迪波罗基姆:一种新型且异常强大的托尔类受体激活剂
Matthew D Morin1, Ying Wang2, Brian T Jones1
1Department of Chemistry and the Skaggs Institute of Chemical Biology , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 United States.
Journal of the American Chemical Society
|October 2, 2018
概括
研究人员发现了diprovocims,这些新型小分子通过诱导托尔类受体 (TLR) - 2二分化来激活免疫系统. 这些有力的化合物作为免疫反应修饰剂具有显著的前景.
科学领域:
- 免疫学
- 医学化学
- 药物发现
背景情况:
- 刺激免疫反应对于治疗干预至关重要.
- 发现新的免疫反应激活剂是一个持续的挑战.
- 托尔类受体 (TLR) 是先天免疫的关键调节者.
研究的目的:
- 发现和描述一种新的小分子免疫反应激活剂.
- 识别调节收费类受体 (TLR) 信号的化合物.
- 开发一种有力且可合成的TLR激动剂.
主要方法:
- 设计用于受体二元化的化合物库的高通量选.
- 功能性测定测量TNF-α从分化THP-1骨髓细胞释放.
- 结构与活性关系研究以优化化合物的效力.
主要成果:
- 一种新型的免疫反应激活剂.
- 迪波罗西姆诱导细胞表面类似受体 (TLR) - 2与TLR1 (TLR1/ TLR2激动剂) 的二分化.
- 优化后的diprovocims具有800倍的功效,其中最强的化合物是在皮科莫尔度时活性.
结论:
- 迪波罗西姆是一种具有独特结构的新型小分子TLR1/TLR2激动剂.
- 这些化合物具有强大作用,可以合成,在人类和小鼠系统中都很活跃.
- 与已知的TLR激动剂相比,Diprovocims具有更高的功效,具有治疗潜力.
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