A Highly Facile and Specific Assay for Cancer-Causing Isocitrate Dehydrogenase Mutant Using 13C4-Labeled 伪-Ketoglutarate and Heteronuclear NMR
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- 作者：He Wen ; Taeho Yun ; Wen Jun Xu ; Seung Hong Choi ; Hyeonjin Kim ; Chul-Kee Park ; Se-Hoon Lee ; Sung-woo Park ; Sang Kook Lee ; Sunghyouk Park
- 刊名：Analytical Chemistry
- 出版年：2013
- 出版时间：December 17, 2013
- 年：2013
- 卷：85
- 期：24
- 页码：11987-11992
- 全文大小：324K
- 年卷期：v.85,no.24(December 17, 2013)
- ISSN：1520-6882
文摘
Isocitrate dehydrogenase mutations with neomorphic activity of converting 伪-ketoglutarate to 2-hydroxyglutarate have been found in many types of cancers. We report an NMR-based assay specific for the mutant using 13C4-labeled 伪-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.