Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery

• Published in: Journal of biomolecular NMR 2020-11, Vol.74 (10-11), p.501-508
• Main Authors: Hanzawa, Hiroyuki, Shimada, Takashi, Takahashi, Mizuki, Takahashi, Hideo
• Format: Article
• Language: English
• Subjects: Antibodies; Biochemistry; Biological and Medical Physics; Biophysics; Drug development; Drug discovery; Gene therapy; Information processing; Magnetic resonance spectroscopy; NMR; NMR spectroscopy; Nuclear magnetic resonance; Perspective; Pharmaceutical industry; Physics; Physics and Astronomy; Protein interaction; Proteins; Spectrometers; Spectroscopy; Spectroscopy/Spectrometry; Spectrum analysis; Therapeutic targets
• ISSN: 0925-2738; 1573-5001
• DOI: 10.1007/s10858-020-00314-0

Recently, there has been increasing interest in new modalities such as therapeutic antibodies and gene therapy at a number of pharmaceutical companies. Moreover, in small-molecule drug discovery at such companies, efforts have focused on hard-to-drug targets such as inhibiting protein–protein interactions. Biomolecular NMR spectroscopy has been used in drug discovery in a variety of ways, such as for the reliable detection of binding and providing three-dimensional structural information for structure-based drug design. The advantages of using NMR spectroscopy have been known for decades (Jahnke in J Biomol NMR 39:87–90, (2007); Gossert and Jahnke in Prog Nucl Magn Reson Spectrosc 97:82–125, (2016)). For tackling hard-to-drug targets and increasing the success in discovering drug molecules, in-depth analysis of drug–target protein interactions performed by biophysical methods will be more and more essential. Here, we review the advantages of NMR spectroscopy as a key technology of biophysical methods and also discuss issues such as using cutting-edge NMR spectrometers and increasing the demand of utilizing conformational dynamics information for promoting small-molecule drug discovery.