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

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.