Stabilizing protein pharmaceuticals by imidazolium-type zwitterions

An imidazolium-carboxylate-type zwitterion, OE₂imC₃C, thermally stabilizes the structure in the vicinity of heme in cytochrome c. However, it remains unclear whether OE₂imC₃C can thermally stabilize protein pharmaceuticals, which are vulnerable to heating and shaking during production and transportation. In this study, we investigated the stabilization of the entire structure and function of insulin by OE₂imC₃C. Insulin in the 60 wt% OE₂imC₃C solution did not aggregate under shaking and heating (1000 rpm and 80 °C) and retained its folded structure. The shaked and heated insulin also exhibited normal function in cell proliferation. In contrast, the secondary structure of insulin in the 40 wt% OE₂imC₃C solution changed, and insulin in the 20 wt% OE₂imC₃C solution aggregated after shaking and heating. Therefore, the 60 wt% OE₂imC₃C solution has potential to stabilize protein pharmaceuticals.