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17:08 03 October 2006
NewScientist.com news service
Debora MacKenzie
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Alexander Heckel, University of Bonn
A new drug, designed with its own built-in antidote, could revolutionise drug safety, allowing effective use of potentially risky drugs.
Researchers have designed an anti-clotting drug that becomes inactive – allowing blood to form clots – when light of a specific frequency is shone on it.
Anti-clotting drugs are widely used in medicine, including in situations where the blood is transported outside of the body for a time, such as during heart surgery or kidney dialysis. But once back in the body, blood that cannot clot can cause catastrophic bleeding and stroke.
Heparin is often used as an anti-clotting agent in such situations, as it has an antidote that can be applied quickly if it is needed. But heparin can cause allergic reactions. Better, more modern anti-clotting agents cannot be used in these situations, however, as they have no fast antidote.
Shine a light
Alexander Heckel and colleagues at the University of Bonn, in Germany, may now have solved the problem. They have been experimenting with a “toolbox” of artificial nucleotides that change shape when bathed in light of a certain wavelength.
The team experimented with a potential anti-clotting drug called an aptamer, which is a string of 15 nucleotides – the building blocks of DNA. This aptamer works by binding and blocking a major molecule involved in the body’s blood-clotting reaction, called thrombin.
The researchers turned off this blocking action by causing the molecule to bend into a hairpin shape. They achieved this by stringing four extra nucleotides on one end of the aptamer. One of these was a shape-changing nucleotide, while the others were nucleotides that would normally bind with the sequence of nucleotides at the other end of the aptamer.
Without the right kind of light, the shape-changing nucleotide did not match its opposite number at the other end of the aptamer, and the two ends did not bind together. But when the light was switched on, the artificial nucleotide changed shape and became a match. This allowed the two ends of the aptamer to bind together in the hairpin shape, switching off the aptamer's anti-clotting action.
The team found it could "turn off" the aptamer in seconds, even when it was already bound to thrombin.
Such light-sensitive artificial nucleotides might be added to other nucleotide-based drugs, the researchers say. This could include drugs to control gene regulation and many crucial proteins. 认领! 哈哈! http://news.sina.com.cn/w/h/2006-10-09/113111189270.shtml
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作者:admin@医学,生命科学 2011-08-12 02:16
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