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
  • 1. Department of Mechanistic Cell Biology, University of Duisburg-Essen, Center of Medical Biotechnology, Faculty of Biology Essen Germany [email protected].
  • 2. Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca Gothenburg 431 83 Sweden [email protected].
  • 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.

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