Characterization of Higher-Order Structures in Protein Pharmaceuticals: a Study of Methods and Advances

doi:10.19803/j.1672-8629.20250615

Abstract

Abstract: Objective To summarize the recent advancements in methods used to characterize the higher-order structures of protein drugs in order to address the challenges to quality control and to provide references for structural analysis of related drugs. Methods By reviewing related literature, the principles and applications of and limitations to mass spectrometry, cryo-electron microscopy, and artificial intelligence prediction in the characterization of protein drug higher-order structures were synthesized. Results There were distinct advantages to different characterization techniques in terms of resolution, throughput, and dynamic information capture. Mass spectrometry excelled in analyzing conformational dynamics, cryo-electron microscopy provided near-atomic-level static structures, while the integration of multiple techniques and computational modeling significantly improved the integrity and reliability of structural information about complex protein systems. Conclusion Despite the progress that has been made in protein drug structure research, currently-used analytical methods are far from perfect. More research and the development of new methods are required to achieve more precise structural analysis, which are expected to provide technical support for the development and quality control of biological drugs.

Key words: Protein Therapeutics, Higher-Order Structure, Cryo-Electron Microscopy, Hydrogen-Deuterium Exchange Mass Spectrometry, AlphaFold

CLC Number:

R954.5

MENG Hexin, WANG Yue, LIU Youping, LIU Bo. Characterization of Higher-Order Structures in Protein Pharmaceuticals: a Study of Methods and Advances[J]. Chinese Journal of Pharmacovigilance, 2025, 22(10): 1177-1182.

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https://zgywjj.magtechjournal.com/EN/Y2025/V22/I10/1177

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