Effect of Additives on Protein Aggregation

Abstract

This paper overviews solution additives that affect protein stability and aggregation during refolding, heating, and freezing processes. Solution additives are mainly grouped into two classes, i.e., protein denaturants and stabilizers. The former includes guanidine, urea, strong ionic detergents, and certain chaotropic salts; the latter includes certain amino acids, sugars, polyhydric alcohols, osmolytes, and kosmotropic salts. However, there are solution additives that are not unambiguously placed into these two classes, including arginine, certain divalent cation salts (e.g., MgCl(2)) and certain polyhydric alcohols (e.g., ethylene glycol). Certain non-ionic or non-detergent surfactants, ionic liquids, amino acid derivatives, polyamines, and certain amphiphilic polymers may belong to this class. They have marginal effects on protein structure and stability, but are able to disrupt protein interactions. Information on additives that do not catalyze chemical reactions nor affect protein functions helps us to design protein solutions for increased stability or reduced aggregation.

Arginine and proline applied as food additives stimulate high freeze tolerance in larvae of Drosophila melanogaster

“…Importantly, sugars, polyols, many amino acids (other than arginine and proline), racemic mixtures of L-and D-proline, and hydroxyproline have only little or no ability to form supramolecular aggregates and to inhibit protein aggregation. These same compounds, however, are known to stabilize native structure of proteins by preferential exclusion (Paleg et al, 1981;Samuel et al, 2000;Myung et al, 2006;Das et al, 2007;Hamada et al, 2009). We observed little or no effect of D-proline and hydroxyproline on larval freeze tolerance in our experiments (Table S3), which suggests that the formation of supramolecular aggregates of proline and arginine and inhibition of aggregation of partially unfolded proteins might represent another mechanism, in addition to preferential exclusion, that explains the high freeze tolerance in D. melanogaster larvae reared on diets augmented specifically with arginine and proline.…”

Production of heterologous cutinases by E. coli and improved enzyme formulation for application on plastic degradation

“…At high concentrations, salts exert specific effects on protein, resulting in the precipitation of these compounds. Salts act on the increase of the interfacial tension between the protein surface and the solvent, changing the solubility (Hamada et al 2009). …”

“…PEG is one of the most versatile water soluble polymers for refolding recombinant proteins and for stabilizing proteins by chemical modification (Hamada et al 2009). In this study, the Pareto chart ( Figure 5) shows the positive effect of the interaction between glycerol and PEG-200 in the activity of CUT-N1.…”

Studies on Recombinant Lipase Production by E. Coli: Effect of Media And Bacterial Expression System Optimization

“…Numerous solution additives had been proved useful for this goal. It had been reported that the non-detergent surfactants are more favourable for aggregation suppression than the detergents [36]. Therefore, we add surfactant to the growth media and observed 2.8 fold enhancements in enzyme activity when compared with production without surfactant.…”