependent upon the base composition of the dinucleotide. On the basis of the NMR data, a model for the drug/deoxydinucleotide complex is presented featuring intercalation of the drug between the bases of the dinucleoside.
利用360兆赫和100兆赫的质子核磁共振研究了广泛使用的抗癌药物柔红霉素的作用方式。从标量耦合常数获得的信息表明，柔红霉素苷元部分A环的构象在与二核苷酸结合时得以维持，但柔红糖胺环部分的构象在结合时发生了改变。在用脱氧二核苷酸滴定药物时，观察到了药物质子的环电流诱导化学位移。化学位移结果表明，柔红霉素与脱氧二核苷酸形成1:1复合物，且药物 - 核苷酸相互作用的强度取决于二核苷酸的碱基组成。基于核磁共振数据，提出了一个药物/脱氧二核苷酸复合物模型，其特点是药物插入二核苷酸碱基之间。
