TRIM21-NUP98 接口可容纳结构多样化的分子降解剂
Yalong Cheng1,2, Longzhi Cao2,3, Panrui Lu2,3
1College of Life Sciences, Beijing Normal University, Beijing 100875, China.
ACS chemical biology
|April 9, 2025
概括
分子粘合剂降解剂利用E3泛素合酶进行向蛋白质破坏. TRIM21-NUP98接口可以结合各种分子,从而实现新的治疗策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 分子粘合剂降解剂通过将标蛋白与E3无素连接酶结合,促进向蛋白降解.
- 目标-E3接口对各种降解剂的适应性在所有分子合剂目标中尚未完全理解.
研究的目的:
- 研究TRIM21-NUP98接口对结构多样化的分子降解剂的适应性.
- 确定针对TRIM21-NUP98复合物的新型分子降解剂.
主要方法:
- 对众多细胞系的公共化合物毒性数据的分析.
- 新型分子降解剂的识别和特征.
- 对已识别的化合物在TRIM21-NUP98接口上结合的确认.
主要成果:
- 确定了PRLX 93936和BMS-214662作为新型分子降解剂,可以激活TRIM21-NUP98接口.
- 证实HGC652,一个先前已知的降解剂,也与这个接口结合.
- 证明TRIM21-NUP98接口可以容纳结构上不同的分子降解剂,包括 (S) -ACE-OH.
结论:
- TRIM21-NUP98接口是多种,结构上不同的分子降解剂的多功能结合点.
- 这种适应性表明,有可能开发更广泛的向蛋白质降解疗法.
- 像PRLX 93936和BMS-214662这样的新型降解剂扩大了调节核孔蛋白水平的工具包.
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