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Questions about a product, technology or experimental design? Give us a call 610-644-8845.

PROTAC Ternary Complex Assays

Advanced validation services to characterize PROTAC efficiency through ternary complex formation and ubiquitination potential analysis

PROTACs (PROteolysis TArgeting Chimeras) are heterobifunctional molecules that combine a target-binding warhead with an E3 ligase-binding moiety, resulting in the formation of a ternary complex between the target protein and the E3 ligase to induce ubiquitination and degradation.

It is increasingly clear that the length and composition of the linker connecting the two ligands plays a crucial role in the physiochemical properties and biological activity of PROTACs. The PROTAC field is rapidly evolving and is currently undergoing an important transition from synthetically manageable alkyl and polyethylene glycol linkers to more complex functional linkers.

Traditionally, ternary complex formation has been assessed using cell-free proximity ligand assays such as TR-FRET, ALPHA screening assays, and SPR-based methods.

Key Insight:

Studies in recent years have shown that protein degradability is strongly influenced by intrinsic characteristics of the protein, especially the protein’s endogenous “Ubiquitination Potential”. Hence correlating Ternary complex formation with ubiquitination potential is crucial in accurately characterizing PROTAC efficiency and helping chemists rationally design.

LifeSensors offers a wide array of services to validate PROTAC ternary complex, PROTAC ubiquitination and determining binding affinities (SPR).

Multiple Ranking Approaches

Multiple approaches to rank PROTAC variants

Fast & Sensitive

Rapid results with high sensitivity detection

Orthogonal Correlation

Correlate activity with orthogonal assays

Complex Evaluation

Evaluate relative population of ternary complexes and correlate with ubiquitination potential

Extensive E3 Ligase Access

Access to ~30 E3 ligases to study selectivity

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