Thermostabilization of proteins by water-miscible additives

Stabilization of protein structure by solvent components is st simple and effective strategy for preserving protein activity under adverse thermal conditions. Glycerol, sugars and some inorganic salts have been known for a long time to hinder protein deactivation when added in high concentrations (> 1 mol L-1). Detailed mechanisms of their action, however, were only partly clarified and empirical protocols are generally followed to accomplish stabilization. This paper is intended to provide a brief survey on the principles of protein stabilization by water-miscible additives. The molecular aspects of stabilization are first analysed, particularly in the light of preferential hydration phenomena. Attention is focused then on the theoretical modeling of solvent effects. The models examined include the solvophobic theory and a molecular-thermodynamic model recently developed by the authors. Evidence emerging from the literature dearly indicates that the complexity of the problem in question prevents a comprehensive rationalization of the influence of additives on stability. Nonetheless some guidelines can be derived that could be beneficial for proper formulation of the media containing stabilizing components.