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首页> 外文期刊>Journal of Hazardous Materials >Targeting ribonucleic acids by toxic small molecules: Structural perturbation and energetics of interaction of phenothiazinium dyes thionine and toluidine blue O to tRNA~(phe)
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Targeting ribonucleic acids by toxic small molecules: Structural perturbation and energetics of interaction of phenothiazinium dyes thionine and toluidine blue O to tRNA~(phe)

机译：通过有毒小分子靶向核糖核酸：吩噻嗪鎓染料硫氨酸和甲苯胺蓝O与tRNA〜（phe）相互作用的结构扰动和能量

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摘要

This study was designed to examine the toxic interaction of two phenothiazinium dyes thionine (TO) and toluidine blue 0 (TBO) with tRNA~(phe)by spectroscopic and calorimetric techniques. While phenothiazinium dye complexation with DNA is known, their bindings to RNA are not fully investigated. The non cooperative binding of both the dyes to tRNA was revealed from absorbance and fluorescence studies. From absorption, steady-state emission, the effect of ferrocyanide ion-induced steady-state fluorescence quenching, circular dichroism, the mode of binding of these dyes into the tRNA helix has been substantiated to be principally by intercalative in nature. Both dyes enhanced the thermal stability of tRNA. Circular dichroism studies provided evidence for the structural perturbations associated with the tRNA structure with induction of optical activity in the CD inactive dye molecules. Results from isothermal titration calorimetry experiments suggested that the binding of both dyes was predominantly entropy driven with a smaller but favorable enthalpy term that increased with temperature. The binding was dependent on the Na~+ concentration, but had a larger non-electrostatic contribution to the Gibbs energy. A small heat capacity value and the enthalpy-entropy compensation in the energetics of the interaction characterized the binding of the dyes to tRNA. This study confirms that the tRNA~(phe) binding affinity is greater for TO compared to TBO. The utility of the present work lies in understanding the potential binding and consequent damage to tRNA by these toxic dyes in their development as therapeutic agents.
机译：本研究旨在通过分光光度法和量热技术研究两种吩噻嗪鎓染料硫氨酸（TO）和甲苯胺蓝0（TBO）与tRNA〜（phe）的毒性相互作用。虽然吩噻嗪鎓染料与DNA的络合作用是已知的，但尚未完全研究它们与RNA的结合。从吸光度和荧光研究中揭示了两种染料与tRNA的非协同结合。从吸收，稳态发射，亚铁氰化物离子诱导的稳态荧光猝灭，圆形二色性的影响，这些染料结合到tRNA螺旋中的方式已被证实主要是通过嵌入的方式实现的。两种染料均增强了tRNA的热稳定性。圆二色性研究为与tRNA结构相关的结构扰动提供了证据，并诱导了CD非活性染料分子中的光学活性。等温滴定量热法实验的结果表明，两种染料的结合主要是由熵引起的，但随着温度的升高，焓值变小但有利。结合依赖于Na +浓度，但是对吉布斯能量具有更大的非静电贡献。小的热容值和相互作用能中的焓-熵补偿表征了染料与tRNA的结合。这项研究证实，与TBO相比，TO的tRNA〜（phe）结合亲和力更大。本工作的实用性在于了解这些有毒染料在其发展为治疗剂时可能对tRNA的结合以及对tRNA的破坏。

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  • 来源
    《Journal of Hazardous Materials》 |2013年第2期|735-745|共11页
  • 作者

    Puja Paul; Gopinatha Suresh Kumar;

  • 作者单位

    Biophysical Chemistry Laboratory, Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India;

    Biophysical Chemistry Laboratory, Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Phenothiazinium dyes; Spectroscopy; Calorimetry; Intercalation;

    机译：吩噻嗪鎓染料;光谱学量热法插层;

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