Computer-Assisted Stabilization of Fibroblast Growth Factor FGF-18
Authors
Vilim, J., Ghazalova, T., Petulova, E., Horackova, A., Stepankova, V., Chaloupkova, R., Bednar, D., Damborsky, J., Prokop, Z.
Source
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL 21 : 5144-5152 (2023)
Abstract
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°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°C and 1-day at 50°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.