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

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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.