page 5
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  The Viagra™ story
            3. Discovery research
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Target for new medicine

Researchers from Pfizer decided to develop a new medicine to treat angina. They decided to target the action of the new medicine onto the enzyme PDE (Phosphodiesterase). This enzyme breaks down the signalling molecule cGMP which causes vasodilation. By preventing the breakdown of cGMP the new medicine would increase vasodilation.

3D image of PDE enzyme
Picture 7. The PDE enzyme that breaks down cGMP and stops it causing vasodilation.
PDE
Enzymes have a very specific shape. Picture 7 shows the shape of PDE. Its active site fits exactly with molecules of cGMP to make them break down (this is called a lock and key - see page 8).

Viagra™ fits into the active site and blocks it. This prevents the PDE from breaking down the cGMP, which then stays in the blood and continues to cause vasodilation.

The first step to developing the new medicine was to isolate and characterise the PDE enzyme.

Characterisation of PDE

Once the PDE had been isolated, researchers could use it to find out the optimum conditions in which it works and also do tests to find efficient inhibitors.

Modern techniques also allow scientists to build up a computer-generated 3-dimensional structure for proteins like the enzyme PDE. This enables molecules to be modified and designed to affect the enzyme. Computers can be used to identify molecules that have the greatest potential to be useful in the treatment of disease and speed up the development of a new medicine.

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Question 4
Look at these statements about isolating an enzyme using cell samples, a homogeniser, a centrifuge and buffer solutions. The statements are mixed up. Put them in the correct order:

You can swap two statements by clicking on one, then on the other.
Move the statements by constantly swapping pairs of statements.

Centrifuge to separate nuclei from cytoplasm and cell debris.
Get samples of tissue that contain enzymes.
Isolate and purify enzyme from cytoplasm solution.
Add buffer solution and homogenise in food blender.
Remove solids with coarse filter.