对细胞内蛋白质的细胞透性双循环抑制剂
Wenlong Lian1, Bisheng Jiang, Ziqing Qian
1Department of Chemistry and Biochemistry, The Ohio State University , 484 West 12th Avenue, Columbus, Ohio 43210, United States.
Journal of the American Chemical Society
|June 28, 2014
概括
循环可以通过将它们与细胞透融合而使细胞具有透性,从而产生双循环. 这一策略产生了强大的酶抑制剂,增强了它们的治疗潜力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药用化学 医学化学
背景情况:
- 循环可以作为治疗药物表现出希望,但与细胞膜透性作斗争.
- 细胞进入是许多循环的治疗应用的主要障碍.
研究的目的:
- 通过将它们与循环细胞透融合,开发细胞透的循环.
- 为了创建蛋白质氨酸酸酶1B和类-类 cis-trans 异构酶 (Pin1) 的新兴抑制剂.
主要方法:
- 循环与循环细胞透的融合,形成双循环结构.
- 测试由此产生的双循环对酶的抑制活性,选择性和蛋白质分解稳定性.
主要成果:
- 成功生成了具有保留目标识别的细胞透性双循环.
- 开发了强效,选择性和蛋白质溶解稳定的蛋白质氨酸酸酶1B和Pin1的抑制剂.
- 在体外证明了新型双循环抑制剂的生物活性.
结论:
- 与循环细胞透的融合是提高循环细胞透性的有效策略.
- 由此产生的双循环是作为酶抑制剂治疗开发的有希望的候选人.
- 这种方法扩大了循环在生物研究和药物发现中的实用性.
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