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dTAG (degradation TAG) is a TPD based approach to target validation that uses a heterobifunctional Degrader targeting an engineered variant of FKBP12 protein. dTAG technology allows rapid and highly selective degradation of a protein of interest, and is generalizable to a range of fusion proteins. It is useful as an alternative to genetic methods for target validation and can be used in cell culture or in vivo. dTAG has potential for validation of targets for which there are no known ligands.
|Cat. No.||Product Name / Activity|
|Degrades mutant FKBP12F36V fusion proteins; useful alternative to genetic methods for target validation|
This technique involves the expression of a protein of interest as a fusion with mutant FKBP12F36V via transgene expression or CRISPR-mediated locus-specific knock-in. dTAG Degraders are heterobifunctional, comprising a synthetic ligand (AP1836), that selectively binds FKBP12F36V linked to an E3 ligase ligand, such as Thalidomide. The dTAG Degrader recruits the fusion protein to the E3 ligase complex, bringing about its ubiquitination and subsequent degradation by the proteasome.
Plasmid vectors for the lentiviral expression and CRISPR-mediated knock-in of FKBP12F36V are available from Addgene.
Figure 1: Schematic showing the mode of action of heterobifunctional dTAG molecules. A protein of interest is expressed as a fusion with a F36V single-point mutated FKBP12. The dTAG molecule initiates the formation of a ternary complex between an E3 ubiquitin ligase and the fusion protein which results in polyubiquitination of the target protein, its recognition by the proteasome and subsequent degradation of the entire protein. dTAG molecules act catalytically, repeatedly engaging and directing the ubiquitination of target molecules.
Tocris offers the following scientific literature for dTAG to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
This brochure highlights the tools and services available from Bio-Techne to support Targeted Protein Degradation research, including:
Degraders (e.g. PROTACs) are bifunctional small molecules, that harness the Ubiquitin Proteasome System (UPS) to selectively degrade target proteins within cells. They consist of three covalently linked components: an E3 ubiquitin ligase ligand, a linker and a ligand for the target protein of interest. Authored in-house, this poster outlines the generation of a toolbox of building blocks for the development of Degraders. The characteristics and selection of each of these components are discussed.