Abstract
The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytical techniques that are commonly used to characterize protein structure, dynamics and conformation in lyophilized solids. The review also discusses the applications of recently developed mass spectrometry based methods (solid-state hydrogen deuterium exchange mass spectrometry (ssHDX-MS) and solid-state photolytic labeling mass spectrometry (ssPL-MS)) and their ability to study proteins in the solid-state at high resolution.
Keywords: Solid-state, lyophilization, protein structure, protein dynamics, protein conformations, protein stability, mass spectrometry, spectroscopy.
Current Pharmaceutical Design
Title:Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids
Volume: 21 Issue: 40
Author(s): Balakrishnan S. Moorthy, Lavanya K. Iyer and Elizabeth M. Topp
Affiliation:
Keywords: Solid-state, lyophilization, protein structure, protein dynamics, protein conformations, protein stability, mass spectrometry, spectroscopy.
Abstract: The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytical techniques that are commonly used to characterize protein structure, dynamics and conformation in lyophilized solids. The review also discusses the applications of recently developed mass spectrometry based methods (solid-state hydrogen deuterium exchange mass spectrometry (ssHDX-MS) and solid-state photolytic labeling mass spectrometry (ssPL-MS)) and their ability to study proteins in the solid-state at high resolution.
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Cite this article as:
Moorthy S. Balakrishnan, Iyer K. Lavanya and Topp M. Elizabeth, Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids, Current Pharmaceutical Design 2015; 21 (40) . https://dx.doi.org/10.2174/1381612821666151008150735
DOI https://dx.doi.org/10.2174/1381612821666151008150735 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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