The first three-dimensional image of how a well-established chemotherapy agent targets and binds to DNA have been created. This scientists say, might help develop better chemotherapy drugs to treat a wide range of cancers.
Scientists at the Indiana University School of Medicine and the Purdue School of Science at Indiana University-Purdue University Indianapolis used X-ray crystallography, which helped them produce the first 3-D molecular level images of bleomycin bound to DNA.
X-ray crystallography is a widely used analytical technique in which X-rays are directed through crystals and results are deduced from the pattern of diffraction of the X-rays.
"Although bleomycin has been studied for 40 years and much is known about the mechanism of action of bleomycin, without an accurate 3-D picture you can't fully understand how the drug targets and sits on the DNA. If you want to improve on the properties of the drug, to make it a better chemo agent, you need to understand in great detail how it works," said Millie M. Georgiadis, Ph.D., associate professor of biochemistry and molecular biology at the IU School of Medicine and at the Purdue School of Science.
"Our 3-D picture of the structure of bleomycin gives us a much better understanding of exactly how the drug interacts with the DNA so we can begin thinking about engineering a better drug, with less toxicity. Since it's a DNA targeting agent, there's no limit to what type of cancers we could target with bleomycin if we can decrease the toxicity," said Dr. Georgiadis, a structural biologist.
The study is published in the Early Edition of the Proceedings of the National Academy of Sciences.