Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/79355
Title: A strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor of N6-methyladenosine demethylase FTO
Authors: Toh, Joel D. W.
Sun, Lingyi
Lau, Lisa Z. M.
Tan, Jackie
Low, Joanne J. A.
Tang, Colin W. Q.
Cheong, Eleanor J. Y.
Tan, Melissa J. H.
Chen, Yun
Hong, Wanjin
Gao, Yong-Gui
Woon, Esther C. Y.
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2015
Source: Toh, J. D. W., Sun, L., Lau, L. Z. M., Tan, J., Low, J. J. A., Tang, C. W. Q., et al. (2015). A strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor of N6-methyladenosine demethylase FTO. Chemical science, 6, 112-122.
Series/Report no.: Chemical science
Abstract: The AlkB family of nucleic acid demethylases are of intense biological and medical interest because of their roles in nucleic acid repair and epigenetic modification. However their functional and molecular mechanisms are unclear, hence, there is strong interest in developing selective inhibitors for them. Here we report the identification of key residues within the nucleotide-binding sites of the AlkB subfamilies that likely determine their substrate specificity. We further provide proof of principle that a strategy exploiting these inherent structural differences can enable selective and potent inhibition of the AlkB subfamilies. This is demonstrated by the first report of a subfamily-selective and cell-active FTO inhibitor 12. The distinct selectivity of 12 for FTO against other AlkB subfamilies and 2OG oxygenases shall be of considerable interest with regards to its potential use as a functional probe. The strategy outlined here is likely applicable to other AlkB subfamilies, and, more widely, to other 2OG oxygenases.
URI: https://hdl.handle.net/10356/79355
http://hdl.handle.net/10220/25115
DOI: 10.1039/C4SC02554G
Schools: School of Biological Sciences 
Rights: © 2015 Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

SCOPUSTM   
Citations 5

94
Updated on Jun 2, 2024

Web of ScienceTM
Citations 5

81
Updated on Oct 24, 2023

Page view(s) 20

704
Updated on Jun 12, 2024

Download(s) 20

264
Updated on Jun 12, 2024

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.