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Influence Of Sorbitol on Protein Crowding in Solution and Freeze-Concentrated Phases



Sheila Khodadadi, Nicholas James Clark, Arnold McAuley, Viviana Cristiglio, Joseph E. Curtis, Evgenyi Y. Shalaev, Susan T. Krueger


Protein stability during processing and storage is of great challenge for biotechnology and pharmaceutical industries. Polyhydroxy compounds are well-known cryo- and lyo-protectors, which minimize destabilization of proteins and biological systems during freeze-drying process. However, freeze-destabilization of proteins is commonly observed even in the presence of these components. In this letter, small-angle neutron scattering was employed to investigate protein crowding in freeze-concentrated solutions of model systems representing pharmaceutical processing conditions in the temperature range of 298 °K to 100 °K. The results demonstrate an increase in large-scale heterogeneity upon cooling to the glass transition and below, as well as two populations of clustered proteins in the freeze-concentrated solution. The interaction distance between proteins is larger in the presence of sorbitol as cryo- lyo-protector than that found in sorbitol-free systems.
Soft Matter


protein interaction, aggregation, amorphous, freeze-drying, small-angle neutron scattering (SANS), differential scanning calorimetry (DSC)


Khodadadi, S. , Clark, N. , McAuley, A. , Cristiglio, V. , Curtis, J. , Shalaev, E. and Krueger, S. (2014), Influence Of Sorbitol on Protein Crowding in Solution and Freeze-Concentrated Phases, Soft Matter, [online], (Accessed April 13, 2024)
Created March 30, 2014, Updated October 12, 2021