[NMR paper] Recent applications of isotopic labeling for protein NMR in drug discovery.

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Recent applications of isotopic labeling for protein NMR in drug discovery.

Related Articles Recent applications of isotopic labeling for protein NMR in drug discovery.

Expert Opin Drug Discov. 2013 Mar 12;

Authors: Hiroaki H

Abstract
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.


PMID: 23480844 [PubMed - as supplied by publisher]



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