University of Frankfurt, Cluster of Excellence Macromolecular Complexes, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Nucleic Acids Res. 2010 Apr;38(6):2111-8. doi: 10.1093/nar/gkp1148. Epub 2009 Dec 8.
Aptamers that can be regulated with light allow precise control of protein activity in space and time and hence of biological function in general. In a previous study, we showed that the activity of the thrombin-binding aptamer HD1 can be turned off by irradiation using a light activatable 'caged' intramolecular antisense-domain. However, the activity of the presented aptamer in its ON state was only mediocre. Here we studied the nature of this loss in activity in detail and found that switching from 5'- to 3'-extensions affords aptamers that are even more potent than the unmodified HD1. In particular we arrived at derivatives that are now more active than the aptamer NU172 that is currently in phase 2 clinical trials as an anticoagulant. As a result, we present light-regulatable aptamers with a superior activity in their ON state and an almost digital ON/OFF behavior upon irradiation.
适体可以通过光进行调控，从而实现蛋白质活性在空间和时间上的精确控制，进而控制生物功能。在之前的一项研究中，我们表明，凝血酶结合适体 HD1 的活性可以通过使用光激活的“笼状”分子内反义结构域的照射来关闭。然而，所呈现的适体在其开启状态下的活性仅为中等水平。在这里，我们详细研究了这种活性丧失的性质，发现从 5'-到 3'-延伸会提供比未修饰的 HD1 更有效的适体。特别是，我们得到了一些衍生物，它们的活性甚至比目前处于 2 期临床试验阶段的抗凝剂 NU172 适体更强。因此，我们提出了在开启状态下具有更高活性的光调控适体，并且在照射后几乎呈现出数字化的开启/关闭行为。
