Silk Sericin-inspired Poly-β-homoserine for Protein Protection

Abstract

Protein stability is a critical factor that limits its application in biopharmaceuticals, clinical diagnostics, and industrial production. The inherent instability of proteins renders them susceptible to loss of activity and function under external environmental stresses, thus necessitating the development of novel stabilizers to improve protein stability. Inspired by sericin, we developed heterochiral poly-β-homoserine (β-HS) that combines resistance to enzymatic degradation, straightforward synthesis, and precise composition control, while exhibiting favorable in vitro safety profile. The β-HS exhibits remarkable stabilizing effects on horseradish peroxidase (HRP) and β-galactosidase (β-Gal) when subjected to elevated temperature and lyophilization, respectively. Our research indicates that β-HS stabilizes proteins by assisting in the maintenance of their conformation and preventing aggregation. Additionally, β-HS demonstrates stabilizing effects on proteins with diverse physicochemical properties. Therefore, this study suggests that the β-HS is a promising candidate for enhancing protein stability.