[Ln(DPA)₃]^3- is a convenient paramagnetic shift reagent for protein NMR studies

(Chemical Equation Presented) Paramagnetic lanthanide ions present outstanding tools for structural biology by NMR spectroscopy. Here we show that the 3:1 complexes between dipicolinic acid and lanthanides are paramagnetic reagents which can site-specifically bind to a wide range of proteins without formation of a covalent bond. The observed pseudocontact shifts can be interpreted by a single magnetic susceptibility anisotropy tensor, enabling its use for structure refinements. The resonance assignment of the paramagnetic spectrum is greatly facilitated by the rapid exchange between bound and free protein, leading to gradual chemical shift changes as the protein is titrated with the paramagnetic dipicolinic acid complex. The association with the paramagnetic lanthanide leads to weak molecular alignment in a magnetic field so that the reagents can be used for the measurement of residual dipolar couplings without the need of protein modification or anisotropic alignment media. The protein samples can be recovered by simple dialysis.