For decades, proteins have been stabilized for biotechnology applications by drying them in the presence of sugars. Engineering of the dried sugar (glassy) formulations is currently based on a combination of weakly predictive metrics and long-term stabilization studies. We have shown that picosecond dynamics in the glass (fast β relaxation), contains a signature that is strongly predictive of long-term protein stability. We have shown that the correlation between protein stability and picosecond dynamics is causal through the dependence of the former on diffusive processes, which are facilitated by the latter. This relationship has potential to provide a highly valuable resource to protein formulators by giving them a rapid and reliable way to evaluate the efficacy of solid protein storage modalities. Work on this project focuses on developing accessible metrologies to extract descriptors of these picosecond material dynamics, and on interpreting them in a way that provides reliable predictions of protein stability. The work involves considerable collaboration with industrial and academic pharmaceutical labs.
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Cicerone, M. T., Zhong, Q., Johnson, J., Aamer, K. A. & Tyagi, M. Surrogate for DebyeWaller factors from dynamic stokes shifts. J. Phys. Chem. Lett. 2, 1464–1468 (2011).
Cicerone, M. T. & Douglas, J. F. β-Relaxation governs protein stability in sugar-glass matrices. Soft Matter 8, 2983–2991 (2012).
Qian, K. K., Grobelny, P. J., Tyagi, M. & Cicerone, M. T. Using the Fluorescence Red Edge Effect to Assess the Long-Term Stability of Lyophilized Protein Formulations. Mol. Pharmaceutics 12, 1141–1149 (2015).