Computer-assisted stabilization of fibroblast growth factor FGF-18
| Autoři | |
|---|---|
| Rok publikování | 2023 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Computational and Structural Biotechnology Journal |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.sciencedirect.com/science/article/pii/S2001037023003665?via%3Dihub |
| Doi | http://dx.doi.org/10.1016/j.csbj.2023.10.009 |
| Klíčová slova | Computer-assisted stabilization; Fibroblast growth factor; Thermostability; Resistance to; Protease; Improved yield; FGF-18 |
| Popis | The fibroblast growth factors (FGF) family holds significant potential for addressing chronic diseases. Specifically, recombinant FGF18 shows promise in treating osteoarthritis by stimulating cartilage formation. However, recent phase 2 clinical trial results of sprifermin (recombinant FGF18) indicate insufficient efficacy. Leveraging our expertise in rational protein engineering, we conducted a study to enhance the stability of FGF18. As a result, we obtained a stabilized variant called FGF18-E4, which exhibited improved stability with 16 degrees C higher melting temperature, resistance to trypsin and a 2.5-fold increase in production yields. Moreover, the FGF18-E4 maintained mitogenic activity after 1-week incubation at 37 degrees C and 1-day at 50 degrees C. Additionally, the inserted mutations did not affect its binding to the fibroblast growth factor receptors, making FGF18-E4 a promising candidate for advancing FGF-based osteoarthritis treatment. |
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