Optimal Isotope Labeling of Aromatic Amino Acid Side Chains for NMR Studies of Protein Dynamics

Aromatic side chains in proteins are often directly evolved in stabilizing the hydrophobic core, protein binding, or enzymatic activity. They are also responsible for specific local dynamic processes, such as histidine tautomerization or ring flips. Despite their importance, they are often not targeted directly by NMR spectroscopy, because of spectroscopic complications and challenges. This chapter addresses state-of-the-art site-selective ¹³C-labeling methods for aromatic side chains, and describes how they solve several of the spectroscopic issues. A special emphasis is put on thereby enabled protein dynamics experiments of aromatic side chains.