通过在人体细胞中进行基于片段的查来发现连接物和标
Christopher G Parker1, Andrea Galmozzi1, Yujia Wang1
1Department of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell
|January 24, 2017
概括
研究人员开发了一个新的平台,结合了基于片段的选和化学蛋白质学,以绘制人体细胞中的小分子蛋白相互作用. 这种方法可以识别新的化学探测器和药物点,进步化学生物学和药物发现.
科学领域:
- 化学生物学
- 蛋白质组学
- 药物发现
背景情况:
- 人类蛋白质组的化学配体的有限可用性阻碍了生物过程研究.
- 目前用于发现化学探针的方法不足以覆盖整个蛋白质组.
研究的目的:
- 开发一个用于在人体细胞中直接绘制小分子蛋白相互作用的平台.
- 识别新的化学探测器和生物活性的小分子,
主要方法:
- 基于碎片的配体发现与定量化学蛋白质的整合.
- 在人体细胞内直接映射可逆的小分子-蛋白相互作用.
- 碎片对应的推进到选择性配体,并与表型选相结合.
主要成果:
- 数以千计的可逆小分子-蛋白相互作用被绘制为地图,许多是特定的.
- 对缺乏先前化学探针的蛋白质进行选择性配体的开发.
- 通过PGRMC2的参与促进脂肪细胞分化的小分子的鉴定.
结论:
- 开发的平台提供了人类细胞中蛋白质结合性的全蛋白质图.
- 促进生物活性小分子及其蛋白标的同时发现.
- 能够研究以前难以探测的蛋白质,如PGRMC2.
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