Unprecedented Sensitivity in a Probe for Monitoring Cathepsin B: Chemiluminescence Microscopy Cell-Imaging of a Natively Expressed Enzyme

Michal E. Roth-Konforti, Christoph R. Bauer, Doron Shabat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Until recently, chemiluminescence cell images could only be obtained using luciferase-activated probes. Moreover, chemiluminescence microscopy cell-imaging has not been demonstrated for natively expressed enzymes like cathepsin B. Herein, we describe the design, synthesis, and evaluation of the first chemiluminescence probe for the detection and imaging of cathepsin B. The probe activation mechanism relies on the release of a dioxetane intermediate, which undergoes chemiexcitation to emit green light with high efficiency under physiological conditions. Using the probe, we obtained clear images of cancerous leukemia and colon cells. This is the first demonstration of chemiluminescence cell images obtained by a probe for a natively expressed endogenous enzyme. We anticipate that the concept presented in this study will be broadly used to develop analogous probes for other important proteases relevant to biomolecular processes.

Original languageEnglish
Pages (from-to)15633-15638
Number of pages6
JournalAngewandte Chemie - International Edition
Volume56
Issue number49
DOIs
StatePublished - 4 Dec 2017

Keywords

  • cathepsin B
  • chemiluminescence
  • dioxetanes
  • live-cell imaging
  • molecular probes

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