PHOTACs Enable Optical Control of Protein Degradation

Martin Reynders, Dirk Trauner

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Proteolysis Targeting Chimeras (PROTACs) are a promising technology to degrade specific target proteins. As bifunctional small molecules, PROTACs induce the ternary complex formation between an E3 ligase and a protein of interest (POI), leading to polyubiquitylation and subsequent proteasomal degradation of the protein in a catalytic fashion. We have developed a strategy to control PROTACs with the spatiotemporal precision of light, which led to light-activated versions, termed PHOTACs (PHOtochemically TArgeted Chimeras). By incorporating an azobenzene photoswitch into the PROTAC, we can reversibly control degradation of the POI, as demonstrated for BRD2-4 and FKBP12. Here, we describe our modular approach and the application of PHOTACs for the optical control of protein levels in detail. PHOTACs hold promise as both research tools and precision pharmaceutics.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages315-329
Number of pages15
DOIs
StatePublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2365
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Chemical Optogenetics
  • Light-activation
  • PHOTAC
  • Photochromic ligand
  • Photocontrol
  • Photopharmacology
  • Photoswitch
  • PROTAC

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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