Navigation Links
X-ray protein probe leads to potential anticancer tactic
Date:9/12/2011

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, PhD,postdoctoral fellow, and Yuhong Du, PhD, 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.


'/>"/>

Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

Related medicine news :

1. New X-Rays Offer Clues on Evolution of the Human Brain
2. First X-ray lasing of SACLA
3. Tests on century-old equipment show how far X-rays have come
4. Greater Caution Urged for X-Rays in Pregnancy, Infants
5. Most X-Rays, Scans Unnecessary for Acute Low Back Pain
6. Powerful 3-D X-rays for kids in braces should be the exception, not the rule
7. Helical CT scans reduce lung cancer mortality by 20% compared to chest X-rays
8. 3 or More X-Rays May Raise Leukemia Risk Among Kids: Study
9. X-rays linked to increased childhood leukemia risk
10. Top down approach helps academic medical center reduce unnecessary emergency department X-rays
11. X-Ray Can Spot Gastric Band Slippage
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet ... product that was developed to enhance the health of felines. The formula is all-natural ... two main herbs in the PawPaws Cat Kidney Support Supplement Soft Chews ...
(Date:6/26/2016)... ... June 26, 2016 , ... ... have been diagnosed with endometriosis. These women need a treatment plan to not ... comprehensive approach that can help for preservation of fertility and ultimately achieving a ...
(Date:6/25/2016)... Austin, TX (PRWEB) , ... June 25, 2016 , ... ... Fellow of the American College of Mohs Surgery and to Dr. Russell Peckham for ... popular and highly effective treatment for skin cancer. The selective fellowship in Mohs Micrographic ...
(Date:6/25/2016)... ... June 25, 2016 , ... "With 30 hand-drawn hand gesture ... said Christina Austin - CEO of Pixel Film Studios. , ProHand Cartoon’s package ... Final Cut Pro X . Simply select a ProHand generator and drag it ...
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern ... Laude and his M.D from the David Geffen School of Medicine at UCLA. He ... Los Angeles to complete his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Research and Markets has announced the addition of the ... to their offering. ... World Market for Companion Diagnostics covers the world market for ... report includes the following: , World IVD ... (N. America, EU, ROW), 2015-2020 , World IVD Companion ...
(Date:6/24/2016)... 24, 2016  Arkis BioSciences, a leading innovator ... more durable cerebrospinal fluid treatments, today announced it ... funding is led by Innova Memphis, followed by ... private investors.  Arkis, new financing will accelerate the ... market release of its in-licensed Endexo® technology. ...
(Date:6/23/2016)... Research and Markets has announced the addition ... Chemical (Sugar, Petrochemical, Glycerin), Inorganic Chemical), Functionality (Filler, Binder, ... Forecast to 2021" report to their offering. ... excipients market is projected to reach USD 8.1 Billion ... forecast period 2016 to 2021. The ...
Breaking Medicine Technology: