Towards the development of activity-based probes for detection of lysine-specific demethylase-1 activity.

Authors :: Ourailidou ME
Lenoci A
Zwergel C
Rotili D
Mai A
Dekker FJ
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2017 Feb 01; Vol. 25 (3), pp. 847-856. Date of Electronic Publication: 2016 Dec 01.
Publication Year :: 2017
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.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Subjects :: Dose-Response Relationship, Drug
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
HeLa Cells
Histone Demethylases metabolism
Humans
Molecular Probes chemical synthesis
Molecular Probes chemistry
Molecular Structure
Structure-Activity Relationship
Tranylcypromine chemical synthesis
Tranylcypromine chemistry
Enzyme Inhibitors pharmacology
Histone Demethylases antagonists & inhibitors
Molecular Probes pharmacology
Tranylcypromine pharmacology

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