當(dāng)使用了過量藥物或者藥物發(fā)生嚴(yán)重的副作用時(shí),，快速的解毒劑就成為拯救病人的關(guān)鍵,。這在抗凝血藥物上尤其明顯,，抗凝血藥物主要用于心臟病人的血栓治療,。但是當(dāng)這種藥物使用過量時(shí),，會(huì)造成致命的大出血,。
??肝磷脂是一種抗凝劑,，并且有特定的抑制藥物。這種抗凝劑被廣泛的使用,，盡管有很多更好的抗凝劑不斷被發(fā)明出來,。德國波恩的一組科學(xué)家Alexander Heckel，Gunter Mayer,，以及Bernd Potzsch最近發(fā)明了一種自身就攜帶了反抗凝因子的抗凝劑,。當(dāng)受到紫外線輻射時(shí)，這些分子的反抗凝因子就會(huì)被激發(fā),，使它們立即停止抗凝血作用,。
??這種物質(zhì)基于一種能和凝血酶結(jié)合的核酸（aptamer），凝血酶是一種在凝血過程中非常重要的蛋白質(zhì),。Aptamer是DNA單鏈分子,，能和其它分子——如凝血酶——結(jié)合。在小組實(shí)驗(yàn)中,，aptamer折疊成三維結(jié)構(gòu),，能和目標(biāo)分子精密結(jié)合?？茖W(xué)家們將另一小段DNA結(jié)合在凝血酶aptamer上,，這個(gè)小片段被激活后可以變?yōu)榉纯鼓蜃印６灰槐患せ?，分子就是一種很好的凝血?jiǎng)?/p>
??當(dāng)aptamer的凝血作用需要被停止時(shí),，科學(xué)家就用紫外線激發(fā)小片段,。這一小段DNA分子和結(jié)合凝血酶的aptamer是配對(duì)的，但是當(dāng)一個(gè)小的核苷酸改變時(shí),，DNA鏈的彼此結(jié)合成雙鏈分子的特性就會(huì)被阻止。
??紫外線能將這些變化的核苷酸分離出去,，所以這些小片段就可以和aptamer結(jié)合,。之前aptamer的三維結(jié)構(gòu)被改變，同時(shí)變化的還有和凝血酶結(jié)合特性以及抗凝血作用,。
英文原文：
Powerful drug comes with an 'off switch'
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.
