在结构上多样化的和蛋白质中选择性修饰的酶级联
Anna-Winona Struck1, Matthew R Bennett1, Sarah A Shepherd1
1School of Chemistry and Manchester Institute of Biotechnology, The University of Manchester , 131 Princess Street, Manchester M1 7DN, United Kingdom.
Journal of the American Chemical Society
|February 12, 2016
概括
这项研究引入了一种使用氨酶和甲基转移酶 (COMT) 选择性修改生物分子中的基的新生物对等化学方法,为标记和衍生提供了更大的灵活性.
科学领域:
- 生物化学
- 化学生物学
- 分子生物学
背景情况:
- 生物对角化学允许对生物分子进行选择性修改,用于各种应用.
- 甲基转移酶 (MTase) 用于标记,但其基质特异性有限.
- 在复杂的生物分子中选择性衍生物化仍然是一个挑战.
研究的目的:
- 开发一种更灵活的方法来选择复杂生物分子中的基.
- 引入一种合酶反应,以顺序化和O-化基.
- 展示新方法的多功能性和区域选择性.
主要方法:
- 使用了涉及真菌氨酶和哺乳动物甲基转移酶 (COMT) 的协同酶反应.
- 氨酸酶将基化为中间类甲基.
- 随后,COMT会对甲基醇部分进行O-化,从而实现选择性修饰.
主要成果:
- 酸酶与COMT的组合使酸酶残留物在和蛋白质中的选择性氧化成为可能.
- 该方法对序列的变化具有很高的耐受性.
- 成功修改多种基质,包括类药物,激素和循环类抗生素.
结论:
- 酸酶-COMT系统提供了一种多功能和区域选择性的方法来修改基.
- 这种方法克服了传统MTases的基质特异性限制.
- 在各种生物应用中提供一种强大的衍生工具,标记和固定生物分子.
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