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Review

Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies

by 1,2 and 1,2,*
1
Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan
2
Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 46; https://doi.org/10.3390/ijms22010046
Received: 14 November 2020 / Revised: 20 December 2020 / Accepted: 21 December 2020 / Published: 22 December 2020
Obtaining high ordered structure (HOS) information is of importance to guarantee the efficacy and safety of monoclonal antibodies (mAbs) in clinical application. Assessment of HOS should ideally be performed in a non-invasive manner under their formulated storage conditions, as any perturbation can introduce unexpected detritions. However, most of the currently available techniques only indirectly report HOS of mAbs and/or require a certain condition to conduct the analyses. Besides, the flexible multidomain architecture of mAbs has hampered atomic-resolution structural analyses using X-ray crystallography and cryo-electron microscopy. In contrast, the ability of nuclear magnetic resonance (NMR) spectroscopy to structurally analyze biomolecules in various conditions in a non-invasive and quantitative manner is suitable to meet the needs. However, the application of NMR to mAbs is not straightforward due to the high molecular weight of the system. In this review, we will discuss how NMR techniques have been applied to HOS analysis of mAbs, along with the recent advances of the novel 15N direct detection NMR strategy that allows for obtaining the structural fingerprint of mAbs at lower temperatures under multiple formulation conditions. The potential application of these NMR strategies will benefit next-generation mAbs, such as antibody-drug conjugates and bispecific antibodies. View Full-Text
Keywords: NMR; high ordered structure; monoclonal antibodies; multi domain; formulation condition; 15N-direct detection NMR; high ordered structure; monoclonal antibodies; multi domain; formulation condition; 15N-direct detection
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MDPI and ACS Style

Tokunaga, Y.; Takeuchi, K. Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies. Int. J. Mol. Sci. 2021, 22, 46. https://doi.org/10.3390/ijms22010046

AMA Style

Tokunaga Y, Takeuchi K. Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies. International Journal of Molecular Sciences. 2021; 22(1):46. https://doi.org/10.3390/ijms22010046

Chicago/Turabian Style

Tokunaga, Yuji, and Koh Takeuchi. 2021. "Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies" International Journal of Molecular Sciences 22, no. 1: 46. https://doi.org/10.3390/ijms22010046

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