Colloquium

The production, processing and utilization of proteins in biotechnology occur under non-ideal solution conditions. Carbohydrates are often used to enhance the liquid-phase stability of the native state of proteins over denatured states. The mechanisms by which sugars increase protein stability in solution are not completely understood. I will discuss the measurement of structural and thermodynamic effects of carbohydrates on the thermal stability of proteins, and the insights that these experiments provide into the mechanism of liquid-phase protein stabilization. An important technical challenge in the development of commercial pharmaceutical products is to ensure prolonged stability during packaging, shipping and storage. Amorphous solids composed of low-molecular-weight organic molecules and water are widely used as matrices for the entrapment and stabilization of labile biomolecules. The rational design of processes for the vitreous stabilization of biological molecules requires further progress in our ability to answer a number of fundamental questions. These include the molecular mechanisms of glass-mediated stabilization, the quantitative prediction of storage stability, and the low-temperature phase behavior of aqueous organic systems. Experiments on the thermal stabilization of proteins and the evaporation kinetics of amorphous water films illustrate some of the many fascinating puzzles in this area. The application of scientific principles to the stabilization of biomolecules in both liquid and glassy states is a challenging activity to which chemical engineers can make valuable contributions.