4.7 Article

Native Mass Spectrometry Can Effectively Predict PROTAC Efficacy

期刊

ACS CENTRAL SCIENCE
卷 6, 期 7, 页码 1223-1230

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.0c00049

关键词

-

资金

  1. Austrian Science Fund [M2334]
  2. Boehringer Ingelheim
  3. Austrian Science Fund (FWF) [M2334] Funding Source: Austrian Science Fund (FWF)

向作者/读者索取更多资源

Protein degraders, also known as proteolysis targeting chimeras (PROTACs), are bifunctional small molecules that promote cellular degradation of a protein of interest (POI). PROTACs act as molecular mediators, bringing an E3 ligase and a POI into proximity, thus promoting ubiquitination and degradation of the targeted POI. Despite their great promise as next-generation pharmaceutical drugs, the development of new PROTACs is challenged by the complexity of the system, which involves binary and ternary interactions between components. Here, we demonstrate the strength of native mass spectrometry (nMS), a label-free technique, to provide novel insight into PROTAC-mediated protein interactions. We show that nMS can monitor the formation of ternary E3-PROTAC-POI complexes and detect various intermediate species in a single experiment. A unique benefit of the method is its ability to reveal preferentially formed E3-PROTAC-POI combinations in competition experiments with multiple substrate proteins, thereby positioning it as an ideal high-throughput screening strategy during the development of new PROTACs.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据