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首页> 外文期刊>RSC Advances >Preferential binding of anticancer drugs to triplex DNA compared to duplex DNA: a spectroscopic and calorimetric study
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Preferential binding of anticancer drugs to triplex DNA compared to duplex DNA: a spectroscopic and calorimetric study

机译：与双相DNA相比，抗癌药物对三重DNA的优先结合：光谱和量热研究

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Adriamycin and actinomycin are frequently used anti-cancer drugs for the treatment of a variety of human cancers. The resistance and side effects are the major drawbacks that have been attributed to their non-specific nature of binding to DNA. Therefore, one efficient strategy is to target drug-delivery to sequence/and structure specific DNA regions so that higher potency can be achieved. We have chosen a positive regulatory region (?183 to ?165 from the transcription start site) in the hmgb1 gene as the sequence specific target and also made DNA triplex (of the same region) as a structure specific target for anti-cancer drugs. The conformational and binding characteristics were studied by UV-vis spectroscopy, circular dichroism, fluorescence spectroscopy, Fourier transform infrared spectroscopy and isothermal titration calorimetry. Binding results showed that in presence of the triplex forming oligonucleotide, the DNA triplex formed by the target DNA had higher binding affinity to the drugs as compared to the DNA duplex alone. The results suggest that an anti-gene approach of DNA triplex in combination with an anti-cancer drug be used as a preferential option in achieving higher efficacy. Furthermore, the DNA triplex structure-specific target can alleviate unwanted side effects from anti-cancer drugs.
机译：Adriamycin和Actinomycin经常使用抗癌药物来治疗各种人类癌症。抗性和副作用是主要缺点，其归因于它们与DNA结合的非特异性性质。因此，一种有效的策略是靶向序列/和结构特异性DNA区域的药物递送，从而可以实现更高的效力。我们在HMGB1基因中选择了正调节区（α183至165），作为序列特异性靶标，也使DNA三链（相同区域的）作为抗癌药物的结构特异性靶标。通过UV-Vis光谱，圆形二色性，荧光光谱，傅里叶变换红外光谱和等温滴定热法研究了构象和结合​​特征。结合结果表明，在三重复合寡核苷酸存在下，与单独的DNA双链体相比，通过靶DNA形成的DNA三链接对药物具有更高的结合亲和力。结果表明，DNA三链与抗癌药物组合的抗基因方法被用作实现更高疗效的优先选择。此外，DNA三链体特异性靶靶可以减轻抗癌药物的不需要的副作用。

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