Chemoselective 15N Tag for Sensitive and High-Resolution Nuclear Magnetic Resonance Profiling of the Carboxyl-Containing Metabolome

被引:48
作者
Ye, Tao [1 ]
Mo, Huaping [2 ,3 ]
Shanaiah, Narasimhamurthy [1 ]
Gowda, G. A. Nagana [1 ]
Zhang, Shucha [1 ]
Raftery, Daniel [1 ]
机构
[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[2] Purdue Univ, Purdue Interdepartmental NMR Facil, W Lafayette, IN 47907 USA
[3] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA
基金
美国国家卫生研究院;
关键词
2-DIMENSIONAL GAS-CHROMATOGRAPHY; FLIGHT MASS-SPECTROMETRY; NMR-SPECTROSCOPY; CONDENSING AGENT; ACID METABOLITES; SYSTEMS BIOLOGY; ORGANIC-ACIDS; BLOOD-PLASMA; TOCSY; QUANTIFICATION;
D O I
10.1021/ac900539y
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Metabolic profiling has received increasing recognition as an indispensable complement to genomics and proteomics for probing biological systems and for clinical applications. H-1 nuclear magnetic resonance (NMR) is widely used in the field but is challenged by spectral complexity and overlap. Improved and simple methods that quantitatively profile a large number of metabolites are sought to make further progress. Here, we demonstrate a simple isotope tagging strategy, in which metabolites with carboxyl groups are chemically tagged with N-15-ethanolamine and detected using a 2D heteronuclear correlation NMR experiment. This method is capable of detecting over 100 metabolites at concentrations as low as a few micromolar in biological samples, both quantitatively and reproducibly. Carboxyl-containing compounds are found in almost all metabolic pathways, and thus this new approach should find a variety of applications.
引用
收藏
页码:4882 / 4888
页数:7
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