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.
Highlights
INTRODUCTIONThe causes of protein inactivation can be classified into physical and chemical processes; the former involves structural unfolding and aggregation, whereas the latter involves chemical modification [1]
This review focuses on the amine compounds that prevent the heat-induced inactivation and aggregation of proteins as solvent additives and provides the following information: 1) We summarize a systematic property of amine compounds that prevents the heat-induced inactivation and aggregation of proteins, such as amino acids, amino acid alkylesters, amidated amino acids, diamines, and naturally occurring polyamines; 2) We introduce the major causes for chemical modifications of proteins, deamidation of Asn residue, β-elimination of disulfide bond, and disulfide exchange; 3) We describe the prevention of such chemical modification by amine compounds from heat treatment
The molecular mechanisms of the amine compounds acting as additive are mainly triggered by the prevention of chemical modifications, which would lead to the prevention of the irreversible inactivation of proteins
Summary
The causes of protein inactivation can be classified into physical and chemical processes; the former involves structural unfolding and aggregation, whereas the latter involves chemical modification [1]. Various kinds of low molecular weight additives have been developed to avoid protein inactivation and aggregation [2]. The inhibition of chemical modifications results in the prevention of heatinduced inactivation of proteins; 4) We introduce the most. 1873-4316/16 $58.00+.00 well-known additive Arg. Arginine prevents the heat-induced aggregation of proteins as well as increases the solubility of aromatic compounds and aggregation-prone unfolded proteins; 5) We discuss the additives regarding the distinction between heat-induced aggregation and refolding-induced misfolding. We discuss why amine compounds from living cells prevent the heat-induced degradation of proteins
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