Issue 4, 2020

Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping

Abstract

Monoamine oxidases MAOA and MAOB catalyze important cellular functions such as the deamination of neurotransmitters. Correspondingly, MAO inhibitors are used for the treatment of severe neuropsychiatric disorders such as depression. A commonly prescribed drug against refractory depression is tranylcypromine, however, the side effects are poorly understood. In order to decipher putative off-targets, we synthesized two tranylcypromine probes equipped with either an alkyne moiety or an alkyne-diazirine minimal photocrosslinker for in situ proteome profiling. Surprisingly, LC–MS/MS analysis revealed low enrichment of MAOA and relatively promiscuous labeling of proteins. Photoprobe labeling paired with fluorescent imaging studies revealed lysosomal trapping which could be largely reverted by the addition of lysosomotropic drugs.

Graphical abstract: Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping

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Article information

Article type
Communication
Submitted
16 4 2020
Accepted
24 7 2020
First published
12 8 2020
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2020,1, 209-213

Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping

J. Drechsel, C. Kyrousi, S. Cappello and S. A. Sieber, RSC Chem. Biol., 2020, 1, 209 DOI: 10.1039/D0CB00048E

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