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.
