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Researchers trick Alzheimer's Enzyme

n, Sharpless' method may have great import in designing drugs to interact with proteins for which we presently have no good compounds. The enzyme selected for the click chemistry test, acetylchonlinesterase, was one of the first brain enzymes identified. It breaks down acetylcholine, the neurotransmitter that propagates nerve signals. Inhibitors of acetylcholinesterase treat the dementia associated with Alzheimer's disease by increasing the amount of acetylcholine in the brain.

Sharpless and his team synthesized molecular building blocks that, when pieced together, create a single larger molecule with no by-products -- an acetylcholinesterase inhibitor. With the blocks in place, the essential ingredient -- the enemy enzyme itself -- goes to work. The trick active spots on the acetylcholinesterase surface act like hands that grab and orient the click components of the inhibitor, snapping them together.

Furthermore, the reaction occurs only when the pieces are held by the target enzyme -- acetylcholinesterase -- next to each other, not when they happen to bump into each other in solution.In other words, the disease-causing enzyme welds the bars of its own prison.


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