针对性抑制NCOA1/STAT6蛋白与蛋白相互作用
Yeongju Lee1, Heeseok Yoon2, Sung-Min Hwang3
1Department of Chemistry and Division of Advanced Material Science, Pohang University of Science and Technology (POSTECH) , Pohang 37673, South Korea.
Journal of the American Chemical Society
|November 2, 2017
概括
一种新型的粘合破坏了NCOA1/STAT6复合体,抑制了STAT6介导的转录. 这种作为一种化学探针和潜在的治疗向蛋白质-蛋白质相互作用.
科学领域:
- 分子生物学
- 结构生物学
- 药物发现
背景情况:
- 转录因子 (TF) 和协同激活蛋白质复合体的形成对转录活性至关重要.
- 针对异常的TF/辅激剂相互作用是一个治疗策略,但调节蛋白质-蛋白质相互作用 (PPI) 是一个挑战.
研究的目的:
- 开发一种针对核受体1 (NCOA1) 的细胞透性稳定.
- 调查NCOA1/STAT6复合物的破坏及其对STAT6介导的转录的影响.
- 阐明了与NCOA1互动的结构基础.
主要方法:
- 针对NCOA1的螺旋的设计和合成.
- 评估在细胞中破坏NCOA1/STAT6复合物的能力.
- 确定与NCOA1复合的的晶体结构.
主要成果:
- 开发了一种针对NCOA1的细胞透,蛋白质稳定的合.
- 接成功破坏了NCOA1/STAT6复合体,抑制了STAT6介导的转录.
- 确定了与NCOA1结合的第一个结晶结构.
结论:
- 合是一种有效的化学探针,用于研究NCOA1/STAT6相互作用.
- 这种代表了开发针对PPI的新疗法的一个有希望的起点.
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