Late metabolic precursors for selective aromatic residue labeling

J Biomol NMR. 2018 Jul;71(3):129-140. doi: 10.1007/s10858-018-0188-z. Epub 2018 May 28.


In recent years, we developed a toolbox of heavy isotope containing compounds, which serve as metabolic amino acid precursors in the E. coli-based overexpression of aromatic residue labeled proteins. Our labeling techniques show excellent results both in terms of selectivity and isotope incorporation levels. They are additionally distinguished by low sample production costs and meet the economic demands to further implement protein NMR spectroscopy as a routinely used method in drug development processes. Different isotopologues allow for the assembly of optimized protein samples, which fulfill the requirements of various NMR experiments to elucidate protein structures, analyze conformational dynamics, or probe interaction surfaces. In the present article, we want to summarize the precursors we developed so far and give examples of their special value in the probing of protein-ligand interaction.

Keywords: Aromatic residues; Chemical shift mapping; Intrinsically disordered proteins; Ligand induced cross-correlation; Protein labeling; Protein overexpression.

Publication types

  • Review

MeSH terms

  • Amino Acids, Aromatic / chemistry*
  • Amino Acids, Aromatic / metabolism
  • Animals
  • Escherichia coli / metabolism
  • Humans
  • Isotope Labeling / methods*
  • Ligands
  • Molecular Probes
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Proteins / chemistry


  • Amino Acids, Aromatic
  • Ligands
  • Molecular Probes
  • Proteins