NMR techniques used with very large biological macromolecules in solution

Methods for the characterization of very large biological macromolecules by NMR in solution are presented. For studies of molecular structures with molecular weights beyond 100,000 Da transverse relaxation in common multidimensional NMR experiments becomes a limiting factor. Novel techniques optimize transverse relaxation based on cross-correlated relaxation between dipole-dipole interactions and chemical shift anisotropy (CSA), and include transverse relaxation-optimized spectroscopy (TROSY), cross-correlated relaxation-enhanced polarization transfer (CRINEPT), and cross-correlated relaxation-induced polarization transfer (CRIPT). In combination with various biochemical isotope-labeling techniques these experimental schemes make possible studies of biological macromolecules with molecular masses of up to 1,000,000 Da by NMR in solution. The physical basis and the implementation of the experiments are discussed.