Adriamycin is known to exert its anti cancer action by inhibiting DNA duplication, RNA transcription and topoisomerase-II enzyme action. Recent findings of its binding to G-quadruplex DNA resulting in telomere dysfunction indicated multiple strategies of its action. The interaction of anticancer drug adriamycin with parallel stranded inter molecular G-quadruplex DNA [d-(TTAGGGT)]4 comprising human telomeric DNA sequence TTAGGG was investigated by absorption, fluorescence, circular dichroism and nuclear magnetic resonance spectroscopy to understand mode of their interaction. The adriamycin binds as monomer to G-quadruplex DNA with affinity (Kb1 = 9.8x105 M-1 and Kb2 = 6.7x105 M-1 ) higher than that reported for daunomycin, at two independent sites, mainly in terminal stacking and groove binding modes. The bound complex formed as a result of specific interactions induces thermal stabilization of DNA by 12.5-28.1°C, which is likely to hinder telomere association with telomerase enzyme and contribute significantly to adriamycin-induced apoptosis in cancer cell lines. The findings have therapeutic potential towards drug designing by way of altering substituent groups on anthracyclines to enhance efficacy using additional mechanism of targeting pathway of telomere maintenance by disrupting telomerase association with telomeres.

中文翻译：

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抗癌药阿霉素与包含人端粒DNA的平行G-四链体DNA [d-（TTAGGGT）] 4的结合可导致热稳定：一项多光谱研究。

已知阿霉素通过抑制DNA复制，RNA转录和拓扑异构酶II酶的作用发挥其抗癌作用。其与导致端粒功能障碍的G-四链体DNA结合的最新发现表明其作用的多种策略。通过吸收，荧光，圆二色性和核磁共振波谱研究了抗癌药阿霉素与包含人端粒DNA序列TTAGGG的平行链分子间G-四链体DNA [d-（TTAGGGT）] 4的相互作用，以了解它们的相互作用方式。阿霉素以单体形式与G-四链体DNA结合，其亲和力（Kb1 = 9.8x105 M-1和Kb2 = 6.7x105 M-1）在两个独立的位点上比道诺霉素更高，主要在末端堆积和凹槽结合模式。由于特异性相互作用而形成的结合复合物在12.5-28.1°C下诱导DNA的热稳定，这很可能会阻止端粒与端粒酶的缔合，并显着促进阿霉素诱导的癌细胞系凋亡。这些发现具有通过改变蒽环类药物上的取代基来增强功效的药物设计的治疗潜力，该机制使用了通过破坏端粒酶与端粒的缔合来靶向端粒维持的靶向途径的其他机制。