title: Towards the development of activity-based probes for detection of lysine-specific demethylase-1 activity.
abstract: The implications of lysine-specific demethylase-1 (LSD1) in tumorigenesis have urged scientists to develop diagnostic tools in order to explore the function of this enzyme. In this work, we present our efforts on the development of tranylcypromine (TCP)-based functionalized probes for activity-based protein profiling (ABPP) of LSD1 activity. Biotinylated forms of selected compounds enabled dose-dependent enzyme labeling of recombinant LSD1. However, treatment with LSD1 inhibitors did not clearly reduce the LSD1 labeling efficiency thus indicating that labeling using these probes is not activity dependent. This calls for alternative strategies to develop probes for ABPP of the enzyme LSD1.
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Ourailidou
authors.affiliation: Department of Drug Chemistry and Technologies, 'Sapienza' University, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lenoci
authors.affiliation: Department of Drug Chemistry and Technologies, 'Sapienza' University, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Clemens
authors.initials: C
authors.lastname: Zwergel
authors.affiliation: Department of Drug Chemistry and Technologies, 'Sapienza' University, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.affiliation: Department of Drug Chemistry and Technologies, 'Sapienza' University, P.le A. Moro 5, 00185 Rome, Italy; Pasteur Institute, Cenci Bolognetti Foundation, 'Sapienza' University, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: antonello.mai@uniroma1.it.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands. Electronic address: f.j.dekker@rug.nl.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Dekker
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014191:Tranylcypromine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D015335:Molecular Probes; D014191:Tranylcypromine; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Enzyme labeling; Irreversible inhibition; Lysine demethylation; Tranylcypromine; Tumorigenesis