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Discovery of 'overdrive' protein could broaden drug design options
Date:2/12/2008

CHAPEL HILL New research by scientists at the University of North Carolina at Chapel Hill shows for the first time that an important family of proteins known to function at the cell surface also functions at a site within the cell.

The findings have potential implications for drug development as they involve G protein-coupled receptors (GPCRs). These molecules are the target of forty to fifty percent of modern medicinal drugs, such as antihistamines and drugs for high blood pressure.

The study identified the first protein to activate the G-protein signaling pathway from within a cell. In humans, reactions to everything from taste and smell to stimulants like adrenaline or caffeine requires G-protein signaling.

Until now, the only known way to turn on a G-protein was via a receptor sitting on a cells surface membrane. This receptor acts like a telegraph operator, accepting outside signals and relaying them inside the cell. It converts an external signal, like caffeine, into action in this case, a nerve signal to the brain.

More than half of all drugs, from asthma and heart medicine to antidepressants, target G-protein receptors. Discovering a protein that activates G-proteins from inside a cell could open up an entirely new pathway for drug development, said Henrik Dohlman, Ph.D., senior study author and a professor of biochemistry and biophysics in UNCs School of Medicine.

No drug is 100 percent effective, 100 percent free of side effects and 100 percent safe. The more options we have biochemically, the more selective we can be in designing new drugs. If we can find another way of modulating G-proteins, we could expand the drug targets that are available to pharmacology, Dohlman said.

The study appeared online Feb.7, 2008, in the journal Current Biology and will be published in the Feb. 14, 2008, print edition. Funding was provided by the National Institutes of Health and a UNC Cell and Molecular Biolo
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Contact: Leslie Lang
llang@med.unc.edu
919-843-9687
University of North Carolina at Chapel Hill
Source:Eurekalert

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