蛋白质化的一个化学探针
1Frick Laboratory, Department of Chemistry , Princeton University , Princeton , New Jersey 08544 , United States.
Journal of the American Chemical Society
|March 28, 2018
概括
研究人员开发了一种新型的化学探针来检测蛋白质氨酸化,这是一个关键的表观遗传调节剂. 这种工具揭示了一个正反循环,在这个循环中,克罗化增强了基因乙化,影响了基因转录.
科学领域:
- 生物化学
- 表观遗传学
- 化学生物学
背景情况:
- 蛋白质氨酸化是一种涉及基因转录的表观遗传调节的新兴后翻译性修饰 (PTM).
- 现有的PTM检测方法,如基于抗体的工具,存在局限性.
研究的目的:
- 开发和验证一种用于检测蛋白质氨酸的新型化学探针.
- 研究 lysine crotonylation 在调节基因乙化和基因转录中的作用.
主要方法:
- 一个水溶性基化学探针的合成,以克罗托尼尔修饰为目标.
- 化学探针用于检测内源性肌化蛋白质,包括基因组.
- 使用探针研究 lysine crotonylation 和 histone acetyltransferase 活动之间的相互作用.
主要成果:
- 开发的化学探针有效地与克罗托尼尔修饰反应.
- 该探测器补充了基于抗体的方法,用于检测内源性肌化蛋白质,如组织蛋白.
- 有证据表明,氨酸化激活了p300的氨酸化活性,从而产生了正反机制.
结论:
- 这种新型的化学探针提供了一种多功能和灵敏的工具来分析蛋白质氨酸的化.
- 氨酸化在通过p300的正反循环调节基因化起作用.
- 这种PTM对于控制基因转录的表观遗传机制至关重要.
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