Targeted Protein Degradation

How do Degrader molecules work?

Schematic showing the catalytic mode of action of Degrader molecules.

Targeted Protein Degradation is a technique that uses heterobifunctional small molecule Degraders, to bring about efficient and highly selective degradation of a target protein of interest. Targeted protein degradation enables investigation of the downstream consequences of protein knockdown and provides an easy-to-use method for target validation.

Bio-Techne provides Active Degrader molecules, including PROTAC Degraders and TAG Degraders (dTAG/aTAG). PROTAC molecules comprise a ligand that binds a target of interest joined by a linker to an E3 ligase ligand. A ternary complex is formed by the simultaneous binding of the Degrader to the target protein and the E3 ligase, which initiates ubiquitination of the target protein and its subsequent destruction by the proteasome. TAG Degraders work on a similar principle, but comprise an E3 ligase ligand linked to a compound that binds a fusion of mutant FKBP12^F36V (for the dTAG system) or MTH1 (for the aTAG system) with a target protein of interest. These Degraders enable the knockdown of proteins for which there are no known ligands.

Bio-Techne supplies a range of other products and services to support Targeted Protein Degradation studies, including Degrader Building Blocks to enable you to create your own Degraders, as well as Ubiquitin-Proteasome System (UPS) Proteins and Assays, Assays for Protein Degradation, and Custom Degraders Services.

Why Use Degraders?

Small molecule Degraders offer several advantages over genetic manipulation for target protein knockdown:

• Degraders are cell-permeable, are suitable for use in vivo and in vitro, and can be applied directly to cells with no need for transfection or expression vectors.
• They are applicable to multiple cell lines with no requirement that cells are easily transfectable
• The duration of effect is adjustable and reversible on compound washout
• They have a catalytic mode of action repeatedly engaging and directing ubiquitination of target molecules, allowing use at sub-stoichiometric concentrations.