Anthracycline anticancer drugs show multiple strategies of action on gene functioning by regulation of telomerase enzyme by apoptotic factors, e.g. ceramide level, p53 activity, bcl-2 protein levels, besides inhibiting DNA/RNA synthesis and topoisomerase-II action. We report binding of epirubicin with G-quadruplex (G4) DNA, [d-(TTAGGGT)]₄, comprising human telomeric DNA sequence TTAGGG, using ¹H and ³¹P NMR spectroscopy. Diffusion ordered spectroscopy, sequence selective changes in chemical shift (~0.33 ppm) and line broadening in DNA signals suggest formation of a well-defined complex. Presence of sequential nuclear Overhauser enhancements at all base quartet steps and absence of large downfield shifts in ³¹P resonances preclude intercalative mode of interaction. Restrained molecular dynamics simulations using AMBER force field incorporating intermolecular drug to DNA interproton distances, involving ring D protons of epirubicin depict external binding close to T1-T2-A3 and G6pT7 sites. Binding induced thermal stabilization of G4 DNA (~36 °C), obtained from imino protons and differential scanning calorimetry, is likely to come in the way of telomerase association with telomeres. The findings pave the way for drug-designing with modifications at ring D and daunosamine sugar.

蒽环类抗癌药通过凋亡因子（例如神经酰胺水平，p53活性，bcl-2蛋白水平）调节端粒酶，显示了多种对基因功能起作用的策略，除了抑制DNA / RNA合成和拓扑异构酶II的作用。我们报告表柔比星与G四联体（G4）DNA，[d-（TTAGGGT）] _4的结合，包括使用¹ H和³¹ P NMR光谱的人类端粒DNA序列TTAGGG 。扩散有序光谱学，化学位移的序列选择性变化（〜0.33 ppm）和DNA信号中的谱线加宽表明形成了定义明确的复合物。在所有基本四重奏步骤中都存在连续核Overhauser增强的情况，并且在^31中没有大的场下偏移P共振排除了相互作用的插入模式。使用AMBER力场结合分子间药物到DNA质子间距离的约束分子动力学模拟，涉及表柔比星的D环质子，描绘了靠近T1-T2-A3和G6pT7位点的外部结合。从亚氨基质子和差示扫描量热法获得的结合诱导的G4 DNA热稳定性（约36°C）可能是端粒酶与端粒的缔合。这些发现为在D环和柔红胺糖上修饰的药物设计铺平了道路。