AlphaScreen selectivity assay for beta-catenin/B-cell lymphoma 9 inhibitors

作者：Zhang Min; Wisniewski John A; Ji Haitao^*

来源：Analytical Biochemistry, 2015, 469: 43-53.

DOI：10.1016/j.ab.2014.09.018

• Protein-protein interactions
• Selectivity
• AlphaScreen
• beta-Catenin
• B-cell lymphoma 9
• E-cadherin

The aberrant formation of the beta-catenin/B-cell lymphoma 9 (BCL9) protein-protein complex is the driving force for many diseases, including cancer. Crystallographic analyses demonstrate that the surface area in beta-catenin for interacting with BCL9 is overlapped with that for the beta-catenin/E-cadherin interaction. In this study, a robust AlphaScreen selectivity assay was developed to quantify inhibitor potency for the beta-catenin/BCL9 interaction and selectivity for beta-catenin/BCL9 over beta-catenin/E-cadherin interactions. A pilot screen was performed to demonstrat the feasibility of this assay. This selectivity assay is highly sensitive and suitable for adaptation to high-throughput screening. The establishment of this assay lays the foundation for the discovery of selective inhibitors specific for beta-catenin/BCL9 interactions.

• 出版日期2015-1-15