DNA and oligonucleotides in the presence of metal ions, drugs and proteins, by spectroscopic methods including electronic and vibrational circular dichroism and uv/visible and IR

在存在金属离子、药物和蛋白质的情况下，通过光谱方法（包括电子和振动圆二色性以及紫外/可见光和红外）检测 DNA 和寡核苷酸

• 批准号: 5445-2008
• 负责人: Wieser, Helmut
• 金额: $ 1.46万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=389143
• 关键词: DNA; oligonucleotides; presence; metal; ions

Anti-cancer drugs have been much studied in a variety of ways. Certainly one needs to acknowledge the enormous efforts that have already been spent on trying to solve the puzzles. Yet despite these efforts, some functional aspects are not yet clear. The methods which we propose to apply, and although they have been known for several years in other domains, may give additional clues for narrowing the gap. Whereas the physical-chemical nature of these methods individually have been well tried for several years, we propose to examine whether their use can give additional information even if the problems cannot be solved completely. The methods we apply are based on standard physical technology, namely combining the capabilities of instrumentation able to observe and measure absorptions in the ultraviolet (UV), visible, and infrared (IR) regions of light. Two phenomena, namely circular dichroism in the UV and IR regions known as "ECD" and "VCD", are of particular interest because they react to certain features of light at specific wavelengths. This suggests that any changes in the chemical structure of DNA, which is the principal target in this endeavour, are due to changes in the normally well behaved and well known double helix and will give different light signals, which in principle one can ascribe to some distortion from the normal helical form. The five drugs we target are ethidium bromide, netropsin, distamycin A, methyl green and AZT. With the methods we use we expect to obtain a more definitive answer how these drugs affect the double helix of DNA, and if these structural changes due the drugs differ, one should in principle get more definitive details about drug action and hence better understand the molecular mechanisms and kinetics how they bind to DNA and what effects such distortions have on the living systems.

抗癌药物已经通过各种方式进行了大量的研究。当然，人们需要承认，为了解决这些难题，人们已经付出了巨大的努力。然而，尽管做出了这些努力，一些功能方面还不清楚。我们建议应用的方法，尽管它们在其他领域已经知道了几年，可能会为缩小差距提供额外的线索。尽管这些方法各自的物理化学性质已经被很好地尝试了好几年，但我们建议检查它们的使用是否可以提供额外的信息，即使问题不能完全解决。我们采用的方法基于标准物理技术，即结合能够观察和测量紫外（UV），可见光和红外（IR）区域光吸收的仪器的能力。两种现象，即被称为“ECD”和“VCD”的紫外和红外区域的圆二色性，特别令人感兴趣，因为它们对特定波长的光的某些特征起反应。这表明，DNA的化学结构的任何变化，这是这项努力的主要目标，都是由于正常表现良好和众所周知的双螺旋结构的变化，并将发出不同的光信号，原则上，人们可以将其归因于正常螺旋形式的一些扭曲。我们针对的五种药物是溴化乙锭、netropsin、distamycin A、甲基绿和AZT。通过我们使用的方法，我们希望获得更明确的答案，这些药物如何影响DNA的双螺旋结构，如果这些结构变化是由于药物不同，原则上应该得到更多关于药物作用的明确细节，从而更好地理解分子机制和动力学，它们如何与DNA结合，以及这种扭曲对生命系统有什么影响。