Navigation Links
Finding of long-sought drug target structure may expedite drug discovery

Researchers have solved the three-dimensional structure of a key biological receptor. The finding has the potential to speed drug discovery in many areas, from arthritis to respiratory disorders to wound healing, because it enables chemists to better examine and design molecules for use in experimental drugs.

The researchers are from the National Institutes of Health, collaborating with labs at The Scripps Research Institute and the University of California, San Diego. The finding is published in the March 10 edition of Science Express.

"This is an important step forward it was impossible until recently to know how this type of receptor is switched on by chemical signals like a tiny machine," said Dr. Kenneth A. Jacobson, chief of the Laboratory of Bioorganic Chemistry in NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and an author on the paper. "The architecture of the activated receptor allows us to think in more detailed terms about the other half of the drug interaction. We hope that we're on the verge of a revolution that will expedite the process of crafting new drugs to treat disease."

With this finding, scientists in Jacobson's lab, including co-author Dr. Zhan-Guo Gao, will next work on testing this drug-engineering approach with similar molecules they have newly synthesized.

Jacobson and Gao are part of the NIDDK's intramural program, which enables basic scientists and clinicians of diverse skills and expertise to collaborate on solutions to some of the most difficult issues of human health. Several compounds from Jacobson's lab are currently in clinical trials as potential treatments for conditions including chronic hepatitis C, psoriasis and rheumatoid arthritis.

"Discoveries like this, with the potential to lead to future treatments in a wide variety of areas, are why NIH funds basic science," said NIDDK Director Dr. Griffin P. Rodgers. "By understanding the body at its smallest components, we can learn how to improve whole-body health."

A receptor is a protein that receives and sends signals to other molecules. The three-dimensional structure of the solved receptor also contains an agonist a chemical command signal from outside the cell in this case, an adenosine molecule. Similar to the function of a telephone receiver, the receptor acts as a sensor, picking up the message from the agonist and transmitting its information, which begins processes inside the cell.

The researchers discovered that a previously known agonist molecule would bind to its receptor target in a way that stabilizes the protein for crystallization. Once crystallized, the structure can be seen by bombarding it with X-rays. The agonist solidifies the protein by connecting to multiple parts of the receptor with its molecular arms, in the process initiating the function of the entire structure. This adenosine receptor, called A2A, counteracts inflammation and responds to organs in distress. It belongs to the G-protein coupled receptor family, which is involved in processes necessary for many drugs currently in use to take effect. These findings may lead to new drugs for many diseases.

The research was also supported by the National Cancer Institute and the National Institute of General Medical Sciences, both components of the NIH.

"Long-term NIH technology investments in structural biology, including the Protein Structure Initiative, have brought diverse teams of investigators together and yielded powerful methods like the ones used in this study," said NIGMS Director Dr. Jeremy M. Berg. "Receptors must undergo substantial changes in shape in order to function, and revealing these molecular dances in such great detail is an impressive accomplishment."


Contact: Amy Reiter
NIH/National Institute of Diabetes and Digestive and Kidney Diseases

Related medicine news :

1. New findings on drug tolerance in TB suggest ideas for shorter cures
2. Latest findings of Dartmouth HIV/AIDS study could turn treatment on its head
3. Research provides new findings on drug delivery with nanoparticles
4. SMFM highlights significance of spina bifida research findings
5. Most Guidelines for Infectious Diseases Dont Come From Clinical Trial Findings
6. International research team reports major findings in prevention and treatment of blood clots
7. VCU findings may help explain some major clinical symptoms of preeclampsia
8. Addiction research: Key findings every month
9. Surprise finding: Pancreatic cancers progress to lethal stage slowly
10. New Finding Suggests Safe Surgical Margins When Removing Breast Cancers
11. $4.37 million NCI grant accelerates recent laboratory finding in Ewings sarcoma
Post Your Comments:
Related Image:
Finding of long-sought drug target structure may expedite drug discovery
(Date:11/27/2015)... ... 2015 , ... An inventor, from Hopkinsville, Ky., thought there ... home, so he invented the patent-pending ELECTRONIC M.D. , The ELECTRONIC M.D. provides ... so, it could help to prevent potential overdose situations. As a result, it ...
(Date:11/27/2015)... Aliso Viejo, CA (PRWEB) , ... November 27, 2015 , ... ... exclusively for use in Final Cut Pro X. With ProSidebar: Fasion, video editors ... banners, or use ProSidebar as a minimalist title opener. Utilize presets featuring self-animating ...
(Date:11/27/2015)... ... November 27, 2015 , ... A simply groundbreaking television ... an interesting show that delves into an array of issues that are presently affecting ... benefit from open dialogue, this show is changing the subjects consumers focus on, one ...
(Date:11/27/2015)... ... November 27, 2015 , ... The men and ... nonprofit healthcare organizations in the country. They have overseen financial turnarounds, shown commitment ... advance the healthcare industry as a whole through their advocacy and professional efforts. ...
(Date:11/26/2015)... ... November 26, 2015 , ... Patients at Serenity Point ... come together on Thanksgiving Day to share the things that they are most ... Serenity Point YouTube channel, patients displayed what they wrote on index cards, describing ...
Breaking Medicine News(10 mins):
(Date:11/27/2015)... 2015  Lannett Company, Inc. (NYSE: LCI ... acquisition of Kremers Urban Pharmaceuticals Inc. (KU), the ... company UCB S.A. (Euronext: UCB). ... KU from UCB for total consideration of approximately ... customary working capital adjustment, a deduction of certain ...
(Date:11/27/2015)... 26, 2015 ... the "2016 Global Tumor Marker Testing ... and Sales Segment Forecasts, Innovative Technologies, Instrumentation ... to their offering. --> ... "2016 Global Tumor Marker Testing Market: ...
(Date:11/26/2015)... Un nuevo enfoque combina la ... cáncer avanzado.   --> Un nuevo ... Bremachlorin para el cáncer avanzado.   --> ... la terapia fotodinámica de Bremachlorin para el cáncer avanzado. ... --> Clinical Cancer Research . --> ...
Breaking Medicine Technology: