Mechanism analysis of sulfobetaines' activity to prevent protein aggregation and application of sulfobetaines to unstable proteins

蛋白质的聚集给药物开发带来了严重的问题。虽然已知磺胺甜菜碱可以防止蛋白质聚集，但其机制尚不清楚。在这里，我们发现磺基甜菜碱加速了蛋白质之间的构象交换率，增加了环的柔韧性。此外，根据蛋白质的特性和缓冲条件，发现磺基甜菜碱使蛋白质不稳定。巯基甜菜碱对蛋白质聚集的预防作用与增强蛋白质的热稳定性无关。磺胺甜菜碱被发现对保护抗体和有效纯化不稳定蛋白质有用。

Aggregation of proteins brings about severe problems in drug development. Although sulfobetaines have been known to prevent protein aggregation, its mechanisms have been elusive. Here we found that sulfobetaines accelerate inter-conformer exchange rates of proteins and increase flexibility of loops. In addition, sulfobetaines were found to make proteins unstable depending on the identity of proteins and buffer conditions. Prevention of protein aggregation by sulfobetaines did not correlate with enhancement of thermostability of proteins. Sulfobetaines were found to be useful for protecting antibodies and for efficient purification of unstable proteins.