Friday, March 21, 2008

3D Imaging of Bleomycin-DNA Binding

Filed under: in the news...

Indiana University School of Medicine and the Purdue School of Science scientists have for the first time successfully imaged a chemotherapy agent, bleomycin, binding to DNA. The research might lead to the development of new chemotherapy agents.

Using X-ray crystallography, the scientists produced 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. She and Eric C. Long, Ph.D., professor of chemistry & chemical biology at the Purdue School of Science, are senior authors of the study.

A combination chemotherapy regimen including bleomycin was successfully pioneered at the IU School of Medicine by oncologist Lawrence H. Einhorn, M.D., distinguished professor of medicine. This multi-agent therapy, which mutes the toxicity of bleomycin, is now the standard of care for testicular cancer. Because it causes lung damage, bleomycin is not typically used to treat other cancers.

Press release: IUPUI Scientists Report First 3-D View of Anti-Cancer Agent

Image Caption: Bleomycin represented in a space-filling rendering bound to DNA, in a gray ball-and-stick rendering. The color scheme highlights the different moieties that make up bleomycin: blue, bithiazole; red, linker; yellow, metal-binding domain; purple, dissacharide; and green, Co (III).

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