轻度调节的阿普坦酶活动:一个抗血素的阿普坦酶与中的蒂米丁核基
Alexander Heckel1, Günter Mayer
1Kekulé-Institute for Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany. heckel@uni-bonn.de
Journal of the American Chemical Society
|January 20, 2005
概括
合成的具有光性组的DNA体可以通过光来开启. 这种光激活的DNA吸纳体技术为治疗应用提供了控制吸纳体功能的新方法.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药用化学 医学化学
背景情况:
- 亚胺是基于核酸的配体,对目标分子具有很高的特异性和亲和力.
- 控制阿普坦酶活性对于治疗应用至关重要,特别是在抗凝剂中.
- 光性保护组提供了一种光触发生物分子激活的方法.
研究的目的:
- 为了合成"子"的DNA体,在蒂米丁残留物上配有光性保护基.
- 为了研究化蒂米丁对抗血栓胺体的功能的影响.
- 为了证明光诱导的aptamer活动的恢复.
主要方法:
- 一个15核酸单链DNA (ssDNA) 抗血素aptamer的化学合成.
- 用光性保护组对提米丁核酸的修饰.
- 通过使用像表面等离子体共振 (SPR) 这样的技术,评估阿巴胺与血栓的结合亲和力.
- 评估阿普坦酶对血液凝固级联的抑制.
- 用366nm光的光化学方法解了经过修改的阿帕特马.
主要成果:
- 合成"化"的ssDNA抗胺胺体与光可变的蒂米丁修饰.
- 在一个关键位置的一个单独的化胺完全取消了对血栓结合的阿帕特马尔.
- 囚禁的阿普塔默未能抑制血液凝固级联.
- 用366纳米光辐射有效地去除了光性保护组.
- 脱恢复了阿普坦对血栓和其抗凝活动的亲和力.
结论:
- 蒂米丁残留物的光可变"化"可以有效地对体功能进行时间控制.
- 光诱导的脱迅速恢复了抗血栓胺体的生物活性.
- 这种光激活的阿普坦体系统对开发可控制的抗凝治疗具有前景.
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