On the relationship between conformation and stability in solid pharmaceutical protein formulations
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Updated: Aug 22, 2026

Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders
Published on: April 14, 2015
Alexander M Klibanov1, Jennifer A Schefiliti
1Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. klibanov@mit.edu
Abstract:
Long-term stability is critical in the successful development of pharmaceuticals, including macromolecular ones, such as proteins. Due to the relative instability of aqueous solutions of proteins, they are typically stores in a freeze-dried (lyophilized) state. However, proteins reversibly (and sometimes even irreversibly) denature upon lyophilization and consequently adopt conformations markedly distinct from the native ones. This phenomenon may profoundly affect deleterious processes in lyophilized proteins, e.g. moisture-induced aggregation, as illustrated in this review with bovine serum and recombinant human albumins.
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