2. Academic Validation
  3. Induced degradation of SNAP-fusion proteins

Induced degradation of SNAP-fusion proteins

  • RSC Chem Biol. 2024 Oct 21;5(12):1232-1247. doi: 10.1039/d4cb00184b.
Savina Abraham Pol 1,  Sara Liljenberg 2,  Jack Barr 2,  Gina Simon 1,  Luis Wong-Dilworth 3,  Danielle L Paterson 2,  Vladimir P Berishvili 2,  Francesca Bottanelli 3,  Farnusch Kaschani 4,  Markus Kaiser 4,  Mariell Pettersson 2,  Doris Hellerschmied 1
Affiliations

Affiliations

  • 1 Department of Mechanistic Cell Biology, University of Duisburg-Essen, Center of Medical Biotechnology, Faculty of Biology Essen Germany doris.hellerschmied@uni-due.de.
  • 2 Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca Gothenburg 431 83 Sweden mariell.pettersson@astrazeneca.com.
  • 3 Institut für Biochemie, Freie Universität Berlin Thielallee 63 Berlin 14195 Germany.
  • 4 Department of Chemical Biology, University of Duisburg-Essen, Center for Medical Biotechnology, Faculty of Biology Essen Germany.
PMID: 39444693 DOI: 10.1039/d4cb00184b
Abstract

Self-labeling protein tags are an efficient means to visualize, manipulate, and isolate engineered fusion proteins with suitable chemical probes. The SNAP-tag, which covalently conjugates to benzyl-guanine and -chloropyrimidine derivatives is used extensively in fluorescence microscopy, given the availability of suitable SNAP-ligand-based probes. Here, we extend the applicability of the SNAP-tag to targeted protein degradation. We developed a set of SNAP PROteolysis TArgeting Chimeras (SNAP-PROTACs), which recruit the VHL or CRBN-ubiquitin E3 Ligases to induce the degradation of SNAP-fusion proteins. Endogenous tagging enabled the visualization and the selective depletion of a SNAP-clathrin light chain fusion protein using SNAP-PROTACs. The addition of PROTACs to the SNAP-tag reagent toolbox facilitates the comprehensive analysis of protein function with a single gene tagging event.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-175417
    SNAP-fusion Protein PROTAC Degrader