PROTAC-mediated crosstalk between E3 ligases

  • Chem Commun (Camb). 2019 Feb 5;55(12):1821-1824. doi: 10.1039/c8cc09541h.
Christian Steinebach  1 ,  Hannes Kehm ,  Stefanie Lindner ,  Lan Phuong Vu ,  Simon Köpff ,  Álvaro López Mármol ,  Corinna Weiler ,  Karl G Wagner ,  Michaela Reichenzeller ,  Jan Krönke ,  Michael Gütschow
Affiliations
  • 1. Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany. [email protected].
PMID: 30672516 DOI: 10.1039/c8cc09541h
Abstract

Small-molecule heterobifunctional degraders can effectively control protein levels and are useful research tools. We assembled proteolysis targeting chimeras (PROTACs) from a Cereblon (CRBN) and a von-Hippel-Lindau (VHL) Ligase ligand and demonstrated a PROTAC-induced heterodimerization of the two E3 Ligases leading to unidirectional and efficient degradation of CRBN.

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