title: Recent applications of isotopic labeling for protein NMR in drug discovery.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nagoya University, Graduate School of Pharmaceutical Sciences, Furocho, Chikusa-kum, Koto-kenkyu-kan, Nagoya, 464-8601, Japan. hiroakih@med.kobe-u.ac.jp
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Hiroaki
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins