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

被引：10

作者：

Ourailidou, Maria E. ^{[1
]}

Lenoci, Alessia ^{[2
]}

Zwergel, Clemens ^{[2
]}

Rotili, Dante ^{[2
]}

Mai, Antonello ^{[2
,3
]}

Dekker, Frank J. ^{[1
]}

机构：

[1] Univ Groningen, Groningen Res Inst Pharm, Dept Chem & Pharmaceut Biol, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands

[2] Sapienza Univ, Dept Drug Chem & Technol, Ple A Moro 5, I-00185 Rome, Italy

[3] Sapienza Univ, Cenci Bolognetti Fdn, Pasteur Inst, Ple A Moro 5, I-00185 Rome, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 03期

基金：

欧洲研究理事会;

关键词：

Lysine demethylation; Tumorigenesis; Tranylcypromine; Irreversible inhibition; Enzyme labeling; LSD1 HISTONE DEMETHYLASE; THERAPEUTIC STRATEGY; BIOLOGICAL-ACTIVITY; STRUCTURAL BASIS; HDAC INHIBITORS; PROTEIN; DERIVATIVES; TRANYLCYPROMINE; TRANS-2-PHENYLCYCLOPROPYLAMINE; MECHANISMS;

D O I：

10.1016/j.bmc.2016.11.043

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：847 / 856

页数：10

共 57 条

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