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

Technology Benefits
·        Reduction in signal background ·        Functional in physiologically relevantconditions (e.g. cell lysate and intracellularly)
Detailed Technology Description
Novel cross-linkers that stabilize E3 ubiquitin ligase-substrate complexes#CNS #Alzheimer'sDisease #Huntington'sDisease #Parkinson'sDisease #diagnostic #cancer #researchtool #reagent
*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. 

*Inventors
NeilKelleherSungjin ParkIoanna NtaiPaul ThomasAlexanderStatsuk*
*Publications
ParkS, Ntai I, Thomas P, Konischcheva E, Kelleher N and Statsuk A (2012)  Mechanism-Based Small Molecule Cross-linkersof HECT Ubiquitin Ligase-Substrate pairs. Biochemistry.51:  8327-9.
Country/Region
USA

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