Small Amine Molecules: Solvent Design Toward Facile Improvement of Protein Stability Against Aggregation and Inactivation

Title:Small Amine Molecules: Solvent Design Toward Facile Improvement of Protein Stability Against Aggregation and Inactivation

Volume: 17 Issue: 2

Author(s): Kentaro Shiraki, Shunsuke Tomita and Naoto Inoue

Affiliation:

Keywords: Amine compound, arginine, polyamine, amino acid derivative, protein aggregation, protein inactivation, solvent additive.

Abstract: Proteins are prone to inactivation in aqueous solutions because chemical modification and aggregation usually occur, particularly at high temperature. This review focuses on the recent advance in practical application with amine compounds that prevent the heat-induced inactivation and aggregation of proteins. Coexistence of amine solutes, typically diamines, polyamines, amino acid esters, and amidated amino acids decreases the heat-induced inactivation rate of proteins by one order of magnitude compared with that in the absence of additives under low concentrations of proteins at physiological pH. The amine compounds mainly suppress chemical modification, typically the β-elimination of disulfide bond and deamidation of asparagine side chain, thereby preventing heat-induced inactivation of proteins. Polyamines do not improve the refolding yield of proteins, owing to decrease in the solubility of unfolded proteins. In contrast, arginine is the most versatile additive for various situations, such as refolding of recombinant proteins, solubilized water-insoluble compounds, and prevention of nonspecific binding to solid surfaces; however, it is not always effective for preventing heat-induced aggregation. Amine compounds will be a key to prevent protein inactivation in solution additives.

Cite this article as:

Shiraki Kentaro, Tomita Shunsuke and Inoue Naoto, Small Amine Molecules: Solvent Design Toward Facile Improvement of Protein Stability Against Aggregation and Inactivation, Current Pharmaceutical Biotechnology 2016; 17 (2) . https://dx.doi.org/10.2174/1389201017666151029110229