Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

X-ray Protein Probe Leads to Potential Anticancer Tactic

13.09.2011
Researchers at Emory University School of Medicine have identified a new type of potential anticancer drug. The compound, named FOBISIN, targets 14-3-3 proteins, important for the runaway growth of cancer cells.

The researchers were using X-rays to see how FOBISIN fits into the clamp-shaped 14-3-3 protein structure. Unexpectedly, the X-rays induced the compound to be permanently bonded to the protein. The finding suggests that compounds like FOBISIN can be used in combination with radiation to trigger potent anticancer activity.

The results were published online Sept. 9 in Proceedings of the National Academy of Sciences Early Edition.

Senior author Haian Fu, PhD, has been studying 14-3-3 proteins for two decades. He is professor of pharmacology and of hematology and oncology at Emory University School of Medicine, and the director of the Emory Chemical Biology Discovery Center.

“Targeting 14-3-3 proteins could be especially valuable because they can impact multiple pathways critical for cancer cell growth,” he says. “14-3-3 proteins have been shown to be dysregulated in a number of cancer types, including lung cancer and breast cancer.”

14-3-3 proteins act as adaptors that clamp onto other proteins. Fu and co-workers Jing Zhao, postdoctoral fellow, and Yuhong Du, assistant professor and associate director of the Discovery Center, sorted through thousands of chemicals to find one (FOBISIN: Fourteen-three-three Binding Small molecule Inhibitor) that prevents 14-3-3 from interacting with its partners. 14-3-3 proteins are found in mammals, plants and fungi. In humans, they come in seven varieties, and FOBISIN appears to inhibit interactions by all seven.

A 14-3-3 proteins’ ability to clamp depends on whether the target protein is phosphorylated, a chemical modification that regulates protein function. FOBISIN’s inhibitory power also requires the presence of phosphorylation in the molecule.

Fu’s group teamed up with the laboratory of Xiaodong Cheng, PhD, co-senior author, professor of biochemistry and a Georgia Research Alliance Eminent Scholar, to examine how FOBISIN fits into its targets.

Scientists use X-rays as a tool to probe protein structure. If a protein and a drug that targets it can be crystallized together, the X-ray diffraction pattern from the crystals reveals the 3D arrangement of the atoms and how the drug interacts with the protein. Research assistant professor John Horton, PhD, and research associate Anup Upadhyay, PhD, in the Cheng laboratory used synchrotron X-ray radiation from the Advanced Photon Source at Argonne National Laboratory for this purpose.

“In this case, the X-rays had an unexpected effect: they caused FOBISIN to become covalently attached to the 14-3-3 protein,” Cheng says.

The finding suggests that compounds like FOBISIN could be developed as “pro-drugs” that upon exposure to radiation, permanently stick to and inhibit their targets. A common strategy in fighting cancer is to combine drugs and radiation so that the drugs increase cells’ sensitivity to radiation. Here, the radiation would activate the drug.

“These compounds could be used in combination with other strategies to enhance the tumor selectivity of the treatment,” Fu says.

The research was funded by the U.S. National Institutes of Health, the Georgia Cancer Coalition, and the Georgia Research Alliance.
Reference:
J. Zhao, Y. Du, J.R. Horton, A.K. Upadhyay, B. Lou, Y. Bai, X. Zhang, L. Du, M. Li, B. Wang, L. Zhang, J.T. Barbieri, F.R. Khuri, X. Cheng and H. Fu. Discovery and structural characterization of a small molecule 14-3-3 protein-protein interaction inhibitor. PNAS Early Edition (2011).

Writer: Quinn Eastman

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service.

Learn more about Emory’s health sciences:
Blog: http://emoryhealthblog.com
Twitter: @emoryhealthsci
Web: http://emoryhealthsciences.org

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

More articles from Life Sciences:

nachricht Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>