title: A highly facile and specific assay for cancer-causing isocitrate dehydrogenase mutant using 13C4-labeled α-ketoglutarate and heteronuclear NMR.
abstract: Isocitrate dehydrogenase mutations with neomorphic activity of converting α-ketoglutarate to 2-hydroxyglutarate have been found in many types of cancers. We report an NMR-based assay specific for the mutant using (13)C4-labeled α-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.
authors.affiliation: College of Pharmacy, Natural Product Research Institute, Seoul National University , Sillim-dong, Gwanak-gu, Seoul 151-742, Korea.
authors.forename: He
authors.initials: H
authors.lastname: Wen
authors.forename: Taeho
authors.initials: T
authors.lastname: Yun
authors.forename: Wen Jun
authors.initials: WJ
authors.lastname: Xu
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Kim
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Sung-woo
authors.initials: SW
authors.lastname: Park
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Sunghyouk
authors.initials: S
authors.lastname: Park
mesh_terms: D002460:Cell Line; D057075:Enzyme Assays / Q000379:methods*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics*
chemical_list: D007656:Ketoglutaric Acids; D007521:Isocitrate Dehydrogenase