Synthesis and evaluation of " Ama-Flash", a photocaged amatoxin prodrug for light-activated RNA Pol II inhibition and cell death

Chem Commun (Camb). 2021 Sep 21;57(75):9558-9561. doi: 10.1039/d1cc03279h.

Abstract

Amanitin is used extensively as a research tool to inhibit RNA Pol II thereby implicating its role in mRNA transcription. Recently, amanitin has gained traction as a toxic payload for targeted therapy. Here we report the first-ever photocaged amanitin analog, that is non-toxic and can be pre-loaded into cells. Light provides a means to inhibit RNA Pol II and provoke cell death on-demand.

MeSH terms

  • Amanitins / chemical synthesis
  • Amanitins / chemistry
  • Amanitins / pharmacology*
  • Animals
  • CHO Cells
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Photochemical Processes
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • RNA Polymerase II / antagonists & inhibitors*
  • RNA Polymerase II / metabolism

Substances

  • Amanitins
  • Prodrugs
  • amatoxin
  • RNA Polymerase II