Computer-assisted stabilization of fibroblast growth factor FGF-18

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) indica...

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Bibliographic Details
Published in:	Computational and structural biotechnology journal Vol. 21; pp. 5144 - 5152
Main Authors:	Jan Vilim, Ghazalova, Tereza, Petulova, Eliska, Horackova, Aneta, Stepankova, Veronika, Chaloupkova, Radka, Bednar, David, Damborsky, Jiri, Prokop, Zbynek
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 01-01-2023 Research Network of Computational and Structural Biotechnology Elsevier
Subjects:	Computer-assisted stabilization FGF-18 Fibroblast growth factor Improved yield Protease Resistance to Thermostability Thermostability Fibroblast growth factor Resistance to FGF-18 Protease Computer-assisted stabilization Improved yield
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Summary:	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. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2001-0370 2001-0370
DOI:	10.1016/j.csbj.2023.10.009