Issue 11, 2022

Methyltetrazine as a small live-cell compatible bioorthogonal handle for imaging enzyme activities in situ

Abstract

Bioorthogonal chemistry combines well with activity-based protein profiling, as it allows for the introduction of detection tags without significantly influencing the physiochemical and biological functions of the probe. In this work, we introduced methyltetrazinylalanine (MeTz-Ala), a close mimic of phenylalanine, into a dipeptide fluoromethylketone cysteine protease inhibitor. Following covalent and irreversible inhibition, the tetrazine allows vizualisation of the captured cathepsin activity by means of inverse electron demand Diels Alder ligation in cell lysates and live cells, demonstrating that tetrazines can be used as live cell compatible, minimal bioorthogonal tags in activity-based protein profiling.

Graphical abstract: Methyltetrazine as a small live-cell compatible bioorthogonal handle for imaging enzyme activities in situ

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Article information

Article type
Paper
Submitted
10 mei 2022
Accepted
07 sep 2022
First published
13 sep 2022
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2022,3, 1325-1330

Methyltetrazine as a small live-cell compatible bioorthogonal handle for imaging enzyme activities in situ

D. Torres-García, M. A. T. van de Plassche, E. van Boven, T. van Leeuwen, M. G. J. Groenewold, A. J. C. Sarris, L. Klein, H. S. Overkleeft and S. I. van Kasteren, RSC Chem. Biol., 2022, 3, 1325 DOI: 10.1039/D2CB00120A

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