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Creative Biolabs offers a comprehensive service package for in vitro evaluations of PROTACs. With skillful techniques and advanced statistical analysis platform, we perform top-quality assays to help our clients evaluate the ternary complex formation of PROTACs.
Following target-PROTAC-E3 ligase ternary complex formation, the target will be ubiquitinated and degraded via PROTAC mediated proteasome degradation. It has already been validated by researchers that PROTAC mediated ubiquitination is dependent on the existence of ternary complex equilibria, also the dose-dependent degradation efficiency of PROTAC is consistent with ternary complex formation mediated machinery. The target protein is preferentially recruited in a stable and positively cooperative ternary complex with the E3 ligase (see Fig.1).
Fig.1 Schematic model of selective PROTAC-induced target degradation. (Gadd, 2017)
To measure ternary complex formation, cooperativity is a metric used to describe favorable or repulsive interactions between target protein and E3 ligase in the ternary complex. It is calculated by the algorithm: α = KdA / KdT,A. If the cooperativity < 1, that means the interactions between target protein and E3 ligase diminish the amount of ternary complex. Conversely, if the cooperativity >1, that means interactions enhance the ternary complex formation.
Fig.2 PROTAC-induced ternary complexes and their biophysical properties. (Hughes, 2017)
Ternary system thermodynamic and kinetic properties, including cooperativity, as well as identification for the ternary structure are essential steps during the PROTAC development. To explore the target-PROTAC-E3 ligase ternary formation for a designed PROTAC, Creative Biolabs has developed a wide range of in vitro assays including biophysical (see Table 1) and cell-based assays. Here are some available assays for your reference, but not limited to these. You are welcomed to contact us for any assays, or just let us know your needs and we will propose an assay plan for you.
Table 1. Application of biophysical techniques to study ternary complex formation. (Hughes, 2017)
With highly experienced scientists and mature assays, Creative Biolabs is committed to tailoring the best assay for our worldwide clients to evaluate the ternary complex formation of target protein-PROTAC-E3 ligase. Please contact us for more information and a detailed quote.