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.