Novel Cross-Linkers that Stabilize E3 Ubiquitin Ligase and Substrate Pairs

NU 2012-088

Inventors

Neil Kelleher

Sungjin Park

Ioanna Ntai

Paul Thomas

Alexander Statsuk*

Short Description

Novel cross-linkers that stabilize E3 ubiquitin ligase-substrate complexes

Abstract

Northwestern researchers have identified small molecule cross-linkers that are designed to stabilize the interaction between HECT-E3 ubiquitin ligases and their downstream substrates. There is a growing need to identify new E3 ligase targets owing to studies that implicate E3 ligases in cancer and neurodegenerative disease. Currently, it is challenging to capture these interactions due to their transient and weak nature. The scientists have designed these novel cross-linkers with directional handles which stabilize and capture the ligase-substrate complex with reduced background binding. In addition to specifically cross-linking E3 ligases to their substrates, the cross-linkers are functional in cell lysates or in whole cells, making them unique in the marketplace. 

Applications

• Biochemical Assays (e.g. immunoprecipitation and protein purification)
• Biophysical assays (e.g. crystallography)

Advantages

• Reduction in signal background
• Functional in physiologically relevant conditions (e.g. cell lysate and intracellularly)

Publications

Park S, Ntai I, Thomas P, Konischcheva E, Kelleher N and Statsuk A (2012) Mechanism-Based Small Molecule Cross-linkers of HECT Ubiquitin Ligase-Substrate pairs. Biochemistry. 51: 8327-9. 

IP Status

US patent and PCT application have been filed.