The application of paramagnetic lanthanoid ions in NMR spectroscopy on proteins

• Paramagnetic lanthanide probes are powerful tools for protein NMR spectroscopy.
• A range of lanthanide complexes has been employed to improve probe properties.
• Various protein linkage chemistries have been investigated.
• The probes already have many applications in the study of protein structures.
• Further improvements of probe design can lead to new applications.

Lanthanoids are gaining popularity as paramagnetic centers for high resolution nuclear magnetic resonance (NMR) spectroscopy. They provide valuable angular and long-distance restraints for structure calculations of proteins and protein complexes. The introduction of lanthanoids into a protein sample is complicated by the many requirements for functional artificial paramagnetic probes. For many applications, the probe needs to be attached site-specifically and rigidly to the protein and the coordination of the lanthanoid by the tag must result in a unique anisotropy of the magnetic susceptibility. The variety of lanthanoid coordination systems that has been explored to design paramagnetic probes that meet these demands is reviewed. Also the applications of the tags are discussed, including protein and protein complex structure determination, assignment of protein NMR spectra and the study of protein dynamics. It is concluded that lanthanoid probes bear great potential for further applications in protein NMR spectroscopy, provided that various aspects can be improved further.