PROTAC stands for Proteolytic Targeting Chimera that has multiple functional units that engage specific proteins of interest within the cells so that can be degraded using cell’s own ubiquitin proteasome system. One of the ligand pf the PROTAC typically refers to “warhead” targets protein of interest and another ligand often refers to “anchor” is used to recruit E3 ubiquitin ligase. Both the warhead and anchor are connected by a chemical linker making a PROTAC.
LifeSensors offer a suite of assays that characterizes a PROTAC from its affinity to bind with proteins of interest to cellular assays that can demonstrate degradation and selectivity.
1. Biophysical assays to monitor ternary complex formation and validating ligand affinity
2. In vitro ubiquitination assays to validate a functional ternary complex
3. Cell based ubiquitination assays to validate cell permeability and function in cells
4. Degradation assays to validate degradation and demonstrate DC50 & selectivity
5. Mass spectrometry to demonstrate selectivity
Yes, LifeSensors offer medicinal chemistry services to design and synthesize PROTACs with novel ligands and demonstrate ubiquitination and degradation in complementary assays.
Yes, LifeSensors has access to 35 E3 ligases where clients can perform rapid screening to identify novel ligands for PROTAC applications. LifeSensors is equipped with state-of-the-art robotics that offers faster turnaround from identifying hits to further validate them in an array of assays.
PROTAC linker is one of the most underestimated factors when a PROTAC is being designed. Both Linker length and linker composition do play crucial role in getting optimal PROTAC efficiency. Multiple studies have highlighted new generation of functional linkers explored with more complexity are offering ternary complex stabilization subsequently improving degradation.