Drug Testers Think Small...continued
A Molecular Test System...
Aurora’s standard test system uses a molecule made of two fluorophores. The first absorbs violet light and would, by itself, emit blue light. But if the two-part molecule is intact, the light energy is transferred to the second fluorophore, which emits green light. It stays intact unless beta-lactamase is around, in which case the molecule is split in two, no energy transfer takes place, and there is no green light.
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Green Fluorescent
Protein (GFP) in
Aequorea victoria |
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The basis for the second set of fluorophores has been provided by evolution. Green fluorescent protein (GFP) is used by the Pacific Northwest jellyfish Aequorea victoria to make a green flash when it is agitated. This is presumably an attempt to confuse its enemies and thus defend itself.
But GFP can also be used in drug hunting. GFP makes its own fluorophore by joining together three of its building blocks in a ring. By changing building blocks in and around the fluorophore, Tsien has improved the strength of the green fluorescence, and modified it to produce blue, cyan and yellow variants.
The union of GFP and BFP (the blue variant of GFP) yields a protease sensor. Proteases chop up proteins, and are important in many diseases. HIV protease, for example, has been a prime target for anti-AIDS drugs. If GFP and BFP are linked, energy can pass between them as with the chemical fluorophores. A protease separates the two proteins, stops the energy transfer, and changes the color of the glow. An anti-protease drug should jam the protease and preserve the GFP-BFP link.
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Biotech Revolutions Index
Biotech Applied Index
