Even though arginine hydrochloride has been recognized as a protein aggregation suppressor in the biopharmaceutical industry, its use has been questioned due to decreasing transition unfolding temperatures (T_m). Four compounds were designed to enhance the role of arginine by changing the length of the carbon chain with removal or N-acetylation of α-amino group. Biophysical properties were observed by differential scanning calorimetry (DSC), dynamic light scattering (DLS), size-exclusion chromatography (SEC), and flow imaging (FI). N-Acetyl-L-arginine (NALA) performed the best at minimizing decrease in T_m with arginine at different pH. NALA also demonstrated relatively higher colloidal stability than arginine hydrochloride, especially in the acidic pH, thereby reducing agitation stress of IgG. Moreover, NALA exhibited a cooperative effect with commercially used glycine buffer for IVIG to maintain the monomer contents with almost no change and suppressed larger particle formation after agitation with heat. The study concludes that the decreasing T_m of proteins by arginine hydrochloride is due to amide group in the α-carbon chain. Moreover, chemical modification on the group compared to removing it will be a breakthrough of arginine's limitations and optimize storage stability of protein therapeutics.

尽管在生物制药工业中盐酸精氨酸已被公认为是蛋白质聚集抑制剂，但由于降低了转变展开温度（T _m），因此其使用受到了质疑。设计了四种化合物，通过去除或去除α-氨基的N-乙酰化作用来改变碳链长度，从而增强精氨酸的作用。通过差示扫描量热法（DSC），动态光散射（DLS），尺寸排阻色谱法（SEC）和流动成像（FI）观察了生物物理特性。N-乙酰基-L-精氨酸（NALA）在最小化T _m降低方面表现最佳与精氨酸在不同的pH值。NALA还显示出比精氨酸盐酸盐更高的胶体稳定性，尤其是在酸性pH值下，从而降低了IgG的搅拌压力。此外，NALA与用于IVIG的商业用甘氨酸缓冲液表现出协同作用，以保持单体含量几乎不变，并抑制了加热搅拌后较大的颗粒形成。研究得出结论，精氨酸盐酸盐使蛋白质的T _m降低是由于α-碳链中的酰胺基。此外，与去除基团相比，对该基团进行化学修饰将是精氨酸局限性的突破，并优化蛋白质治疗剂的储存稳定性。