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A Highly Facile and Specific Assay for Cancer-Causing Isocitrate Dehydrogenase Mutant Using C-13(4)-Labeled alpha-Ketoglutarate and Heteronuclear NMR

Authors
Wen, HeYun, TaehoXu, Wen JunChoi, Seung HongKim, HyeonjinPark, Chul-KeeLee, Se-HoonPark, Sung-wooLee, Sang KookPark, Sunghyouk
Issue Date
17-Dec-2013
Publisher
American Chemical Society
Citation
Analytical Chemistry, v.85, no.24, pp 11987 - 11992
Pages
6
Journal Title
Analytical Chemistry
Volume
85
Number
24
Start Page
11987
End Page
11992
URI
https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/13050
DOI
10.1021/ac402947a
ISSN
0003-2700
1520-6882
Abstract
Isocitrate dehydrogenase mutations with neomorphic activity of converting a-ketoglutarate to 2-hydroxyglutarate have been found in many types of cancers. We report an NMR-based assay specific for the mutant using C-13(4)-labeled alpha-ketoglutarate. It can be done in a complex mixture without extraction, give time-dependent absolute quantitation, and be applied to enzyme inhibition studies. Its merits over conventional assays should facilitate inhibitor developments for a new class of target-oriented anticancer agents.
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