Development of paramagnetic NMR as a new tool for drug discovery

Paramagnetic metal ions, in particular lanthanides, elicit large effects in NMR spectra. We have shown that pseudocontact shifts (PCS) induced by a site-specifically attached lanthanide ion can easily be measured for low-molecular weight compounds bound to proteins, and that the PCSs define all one wants to know about the binding mode of the compound, i.e. its position and orientation relative to the protein, its structure and its binding affinity. We are developing and using lanthanide tags to make this technique generally available for drug discovery.