利用库林E3联酶适配蛋白SKP1进行向蛋白质降解
Seong Ho Hong1,2, Akane Osa1,2, Oscar W Huang3
1Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720 USA.
bioRxiv : the preprint server for biology
|October 31, 2023
概括
研究人员开发了一种新的PROTAC策略,使用SKP1适配蛋白来降解引起疾病的蛋白质. 这种新的方法将向蛋白质降解的范围扩大到传统的E3结合酶之外.
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:
- 使用蛋白质溶解向化马 (PROTACs) 的向蛋白质降解提供了一种通过ubiquitination和proteasomal降解消除致病蛋白质的治疗策略.
- 目前的PROTACs主要利用来自Cullin-RING E3泛素连接酶 (如cereblon和VHL) 的基质受体.
- 对于Cullin-RING E3泛素化酶复合体中的核心组件在PROTAC应用中的潜力仍未得到充分探索.
结论:
- 库林-RING E3 泛素结合酶复合体内的核心适配蛋白是新型 PROTAC 应用的可行目标.
- 共价化学蛋白质组策略是有效的,用于识别这些必不可少的蛋白质降解机械元件的招募者.
- 这项工作扩大了PROTAC技术用于治疗性蛋白质消除的目标范围.
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