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Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery

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Abstract

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.

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Acknowledgements

We thank Takeshi Takizawa and Osamu Ubukata for help with the NMR analysis. We also thank Prof. Kohei Tsumoto and Dr. Satoshi Nagatoishi of Tokyo University for assistance in the use of ITC. In addition, we thank Prof. Toshiya Senda of the Institute of Materials Structure Science and staff at the Photon Factory (Tsukuba, Japan) for their assistance in the use of the synchrotron beamline. HT express his thanks to the financial support of JSPS KAKENHI Grants 18H04626, 18H05426, and 18H02393.

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Authors and Affiliations

  1. Structure-Based Drug Design Group, Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd, 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo, 134-8630, Japan

    Hiroyuki Hanzawa, Takashi Shimada & Mizuki Takahashi

  2. Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan

    Hideo Takahashi

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  1. Hiroyuki Hanzawa
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  2. Takashi Shimada
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  3. Mizuki Takahashi
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  4. Hideo Takahashi
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Correspondence to Hiroyuki Hanzawa.

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Hanzawa, H., Shimada, T., Takahashi, M. et al. Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery. J Biomol NMR 74, 501–508 (2020). https://doi.org/10.1007/s10858-020-00314-0

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