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 reverte

SUBMITTER: Drechsel J 

PROVIDER: S-EPMC8341850 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature