Introduction: Nuclear magnetic resonance (NMR) applications in drug discovery are classified into two categories: ligand-based methods and protein-based methods. The latter is based on the observation of the (1)H-(15)N HSQC spectra of a protein with and without lead compounds. However, in order to take this strategy, isotopic labeling is an absolute necessity. Given that each (1)H-(15)N HSQC signal corresponds to a residue of the target protein, signal changes provide specific information on whether a compound will fit into a pocket. Thus, this protein-based method is particularly suitable for fragment-based approaches, such as "SAR-by-NMR" and "fragment-growing." Alternatively, the information from a protein interface may be used to develop inhibitors for protein-protein interactions.
Areas covered: This review discusses at the experimental procedures for preparing isotopically labeled protein and introduces selected topics on atom-specific and residue-selective isotope labeling, which may facilitate the development of PPI/PA inhibitors. Furthermore, the author reviews the recent applications of "in-cell" NMR spectroscopy, which is now considered as an important tool in drug delivery research.
Expert opinion: Many recent advances in labeling methods have succeeded in expanding NMR's potential for drug discovery. In addition to those methods, another new technique called "in-cell NMR" allows the observation of protein-ligand interactions inside living cells. In other words, "in-cell NMR" may become a pharmaceutical NMR technique for drug delivery.