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Researchers trick Alzheimer's Enzyme

According to researchers in Scripps Research Institute, chemists have tricked an enzyme essential in Alzheimer's disease into blocking its own debilitating action.// A team led by Nobel laureate K. Barry Sharpless developed the chemical trick, called "click chemistry," to make a molecule that blocks neurotransmitter destruction caused by the brain enzyme acetylcholinesterase.

The destructive enzyme catalyzes the so-called "click reaction" that creates its own worst enemy -- its most potent inhibitor. "Think of this as a Trojan Horse approach for battling disease, but this horse goes the Greeks one better," Sharpless, W.M. Keck professor of chemistry at Scripps, said in a prepared statement.

Once the disease-causing enzyme assembles the horse, Sharpless explained, out march the inhibitors, chemical soldiers who stop the enzyme cold. By assembling its own inhibitor, the enzyme actually designs the drug that will best halts its progress.

James Olds, neuroscientist, director of the Krasnow Institute for Neurobiology at George Mason University in Fairfax, is indeed a revolutionary method in rational drug design."It may have great applicability to improving the specificity of drugs, particularly those currently used in the treatment of neurological and psychiatric diseases."

Molecular drug designers make inhibitor molecules that fit snuggly into the active sites of target enzymes, blocking their action on other molecules. Many diseases -- cancer, AIDS, Alzheimer's, arthritis and anthrax, for instance -- induce unnatural functions in enzymes. Inhibiting enzyme action can treat these diseases.

Enzyme active sites are also highly specific, so drugs react only with the sites and nowhere else. A major problem of current drugs is that they are 'dirty', that is, they have side effects -- often untoward -- because they interact with proteins or enzymes other than the ones planned for.

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