Optical control of acetylcholinesterase with a tacrine switch

Johannes Broichhagen, Innokentij Jurastow, Katharina Iwan, Wolfgang Kummer, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

Photochromic ligands have been used to control a variety of biological functions, especially in neural systems. Recently, much effort has been invested in the photocontrol of ion channels and G-protein coupled receptors found in the synapse. Herein, we describe the expansion of our photopharmacological approach toward the remote control of an enzyme. Building on hallmark studies dating from the late 1960s, we evaluated photochromic inhibitors of one of the most important enzymes in synaptic transmission, acetylcholinesterase (AChE). Using structure-based design, we synthesized several azobenzene analogues of the well-known AChE inhibitor tacrine (THA) and determined their effects on enzymatic activity. One of our compounds, AzoTHA, is a reversible photochromic blocker of AChE in vitro and ex vivo with high affinity and fast kinetics. As such, AzoTHA can be used to control synaptic transmission on the neuromuscular endplate based on the light-dependent clearance of a neurotransmitter.

Original languageEnglish (US)
Pages (from-to)7657-7660
Number of pages4
JournalAngewandte Chemie - International Edition
Volume53
Issue number29
DOIs
StatePublished - Jul 14 2014

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Keywords

  • acetylcholinesterase
  • photochromic blockers
  • photopharmacology
  • tacrine
  • tracheal tensometry

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Broichhagen, J., Jurastow, I., Iwan, K., Kummer, W., & Trauner, D. (2014). Optical control of acetylcholinesterase with a tacrine switch. Angewandte Chemie - International Edition, 53(29), 7657-7660. https://doi.org/10.1002/anie.201403666