LANTHANIDE SHIFT-REAGENTS

The first report by Hinckley more than 20 years ago of the use of lanthanide complexes to simplify unresolved proton resonances in low-field nuclear magnetic resonance (NMR) spectra marked the start of the application of the lanthanide-induced shift (LIS) method to a variety of NMR problems. A year later, Morallee et al. presented that the line broadenings induced by the gadolinium(III)-lysozyme complex in the proton resonances of fl-methyl-N-acetylglucosamine could be analyzed in terms of the absolute distance between the Gd(III) ion and various sugar protons. These observations stimulated much interest and activity in the use oflanthanides as NMR shift and relaxation reagents, in applications ranging from qualitative spectral simplification, proof of molecular stereochemistry, and quantitative analysis of dynamic solution structures to the most recent applications in NMR spectroscopy of perfused cells, organs, and intact animals and magnetic resonance imaging (MRI). This chapter describes LIS methodologies and their application to study proteins in solution. The qualitative uses of lanthanides to simplify complex NMR spectra are not mentioned because highfield magnets and two- and three-dimensional methods have eliminated the need for LIS measurements for this purpose. The use of lanthanides as shift and relaxation reagents in organic solutions has been reviewed extensively, as well as well as their applications as NMR structural probes in aqueous solutions, particularly for biological systems including peptides and proteins. © 1993, Elsevier Inc. All rights reserved.